ARYL-N-ARYL DERIVATIVES FOR TREATING A RNA VIRUS INFECTION

Abstract

A compound of formula (Ie):

##STR00001##

wherein Y.sup.1 represents an aryl group, X.sup.2 represents a —O— group, a —NH— group, a —S— group, a —CO—NH— group, a —NH—CO—NH— group, a —NH—CO— group, a —CH(OH)— group, a —CH(COOH)NH— group, a —CH(COOCH.sub.3)NH— group, a —C(OH)(CH.sub.2OH)—, a

##STR00002##

group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms, a —SO.sub.2— group, or a —SO.sub.2—NH— group, Y.sup.2 represents a hydrogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a —CHC(OH).sub.2, a COOR.sub.f, wherein R.sub.f represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, a morpholinyl group, a dihydropyranyl group, a

##STR00003##

group, a

##STR00004##

group, a —PO(OR.sub.f)(OR′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, an oxetanyl group, a —Si(CH.sub.3).sub.3 group, a —NHCOO—(C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, or any of its pharmaceutically acceptable salt and pharmaceutical compositions containing them and to synthesis process for manufacturing them.

Claims

1-15. (canceled)

16. A compound of formula (Ie): ##STR00230## wherein: ##STR00231## ring and ##STR00232## ring independently mean a phenylene or a pyridylene group, Y.sup.1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, the aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, R.sub.a, R.sub.b, R.sub.c and R.sub.d independently represent a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, X.sup.2 represents a —O— group, a —NH— group, a —S— group, a —CO—NH— group, a —NH—CO—NH— group, a —NH—CO— group, a —CH(OH)— group, a —CH(COOH)NH— group, a —CH(COOCH.sub.3)NH— group, a —C(OH)(CH.sub.2OH)—, a ##STR00233## group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms such as a triazole, a tetrazole or an oxadiazole, a —SO.sub.2— group, or a —SO.sub.2—NH— group, n is 0, 1, 2 or 3, m and m′ are independently 0, 1 or 2, Y.sup.2 represents a hydrogen atom, a hydroxyl group, a (C.sub.1-C.sub.4)alkoxy group, a —CHC(OH).sub.2, a COOR.sub.f, wherein R.sub.f represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, a morpholinyl group, a dihydropyranyl group, a ##STR00234## group, a ##STR00235## group, a —PO(OR′.sub.f)(OR′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, an oxetanyl group, a —Si(CH.sub.3).sub.3 group, a —NHCOO—(C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.5)cycloalkyl group, the (C.sub.3-C.sub.5)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and the (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on the R.sup.1 and/or R.sup.2 by an oxygen atom, or alternatively X.sup.2—Y.sup.2 represents a group —CONR.sub.cR.sub.d, wherein R.sub.c and R.sub.d form, together with the nitrogen atom a heterocyclic group, optionally substituted by a hydroxy group or a (C.sub.1-C.sub.4)alkyl group, R and R′ independently represent a (C.sub.1-C.sub.4)alkyl group, a —S—(C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, a halogen atom, such as a fluoro atom, a trifluoromethyl group, a —SO.sub.2(C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkenyl group, a (C.sub.1-C.sub.5)alkoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H or SO.sub.2—CH.sub.3 group, a —OH group, a —CONHR.sub.g, wherein R.sub.g represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, a —O—SO.sub.2—OR.sub.c group, a azetidinyl group, a morpholinyl group, or a cyano group, R″ represents a hydrogen atom, a (C.sub.1-C.sub.4)alkyl group optionally substituted by a —COOH group, or any of its pharmaceutically acceptable salt.

17. The compound of formula (Ie) according to claim 16, wherein ##STR00236## ring and ##STR00237## ring both represent a phenylene group or ##STR00238## ring represents a pyridylene group and ##STR00239## ring represents a phenylene group, or any of its pharmaceutically acceptable salt.

18. The compound of formula (Ie) according to claim 16, wherein R″ is a hydrogen atom or any of its pharmaceutically acceptable salt.

19. The compound of formula (Ie) according to claim 16, wherein Y.sup.1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, the aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, or any of its pharmaceutically acceptable salt.

20. The compound of formula (Ie) according to claim 16, wherein X.sup.2 represents a —O— group, a —NH— group, a —S— group, a —CO—NH— group, a —NH—CO—NH— group, a —NH—CO— group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, a tetrazole or an oxadiazole, a —SO.sub.2— group, or a —SO.sub.2—NH— group, or any of its pharmaceutically acceptable salt.

21. The compound of formula (Ie) according to claim 16, wherein Y.sup.2 represents a hydrogen atom, a hydroxyl group, a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.5)cycloalkyl group, the (C.sub.3-C.sub.5)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and the (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on the R.sup.1 and/or R.sup.2 by an oxygen atom, or any of its pharmaceutically acceptable salt.

22. The compound of formula (Ie) according to claim 16, wherein R and R′ independently represent a (C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, a halogen atom, such as a fluoro atom, a trifluoromethyl group, or a —SO.sub.3H or SO.sub.2—CH.sub.3 group, or any of its pharmaceutically acceptable salt.

23. The compound of formula (Ie) according to claim 16, wherein ##STR00240## ring and ##STR00241## ring both represent a phenylene group, R″ is a hydrogen atom, Y.sup.1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, the aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, X.sup.2 represents a —O— group, a —CO—NH— group, a —NH—CO—NH— group, a —NH—CO— group, a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, a tetrazole or an oxadiazole, or a —SO.sub.2—NH— group, Y.sup.2 represents a hydrogen atom, a hydroxyl group, a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.5)cycloalkyl group, the (C.sub.3-C.sub.5)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and the (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on the R.sup.1 and/or R.sup.2 by an oxygen atom, and R and R′ independently represent a (C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, a halogen atom, such as a fluoro atom, a trifluoromethyl group, a —SO.sub.3H or SO.sub.2—CH.sub.3 group, or a morpholinyl group, or any of its pharmaceutically acceptable salt.

24. The compound of formula (Ie) according to claim 16, wherein ##STR00242## ring and ##STR00243## ring both represent a phenylene group, R″ is a hydrogen atom, Y.sup.1 represents a phenyl group or a pyridyl group, X.sup.2 represents a —O— group, a —CO—NH— group, a —NH—CO— group, or a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, tetrazole or an oxadiazole, Y.sup.2 represents a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.5)cycloalkyl group, and R and R′ independently represent a (C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, or a morpholinyl group, or any of its pharmaceutically acceptable salt.

25. The compound of formula (Ie) according to claim 16 selected from ##STR00244## ##STR00245## ##STR00246## ##STR00247## ##STR00248## ##STR00249## ##STR00250## ##STR00251## ##STR00252## ##STR00253## ##STR00254## ##STR00255## ##STR00256## ##STR00257## ##STR00258## ##STR00259## ##STR00260## ##STR00261## ##STR00262## ##STR00263## ##STR00264## ##STR00265## ##STR00266## ##STR00267## ##STR00268## or any of its pharmaceutically acceptable salt.

26. A method for treating and/or preventing a subject from a RNA virus infection caused by a virus belonging to group IV or V of the Baltimore classification comprising the administration of a therapeutically effective quantity of a compound of formula (Ie) according to claim 16 or any of compounds (36) to (206) ##STR00269## ##STR00270## ##STR00271## ##STR00272## ##STR00273## ##STR00274## ##STR00275## ##STR00276## ##STR00277## ##STR00278## ##STR00279## ##STR00280## ##STR00281## ##STR00282## ##STR00283## ##STR00284## ##STR00285## ##STR00286## ##STR00287## ##STR00288## ##STR00289## ##STR00290## ##STR00291## ##STR00292## ##STR00293## ##STR00294## ##STR00295## ##STR00296## or any of its pharmaceutically acceptable salts comprising at least of administering the compound in a patient in need thereof.

27. The method according to claim 26, wherein the RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification is selected from RSV, Chikungunya, influenza and Dengue.

28. A pharmaceutical composition comprising at least one compound as defined in claim 16 or anyone of its pharmaceutically acceptable salts, or at least any of compounds (36) to (206) ##STR00297## ##STR00298## ##STR00299## ##STR00300## ##STR00301## ##STR00302## ##STR00303## ##STR00304## ##STR00305## ##STR00306## ##STR00307## ##STR00308## ##STR00309## ##STR00310## ##STR00311## ##STR00312## ##STR00313## ##STR00314## ##STR00315## ##STR00316## ##STR00317## ##STR00318## ##STR00319## ##STR00320## ##STR00321## or any of its pharmaceutically acceptable salts and also at least one pharmaceutically acceptable excipient.

29. A synthesis process for manufacturing a compound of formula (Ie) as defined in claim 16 or anyone of its pharmaceutically acceptable salts or a compound of formula (Ie) selected from ##STR00322## ##STR00323## ##STR00324## ##STR00325## ##STR00326## ##STR00327## ##STR00328## ##STR00329## ##STR00330## ##STR00331## ##STR00332## ##STR00333## ##STR00334## ##STR00335## ##STR00336## ##STR00337## ##STR00338## ##STR00339## ##STR00340## or anyone of its pharmaceutically acceptable salts, comprising at least a step of coupling a compound of formula (IIe) ##STR00341##  with a compound of formula (IIIe) ##STR00342## wherein X.sup.1, Y.sup.1, R, R′, m, m′, ##STR00343## ring, ##STR00344## ring, X.sup.2, Y.sup.2R.sub.a and R.sub.b are as defined above X is a chlorine atom, an iodine atom or a bromine atom and Y.sup.1 is a phenyl group, a pyridine group, a pyrazine group, a pyridazine group or a pyrimidine group, in presence of an inorganic base and a diphosphine and in the presence of an organometallic catalyst, to obtain a compound of formula (e) as defined in claim 16 or anyone of its pharmaceutically acceptable salts or a compound as defined or anyone of its pharmaceutically acceptable salts.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0052] The inventors have surprisingly found that aryl-N-aryl compounds are endowed with a broad-spectrum activity against RNA viruses, and more particularly single-stranded RNA viruses belonging to Group IV or V of the Baltimore classification. Groups IV and V include respectively (+)ssRNA viruses and (−)ssRNA viruses; which also refer to positive-sense single-stranded RNA viruses and negative-sense single-stranded RNA viruses.

[0053] For reference, the content of the «Baltimore classification» is considered in light of the Classification and Nomenclature of viruses as set forth in the 10th report on Virus Taxonomy dated 2017.

[0054] The present document discloses a compound of formula (I)

##STR00005## [0055] wherein:

##STR00006##

ring and

##STR00007##

ring independently mean a phenylene or a pyridylene group, [0056] wherein the group

##STR00008##

is in meta or para position on the

##STR00009##

ring, in particular in meta position, with respect to the —NH— group, [0057] X.sup.1 represents an alkenylene group, in particular an ethenylene group, a —NH—CO— group, a —CO—NH— group, a —CR.sub.aR.sub.bO— group, [0058] Y.sup.1 represents an aryl group selected from a 2-pyridyl group or a pyrimidinyl group, wherein one of the nitrogen atom of the pyrimidinyl group is in ortho position with respect to X.sup.1, [0059] or alternatively X.sup.1—Y.sup.1 represents a group (A) of formula

##STR00010## [0060] X.sup.2 represents a —CO—NH— group, a —NH—CO—NH— group, a —OCH.sub.2— group, a —NH—CO— group or a —SO.sub.2—NH— group, [0061] n is 0, 1, 2 or 3, [0062] m and m′ are independently 0, 1 or 2, [0063] Y.sup.2 represents a hydrogen atom, a hydroxyl group or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.8)cycloalkyl group, said (C.sub.3-C.sub.8)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and said (C.sub.3-C.sub.5)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, [0064] R and R′ independently represent a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, a (C.sub.1-C.sub.5)alkoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, R.sub.a, R.sub.b, R.sub.c and R.sub.d independently represent a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, [0065] provided that when X.sup.1 is a —CR.sub.aR.sub.bO— group, Y.sup.1 may further be a 3-pyridyl, a 4-pyridyl or a phenyl group optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group,

[0066] or any of its pharmaceutically acceptable salt,

[0067] for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification and in particular a Chikungunya viral infection, a Dengue viral infection, an Influenza viral infection or a RSV viral infection or a virus-related condition.

[0068] According to a first aspect, the present invention relates to a compound of formula (Ie),

##STR00011##

[0069] wherein

[0070] Y.sup.1, R, R′, R.sub.a, R.sub.b, m, m′,

##STR00012##

ring,

##STR00013##

ring, X.sup.2, n and Y.sup.2 are as defined above for formula (I)

[0071] or any of its pharmaceutically acceptable salt. [0072] Still according to said first aspect, the present invention further relates to compounds of formula (Ie), wherein the group

##STR00014##

is in meta or para position and preferably in meta position on the

##STR00015##

ring, with respect to the —NH— group, [0073] m is 0, n is 0, 1, 2 or 3, [0074] Y.sup.1 represents a pyridyl or a phenyl group optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group and a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, [0075] Y.sup.2 represents a hydrogen atom, a hydroxyl group or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom or a (C.sub.1-C.sub.2)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.6)cycloalkyl group, said (C.sub.3-C.sub.6)cycloalkyl group being optionally substituted by one or two halogen atom(s) and said (C.sub.3-C.sub.6)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom,

[0076] or any of its pharmaceutically acceptable salt.

[0077] According to a second aspect, the present invention relates to compounds of formula (Ie) as defined above for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification, and in particular a Chikungunya viral infection, a Dengue viral infection, an Influenza viral infection or a RSV viral infection or a virus-related condition.

[0078] According to a third aspect, the present invention relates to a compound of formula (Ie)

##STR00016##

[0079] wherein

##STR00017##

ring and

##STR00018##

ring independently mean a phenylene or a pyridylene group, [0080] Y represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, said aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, [0081] X.sup.2 represents [0082] a —O— group, [0083] a —NH— group, [0084] a —S— group, [0085] a —CO—NH— group, [0086] a —NH—CO—NH— group, [0087] a —NH—CO— group, [0088] a —CH(OH)— group, [0089] a —CH(COOH)NH— group, [0090] a —CH(COOCH.sub.3)NH— group, [0091] a —C(OH)(CH.sub.2OH)—, [0092] a

##STR00019##  group, [0093] a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or heteroatoms such as a triazole, a tetrazole or an oxadiazole, [0094] a —SO.sub.2— group, [0095] or [0096] a —SO.sub.2—NH— group, [0097] n is 0, 1, 2 or 3, [0098] m and m′ are independently 0, 1 or 2, [0099] Y.sup.2 represents [0100] a hydrogen atom, [0101] a hydroxyl group, [0102] a (C.sub.1-C.sub.4)alkoxy group, [0103] a —CHC(OH).sub.2, [0104] a COOR.sub.f, wherein R.sub.f represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, [0105] a morpholinyl group, [0106] a dihydropyranyl group, a

##STR00020##  group, [0107] a

##STR00021##  group, [0108] a —PO(OR.sub.f)(OR′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, [0109] an oxetanyl group, [0110] a —Si(CH.sub.3).sub.3 group, [0111] a —NHCOO—(C.sub.1-C.sub.4)alkyl group, [0112] or [0113] a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.8)cycloalkyl group, said (C.sub.3-C.sub.8)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and said (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, [0114] or alternatively X.sup.2—Y.sup.2 represents a group —CONR.sub.cR.sub.d, wherein R.sub.c and R.sub.d form, together with the nitrogen atom a heterocyclic group, optionally substituted by a hydroxy group or a (C.sub.1-C.sub.4)alkyl group, [0115] R and R′ independently represent [0116] a (C.sub.1-C.sub.4)alkyl group, [0117] a —S—(C.sub.1-C.sub.4)alkyl group, [0118] a (C.sub.3-C.sub.6)cycloalkyl group, [0119] a halogen atom, such as a fluoro atom, [0120] a trifluoromethyl group, [0121] a —SO.sub.2(C.sub.1-C.sub.4)alkyl group, [0122] a (C.sub.3-C.sub.6)cycloalkenyl group, [0123] a (C.sub.1-C.sub.5)alkoxy group, [0124] a —SO.sub.2—NR.sub.aR.sub.b group, [0125] a —SO.sub.3H or SO.sub.2—CH.sub.3 group, [0126] a —OH group, [0127] a —CONHR.sub.g, wherein R.sub.g represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, [0128] a —O—SO.sub.2—OR.sub.c group, [0129] a azetidinyl group, [0130] a morpholinyl group, or [0131] a cyano group, [0132] R″ represents a hydrogen atom, a (C.sub.1-C.sub.4)alkyl group optionally substituted by a —COOH group, [0133] or any of its pharmaceutically acceptable salt.

[0134] According to a fourth aspect, the present invention relates to a compound of formula (Ie) as defined above for use as a medicament.

[0135] According to a fifth aspect, the present invention relates to a compound of formula (Ie) as defined above, for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification, and in particular a Chikungunya viral infection, a Dengue viral infection, an Influenza viral infection or a RSV viral infection or a virus-related condition.

[0136] The above-mentioned compounds (I) and (Ie) are particularly suitable for treating or preventing a virus infection or related condition, in particular a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification or related condition, and most preferably a Chikungunya viral infection, a Dengue viral infection, an Influenza viral infection or a RSV viral infection or a virus-related condition.

[0137] The above-mentioned compounds are even more particularly suitable for treating or preventing a Chikungunya viral infection, a Dengue viral infection or a RSV viral infection or a virus-related condition, most particularly a RSV viral infection.

[0138] Further aspects of the present invention will be described herein after such as the use of new compounds of formula (Ie) as a medicament, a pharmaceutical composition and a synthetic process.

[0139] According to a particular embodiment, a subject-matter of the present document describes a compound of formula (I) as defined above, wherein the alkenylene group is a (E)-alkenylene group, [0140] m and m′ are independently 0 or 1, [0141] Y.sup.2 represents a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.2)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.6)cycloalkyl group, said (C.sub.3-C.sub.6)cycloalkyl group being optionally substituted by one or two halogen atoms and said (C.sub.3-C.sub.6)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, [0142] R and R′ independently represent a halogen atom, a (C.sub.1-C.sub.2)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, or a (C.sub.1-C.sub.2)alkoxy group,

[0143] or any of its pharmaceutically acceptable salt,

[0144] for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification, and in particular a Chikungunya viral infection a Dengue viral infection, an Influenza viral infection or a RSV viral infection or a virus-related condition.

[0145] According to a further embodiment, the present document describes a compound of formula (I)

##STR00022## [0146] wherein:

##STR00023##

ring and

##STR00024##

ring independently mean a phenylene or a pyridylene group, [0147] wherein the group

##STR00025##

is m meta or para position on the

##STR00026##

ring, with respect to the —NH— group, [0148] X.sup.1 represents an alkenylene group, a —NH—CO— group, a —CO—NH— group, a —CR.sub.aR.sub.bO— group, [0149] Y.sup.1 represents an aryl group selected from a 2-pyridyl group or a pyrimidinyl group, wherein one of the nitrogen atom of the pyrimidinyl group is in ortho position with respect to X.sup.1, [0150] or alternatively X.sup.1—Y.sup.1 represents a group (A) of formula

##STR00027## [0151] X.sup.2 represents a —CO—NH— group, a —NH—CO—NH— group, a —OCH.sub.2— group, [0152] a —NH—CO— group or a —SO.sub.2—NH— group, [0153] n is 0, 1, 2 or 3, [0154] m and m′ are independently 0, 1 or 2, [0155] Y.sup.2 represents a hydrogen atom, a hydroxyl group or a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.8)cycloalkyl group, said (C.sub.3-C.sub.8)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and said (C.sub.3-C.sub.5)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, [0156] R and R′ independently represent a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, a (C.sub.1-C.sub.5)alkoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, [0157] R.sub.a, R.sub.b, R.sub.c and R.sub.d independently represent a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, [0158] provided that when X.sup.1 is a —CR.sub.aR.sub.bO— group, Y.sup.1 may further be a 3-pyridyl, a 4-pyridyl or a phenyl group optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group, a —SO.sub.2—NR.sub.aR.sub.b group, a —SO.sub.3H group, a —OH group, a —O—SO.sub.2—OR.sub.c group or a —O—P(═O)—(OR.sub.c)(OR.sub.d) group, [0159] and provided that when Y.sup.1—X.sup.1 represents a 2-pyridylethenylene group, X.sup.2 represents a —CO—NH— group and Y.sup.2 represents a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group, and m′ is different from 0,

[0160] or any of its pharmaceutically acceptable salt,

[0161] for use in the treatment and/or prevention of a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification.

[0162] According to a particular embodiment, the present invention relates to a compound of formula (Ie) as defined above, wherein

##STR00028##

ring and

##STR00029##

ring both represent a phenylene group or

##STR00030##

ring [0163] represents a pyridylene group and

##STR00031## [0164] ring represents a phenylene group, [0165] or any of its pharmaceutically acceptable salt.

[0166] In another embodiment, the present invention relates to a compound of formula (Ie) as defined above, wherein [0167] m and m′ are independently 0 or 1, [0168] Y.sup.2 represents a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.2)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.6)cycloalkyl group, said (C.sub.3-C.sub.6)cycloalkyl group being optionally substituted by one or two halogen atom(s) and said (C.sub.3-C.sub.6)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, [0169] R and R′ independently represent a halogen atom, a (C.sub.1-C.sub.2)alkyl group, a (C.sub.3-C.sub.6)cycloalkyl group, or a (C.sub.1-C.sub.2)alkoxy group, [0170] or any of its pharmaceutically acceptable salt.

[0171] In another embodiment, the present invention relates to the compound of formula (Ie), wherein R″ is a hydrogen atom or any of its pharmaceutically acceptable salt.

[0172] In another embodiment, the present invention relates to the compound of formula (Ie), wherein

[0173] Y.sup.1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, said aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group,

[0174] or any of its pharmaceutically acceptable salt.

[0175] In another embodiment, the present invention relates to the compound of formula (Ie), wherein X.sup.2 represents [0176] a —O— group, [0177] a —NH— group, [0178] a —S— group, [0179] a —CO—NH— group, [0180] a —NH—CO—NH— group, [0181] a —NH—CO— group, [0182] a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, a tetrazole or an oxadiazole, [0183] a —SO.sub.2— group, [0184] or [0185] a —SO.sub.2—NH— group,

[0186] or any of its pharmaceutically acceptable salt.

[0187] In another embodiment, the present invention relates to the compound of formula (Ie), wherein Y.sup.2 represents

[0188] a hydrogen atom,

[0189] a hydroxyl group,

[0190] a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group,

[0191] or

[0192] a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.8)cycloalkyl group, said (C.sub.3-C.sub.5)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and said (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom, or any of its pharmaceutically acceptable salt.

[0193] In another embodiment, the present invention relates to the compound of formula (Ie), wherein R and R′ independently represent

[0194] a (C.sub.1-C.sub.4)alkyl group,

[0195] a (C.sub.3-C.sub.6)cycloalkyl group,

[0196] a halogen atom, such as a fluoro atom,

[0197] a trifluoromethyl group, or

[0198] a —SO.sub.3H or SO.sub.2—CH.sub.3 group,

[0199] or any of its pharmaceutically acceptable salt.

[0200] In another embodiment, the present invention relates to the compound of formula (Ie), wherein

##STR00032##

ring and

##STR00033##

ring both represent a phenylene group,

[0201] R″ is a hydrogen atom,

[0202] Y.sup.1 represents an aryl group selected from a phenyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl or a pyrimidinyl group, said aryl group being optionally substituted by one or two substituent(s) selected from a halogen atom, a (C.sub.1-C.sub.4)alkyl group, a cyano group, a (C.sub.1-C.sub.5)alkoxy group, a trifluoromethyl group, a trifluoromethoxy group,

[0203] X.sup.2 represents

[0204] a —O— group,

[0205] a —CO—NH— group,

[0206] a —NH—CO—NH— group,

[0207] a —NH—CO— group,

[0208] a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, a tetrazole or an oxadiazole,

[0209] or

[0210] a —SO.sub.2—NH— group,

[0211] Y.sup.2 represents

[0212] a hydrogen atom,

[0213] a hydroxyl group,

[0214] a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group,

[0215] or

[0216] a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.8)cycloalkyl group, said (C.sub.3-C.sub.5)cycloalkyl group being optionally substituted by one or two (C.sub.1-C.sub.4)alkyl group, halogen atom or (C.sub.1-C.sub.4)alkoxy group and said (C.sub.3-C.sub.8)cycloalkyl group being optionally interrupted on said R.sup.1 and/or R.sup.2 by an oxygen atom,

[0217] and

[0218] R and R′ independently represent

[0219] a (C.sub.1-C.sub.4)alkyl group,

[0220] a (C.sub.3-C.sub.6)cycloalkyl group,

[0221] a halogen atom, such as a fluoro atom,

[0222] a trifluoromethyl group,

[0223] a —SO.sub.3H or SO.sub.2—CH.sub.3 group, or

[0224] a morpholinyl group,

[0225] or any of its pharmaceutically acceptable salt.

[0226] In another embodiment, the present invention relates to the compound of formula (Ie), wherein

##STR00034##

ring and

##STR00035##

ring both represent a phenylene group,

[0227] R″ is a hydrogen atom,

[0228] Y.sup.1 represents a phenyl group or a pyridyl group,

[0229] X.sup.2 represents

[0230] a —O— group,

[0231] a —CO—NH— group,

[0232] a —NH—CO— group,

[0233] or

[0234] a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms such as a triazole, tetrazole or an oxadiazole,

[0235] Y.sup.2 represents

[0236] a —PO(OR.sub.f)(R′.sub.f) group, wherein R.sub.f and R′.sub.f independently represents a hydrogen atom or a (C.sub.1-C.sub.4)alkyl group,

[0237] or

[0238] a —CR.sup.1R.sup.2R.sup.3 group, wherein R.sup.1, R.sup.2 and R.sup.3 independently represent a hydrogen atom, a fluorine atom or a (C.sub.1-C.sub.4)alkyl group, being understood that no more than one of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom, or R.sup.1 and R.sup.2 form together with the carbon atom bearing them a (C.sub.3-C.sub.5)cycloalkyl group,

[0239] and

[0240] R and R′ independently represent

[0241] a (C.sub.1-C.sub.4)alkyl group,

[0242] a (C.sub.3-C.sub.6)cycloalkyl group, or

[0243] a morpholinyl group,

[0244] or any of its pharmaceutically acceptable salt.

[0245] Any combination of the above-defined embodiments for R, R′, R″, m, m′,

##STR00036##

ring,

##STR00037##

ring, X.sup.1, X.sup.2, n, Y.sup.1, Y.sup.2, R.sub.a and R.sub.b with each other does form part of the instant invention.

[0246] According to a preferred embodiment of the present invention, the compound of formula (Ie) is chosen from: [0247] (36) N-(2-cyclopentylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0248] (37) N-isopentyl-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0249] (38) N-(2-cyclohexylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0250] (39) N-(2-cyclopentylethyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0251] (40) N-(2-cyclopentylethyl)-3-((3-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0252] (41) N-(2-cyclopentylethyl)-3-((6-(pyridin-2-ylmethoxy)pyridin-3-yl)amino)benzamide [0253] (42) N-(2-cyclopentylethyl)-6-((4-(pyridin-2-ylmethoxy)phenyl)amino)picolinamide [0254] (43) N-(2-cyclopentylethyl)-3-((3-methoxy-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0255] (44) N-(2-cyclopentylethyl)-3-((5-(pyridin-2-ylmethoxy)pyridin-2-yl)amino)benzamide [0256] (45) N-(2-cyclopropylethyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0257] (46) N-(2-cyclobutylethyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0258] (47) N-(2-cyclohexylethyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0259] (48) N-(2-cyclobutylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0260] (49) N-(2-cyclopropylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0261] (50) N-(2-cyclopentylethyl)-3-((4-((2-fluorobenzyl)oxy)phenyl)amino)benzamide [0262] (51) 3-((4-((2-cyanobenzyl)oxy)phenyl)amino)-N-(2-cyclopentylethyl)benzamide [0263] (52) 3-((4-(benzyloxy)phenyl)amino)-N-(2-cyclopentylethyl)benzamide [0264] (53) N-(2-cyclopentylethyl)-3-((3-hydroxy-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0265] (54) N-isopentyl-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0266] (55) N-(2-cyclopentylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzenesulfonamide [0267] (56) N-(2-cyclohexylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzenesulfonamide [0268] (57) 3-((2-ethyl-4-(pyridin-2-ylmethoxy)phenyl)amino)-N-isopentylbenzamide [0269] (58) N-(2-cyclopentylethyl)-3-((2-ethyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0270] (59) N-(2-cyclopropylethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzenesulfonamide [0271] (60) N-(2-cyclopentylethyl)-3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0272] (61) 3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)-N-isopentylbenzamide [0273] (62) N-(cyclopentylmethyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0274] (63) N-((3-methyloxetan-3-yl)methyl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0275] (64) N-(pentan-2-yl)-3-((4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0276] (65) 3-((4-(pyridin-2-ylmethoxy)phenyl)amino)-N-(3,3,3-trifluoropropyl)benzamide [0277] (66) N-(2-cyclopentylethyl)-3-((2-methyl-4-(1-(pyridin-2-yl)ethoxy)phenyl)amino)benzamide [0278] (67) N-isopentyl-3-((2-methyl-4-(1-(pyridin-2-yl)ethoxy)phenyl)amino)benzamide [0279] (68) 1-isopentyl-3-(3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)phenyl)urea [0280] (69) 3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)-N-(oxetan-3-yl)benzamide [0281] (70) N-(2-(3,3-difluorocyclobutyl)ethyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0282] (71) N-cyclopentyl-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0283] (72) 3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)-N-(4-methylpentyl)benzamide [0284] (73) 3-(3-cyclopentylpropoxy)-N-(4-(pyridin-2-ylmethoxy)phenyl)aniline [0285] (74) 3-((2-methylpentyl)oxy)-N-(4-(pyridin-2-ylmethoxy)phenyl)aniline [0286] (75) N-(2-(cyclohexyl)ethyl)-3-((2-ethyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0287] (76) N-(2-(cyclohexyl)ethyl)-3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0288] (77) N-(1-methylbutyl)-3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0289] (78) N-(1-methylbutyl)-3-((2-ethyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0290] (79) N-(2-(cyclohexyl)ethyl)-3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzenesulfonamide [0291] (80) (3-(cyclohexyl)propanamide), N-[3-([2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl]amino)phenyl]-(81) N-(3-methylbutyl)-4-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0292] (82) N-(2-(cyclopentyl)ethyl)-3-((2-cyclopropyl-4-(phenylmethoxy)phenyl)amino)benzamide [0293] (83) 3-(3-cyclohexylpropoxy)-N-(2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)aniline [0294] (84) 3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzamide [0295] (85) N-(2-cyclohexylethyl)-3-((2-cyclopropyl-4-(pyridin-3-ylmethoxy)phenyl)amino)benzamide [0296] (86) N-(2-cyclohexylethyl)-6-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)picolinamide [0297] (87) 3-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)benzenesulfonamide [0298] (88) N-(2-cyclohexylethyl)-5-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)nicotinamide [0299] (89) N-(2-cyclopentylethyl)-3-((2-cyclopropyl-4-(pyridin-4-ylmethoxy)phenyl)amino)benzamide [0300] (90) N-(2-cyclohexylethyl)-2-((2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl)amino)isonicotinamide [0301] (91) N-(3-{[4-(benzyloxy)-2-tert-butylphenyl]amino}phenyl)-3-cyclohexylpropanamide [0302] (92) N-(3-{[4-(benzyloxy)-2-(cyclopent-1-en-1-yl)phenyl]amino}phenyl)-3-cyclohexylpropanamide [0303] (93) N-(3-{[4-(benzyloxy)-2-cyclopentylphenyl]amino}phenyl)-3-cyclohexylpropanamide [0304] (94) N-(3-{[4-(benzyloxy)-2-(methylsulfanyl)phenyl]amino}phenyl)-3-cyclohexylpropanamide [0305] (95) N1-[4-(benzyloxy)-2-cyclopropylphenyl]-N3-(3-cyclohexylpropyl)benzene-1,3-diamine [0306] (96) 1-(2-cyclohexylethyl)-3-[3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenyl]urea [0307] (97) 1-(3-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}phenyl)-4-cyclohexylbutan-1-ol [0308] (98) N-(3-{[4-(benzyloxy)-2-(trifluoromethyl)phenyl]amino}phenyl)-3-cyclohexylpropanamide [0309] (99) 3-cyclohexyl-N-[3-({4-[(4-fluorophenyl)methoxy]-2-(trifluoromethyl)phenyl}amino)phenyl]propanamide [0310] (100) N-{3-[4-(cyclohexylmethyl)-1H-1,2,3-triazol-1-yl]phenyl}-2-cyclopropyl-4-[(pyridin-2-yl)methoxy]aniline [0311] (101) 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}-N-(2-cyclohexylethyl)benzamide [0312] (102) 1-cyano-N-[3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-2-methylphenyl]cyclopropane-1-carboxamide [0313] (103) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-N-(3-cyclohexylpropyl)benzamide [0314] (104) 3-{[4-(benzyloxy)-2-(trifluoromethyl)phenyl]amino}-N-(2-cyclopentylethyl)benzamide [0315] (105) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)-2-methylphenyl]-2-cyclopropylaniline [0316] (106) 2-cyclopropyl-N-{3-[(4-methylpentyl)oxy]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0317] (107) N-(3-{[4-(benzyloxy)-2-methanesulfonylphenyl]amino}phenyl)-3-cyclohexylpropanamide [0318] (108) N′1-[3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-2-methylphenyl]cyclopropane-1,1-dicarboxamide [0319] (109) [3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-2-methylphenoxy]phosphonic acid [0320] (110) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-N-(cyclohexylmethyl)benzamide [0321] (111) N-(2-cyclohexylethyl)-3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}(methyl)amino)benzamide [0322] (112) 2-cyclopropyl-N-{3-[4-(3-methylbutyl)-1H-1,2,3-triazol-1-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0323] (113) N-(cyclopentylmethyl)-2-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)benzamide [0324] (114) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]-2-(morpholin-4-yl)aniline [0325] (115) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-N-(2-cyclohexylethyl)benzamide [0326] (116) N-(5-{[4-(benzyloxy)-2-(trifluoromethyl)phenyl]amino}-2-fluorophenyl)-3-cyclohexylpropanamide [0327] (117) N-(2-cyclohexylethyl)-4-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)pyridine-2-carboxamide [0328] (118) N-{3-[1-(3-cyclohexylpropyl)-1H-1,2,3,4-tetrazol-5-yl]phenyl}-2-cyclopropyl-4-[(pyridin-2-yl)methoxy]aniline [0329] (119) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]-2-(propan-2-yl)aniline [0330] (120) 2-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-N-(3,3,3-trifluoropropyl)benzamide [0331] (121) 3-cyclohexyl-N-[2-fluoro-5-({4-[(4-fluorophenyl)methoxy]-2-methylphenyl}amino)phenyl]propanamide [0332] (122) 4-(benzyloxy)-N-[2-(3-cyclohexylpropanesulfonyl)phenyl]-2-cyclopropylaniline [0333] (123) 2-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-N-(3-methylbutyl)benzamide [0334] (124) 3-{[4-(benzyloxy)-2-(trifluoromethyl)phenyl]amino}-N-(2-cyclohexylethyl)benzene-1-sulfonamide [0335] (125) 3-cyclohexyl-N-[2-fluoro-5-({4-[(4-fluorophenyl)methoxy]-2-(trifluoromethyl)phenyl}amino)phenyl]propanamide [0336] (126) 2-cyclopropyl-N-{3-[1-(4-methylpentyl)-1H-1,2,3,4-tetrazol-5-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0337] (127) 2-cyclopropyl-N-{3-[5-(3-methylbutyl)-1,2,4-oxadiazol-3-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0338] (128) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-6-cyano-N-(propan-2-yl)benzamide [0339] (129) N-{3-[5-(2-cyclohexylethyl)-1,2,4-oxadiazol-3-yl]phenyl}-2-cyclopropyl-4-[(pyridin-2-yl)methoxy]aniline [0340] (130) N-{3-[5-(2-cyclohexylethyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-cyclopropyl-4-[(pyridin-2-yl)methoxy]aniline [0341] (131) 2-(azetidin-1-yl)-4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]aniline [0342] (132) N-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenyl)-3-cyclohexylpropanamide [0343] (133) [3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenoxy]phosphonic acid [0344] (134) tert-butyl 4-[3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)benzoyl]piperazine-1-carboxylate [0345] (135) 2-(3-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}phenyl)-2-[(2-cyclohexylethyl)amino]aceticacid [0346] (136) N-(1-cyanocyclopropyl)-2-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)benzamide [0347] (137) N-(3-cyclobutoxyphenyl)-2-cyclopropyl-4-[(pyridin-2-yl)methoxy]aniline [0348] (138) methyl 2-(3-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}phenyl)-2-[(2-cyclohexylethyl)amino]acetate [0349] (139) 2-{[4-(benzyloxy)-2-methylphenyl]amino}-N-(2-cyclohexylethyl)benzamide [0350] (140) 3-cyclohexyl-N-[3-({4-[(4-fluorophenyl)methoxy]-2-methylphenyl}amino)phenyl]propanamide [0351] (141) 2-cyclopropyl-4-[(pyridin-2-yl)methoxy]-N-{3-[(trimethylsilyl)oxy]phenyl}aniline [0352] (142) 4-(benzyloxy)-N-[3-(3-cyclohexylpropanesulfonyl)phenyl]-2-cyclopropylaniline [0353] (143) N-(2-cyclohexylethyl)-2-[(2-cyclopropyl-4-{[4-(trifluoromethoxy)phenyl]methoxy}phenyl)amino]pyridine-4-carboxamide [0354] (144) tert-butyl N-[2-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)ethyl]carbamate [0355] (145) 2-cyclopropyl-N-{3-[4-(2-methylpropyl)-1H-1,2,3-triazol-1-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0356] (146) N-(5-{[4-(benzyloxy)-2-methylphenyl]amino}-2-fluorophenyl)-3-cyclohexylpropanamide [0357] (147) 2-cyclopropyl-N-{3-[2-(2-methylpropyl)-2H-1,2,3,4-tetrazol-5-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0358] (148) N-[3-(3-cyclohexylpropoxy)phenyl]-2-methyl-4-[(pyridazin-3-yl)methoxy]aniline [0359] (149) 4-(benzyloxy)-N-{3-[(3-cyclohexylpropyl)sulfanyl]phenyl}-2-cyclopropylaniline [0360] (150) N-(3-{[4-(benzyloxy)-2-fluorophenyl]amino}phenyl)-3-cyclohexylpropanamide [0361] (151) 2-cyclopropyl-N-[3-(oxetan-3-yloxy)phenyl]-4-[(pyridin-2-yl)methoxy]aniline [0362] (152) N-[3-(3-cyclohexylpropoxy)phenyl]-2-methyl-4-[(pyrimidin-2-yl)methoxy]aniline [0363] (153) 3-cyclohexyl-N-{3-[(2-methyl-4-{[4-(trifluoromethoxy)phenyl]methoxy}phenyl)amino]phenyl}propanamide [0364] (154) 4-(benzyloxy)-N-[2-(3-cyclohexylpropoxy)phenyl]-2-cyclopropylaniline [0365] (155) 2-(3-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}phenyl)-4-cyclohexylbutane-1,2-diol [0366] (156) N-[3-(3-cyclohexylpropoxy)phenyl]-2-cyclopropyl-N-methyl-4-[(pyridin-2-yl)methoxy]aniline [0367] (157) 3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenol [0368] (158) 3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenyl diethyl phosphate [0369] (159) N-(2-cyclohexylethyl)-3-[(2-cyclopropyl-4-{[4-(trifluoromethoxy)phenyl]methoxy}phenyl)amino]benzene-1-sulfonamide [0370] (160) N-[3-(3-cyclohexylpropoxy)phenyl]-2-methyl-4-[(pyrimidin-4-yl)methoxy]aniline [0371] (161) 2-cyclopropyl-N-{3-[2-(3-methylbut-2-en-1-yl)-2H-1,2,3,4-tetrazol-5-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0372] (162) 3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)-2-methylphenyl diethyl phosphate [0373] (163) 2-cyclopropyl-N-{3-[2-(2-methoxyethyl)-2H-1,2,3,4-tetrazol-5-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0374] (164) 2-cyclopropyl-N-{3-[1-(cyclopropylmethyl)-1H-1,2,3,4-tetrazol-5-yl]phenyl}-4-[(pyridin-2-yl)methoxy]aniline [0375] (165) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]-2-(oxan-4-yl)aniline [0376] (166) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]-2-(3,6-dihydro-2H-pyran-4-yl)aniline [0377] (167) 5-(3-cyclohexylpropoxy)-N-{2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}pyridin-3-amine [0378] (168) 5-{[4-(benzyloxy)-2-(trifluoromethyl)phenyl]amino}-2-fluorobenzamide [0379] (169) 3-cyclohexyl-N-{3-[(2-cyclopropyl-4-{[4-(trifluoromethyl)phenyl]methoxy}phenyl)amino]phenyl}propanamide [0380] (170) 3-cyclohexyl-N-[3-({2-cyclopropyl-4-[(4-methoxyphenyl)methoxy]phenyl}amino)phenyl]propanamide [0381] (171) 2-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)ethan-1-ol [0382] (172) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]aniline [0383] (173) ethyl 5-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)pentanoate [0384] (174) 4-(benzyloxy)-N-[3-(2-methoxyethoxy)phenyl]-2-methylaniline [0385] (175) 4-(benzyloxy)-N-[3-(cyclopentylmethoxy)phenyl]-2-methylaniline [0386] (176) N-[3-(3-cyclohexylpropoxy)phenyl]-2-methyl-4-[(pyrimidin-5-yl)methoxy]aniline [0387] (177) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)phenyl]-2-methylaniline [0388] (178) 3-{1-[3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenyl]-1H-1,2,3-triazol-4-yl}propan-1-ol [0389] (179) 2-cyclopropyl-N-[3-(1,3-oxazol-5-yl)phenyl]-4-[(pyridin-2-yl)methoxy]aniline [0390] (180) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-6-methyl-N-(propan-2-yl)benzamide [0391] (181) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-N-(propan-2-yl)-6-(trifluoromethyl)benzamide [0392] (182) [3-({2-cyclopropyl-4-[(pyridin-2-yl)methoxy]phenyl}amino)phenoxy](methoxy)phosphinic acid [0393] (183) 5-(benzyloxy)-2-{[3-(3-cyclohexylpropoxy)phenyl]amino}benzonitrile [0394] (184) 2-{[4-(benzyloxy)phenyl]amino}-N-(2-cyclohexylethyl)benzamide [0395] (185) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)-4-methylphenyl]-2-cyclopropylaniline [0396] (186) 4-(benzyloxy)-N-[3-(3-cyclohexylpropoxy)-5-methylphenyl]-2-cyclopropylaniline [0397] (187) 4-(benzyloxy)-N-[5-(3-cyclohexylpropoxy)-2-methylphenyl]-2-cyclopropylaniline [0398] (188) 4-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-2-(3-cyclohexylpropoxy)benzamide [0399] (189) 3-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-5-(3-cyclohexylpropoxy)benzamide [0400] (190) N-(2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}phenyl)-3-cyclohexylpropanamide [0401] (191) 3-{[4-(benzyloxy)-2-methylphenyl][3-(3-cyclohexylpropoxy)phenyl]amino}propanoic acid [0402] (192) 2-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)acetic acid [0403] (193) 5-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)pentanoic acid [0404] (194) methyl 2-(3-{[4-(benzyloxy)-2-methylphenyl]amino}phenoxy)acetate [0405] (195) 4-(benzyloxy)-2-methyl-N-[3-(trifluoromethoxy)phenyl]aniline [0406] (196) 4-(benzyloxy)-2-methyl-N-{3-[(oxan-4-yl)methoxy]phenyl}aniline [0407] (197) 4-(3-cyclohexylpropoxy)-N-{2-methyl-4-[(pyridin-3-yl)methoxy]phenyl}pyridin-2-amine [0408] (198) 6-(3-cyclohexylpropoxy)-N-{2-methyl-4-[(pyridin-3-yl)methoxy]phenyl}pyridin-2-amine [0409] (199) N-[4-(benzyloxy)-2-methylphenyl]-4-(3-cyclohexylpropoxy)pyridin-2-amine [0410] (200) N-[4-(benzyloxy)-2-methylphenyl]-6-(3-cyclohexylpropoxy)pyridin-2-amine [0411] (201) N-[3-(3-cyclohexylpropoxy)phenyl]-2-methyl-4-[(pyrazin-2-yl)methoxy]aniline [0412] (202) N-(5-{[4-(benzyloxy)-2-fluorophenyl]amino}-2-fluorophenyl)-3-cyclohexylpropanamide [0413] (203) N-[3-(morpholin-4-yl)propyl]-3-({4-[(pyridin-2-yl)methoxy]phenyl}amino)benzamide [0414] (204) 2-cyclopropyl-4-[(pyridin-2-yl)methoxy]-N-[3-(1H-1,2,3,4-tetrazol-5-yl)phenyl]aniline [0415] (205) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-6-cyclopropyl-N-(propan-2-yl)benzamide [0416] (206) 2-{[4-(benzyloxy)-2-cyclopropylphenyl]amino}-6-chloro-N-(propan-2-yl)benzamide

[0417] and their pharmaceutically acceptable salts.

[0418] The present invention extends to compounds (36) to (206) and their pharmaceutically acceptable salts, such as hydrobromide, tartrate, citrate, trifluoroacetate, ascorbate, hydrochloride, tosylate, triflate, maleate, mesylate, formate, acetate and fumarate.

[0419] According to another aspect, a subject-matter of the present invention relates to compounds (36) to (206) or any of its pharmaceutically acceptable salts, for use as a medicament.

[0420] According to another aspect, a subject-matter of the present invention relates to a compound of formula (Ie) as defined above or any of its pharmaceutically acceptable salts, and any of compounds (36) to (206) or any of its pharmaceutically acceptable salts, for use as an agent for preventing, inhibiting or treating a RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification.

[0421] Compounds (38), (40), (43), (45), (46), (48), (49), (61), (62), (64), (35), (68), (82), (98), (119), (121), (132), (140), (150), (151), (156), (169), (175), (176) and (192) or any of its pharmaceutically acceptable salts may be particularly useful for preventing, inhibiting or treating dengue infection.

[0422] Compounds (36), (38), (39), (45), (46), (47), (54), (57), (60), (61), (64), (68), (70), (71), (72), (75)-(80), (82)-(86), (88)-(142), (147)-(156), (164)-(166) and (179) or any of its pharmaceutically acceptable salts may be particularly useful for preventing, inhibiting or treating RSV infection.

[0423] Compounds (36)-(41), (43), (45)-(52), (53), (54), (57), (58), (60)-(62), (64), (68), (70), (71) and (73) or any of its pharmaceutically acceptable salts may be particularly useful for preventing, inhibiting or treating Chikungunya infection.

[0424] The compounds of the invention may exist in the form of free bases or of addition salts with pharmaceutically acceptable acids.

[0425] «Pharmaceutically acceptable salt thereof» refers to salts which are formed from acid addition salts formed with inorganic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and the like), as well as salts formed with organic acids such as acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, palmoic acid, alginic acid, polyglutamic acid, naphthalene sulfonic acid, naphthalene disulfonic acid, and poly-galacturonic acid.

[0426] Suitable physiologically acceptable acid addition salts of compounds of formula (Ie) include hydrobromide, tartrate, citrate, trifluoroacetate, ascorbate, hydrochloride, tosylate, triflate, maleate, mesylate, formate, acetate and fumarate.

[0427] The compounds of formula (Ie) and any of compounds (36) to (206) or any of their pharmaceutically acceptable salts may form solvates or hydrates and the invention includes all such solvates and hydrates.

[0428] The compounds of formula (Ie) may be present as well under tautomer forms and are part of the invention.

[0429] The terms “hydrates” and “solvates” simply mean that the compounds (Ie) according to the invention can be in the form of a hydrate or solvate, i.e. combined or associated with one or more water or solvent molecules. This is only a chemical characteristic of such compounds, which can be applied for all organic compounds of this type.

[0430] In the context of the present invention, the term: [0431] “halogen” is understood to mean chlorine, fluorine, bromine, or iodine, and in particular denotes chlorine, fluorine or bromine, [0432] “(C.sub.1-C.sub.x)alkyl”, as used herein, respectively refers to a C.sub.1-C.sub.x normal, secondary or tertiary saturated hydrocarbon, for example (C.sub.1-C.sub.6)alkyl. Examples are, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, butyl, pentyl, [0433] an “alkenylene” means a divalent (C.sub.1-C.sub.x)alkyl group comprising a double bond, and more particularly a ethenylene group, also known as vinylene or 1,2-ethenediyl, [0434] “(C.sub.3-C.sub.6)cycloalkyl”, as used herein, refers to a cyclic saturated hydrocarbon. Examples are, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, [0435] “(C.sub.3-C.sub.6)cycloalkenyl”, as used herein, refers to a cyclic non aromatic hydrocarbon comprising at least one unsaturated bond. Examples are, but not limited to, cyclopentenyl and cyclohexenyl, [0436] “(C.sub.1-C.sub.x)alkoxy”, as used herein, refers to a 0-(C.sub.1-C.sub.x)alkyl moiety, wherein alkyl is as defined above, for example (C.sub.1-C.sub.6)alkoxy. Examples are, but are not limited to, methoxy, ethoxy, 1-propoxy, 2-propoxy, butoxy, pentoxy, [0437] “aryl”, as used herein, refers to a monocyclic aromatic group containing 6 carbon atoms and containing between 0 and 2 heteroatoms, such as nitrogen, oxygen or sulphur, and in particular nitrogen. By way of examples of aryl groups, mention may be made of, but not limited to: phenyl, pyridine, pyrimidine, pyridazine, pyrazine and the like. In the framework of the present invention, the aryl is advantageously phenyl, pyridazine, pyrazine, pyridine, such as 2-pyridine or 3-pyridine and pyrimidine. The aryl is even more advantageously phenyl and pyridine, [0438] a “divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms” as used herein, means a divalent ring consisting of an aromatic ring comprising 5 chains and 1, 2, 3 or 4 heteroatoms selected from nitrogen and oxygen atoms. In one embodiment, it comprises at least 1 heteroatom, and preferably at least one nitrogen atom. In another embodiment, it comprises at least 2 heteroatoms, with for example at least one nitrogen atom. According to a further embodiment, it comprises 2, 3 or 4 nitrogen atoms, preferably 3 nitrogen atoms. According to an even further embodiment, it comprises one nitrogen atom and one oxygen atom or two nitrogen atoms and one oxygen atom. Examples are, but not limited to, divalent triazole, such as 1,2,3- or 1,2,4-triazoles, oxadiazoles, such as 1,2,4-oxadiazole or 1,2,3-oxadiazole and divalent diazoles such as diazole and imidazole.

[0439] The compounds of formula (Ie) can comprise one or more asymmetric carbon atoms. They can thus exist in the form of enantiomers or of diastereoisomers. These enantiomers, diastereoisomers and their mixtures, including the racemic mixtures, are encompassed within the scope of the present invention.

[0440] The compounds of the present invention can be prepared by conventional methods of organic synthesis practiced by those skilled in the art. The general reaction sequences outlined below represent a general method useful for preparing the compounds of the present invention and are not meant to be limiting in scope or utility.

[0441] The compounds of general formula (I) and (Ie) can be prepared according to scheme 1 below.

##STR00038##

[0442] The synthesis is based on a coupling reaction starting from a halogeno aromatic compound of formula (III), wherein R, R′, m, m′,

##STR00039##

ring,

##STR00040##

ring, X.sup.1, X.sup.2, n, Y.sup.1, Y.sup.2 are as defined above and X is a chlorine atom, an iodine atom or a bromine atom.

[0443] According to one embodiment, procedure (A1) may advantageously be used when the group

##STR00041##

is meta or para position on the

##STR00042##

ring, with respect to the —NH— group.

[0444] According to route (A1), the compound of formula (III) may be placed in a protic solvent such as tert-butanol. The compound of formula (II) may then be added, for example in a molar ratio ranging from 1 to 1.5 with respect to the compound of formula (III) in presence of an inorganic base, such as Cs.sub.2CO.sub.3 or K.sub.2CO.sub.3, for example in a molar ratio ranging from 1 to 5 still with respect to the compound of formula (III), in the presence of a diphosphine, such as Xantphos (4,5-Bis(diphenylphosphino)-9,9-dimethylxanthine), X-Phos (2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) or rac-BINAP in particular in an amount ranging from 2 mol % to 15 mol % relative to the total amount of compound of formula (III), and in the presence of an organometallic catalyst, such as Pd(OAc).sub.2, Pd.sub.2dba.sub.3 or BrettPhos Pd G3, in an amount ranging from 2 mol % to 25 mol % relative to the total amount of compound of formula (III). The reaction mixture can then be heated at a temperature ranging from 80 to 130° C., for example at 90° C., and stirred for a time ranging from 15 to 25 hours, for example during 20 hours, under inert gas and for example argon. The reaction mixture can be concentrated under reduced pressure and the residue can be diluted with an organic solvent such as ethyl acetate. The organic phase can be washed with water, decanted, dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give a compound of formula (I) and (Ie).

[0445] According to one embodiment, procedure (A2) may advantageously be used when the group

##STR00043##

is in ortho position on the

##STR00044##

ring, with respect to the —NH— group.

[0446] According to procedure (A2), the compound of formula (II) may be placed in a polar aprotic solvent such as dimethylsulfoxide. The compound of formula (III) may then be added, for example in a molar ratio ranging from 1 to 1.5 with respect to the compound of formula (II) in presence of an inorganic base, such as Cs.sub.2CO.sub.3 or K.sub.2CO.sub.3, for example in a molar ratio ranging from 1 to 5 still with respect to the compound of formula (II), in the presence of a ligand, such as L-proline in particular in an amount ranging from 2 mol % to 25 mol % relative to the total amount of compound of formula (II), and in the presence of an organometallic catalyst, such as CuI, in an amount ranging from 2 mol % to 25 mol % relative to the total amount of compound of formula (II). The reaction mixture can then be heated at a temperature ranging from 80 to 130° C., for example at 90° C., and stirred for a time ranging from 15 to 25 hours, for example during 20 hours, under inert gas and for example argon. The reaction mixture can be diluted with an organic solvent such as ethyl acetate. The organic phase can be washed with water, decanted, dried over magnesium sulphate, filtered and then concentrated under reduced pressure to give a compound of formula (I) and (Ie).

[0447] The starting compounds of formula (II), (III) are available or can be prepared according to methods known to the person skilled in the art.

[0448] Accordingly, the present document further describes the synthesis process for manufacturing new compounds of formula (I) and (Ie) as defined above, comprising at least a step of coupling a compound of formula (II)

##STR00045##

with a compound of formula (III)

##STR00046##

[0449] wherein X.sup.1, Y.sup.1, R, R′, m, m′,

##STR00047##

ring,

##STR00048##

ring, X.sup.2, Y.sup.2 are as defined above and X is a chlorine atom, an iodine atom or a bromine atom, in presence of an inorganic base and a diphosphine and in the presence of an organometallic catalyst, to obtain a compound of formula (I) or (Ie).

[0450] The compounds of general formula (Ie) according to the invention can be prepared according to scheme 1′ below.

##STR00049##

[0451] The synthesis is based on a coupling reaction starting from a halogeno aromatic compound of formula (IIIe) with a compound of formula (IIe), wherein R, R′, R″, m, m′,

##STR00050##

ring,

##STR00051##

ring, X.sup.1, X.sup.2, n, Y.sup.1, Y.sup.2, R.sub.a and R.sub.b are as defined above and X is a chlorine atom, an iodine atom or a bromine atom.

[0452] More particularly, the present invention relates to the synthesis process for manufacturing the compounds of formula (Ie) as defined above, comprising at least a step of coupling a compound of formula (IIe)

##STR00052##

with a compound of formula (IIIe)

##STR00053##

[0453] wherein X.sup.1, Y.sup.1, R, R′, m, m′,

##STR00054##

ring,

##STR00055##

ring, X.sup.2, Y.sup.2 R.sub.a and R.sub.b are as defined above X is a chlorine atom, an iodine atom or a bromine atom and Y.sup.1 is a phenyl group, a pyridine group, a pyrazine group, a pyridazine group or a pyrimidine group, in presence of an inorganic base and a ligand and in the presence of an organometallic catalyst, to obtain a compound of formula (Ie).

[0454] To afford (Ie) when R″≠H, an additional step (K) may be implemented, in which the compound can be placed in an anhydrous polar solvent such as anhydrous N,N-dimethylformamide in the presence of NaH in a molar ratio ranging from 2 to 5, for example 3, and the reaction mixture can be stirred at room temperature for a time ranging from 10 minutes to 50 minutes, for example 30 minutes. The halide derivative R″—X can then be added and the resulting reaction mixture can be stirred at a temperature ranging from 70 to 110° C., for example at 90° C., for a time ranging from 2 hours to 10 hours, for example 5 hours. Upon cooling to room temperature, the reaction mixture can be concentrated under reduced pressure and the resulting residue can be diluted with an organic solvent such as ethyl acetate. The organic phase can then be washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give a compound of formula (Ie) where R″≠H.

[0455] More particularly, compounds of formula (IIe), when used to prepare compounds of formula (Ie) with R.sub.a═R.sub.b═H, can be prepared according to scheme 6 below. In the case where either R.sub.a or R.sub.b≠H, a route starting from the 4-nitrophenol derivative and the suitable alcohol derivative and using classical Mitsunobu conditions can generate such compounds, and for example compounds 66 and 67 as defined in table I herein after.

[0456] Preparation of (IIe) for (Ie)

##STR00056##

[0457] Intermediate compounds of formulae (IIe) and (IVe) are useful for preparing compounds of formula (Ie) according to the invention.

[0458] According to route (I), the 4-nitrophenol derivative may be placed in a polar solvent such as N,N-dimethylformamide. 2-(Bromomethyl)aryl derivative may then be added, for example in a molar ratio ranging from 1 to 2 with respect to the 4-nitrophenol derivative in presence of an inorganic base, such as Cs.sub.2CO.sub.3 or K.sub.2CO.sub.3, for example in a molar ratio ranging from 1 to 5 still with respect to the 4-nitrophenol derivative. The reaction mixture can then be heated at a temperature ranging from 50 to 150° C., for example at 90° C. and stirred for a time ranging from 15 to 30 hours, for example during 24 hours, under inert gas and for example argon. The reaction mixture can be concentrated under reduced pressure and the residue can be partitioned between an organic solvent, such as dichloromethane, and water. The organic phase can be washed with water, decanted, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a compound of formula (IVe).

[0459] According to route (C), the compound of formula (IVe) and tin (II) chloride dihydrate in a ratio ranging from 3 to 8 equivalents are placed in a protic solvent such as ethanol. The reaction mixture can then be heated at a temperature ranging from 40 to 80° C., for example at 60° C. and stirred for a time ranging from 15 to 25 hours, for example during 20 hours. The mixture can be poured into 1N NaOH aqueous solution and extracted with an organic solvent such as ethyl acetate. The organic phase can then be washed with water and a saturated aqueous solution of brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a compound of formula (IIe).

[0460] More particularly, compounds of formula (IIe), when used to prepare compounds of formula (Ie) with R.sub.a═R.sub.b═H and with one R′ group (i.e. R.sub.c′) being different from H and Me, can be prepared according to scheme 7 below.

[0461] Preparation of (IIe) for (e), when R.sub.c′≠Me and R.sub.c′≠H

##STR00057##

[0462] Intermediate compounds of formulae (IIe), (IVe) and (Ve) are useful for preparing compounds of formula (Ie) according to the invention.

[0463] According to route (I), the 4-nitrophenol derivative may be placed in a polar solvent such as N,N-dimethylformamide. 2-(Bromomethyl)aryl derivative may then be added, for example in a molar ratio ranging from 1 to 2 with respect to the 4-nitrophenol derivative in presence of an inorganic base, such as Cs.sub.2CO.sub.3 or K.sub.2CO.sub.3, for example in a molar ratio ranging from 1 to 5 still with respect to the 4-nitrophenol derivative. The reaction mixture can then be heated at a temperature ranging from 50 to 150° C., for example at 90° C. and stirred for a time ranging from 15 to 30 hours, for example during 24 hours, under inert gas and for example argon. The reaction mixture can be concentrated under reduced pressure and the residue can be partitioned between an organic solvent, such as dichloromethane, and water. The organic phase can be washed with water, decanted, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a compound of formula (Ve).

[0464] According to route (J), the compound of formula (Ve) and an organometallic catalyst such as Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 in an amount ranging from 2 mol % to 20 mol % relative to the amount of the compound of formula (Ve) may be placed in an apolar solvent such as 1,4-dioxane. A boronic acid R.sub.c′—B(OH).sub.2 is then added, for example in a molar ratio ranging from 1 to 5 with respect to the compound of formula (Ve), in presence of an inorganic base, such as K.sub.3PO.sub.4 or K.sub.2CO.sub.3, for example in a molar ratio ranging from 2 to 5 still with respect to the compound of formula (Ve). The reaction mixture can then be heated at a temperature ranging from 50 to 150° C., for example at 100° C., and stirred for a time ranging from 10 to 70 hours, for example during 20 hours, under inert gas and for example argon. The reaction mixture can be concentrated under reduced pressure to give a compound of formula (IVe).

[0465] According to route (C), the compound of formula (IVe) and tin (II) chloride dihydrate in a ratio ranging from 3 to 8 equivalents may be placed in a protic solvent such as ethanol. The reaction mixture can then be heated at a temperature ranging from 40 to 80° C., for example at 60° C. and stirred for a time ranging from 15 to 25 hours, for example during 20 hours. The mixture can be poured into 1N NaOH aqueous solution and extracted with an organic solvent such as ethyl acetate. The organic phase can then be washed with water and a saturated aqueous solution of brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a compound of formula (IIe).

[0466] The chemical structures and spectroscopic data of some compounds of formula (Ie) of the invention are illustrated respectively in the following Table I and Table II.

TABLE-US-00001 TABLE I (Ie) [00058] (Ie)  36 [00059]  37 [00060]  38 [00061]  39 [00062]  40 [00063]  41 [00064]  42 [00065]  43 [00066]  44 [00067]  45 [00068]  46 [00069]  47 [00070]  48 [00071]  49 [00072]  50 [00073]  51 [00074]  52 [00075]  53 [00076]  54 [00077]  55 [00078]  56 [00079]  57 [00080]  58 [00081]  59 [00082]  60 [00083]  61 [00084]  62 [00085]  63 [00086]  64 [00087]  65 [00088]  66 [00089]  67 [00090]  68 [00091]  69 [00092]  70 [00093]  71 [00094]  72 [00095]  73 [00096]  74 [00097]  75 [00098]  76 [00099]  77 [00100]  78 [00101]  79 [00102]  80 [00103]  81 [00104]  82 [00105]  83 [00106]  84 [00107]  85 [00108]  86 [00109]  87 [00110]  88 [00111]  89 [00112]  90 [00113]  91 [00114]  92 [00115]  93 [00116]  94 [00117]  95 [00118]  96 [00119]  97 [00120]  98 [00121]  99 [00122] 100 [00123] 101 [00124] 102 [00125] 103 [00126] 104 [00127] 105 [00128] 106 [00129] 107 [00130] 108 [00131] 109 [00132] 110 [00133] 111 [00134] 112 [00135] 113 [00136] 114 [00137] 115 [00138] 116 [00139] 117 [00140] 118 [00141] 119 [00142] 120 [00143] 121 [00144] 122 [00145] 123 [00146] 124 [00147] 125 [00148] 126 [00149] 127 [00150] 128 [00151] 129 [00152] 130 [00153] 131 [00154] 132 [00155] 133 [00156] 134 [00157] 135 [00158] 136 [00159] 137 [00160] 138 [00161] 139 [00162] 140 [00163] 141 [00164] 142 [00165] 143 [00166] 144 [00167] 145 [00168] 146 [00169] 147 [00170] 148 [00171] 149 [00172] 150 [00173] 151 [00174] 152 [00175] 153 [00176] 154 [00177] 155 [00178] 156 [00179] 157 [00180] 158 [00181] 159 [00182] 160 [00183] 161 [00184] 162 [00185] 163 [00186] 164 [00187] 165 [00188] 166 [00189] 167 [00190] 168 [00191] 169 [00192] 170 [00193] 171 [00194] 172 [00195] 173 [00196] 174 [00197] 175 [00198] 176 [00199] 177 [00200] 178 [00201] 179 [00202] 180 [00203] 181 [00204] 182 [00205] 183 [00206] 184 [00207] 185 [00208] 186 [00209] 187 [00210] 188 [00211] 189 [00212] 190 [00213] 191 [00214] 192 [00215] 193 [00216] 194 [00217] 195 [00218] 196 [00219] 197 [00220] 198 [00221] 199 [00222] 200 [00223] 201 [00224] 202 [00225] 203 [00226] 204 [00227] 205 [00228] 206 [00229]

TABLE-US-00002 TABLE II Ex Characterization 36 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.2 Hz, 1H), 8.30 (t, J = 5.4 Hz, 1H), 8.03 (s, 1H), 7.84 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.39-7.32 (m, 2H), 7.20 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 9.0 Hz, 3H), 6.97 (d, J = 9.0 Hz, 2H), 5.14 (s, 2H), 3.22 (dd, J = 13.3, 6.8 Hz, 2H), 1.86-1.70 (m, 3H), 1.62-1.42 (m, 7H), 1.10-1.07 (m, 2H). [M + H].sup.+ = 416.0 37 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.28 (t, J = 5.2 Hz, 1H), 8.03 (s, 1H), 7.84 (td, J = 7.7, 1.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.39-7.31 (m, 2H), 7.20 (d, J = 7.7 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 7.05 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 5.13 (s, 2H), 3.23 (dd, J = 13.2, 6.6 Hz, 2H), 1.59 (d, J = 6.6 Hz, 1H), 1.39 (dd, J = 13.2, 6.6 Hz, 2H), 0.89 (d, J = 6.6 Hz, 6H). [M + H].sup.+ = 390.0 38 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.2 Hz, 1H), 8.26 (t, J = 5.4 Hz, 1H), 8.03 (s, 1H), 7.84 (td, J = 7.7, 1.7 Hz, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.39-7.31 (m, 2H), 7.20 (d, J = 7.8 Hz, 1H), 7.13 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.03 (s, 1H), 6.97 (d, J = 9.0 Hz, 2H), 5.13 (s, 2H), 3.23 (dd, J = 13.2, 6.8 Hz, 2H), 1.77-1.55 (m, 5H), 1.39 (dd, J = 14.1, 6.8 Hz, 2H), 1.31- 1.12 (m, 4H), 0.97-0.79 (m, 2H). [M + H].sup.+ = 430.3 39 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.3 Hz, 1H), 8.26 (t, J = 5.5 Hz, 1H), 7.85 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.47 (s, 1H), 7.35 (dd, J = 6.9, 5.5 Hz, 1H), 7.20-7.05 (m, 4H), 6.97 (d, J = 2.7 Hz, 1H), 6.85 (dd, J = 8.6, 2.7 Hz, 1H), 6.75 (d, J = 7.7 Hz, 1H), 5.16 (s, 2H), 3.21 (dd, J = 13.4, 6.5 Hz, 2H), 2.14 (s, 3H), 1.82-1.70 (m, 2H), 1.64-1.39 (m, 6H), 1.12- 1.07 (m, 3H). .sup.13C NMR (75 MHz, d.sub.6-DMSO) δ 165.1, 155.5, 153.2, 147.6, 145.4, 135.5, 134.4, 132.7, 132.3, 127.3, 123.6, 121.5, 120.1, 117.8, 115.6, 114.6, 114.2, 111.3, 111.2, 35.9, 34.0, 30.7, 23.2, 16.6 [M + H].sup.+ = 430.3 40 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.59 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.36-7.31 (m, 1H), 7.24-7.17 (m, 2H), 7.10 (d, J = 7.7 Hz, 1H), 7.03-6.98 (m, 1H), 6.95 (d, J = 2.4 Hz, 1H), 6.90 (dd, J = 8.6, 2.6 Hz, 1H), 6.78 (d, J = 8.6 Hz, 1H), 6.25 (t, J = 5.3 Hz, 1H), 5.78 (s, 2H), 5.18 (s, 1H), 3.42 (dd, J = 14.5, 6.0 Hz, 2H), 2.30 (s, 3H), 1.88-1.73 (m, 3H), 1.63-1.47 (m, 6H), 1.15-1.10 (m, 2H). 41 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.56 (d, J = 4.1 Hz, 1H), 8.32 (t, J = 5.7 Hz, 1H), 8.13 (s, 1H), 7.97 (d, J = 2.7 Hz, 1H), 7.81 (td, J = 7.7, 1.7 Hz, 1H), 7.57 (dd, J = 8.8, 2.8 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.34 (s, 1H), 7.33-7.29 (m, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.18 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 8.6 Hz, 1H), 6.93 (d, J = 8.8 Hz, 1H), 5.38 (s, 1H), 3.22 (dd, J = 13.8, 6.3 Hz, 1H), 1.83-1.70 (m, 1H), 1.62-1.40 (m, 1H). 42 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.8 Hz, 1H), 7.85 (t, J = 5.5 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.61-7.51 (m, 3H), 7.24 (d, J = 9.0 Hz, 3H), 6.99 (d, J = 8.9 Hz, 2H), 6.77 (dd, J = 6.5, 2.7 Hz, 1H), 6.43 (s, 1H), 5.21 (s, 2H), 3.44 (dd, J = 14.1, 6.4 Hz, 2H), 1.89-1.79 (m, 3H), 1.66-1.53 (m, 6H), 1.18-1.12 (m, 2H). 43 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.58 (d, J = 4.2 Hz, 1H), 7.71 (td, J = 7.7, 1.7 Hz, 1H), 7.58 (d, J = 7.7 Hz, 1H), 7.36 (s, 1H), 7.25-7.17 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H), 7.04 (dd, J = 8.0, 1.5 Hz, 1H), 6.82 (d, J = 8.5 Hz, 1H), 6.73 (d, J = 2.4 Hz, 1H), 6.61 (dd, J = 8.5, 2.5 Hz, 1H), 6.03 (s, 1H), 5.65 (s, 1H), 5.26 (s, 2H), 3.87 (s, 3H), 3.44 (dd, J = 14.5, 6.0 Hz, 2H), 1.86-1.76 (m, 3H), 1.57- 1.52 (m, 5H), 1.18-1.08 (m, 2H). [M + H].sup.+ = 446.4 44 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.99 (s, 1H), 8.58 (d, J = 4.1 Hz, 1H), 8.31 (t, J = 5.6 Hz, 1H), 7.97 (d, J = 3.1 Hz, 1H), 7.94 (s, 1H), 7.84 (tt, J = 4.7, 2.4 Hz, 2H), 7.54 (d, J = 7.8 Hz, 1H), 7.41 (dd, J = 9.0, 3.1 Hz, 1H), 7.35 (dd, J = 7.0, 5.3 Hz, 1H), 7.30-7.21 (m, 2H), 6.84 (d, J = 9.0 Hz, 1H), 5.17 (s, 2H), 3.24 (dd, J = 13.9, 6.3 Hz, 2H), 1.84-1.72 (m, 3H), 1.64-1.43 (m, 6H), 1.18- 1.02 (m, 2H). [M + H].sup.+ = 417.4 45 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.59 (d, J = 4.8 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.27-7.22 (m, 1H), 7.19 (d, J = 7.8 Hz, 1H), 7.15-7.12 (m, 1H), 7.11 (d, J = 8.6 Hz, 1H), 7.06 (d, J = 7.7 Hz, 1H), 6.89 (d, J = 2.8 Hz, 1H), 6.81-6.76 (m, 1H), 6.36 (t, J = 5.3 Hz, 1H), 5.45 (s, 1H), 5.17 (s, 1H), 3.49 (dd, J = 12.9, 6.8 Hz, 2H), 2.18 (s, 3H), 1.48 (dd, J = 12.9, 6.8 Hz, 2H), 0.76-0.62 (m, 1H), 0.45 (dt, J = 8.0, 5.0 Hz, 1H), 0.07 (dt, J = 8.0, 5.0 Hz, 1H). [M + H].sup.+ = 402.3 46 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.26-7.23 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 7.14-7.11 (m, 2H), 7.04 (d, J = 7.7 Hz, 1H), 6.90 (d, J = 2.9 Hz, 1H), 6.80 (dd, J = 9.3, 3.0 Hz, 2H), 5.98 (s, 1H), 5.32 (s, 1H), 5.20 (s, 2H), 3.35 (dd, J = 13.4, 6.7 Hz, 1H), 2.35 (dt, J = 15.5, 7.8 Hz, 1H), 2.20 (s, 3H), 2.15-2.02 (m, 2H), 1.94-1.79 (m, 2H), 1.68-1.63 (m, 4H). [M + H].sup.+ = 416.3 47 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.3 Hz, 1H), 8.22 (t, J = 5.6 Hz, 1H), 7.85 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H), 7.35 (dd, J = 6.9, 5.2 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.11-7.04 (m, 3H), 6.97 (d, J = 2.7 Hz, 1H), 6.85 (dd, J = 8.6, 2.8 Hz, 1H), 6.75 (d, J = 7.7 Hz, 1H), 5.16 (s, 2H), 3.22 (dd, J = 13.2, 6.6 Hz, 2H), 2.14 (s, 3H), 1.73-1.63 (m, 5H), 1.42- 1.35 (m, 2H), 1.32-1.11 (m, 4H), 0.94-0.83 (m, 2H). [M + H].sup.+ = 444.4 48 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.35-7.28 (m, 1H), 7.25-7.19 (m, 2H), 7.08 (d, J = 8.9 Hz, 2H), 7.00 (dd, J = 8.4, 1.9 Hz, 1H), 6.95 (d, J = 8.9 Hz, 2H), 5.98 (s, 1H), 5.61 (s, 1H), 5.20 (s, 2H), 3.35 (dd, J = 13.5, 6.5 Hz, 2H), 2.36 (dt, J = 15.6, 7.9 Hz, 1H), 2.16-2.00 (m, 2H), 1.97-1.79 (m, 2H), 1.72-1.65 (m, 4H). [M + H].sup.+ = 402.3 49 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.31 (t, J = 5.6 Hz, 1H), 8.02 (s, 1H), 7.84 (td, J = 7.7, 1.8 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.37 (d, J = 1.9 Hz, 1H), 7.36-7.31 (m, 1H), 7.20 (d, J = 7.7 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 9.0 Hz, 1H), 6.97 (d, J = 9.0 Hz, 2H), 5.13 (s, 2H), 3.27 (dd, J = 14.3, 7.1 Hz, 2H), 1.40 (dd, J = 14.3, 7.1 Hz, 2H), 0.70 (m, 1H), 0.39 (dd, J = 12.0, 3.9 Hz, 2H), 0.04 (dd, J = 12.0, 3.9 Hz, 2H). [M + H].sup.+ = 388.3 50 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.31 (t, J = 5.6 Hz, 1H), 8.05 (s, 1H), 7.57 (td, J = 7.4, 1.5 Hz, 1H), 7.47-7.36 (m, 2H), 7.30-7.19 (m, 3H), 7.15 (d, J = 7.7 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 7.05-7.0 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.10 (s, 2H), 3.23 (dd, J = 13.8, 6.3 Hz, 2H), 1.86- 1.72 (m, 3H), 1.62-1.45 (m, 6H), 1.11-1.04 (m, 2H). .sup.13C NMR (75 MHz, d.sub.6-DMSO) δ 164.6, 160.2, 156.9, 151.1, 143.3, 134.4, 134.2, 128.9, 128.8, 128.4, 127.1, 122.7, 122.7, 122.4, 122.2, 118.7, 117.4, 115.3, 114.9, 113.8, 113.4, 111.8, 62.0, 35.6, 33.7, 30.4, 22.9 51 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.30 (t, J = 5.5 Hz, 1H), 8.07 (s, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.81-7.72 (m, 2H), 7.62-7.55 (m, 1H), 7.40 (s, 1H), 7.22 (d, J = 7.7 Hz, 1H), 7.16 (d, J = 7.7 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 7.01 (d, J = 9.1 Hz, 2H), 5.21 (s, 2H), 3.23 (dd, J = 13.9, 6.2 Hz, 2H), 1.79-1.70 (m, 3H), 1.60-1.49 (m, 7H). 52 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.29 (t, J = 5.6 Hz, 1H), 8.01 (s, 1H), 7.44 (dd, J = 9.5, 4.1 Hz, 3H), 7.41-7.30 (m, 4H), 7.20 (d, J = 7.7 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.00 (s, 1H), 6.97 (d, J = 9.0 Hz, 2H), 5.07 (s, 2H), 3.23 (dd, J = 13.7, 6.2 Hz, 2H), 1.79- 1.70 (m, 3H), 1.63-1.46 (m, 6H). 53 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.76 (d, J = 5.0 Hz, 1H), 8.32 (t, J = 5.3 Hz, 1H), 8.25 (t, J = 6.7 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.70 (s, 1H), 7.44 (s, 1H), 7.31-7.14 (m, 2H), 7.07 (d, J = 7.1 Hz, 1H), 6.93 (d, J = 8.6 Hz, 1H), 6.67 (d, J = 2.4 Hz, 1H), 6.49 (dd, J = 8.6, 2.3 Hz, 1H), 5.27 (s, 2H), 3.23 (dd, J = 13.4, 6.4 Hz, 2H), 1.82-1.73 (m, 3H), 1.62-1.43 (m, 6H), 1.12-1.04 (m, 2H). [M + H].sup.+ = 432.3 54 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.0 Hz, 1H), 8.23 (t, J = 5.6 Hz, 1H), 7.85 (td, J = 7.7, 1.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H), 7.36 (dd, J = 6.9, 5.3 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.12-7.04 (m, 3H), 6.97 (d, J = 2.8 Hz, 1H), 6.85 (dd, J = 8.6, 2.9 Hz, 1H), 6.74 (dd, J = 7.9, 1.5 Hz, 1H), 5.16 (s, 2H), 3.22 (dd, J = 13.8, 6.3 Hz, 2H), 2.14 (s, 3H), 1.68-1.51 (m, 1H), 1.38 (dd, J = 14.4, 6.9 Hz, 2H), 0.89 (d, J = 6.6 Hz, 6H). [M + H].sup.+ = 404.3 55 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 1.7 Hz, 1H), 7.29-7.21 (m, 3H), 7.07 (d, J = 8.9 Hz, 2H), 7.05-7.01 (m, 1H), 6.95 (d, J = 8.9 Hz, 2H), 5.89 (s, 1H), 5.19 (s, 2H), 4.67 (t, J = 6.1 Hz, 1H), 2.95 (dd, J = 14.3, 6.6 Hz, 2H), 1.78-1.62 (m, 3H), 1.60-1.42 (m, 6H), 1.05-0.94 (m, 2H). [M + H].sup.+ = 452.3 56 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.2 Hz, 1H), 8.29 (s, 1H), 7.85 (td, J = 7.7, 1.8 Hz, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.42 (t, J = 5.6 Hz, 1H), 7.38-7.27 (m, 3H), 7.10-7.06 (m, 4H), 7.01 (d, J = 9.0 Hz, 2H), 5.16 (s, 2H), 2.81-2.69 (m, 2H), 1.64-1.53 (m, 5H), 1.26-1.10 (m, 6H), 0.83-0.69 (m, 2H). [M + H].sup.+ = 466.3 57 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.59 (d, J = 4.5 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.28-7.16 (m, 2H), 7.16-7.09 (m, 2H), 7.04 (d, J = 7.7 Hz, 1H), 6.92 (d, J = 2.8 Hz, 1H), 6.81-6.72 (m, 2H), 6.23 (t, J = 5.3 Hz, 1H), 5.44 (s, 1H), 5.18 (s, 2H), 3.41 (dd, J = 14.6, 6.0 Hz, 2H), 2.54 (q, J = 7.5 Hz, 2H), 1.72-1.57 (m, 1H), 1.46 (dd, J = 14.7, 7.1 Hz, 2H), 1.14 (t, J = 7.5 Hz, 3H), 0.92 (d, J = 6.6 Hz, 6H). [M + H].sup.+ = 418.3 58 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.27-7.19 (m, 1H), 7.17-7.11 (m, 3H), 7.04 (d, J = 7.8 Hz, 1H), 6.93 (d, J = 2.9 Hz, 1H), 6.83-6.73 (m, 2H), 6.13 (t, J = 5.2 Hz, 1H), 5.38 (s, 1H), 5.20 (s, 2H), 3.42 (dd, J = 14.4, 6.1 Hz, 2H), 2.56 (q, J = 7.5 Hz, 2H), 1.86-1.75 (m, 3H), 1.66-1.49 (m, 6H), 1.15 (t, J = 7.5 Hz, 3H), 1.11-1.07 (m, 2H). [M + H].sup.+ = 444.2 59 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.29 (s, 1H), 7.84 (td, J = 7.7, 1.8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 5.8 Hz, 1H), 7.39-7.28 (m, 3H), 7.12-7.06 (m, 4H), 7.00 (d, J = 9.0 Hz, 2H), 5.15 (s, 2H), 2.78 (dd, J = 13.4, 7.0 Hz, 2H), 1.28-1.20 (m, 2H), 0.71- 0.57 (m, 1H), 0.37-0.29 (m, 2H), −0.02-−0.08 (m, 2H). [M + H].sup.+ = 424.2 60 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.26-7.19 (m, 3H), 7.16 (d, J = 8.6 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 6.95 (dd, J = 7.7, 1.7 Hz, 1H), 6.78 (dd, J = 8.6, 2.9 Hz, 1H), 6.68 (d, J = 2.9 Hz, 1H), 6.03 (s, 1H), 5.71 (s, 1H), 5.18 (s, 2H), 3.43 (dd, J = 9.8, 4.7 Hz, 2H), 1.90-1.78 (m, 5H), 1.66-1.51 (m, 4H), 1.17-1.09 (m, 3H), 0.94-0.87 (m, 2H), 0.67-0.59 (m, 2H). .sup.13C NMR (75 MHz, CDCl.sub.3) δ 165.4, 155.1, 152.7, 146.9, 143.9, 135.4, 134.5, 133.8, 132.2, 127.0, 120.9, 120.3, 119.0, 115.3, 114.4, 111.8, 111.2, 110.0, 68.6, 37.2, 35.6, 33.6, 30.4, 22.8, 9.3, 4.9 [M + H].sup.+ = 456.4 61 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.5 Hz, 1H), 7.72 (td, J = 7.7, 1.6 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.28-7.18 m, 3H), 7.15 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 6.93 (dd, J = 7.9, 1.7 Hz, 1H), 6.77 (dd, J = 8.6, 2.9 Hz, 1H), 6.67 (d, J = 2.8 Hz, 1H), 6.11 (s, 1H), 5.74 (s, 1H), 5.17 (s, 2H), 3.44 (dd, J = 14.5, 6.0 Hz, 2H), 1.91-1.82 (m, 1H), 1.71-1.60 (m, 1H), 1.48 (dd, J = 14.7, 7.1 Hz, 2H), 0.94 (d, J = 6.6 Hz, 6H), 0.92-0.85 (m, 2H), 0.66-0.56 (m, 2H). [M + H].sup.+ = 430.3 62 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.2 Hz, 1H), 8.34 (t, J = 5.6 Hz, 1H), 8.04 (s, 1H), 7.85 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.37-1.33 (m, 2H), 7.21 (d, J = 7.7 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 7.10-7.01 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.14 (s, 2H), 3.15 (t, J = 6.3 Hz, 2H), 2.19-2.07 (m, 1H), 1.72-1.44 (m, 6H), 1.30-1.18 (m, 2H). [M + H].sup.+ = 402.3 63 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.52 (t, J = 6.0 Hz, 1H), 8.07 (s, 1H), 7.85 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.39 (s, 1H), 7.35 (dd, J = 7.3, 5.7 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 7.07 (d, J = 8.9 Hz, 2H), 7.09-7.03 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.14 (s, 2H), 4.47 (d, J = 5.7 Hz, 2H), 4.19 (d, J = 5.7 Hz, 2H), 3.42 (d, J = 6.1 Hz, 2H), 1.24 (s, 3H). [M + H].sup.+ = 404.2 64 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.04-8.01 (m, 2H), 7.85 (td, J = 7.7, 1.8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.37-7.33 (m, 2H), 7.21 (d, J = 7.7 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.02-7.00 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.14 (s, 2H), 4.05- 3.92 (m, 1H), 1.57-1.25 (m, 4H), 1.11 (d, J = 6.6 Hz, 3H), 0.87 (t, J = 7.2 Hz, 3H). [M + H].sup.+ = 390.1 65 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.58 (d, J = 4.1 Hz, 1H), 8.54 (d, J = 5.7 Hz, 1H), 8.08 (s, 1H), 7.85 (td, J = 7.7, 1.8 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 7.37-7.32 (m, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 7.03-7.01 (m, 1H), 6.98 (d, J = 9.0 Hz, 2H), 5.14 (s, 2H), 3.46 (dd, J = 12.6, 6.8 Hz, 2H), 2.50 (dd, J = 12.6, 6.8 Hz, 2H). [M + H].sup.+ = 416.1 66 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.56 (d, J = 4.2 Hz, 1H), 8.25 (t, J = 5.7 Hz, 1H), 7.80 (td, J = 7.7, 1.7 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.40 (s, 1H), 7.30 (dd, J = 6.9, 5.4 Hz, 1H), 7.12 (d, J = 7.7 Hz, 1H), 7.09-7.05 (m, 2H), 7.02 (d, J = 10.0 Hz, 1H), 6.95 (d, J = 11.7 Hz, 1H), 6.84 (d, J = 2.8 Hz, 1H), 6.69 (dd, J = 8.6, 2.9 Hz, 2H), 5.41 (q, J = 6.5 Hz, 1H), 3.20 (dd, J = 13.6, 6.4 Hz, 1H), 2.08 (s, 3H), 1.82-1.70 (m, 4H), 1.58 (d, J = 6.5 Hz, 3H), 1.54-1.42 (m, 5H), 1.09 (t, J = 7.0 Hz, 3H). [M + H].sup.+ = 444.2 67 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.56 (d, J = 4.2 Hz, 1H), 8.23 (t, J = 5.6 Hz, 1H), 7.80 (td, J = 7.7, 1.7 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.40 (s, 1H), 7.30 (ddd, J = 7.5, 4.8, 1.0 Hz, 1H), 7.12 (d, J = 7.8 Hz, 1H), 7.09-7.05 (m, 2H), 7.02 (d, J = 9.5 Hz, 1H), 6.95 (d, J = 11.8 Hz, 1H), 6.85 (d, J = 2.8 Hz, 1H), 6.73-6.65 (m, 2H), 5.42 (q, J = 6.4 Hz, 1H), 3.21 (dd, J = 13.7, 6.4 Hz, 2H), 2.08 (s, 3H), 1.58 (d, J = 6.5 Hz, 4H), 1.37 (dd, J = 14.4, 6.9 Hz, 2H), 0.88 (d, J = 6.6 Hz, 6H). [M + H].sup.+ = 418.3 68 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.5 Hz, 1H), 8.15 (s, 1H), 7.85 (td, J = 7.9, 1.5 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.39-7.31 (m, 1H), 7.18 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.96- 6.90 (m, 2H), 6.82 (dd, J = 8.6, 2.8 Hz, 1H), 6.73 (s, 1H), 6.67 (d, J = 7.9 Hz, 1H), 6.21 (d, J = 7.9 Hz, 1H), 5.92 (t, J = 5.4 Hz, 1H), 5.14 (s, 2H), 3.06 (dd, J = 13.3, 6.7 Hz, 2H), 2.14 (s, 3H), 1.57 (td, J = 13.3, 6.7 Hz, 1H), 1.33-1.25 (m, 2H), 0.88 (d, J = 6.7 Hz, 6H). [M + H].sup.+ = 419.4 69 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.93 (d, J = 6.4 Hz, 1H), 8.59 (d, J = 4.8 Hz, 1H), 7.85 (td, J = 7.8, 1.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.36 (dd, J = 6.7, 5.0 Hz, 1H), 7.23-7.12 (m, 3H), 7.08 (d, J = 8.6 Hz, 1H), 6.97 (d, J = 2.8 Hz, 1H), 6.85 (dd, J = 8.6, 2.9 Hz, 1H), 6.77 (d, J = 7.5 Hz, 1H), 5.16 (s, 2H), 4.96 (dd, J = 14.0, 7.1 Hz, 1H), 4.74 (t, J = 6.9 Hz, 2H), 4.57 (t, J = 6.4 Hz, 2H), 2.14 (s, 3H). [M + H].sup.+ = 490.3 70 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.5 Hz, 1H), 8.29 (t, J = 5.7 Hz, 1H), 7.85 (dd, J = 7.7, 6.1 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.47 (s, 1H), 7.40-7.32 (m, 1H), 7.17 (s, 1H), 7.12- 7.04 (m, 3H), 6.97 (d, J = 2.7 Hz, 1H), 6.85 (dd, J = 8.6, 2.7 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 5.16 (s, 2H), 3.19 (dd, J = 12.5, 6.4 Hz, 2H), 2.76-2.57 (m, 3H), 2.33-2.15 (m, 2H), 2.14 (s, 3H), 1.68 (q, J = 6.8 Hz, 2H). [M + H].sup.+ = 452.3 71 .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J = 4.6 Hz, 1H), 8.11 (d, J = 7.3 Hz, 1H), 7.85 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.44 (s, 1H), 7.36 (dd, J = 7.3, 4.8 Hz, 1H), 7.14 (dd, J = 14.1, 6.3 Hz, 2H), 7.07 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 2.7 Hz, 1H), 6.85 (dd, J = 8.6, 2.8 Hz, 1H), 6.73 (d, J = 7.5 Hz, 1H), 5.16 (s, 2H), 4.17 (dd, J = 14.0, 7.1 Hz, 1H), 2.14 (s, 3H), 1.93-1.79 (m, 2H), 1.71-1.62 (m, 2H), 1.58-1.46 (m, 4H). [M + H].sup.+ = 402.3 72 [.sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.27-7.21 (m, 1H), 7.20 (d, J = 7.6 Hz, 1H), 7.16 (s, 1H), 7.12 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.90 (d, J = 2.7 Hz, 1H), 6.83-6.73 (m, 2H), 6.14 (s, 1H), 5.39 (s, 1H), 5.18 (s, 2H), 3.39 (dd, J = 13.2, 7.1 Hz, 2H), 2.19 (s, 3H), 1.63-1.50 (m, 3H), 1.27-1.20 (m, 2H), 0.88 (d, J = 6.6 Hz, 6H). [M + H].sup.+ = 418.3 73 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.59 (d, J = 5.2 Hz, 1H), 7.71 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.21 (dd, J = 7.0, 5.2 Hz, 1H), 7.12-7.03 (m, 3H), 6.96-6.89 (m, 2H), 6.50-6.44 (m, 2H), 6.38 (dd, J = 7.7, 1.7 Hz, 1H), 5.55 (br s, 1H), 5.18 (s, 2H), 3.88 (t, J = 6.6 Hz, 2H), 1.82- 1.68 (m, 7H), 1.66-1.46 (m, 5H), 1.17-1.04 (m, 3H). [M + H].sup.+ = 403.4 74 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.22 (d, J = 7.0 Hz, 1H), 7.14-7.04 (m, 3H), 6.98-6.93 (m, 2H), 6.51-6.45 (m, 2H), 6.42-6.35 (m, 1H), 5.49 (s, 1H), 5.19 (s, 2H), 3.76 (dd, J = 9.0, 5.8 Hz, 1H), 3.66 (dd, J = 9.0, 5.8 Hz, 1H), 1.94-1.83 (m, 1H), 1.51-1.32 (m, 4H), 1.21-1.13 (m, 2H), 0.99 (d, J = 6.7 Hz, 3H), 0.91 (t, J = 7.1 Hz, 3H). [M + H].sup.+ = 377.3 75 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.8 Hz, 1H), 7.74 (td, J = 7.7, 1.7 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.22 (dd, J = 7.5, 1.6 Hz, 1H), 7.19-7.12 (m, 3H), 7.03 (d, J = 7.7 Hz, 1H), 6.94 (d, J = 2.9 Hz, 1H), 6.81 (dd, J = 8.6, 2.9 Hz, 1H), 6.77 (dd, J = 8.0, 1.8 Hz, 1H), 5.99 (s, 1H), 5.33 (s, 1H), 5.21 (s, 2H), 3.44 (dd, J = 14.4, 6.1 Hz, 2H), 2.56 (q, J = 7.5 Hz, 2H), 1.81-1.65 (m, 6H), 1.48 (dd, J = 14.6, 7.0 Hz, 2H), 1.37-1.27 (m, 2H), 1.16 (t, J = 7.5 Hz, 4H), 0.99-0.91 (m, 2H). [M + H].sup.+ = 458.1 76 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.1 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.25-7.20 (m, 2H), 7.16 (d, J = 8.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 6.96 (t, J = 7.8 Hz, 1H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 5.99 (s, 1H), 5.71 (s, 1H), 5.18 (s, 2H), 3.45 (dd, J = 14.6, 7.0 Hz, 2H), 1.91-1.82 (m, 1H), 1.77-1.72 (m, 5H), 1.49 (dd, J = 14.6, 7.0 Hz, 2H), 1.30-1.17 (m, 3H), 1.02-0.83 (m, 5H), 0.63 (q, J = 5.8 Hz, 2H). [M + H].sup.+ = 470.4 77 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.25-7.16 (m, 3H), 7.13 (d, J = 8.6 Hz, 1H), 7.03 (d, J = 7.7 Hz, 1H), 6.90 (d, J = 2.7 Hz, 1H), 6.83-6.75 (m, 2H), 5.81 (d, J = 8.1 Hz, 1H), 5.33 (s, 1H), 5.20 (s, 2H), 4.23-4.08 (m, 1H), 2.20 (s, 3H), 1.55-1.45 (m, 2H), 1.44-1.32 (m, 2H), 1.21 (d, J = 6.6 Hz, 3H), 0.93 (t, J = 7.1 Hz, 3H). [M + H].sup.+ = 404.4 78 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.8 Hz, 1H), 7.74 (td, J = 7.7, 1.7 Hz, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.22 (dd, J = 8.1, 2.5 Hz, 1H), 7.18-7.12 (m, 3H), 7.01 (d, J = 7.9 Hz, 1H), 6.94 (d, J = 2.9 Hz, 1H), 6.81 (dd, J = 8.7, 3.0 Hz, 1H), 6.76 (dd, J = 8.1, 1.7 Hz, 1H), 5.80 (d, J = 8.7 Hz, 1H), 5.32 (s, 1H), 5.21 (s, 2H), 4.23-4.14 (m, 1H), 2.57 (q, J = 7.5 Hz, 2H), 1.55-1.34 (m, 4H), 1.21 (d, J = 6.6 Hz, 3H), 1.17 (t, J = 7.6 Hz, 3H), 0.93 (t, J = 7.1 Hz, 3H). [M + H].sup.+ = 418.4 79 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.62 (d, J = 4.8 Hz, 1H), 7.74 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.34-7.28 (m, 1H), 7.27-7.21 (m, 3H), 7.16 (d, J = 8.7 Hz, 1H), 7.00-6.94 (m, 1H), 6.80 (dd, J = 8.7, 2.8 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 5.77 (s, 1H), 5.19 (s, 2H), 4.23 (t, J = 6.0 Hz, 1H), 2.99 (dd, J = 14.0, 7.0 Hz, 2H), 1.93-1.87 (m, 1H), 1.70-1.56 (m, 5H), 1.35 (dd, J = 14.0, 7.0 Hz, 2H), 1.22-1.10 (m, 4H), 0.94-0.88 (m, 2H), 0.87-0.80 (m, 2H), 0.67-0.59 (m, 2H). [M + H].sup.+ = 506.4 80 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.4 Hz, 1H), 7.72 (td, J = 7.7, 1.6 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.26-7.08 (m, 5H), 6.83 (d, J = 7.9 Hz, 1H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 6.60 (d, J = 7.2 Hz, 1H), 5.64 (s, 1H), 5.17 (s, 2H), 2.37-2.28 (m, 2H), 1.87 (dq, J = 8.3, 5.2 Hz, 1H), 1.73-1.56 (m, 10H), 1.31-1.14 (m, 8H), 0.99-0.83 (m, 5H), 0.61 (q, J = 5.2 Hz, 2H). [M + H].sup.+ = 470.4 81 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.8 Hz, 1H), 7.74 (td, J = 7.7, 1.8 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 7.7 Hz, 1H), 7.24 (d, J = 6.6 Hz, 1H), 7.18 (d, J = 8.7 Hz, 1H), 6.85-6.74 (m, 3H), 6.67 (d, J = 2.9 Hz, 1H), 5.93 (t, J = 5.2 Hz, 1H), 5.80 (s, 1H), 5.19 (s, 2H), 3.51-3.40 (m, 2H), 1.93-1.82 (m, 1H), 1.76-1.66 (m, 1H), 1.50 (dd, J = 14.7, 7.1 Hz, 2H), 0.95 (d, J = 6.6 Hz, 6H), 0.93-0.87 (m, 2H), 0.67-0.57 (m, 2H). [M + H].sup.+ = 430.3 82 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.45-7.33 (m, 5H), 7.21 (d, J = 7.8 Hz, 1H), 7.16 (d, J = 8.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 6.5 Hz, 1H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.66 (d, J = 2.7 Hz, 1H), 6.02 (s, 1H), 5.70 (s, 1H), 5.03 (s, 2H), 3.48 (dd, J = 14.0, 7.0 Hz, 2H), 1.92-1.76 (m, 5H), 1.61 (dd, J = 14.2, 7.1 Hz, 5H), 1.17-1.10 (m, 2H), 0.94-0.87 (m, 2H), 0.67-0.59 (m, 2H). [M + H].sup.+ = 455.3 83 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.25-7.20 (m, 1H), 7.18 (d, J = 8.7 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.9 Hz, 1H), 6.45 (d, J = 8.0 Hz, 1H), 6.42 (t, J = 2.1 Hz, 1H), 6.37 (d, J = 8.1 Hz, 1H), 5.60 (s, 1H), 5.17 (s, 2H), 3.88 (t, J = 6.6 Hz, 2H), 1.88 (tt, J = 8.4, 5.4 Hz, 1H), 1.80-1.62 (m, 8H), 1.26 (ddt, J = 24.7, 14.6, 6.6 Hz, 7H), 0.91 (dd, J = 12.6, 6.2 Hz, 4H), 0.62 (q, J = 5.9 Hz, 2H). [M + H].sup.+ = 457.4 84 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.6 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.34-7.30 (m, 1H), 7.28-7.21 (m, 2H), 7.17-7.14 (m, 2H), 6.98 (dd, J = 7.9, 1.8 Hz, 1H), 6.79 (dd, J = 8.6, 2.9 Hz, 1H), 6.68 (d, J = 2.9 Hz, 1H), 6.07 (s, 1H), 5.73 (s, 2H), 5.17 (s, 2H), 1.91-1.82 (m, 1H), 0.95-0.86 (m, 2H), 0.66-0.58 (m, 2H). [M + H].sup.+ = 360.0 85 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.69 (d, J = 1.6 Hz, 1H), 8.59 (dd, J = 4.8, 1.4 Hz, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.34 (dd, J = 7.8, 4.9 Hz, 1H), 7.30-7.29 (m, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 6.96 (dd, J = 8.0, 1.7 Hz, 1H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.66 (d, J = 2.8 Hz, 1H), 6.01 (s, 1H), 5.74 (s, 1H), 5.05 (s, 2H), 3.45 (dd, J = 14.6, 7.0 Hz, 2H), 1.92-1.82 (m, 1H), 1.79-1.59 (m, 6H), 1.49 (dd, J = 14.6, 7.0 Hz, 2H), 1.41-1.29 (m, 1H), 1.19-1.13 (m, 2H), 1.01-0.87 (m, 4H), 0.67-0.60 (m, 2H). [M + H].sup.+ = 470.4 86 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.86-7.82 (m, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.60-7.51 (m, 3H), 7.33 (d, J = 8.7 Hz, 1H), 7.25-7.22 (m, 1H), 6.82 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 6.65 (dd, J = 6.6, 2.6 Hz, 1H), 6.39 (s, 1H), 5.19 (s, 2H), 3.46 (dd, J = 14.6, 7.0 Hz, 2H), 1.97-1.87 (m, 1H), 1.81-1.61 (m, 7H), 1.52 (dd, J = 14.6, 7.0 Hz, 2H), 1.43- 1.29 (m, 1H), 1.29-1.12 (m, 3H), 1.02-0.90 (m, 4H), 0.68-0.61 (m, 2H). [M + H].sup.+ = 471.3 87 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.74 (td, J = 7.7, 1.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.32-7.29 (m, 3H), 7.24-7.22 (m, 1H), 7.15 (d, J = 8.6 Hz, 1H), 7.00-6.94 (m, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.67 (d, J = 2.9 Hz, 1H), 5.76 (s, 1H), 5.18 (s, 2H), 4.74 (s, 2H), 1.90-1.81 (m, 1H), 0.95-0.87 (m, 2H), 0.66-0.60 (m, 2H). [M + H].sup.+ = 396.2 88 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.8 Hz, 1H), 8.29 (d, J = 1.7 Hz, 1H), 8.27 (d, J = 2.8 Hz, 1H), 7.74 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.51-7.48 (m, 1H), 7.23 (d, J = 7.0 Hz, 1H), 7.14 (d, J = 8.6 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.8 Hz, 1H), 6.08 (s, 1H), 5.74 (s, 1H), 5.18 (s, 2H), 3.47 (dd, J = 14.7, 7.0 Hz, 2H), 1.90-1.80 (m, 1H), 1.78-1.61 (m, 6H), 1.50 (dd, J = 14.7, 7.0 Hz, 2H), 1.38-1.30 (m, 2H), 1.01-0.86 (m, 4H), 0.67-0.60 (m, 2H). [M + H].sup.+ = 471.3 89 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.62 (d, J = 6.0 Hz, 2H), 7.36 (d, J = 6.0 Hz, 2H), 7.32-7.29 (m, 1H), 7.23 (t, J = 7.9 Hz, 1H), 7.17 (d, J = 8.6 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 6.96 (dd, J = 8.0, 1.6 Hz, 1H), 6.74 (dd, J = 8.6, 2.9 Hz, 1H), 6.66 (d, J = 2.8 Hz, 1H), 6.07 (s, 1H), 5.74 (s, 1H), 5.05 (s, 2H), 3.44 (dd, J = 14.5, 6.0 Hz, 2H), 1.92-1.77 (m, 4H), 1.71-1.50 (m, 7H), 1.18-1.10 (m, 2H), 0.96-0.86 (m, 2H), 0.68-0.59 (m, 2H). [M + H].sup.+ = 456.4 90 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 5.5 Hz, 1H), 8.22 (d, J = 5.5 Hz, 1H), 7.73 (td, J = 7.7, 1.6 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 8.7 Hz, 1H), 7.23 (d, J = 7.9 Hz, 1H), 6.90-6.79 (m, 3H), 6.68 (d, J = 2.8 Hz, 1H), 6.56 (s, 1H), 5.96 (s, 1H), 5.19 (s, 2H), 3.43 (dd, J = 14.8, 7.0 Hz, 2H), 1.94-1.84 (m, 1H), 1.78-1.61 (m, 6H), 1.48 (dd, J = 14.8, 7.0 Hz, 2H), 1.38-1.14 (m, 4H), 1.01-0.88 (m, 3H), 0.66-0.61 (m, 2H). [M + H].sup.+ = 471.3 91 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 7.48 (d, J = 7.1 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.37-7.32 (m, 1H), 7.01-6.96 (m, 2H), 6.96-6.85 (m, 4H), 6.71 (s, 1H), 6.21 (d, J = 8.2 Hz, 1H), 5.08 (s, 2H), 2.26-2.17 (m, 2H), 1.64 (dt, J = 17.6, 10.7 Hz, 5H), 1.43 (q, J = 7.0 Hz, 2H), 1.32 (s, 9H), 1.17 (qd, J = 19.9, 17.7, 8.0 Hz, 4H), 0.86 (q, J = 10.4, 9.1 Hz, 2H) [M + H].sup.+ = 485.3 92 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.52-7.22 (m, 5H), 6.76-6.53 (m, 3H), 6.01 (s, 1H), 4.97 (s, 2H), 4.50 (s, 2H), 2.62 (t, J = 6.6 Hz, 2H), 1.89 (p, J = 7.5 Hz, 2H) [M + H].sup.+ = 495.3 93 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.55 (s, 1H), 7.55-7.27 (m, 5H), 7.17 (s, 1H), 7.08-6.73 (m, 6H), 6.27 (d, J = 8.9 Hz, 1H), 5.08 (s, 2H), 3.26-3.13 (m, 1H), 2.28-2.15 (m, 2H), 1.89 (d, J = 6.1 Hz, 2H), 1.79-1.36 (m, 14H), 1.28-1.04 (m, 4H), 0.87 (q, J = 10.4, 8.9 Hz, 2H) .sup.13C NMR (151 MHz, DMSO) δ 171.6, 156.2, 149.1, 144.4, 140.5, 137.8, 133.5, 129.3, 128.8, 128.2, 128.2, 127.9, 113.5, 112.9, 109.1, 108.5, 104.4, 69.8, 37.2, 34.4, 34.2, 33.1, 33.0, 26.6, 26.2, 25.6 [M + H].sup.+ = 497.3 94 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 7.49 (d, J = 7.1 Hz, 2H), 7.42 (t, J = 7.3 Hz, 2H), 7.38-7.32 (m, 1H), 7.16 (s, 1H), 7.07 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 7.9 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.89-6.85 (m, 2H), 6.81 (dd, J = 8.5, 2.8 Hz, 1H), 6.30 (d, J = 7.6 Hz, 1H), 5.13 (s, 2H), 2.35 (s, 3H), 2.27-2.21 (m, 2H), 1.72-1.59 (m, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.25-1.11 (m, 4H), 0.93-0.81 (m, 2H) [M + H].sup.+ = 475.2 95 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 6.9 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.35-7.29 (m, 1H), 7.01 (d, J = 8.6 Hz, 2H), 6.82 (t, J = 7.5 Hz, 1H), 6.76 (dd, J = 8.6, 2.9 Hz, 1H), 6.46 (d, J = 2.9 Hz, 1H), 5.97 (s, 3H), 5.03 (s, 2H), 2.88 (t, J = 7.1 Hz, 2H), 1.97 (s, 1H), 1.65 (d, J = 10.9 Hz, 5H), 1.48 (q, J = 7.4 Hz, 2H), 1.23-1.07 (m, 6H), 0.90-0.79 (m, 4H), 0.64-0.55 (m, 2H) [M + H].sup.+ = 455.3 96 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.4 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.28-7.20 (m, 1H), 7.15 (d, J = 8.6 Hz, 1H), 7.11 (t, J = 8.1 Hz, 1H), 6.81 (t, J = 2.0 Hz, 1H), 6.76 (dd, J = 8.7, 2.9 Hz, 1H), 6.67-6.63 (m, 2H), 6.57 (dd, J = 8.0, 1.6 Hz, 1H), 6.33 (s, 1H), 5.16 (s, 2H), 4.81 (t, J = 5.5 Hz, 1H), 3.24 (dd, J = 13.9, 6.4 Hz, 2H), 1.92-1.79 (m, 1H), 1.72-1.57 (m, 5H), 1.38 (dd, J = 13.9, 6.9 Hz, 2H), 1.29-1.12 (m, 4H), 0.97-0.81 (m, 4H), 0.66- 0.55 (m, 2H) [M + H].sup.+ = 485.5 97 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.36-7.30 (m, 1H), 7.28 (s, 1H), 7.01 (t, J = 8.7 Hz, 2H), 6.77 (dd, J = 8.6, 2.9 Hz, 1H), 6.67 (s, 1H), 6.56 (d, J = 7.5 Hz, 1H), 6.52 (dd, J = 8.0, 1.7 Hz, 1H), 6.48 (d, J = 2.8 Hz, 1H), 5.05 (s, 2H), 4.91 (d, J = 4.1 Hz, 1H), 4.33 (q, J = 5.2 Hz, 1H), 1.95 (ddd, J = 13.7, 8.4, 5.3 Hz, 1H), 1.68-1.57 (m, 5H), 1.54- 1.40 (m, 2H), 1.38-1.26 (m, 1H), 1.26-1.06 (m, 7H), 0.88-0.75 (m, 4H), 0.66-0.57 (m, 2H) [M + H].sup.+ = 470.3 98 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.48 (d, J = 7.2 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.36 (d, J = 7.1 Hz, 1H), 7.30 (dd, J = 6.8, 3.7 Hz, 4H), 7.03 (d, J = 2.6 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.42 (d, J = 7.8 Hz, 1H), 5.17 (s, 2H), 2.28-2.20 (m, 2H), 1.72- 1.56 (m, 5H), 1.44 (q, J = 7.1 Hz, 2H), 1.25-1.09 (m, 4H), 0.93-0.81 (m, 2H) [M + H].sup.+ = 497.1 99 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.53 (dd, J = 8.5, 5.7 Hz, 2H), 7.34-7.27 (m, 4H), 7.24 (t, J = 8.9 Hz, 2H), 7.06-6.99 (m, 2H), 6.94 (d, J = 8.1 Hz, 1H), 6.42 (d, J = 8.8 Hz, 1H), 5.15 (s, 2H), 2.28-2.20 (m, 2H), 1.72-1.56 (m, 5H), 1.44 (q, J = 7.1 Hz, 2H), 1.25-1.07 (m, 4H), 0.87 (s, 2H) [M + H].sup.+ = 515.1 100 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.63 (s, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.32-7.26 (m, 1H), 7.26-7.22 (m, 2H), 7.20 (d, J = 8.7 Hz, 1H), 7.04 (dd, J = 7.9, 1.2 Hz, 1H), 6.86-6.77 (m, 2H), 6.69 (d, J = 2.9 Hz, 1H), 5.18 (s, 2H), 2.65 (d, J = 6.8 Hz, 2H), 1.96-1.85 (m, 1H), 1.79-1.64 (m, 6H), 1.29-1.17 (m, 3H), 1.04-0.97 (m, 2H), 0.95-0.89 (m, 2H), 0.66-0.61 (m, 2H) [M + H].sup.+ = 480.6 101 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.40 (s, 1H), 7.61 (d, J = 6.9 Hz, 1H), 7.48 (d, J = 7.1 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.16 (t, J = 7.7 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 7.00 (d, J = 2.8 Hz, 1H), 6.90 (dd, J = 8.6, 2.8 Hz, 1H), 6.61 (t, J = 7.4 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 5.09 (s, 2H), 3.27 (d, J = 6.8 Hz, 2H), 1.74 (d, J = 12.2 Hz, 2H), 1.64 (dd, J = 20.5, 11.1 Hz, 3H), 1.44 (q, J = 6.9 Hz, 2H), 1.31 (s, 9H), 1.26-1.13 (m, 4H), 0.90 (q, J = 13.3, 12.5 Hz, 2H) .sup.13C NMR (151 MHz, DMSO) δ 169.5, 156.0, 148.9, 147.5, 137.7, 132.5, 132.3, 130.2, 128.9, 128.8, 128.3, 128.2, 116.1, 115.7, 114.6, 113.4, 112.7, 69.8, 37.2, 37.0, 35.2, 35.1, 33.2, 30.5, 26.6, 26.2 [M + H].sup.+ = 485.3 102 1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.4 Hz, 1H), 7.99 (s, 1H), 7.73 (td, J = 7.7, 1.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 6.8 Hz, 1H), 7.13 (dd, J = 7.9, 1.4 Hz, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.93 (d, J = 8.5 Hz, 1H), 6.82 (dd, J = 7.7, 1.4 Hz, 1H), 6.77-6.73 (m, 2H), 5.51 (bs, 1H), 5.17 (s, 2H), 2.20 (s, 3H), 1.81 (dd, J = 8.2, 4.5 Hz, 2H), 1.62 (dd, J = 8.1, 4.5 Hz, 2H), 0.90 (dt, J = 6.1, 4.2 Hz, 2H), 0.64 (td, J = 5.9, 4.2 Hz, 2H) 103 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.43 (t, J = 5.6 Hz, 1H), 7.64-7.56 (m, 1H), 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (dd, J = 8.3, 6.0 Hz, 1H), 7.20 (t, J = 7.2 Hz, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.83 (dd, J = 8.7, 2.9 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 6.67 (t, J = 7.4 Hz, 1H), 6.60 (d, J = 2.9 Hz, 1H), 5.07 (s, 2H), 3.22 (q, J = 6.8 Hz, 2H), 1.90-1.78 (m, 1H), 1.67 (t, J = 13.7 Hz, 4H), 1.58 (d, J = 7.0 Hz, 1H), 1.53 (q, J = 7.3 Hz, 2H), 1.27-1.08 (m, 6H), 0.87 (ddd, J = 8.4, 6.2, 4.3 Hz, 4H), 0.65-0.59 (m, 2H) [M + H].sup.+ = 483.2 104 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.25 (t, J = 5.6 Hz, 1H), 7.48 (d, J = 5.9 Hz, 3H), 7.45-7.28 (m, 6H), 7.23-7.11 (m, 3H), 6.87-6.80 (m, 1H), 5.18 (s, 2H), 3.21 (q, J = 6.3 Hz, 2H), 1.76 (s, 3H), 1.52 (ddq, J = 27.4, 13.0, 7.2 Hz, 6H), 1.08 (d, J = 3.5 Hz, 2H) [M + H].sup.+ = 483.1 105 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 7.1 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.35-7.30 (m, 1H), 6.90-6.84 (m, 2H), 6.76 (dd, J = 8.6, 2.8 Hz, 1H), 6.53-6.48 (m, 2H), 6.38 (d, J = 8.1 Hz, 1H), 6.11 (d, J = 8.1 Hz, 1H), 5.04 (s, 2H), 3.90 (t, J = 6.3 Hz, 2H), 2.07 (s, 3H), 1.89 (ddd, J = 13.7, 8.4, 5.3 Hz, 1H), 1.75-1.60 (m, 7H), 1.36-1.12 (m, 6H), 0.89 (q, J = 10.6, 9.6 Hz, 2H), 0.83-0.77 (m, 2H), 0.62-0.56 (m, 2H) [M + H].sup.+ = 470.4 106 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.3 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.25-7.20 (m, 1H), 7.18 (d, J = 8.7 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.9 Hz, 1H), 6.48-6.44 (m, 1H), 6.42 (t, J = 2.1 Hz, 1H), 6.37 (dd, J = 8.0, 1.8 Hz, 1H), 5.17 (s, 2H), 3.89 (t, J = 6.7 Hz, 2H), 1.94-1.82 (m, 1H), 1.80-1.70 (m, 2H), 1.65-1.52 (m, 1H), 1.35-1.26 (m, 2H), 0.95-(m, 2H) [M + H].sup.+ = 417.4 107 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.48 (d, J = 7.1 Hz, 2H), 7.45-7.39 (m, 4H), 7.38- 7.34 (m, 3H), 7.32 (dd, J = 8.9, 2.7 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.69 (d, J = 7.4 Hz, 1H), 5.15 (s, 2H), 3.19 (s, 3H), 2.31- (q, J = 7.1 Hz, 2H), 1.23-1.08 (m, 4H), 0.95-0.82 (m, 2H) [M + H].sup.+ = 507.2 108 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 10.11 (s, 1H), 8.52 (d, J = 4.2 Hz, 1H), 7.65 (td, J = 7.7, 1.7 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 7.15 (dd, J = 7.1, 5.2 Hz, 1H), 7.00 (t, J = 8.0 Hz, 1H), 6.83 (dd, J = 7.2, 2.1 Hz, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.68-6.66 (m, 2H), 5.09 (s, 2H), 2.14 (s, 3H), 1.80-1.69 (m, 3H), 1.37 (dd, J = 7.8, 4.6 Hz, 2H), 0.86-0.76 (m, 2H), 0.60- 0.53 (m, 2H) [M + H].sup.+ = 457.3 109 .sup.1H NMR (300 MHz, DMSO) δ 8.59 (d, J = 4.8 Hz, 1H), 7.85 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.36 (dd, J = 7.0, 5.3 Hz, 1H), 6.94-6.85 (m, 1H), 6.80 (dd, J = 8.6, 2.8 Hz, 1H), 6.72- 2.7 Hz, 1H), 6.20 (d, J = 8.1 Hz, 1H), 5.14 (s, 2H), 2.14 (s, 3H), 1.94- 1.85 (m, 1H), 0.87-2H) .sup.13C NMR (151 MHz, DMSO) δ 157.4, 155.5, 150.7, 149.5, 147.0, 140.0, 137.4, 135.5, 126.2, 126.0, 123.3, 122.2, 116.1, 116.0, 112.6, 111.5, 110.8, 110.3, 70.9, 11.5, 11.0, 8.9 [M + H].sup.+ = 427.2 110 1H NMR (400 MHz, DMSO-d6) δ 9.49 (s, 1H), 8.43 (s, 1H), 7.61 (d, J = 7.7 Hz, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.83 (dd, J = 8.6, 2.8 Hz, 1H), 6.75 (d, J = 8.4 Hz, 1H), 6.68 (t, J = 7.4 Hz, 1H), 6.60 (d, J = 2.8 Hz, 1H), 5.07 (s, 2H), 3.11 (t, J = 6.3 Hz, 2H), 1.84 (s, 1H), 1.71 (t, J = 13.5 Hz, 4H), 1.60 (d, J = 26.4 Hz, 2H), 1.20 (dd, J = 23.1, 8.6 Hz, 3H), 1.00-0.91 (m, 2H), 0.91-0.84 (m, 2H), 0.62 (d, J = 5.1 Hz, 2H) [M + H].sup.+ = 455.2 111 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.74 (td, J = 7.7, 1.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.27-7.22 (m, 1H), 7.15 (t, J = 7.9 Hz, 1H), 7.09-7.06 (m, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.59 (dd, J = 8.3, 2.1 Hz, 1H), 6.54 (d, J = 2.9 Hz, 1H), 5.98 (t, J = 6.0 Hz, 1H), 5.18 (s, 2H), 3.44 (dd, J = 14.6, 7.0 Hz, 2H), 3.28 (s, 3H), 1.88-1.79 (m, 1H), 1.77-1.61 (m, 7H), 1.48 (dd, J = 14.6, 7.0 Hz, 2H), 1.23-1.14 (m, 2H), 1.00- 0.91 (m, 2H), 0.86-0.78 (m, 2H), 0.65-0.58 (m, 2H) [M + H].sup.+ = 484.4 112 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.64 (s, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.25-7.21 (m, 2H), 7.19 (d, J = 6.4 Hz, 1H), 7.03 (dd, J = 7.9, 1.2 Hz, 1H), 6.85-6.78 (m, 2H), 6.69 (d, J = 2.9 Hz, 1H), 5.18 (s, 2H), 2.85- 2.74 (m, 2H), 1.95-1.86 (m, 1H), 1.67-1.58 (m, 3H), 0.96 (d, J = 6.2 Hz, 6H), 0.94-0.88 (m, 2H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 454.5 113 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 9.14 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.37 (dd, J = 7.8, 1.4 Hz, 1H), 7.23 (d, J = 7.5 Hz, 1H), 7.18 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 7.8 Hz, 1H), 6.77 (dd, J = 8.7, 2.9 Hz, 1H), 6.69-6.63 (m, 2H), 6.13 (bs, 1H), 5.18 (s, 2H), 3.38 (dd, J = 7.2, 5.8 Hz, 2H), 2.16 (dt, J = 15.0, 7.5 Hz, 1H), 2.02-1.91 (m, 1H), 1.88-1.77 (m, 2H), 1.72-1.58 (m, 4H), 1.35-1.22 (m, 2H), 0.97-0.89 (m, 2H), 0.65- 0.58 (m, 2H) [M + H].sup.+ = 442.4 114 1H NMR (500 MHz, DMSO-d6) δ 7.46 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.36-7.30 (m, 1H), 7.12-7.06 (m, 1H), 7.00 (t, J = 8.1 Hz, 1H), 6.93 (s, 1H), 6.66 (dd, J = 6.5, 2.8 Hz, 2H), 6.46 (dd, J = 7.9, 1.8 Hz, 1H), 6.41 (t, J = 2.2 Hz, 1H), 6.25 (dd, J = 8.1, 2.3 Hz, 1H), 5.06 (s, 2H), 3.84 (t, J = 6.5 Hz, 2H), 3.67-3.59 (m, 4H), 2.87-2.80 (m, 4H), 1.72-1.58 (m, 7H), 1.30-1.09 (m, 6H), 0.87 (q, J = 10.0, 9.5 Hz, 2H) .sup.13C NMR (151 MHz, DMSO) δ 160.0, 154.9, 147.0, 146.0, 137.8, 130.0, 129.2, 128.8, 128.2, 128.2, 123.4, 108.8, 107.7, 107.2, 104.5, 101.4, 69.9, 67.8, 66.7, 51.1, 37.3, 33.7, 33.3, 26.6, 26.6, 26.3 [M + H].sup.+ = 501.2 115 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.40 (t, J = 5.6 Hz, 1H), 7.59 (dd, J = 7.9, 1.4 Hz, 1H), 7.49-7.43 (m, 2H), 7.42-7.37 (m, 2H), 7.36-7.30 (m, 1H), 7.20 (s, 1H), 7.12 (d, J = 8.7 Hz, 1H), 6.83 (dd, J = 8.7, 2.9 Hz, 1H), 6.78-6.71 (m, 1H), 6.70-6.64 (m, 1H), 6.59 (d, J = 2.9 Hz, 1H), 5.07 (s, 2H), 3.30-3.23 (m, 2H), 1.84 (ddd, J = 13.8, 8.4, 5.3 Hz, 1H), 1.73 (d, J = 13.0 Hz, 2H), 1.69-1.57 (m, 3H), 1.44 (q, J = 6.9 Hz, 2H), 1.31 (ddt, J = 10.8, 7.3, 3.6 Hz, 1H), 1.26- 1.09 (m, 3H), 0.97-0.84 (m, 4H), 0.66-0.58 (m, 2H) [M + H].sup.+ = 469.2 116 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.45 (s, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.36 (d, J = 7.1 Hz, 2H), 7.27 (d, J = 3.2 Hz, 4H), 7.00 (dd, J = 10.4, 9.0 Hz, 1H), 6.46 (dt, J = 8.6, 3.4 Hz, 1H), 5.16 (s, 2H), 2.34 (t, J = 7.6 Hz, 2H), 1.73-1.55 (m, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.24-1.09 (m, 4H), 0.94-0.80 (m, 2H) [M + H].sup.+ = 515.1 117 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.9 Hz, 1H), 8.12 (d, J = 5.6 Hz, 1H), 7.99 (t, J = 5.7 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.55-7.51 (m, 2H), 7.28-7.21 (m, 1H), 7.16 (d, J = 8.6 Hz, 1H), 6.81 (dd, J = 8.6, 2.9 Hz, 1H), 6.67-6.61 (m, 2H), 5.19 (s, 2H), 3.45 (dd, J = 14.5, 6.2 Hz, 2H), 1.84 (td, J = 8.4, 4.2 Hz, 1H), 1.77-1.65 (m, 6H), 1.51 (dd, J = 14.6, 6.2 Hz, 2H), 1.21-1.16 (m, 2H), 1.00-0.94 (m, 1H), 0.93-0.86 (m, 4H), 0.64-0.59 (m, 2H) [M + H].sup.+ = 471.4 118 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.65 (t, J = 1.5 Hz, 1H), 7.56 (t, J = 8.9 Hz, 2H), 7.31 (t, J = 7.9 Hz, 1H), 7.26-7.20 (m, 2H), 6.95 (dd, J = 8.1, 1.7 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.71 (d, J = 2.9 Hz, 1H), 5.19 (s, 2H), 4.60 (t, J = 7.2 Hz, 2H), 2.10-2.00 (m, 2H), 1.95-1.85 (m, 1H), 1.73-1.67 (m, 6H), 1.31-1.13 (m, 5H), 0.96-0.89 (m, 4H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 509.6 119 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.47 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.36 1H), 7.19 (s, 1H), 7.03 (d, J = 8.6 Hz, 1H), 6.97-6.91 (m, 2H), 6.84 (dd, J = 8.6, 2.9 Hz, 1H), 6.15 (d, J = 8.0 Hz, 2H), 6.06 (t, J = 2.1 Hz, 1H), 5.08 (s, 2H), 3.80 (t, J = 6.5 Hz, 2H), 3.15 (p, J = 6.8 Hz, 1H), 1.73-1.55 (m, 7H), 1.28-1.12 (m, 6H), 1.10 (d, J = 6.9 Hz, 6H), 0.92-0.80 (m, 2H) [M + H].sup.+ = 458.3 120 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 9.12 (s, 1H), 8.60 (d, J = 4.1 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.36 (dd, J = 7.9, 1.3 Hz, 1H), 7.26-7.21 (m, 2H), 7.17 (d, J = 8.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.78 (dd, J = 8.6, 2.9 Hz, 1H), 6.70-6.63 (m, 2H), 6.36 (t, J = 5.5 Hz, 1H), 5.18 (s, 2H), 3.71 (dd, J = 12.7, 6.3 Hz, 2H), 2.56-2.39 (m, 2H), 2.01-1.89 (m, 1H), 0.96-0.88 (m, 2H), 0.66-0.57 (m, 2H) [M + H].sup.+ = 456.3 121 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 7.50 (dd, J = 8.5, 5.7 Hz, 2H), 7.26-7.18 (m, 4H), 7.02 (d, J = 8.6 Hz, 1H), 6.96 (dd, J = 10.4, 9.0 Hz, 1H), 6.91 (d, J = 2.8 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.39-6.31 (m, 1H), 5.04 (s, 2H), 2.33 (t, J = 7.6 Hz, 2H), 2.13 (s, 3H), 1.65 (dt, J = 18.2, 10.5 Hz, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.16 (td, J = 20.4, 19.2, 11.1 Hz, 4H), 0.87 (q, J = 10.6, 9.5 Hz, 2H) [M + H].sup.+ = 479.2 122 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.79 (s, 1H), 7.67 (dd, J = 7.9, 1.4 Hz, 1H), 7.43 (dt, J = 19.3, 7.3 Hz, 5H), 7.37-7.30 (m, 1H), 7.15 (d, J = 8.6 Hz, 1H), 6.92-6.86 (m, 2H), 6.73 (d, J = 8.4 Hz, 1H), 6.67 (d, J = 2.8 Hz, 1H), 5.10 (s, 2H), 3.36-3.32 (m, 2H), 1.78 (ddd, J = 13.7, 8.4, 5.3 Hz, 1H), 1.66-1.48 (m, 7H), 1.22-1.03 (m, 6H), 0.87-0.70 (m, 4H), 0.68-0.59 (m, 2H) [M + H].sup.+ = 504.3 123 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 9.16 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 7.72 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 6.7 Hz, 1H), 7.26-7.21 (m, 1H), 7.18 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.3 Hz, 1H), 6.77 (dd, J = 8.6, 2.9 Hz, 1H), 6.68-6.63 (m, 2H), 6.05 (t, J = 5.6 Hz), 1H), 5.18 (s, 2H), 3.46 (dd, J = 14.6, 7.1 Hz, 2H), 2.03-1.92 (m, 1H), 1.78-1.63 (m, 1H), 1.52 (dd, J = 14.7, 7.1 Hz, 2H), 0.99-0.90 (m, 8H), 0.64-0.58 (m, 2H) [M + H].sup.+ = 430.4 124 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.82 (s, 1H), 7.48 (d, J = 7.1 Hz, 2H), 7.42 (s, 2H), 7.39-7.26 (m, 6H), 7.08-7.03 (m, 2H), 6.90-6.84 (m, 1H), 5.20 (s, 2H), 2.73 (d, J = 6.3 Hz, 2 H), 1.65- 1.49 (m, 5H), 1.22 (t, J = 5.7 Hz, 3H), 1.19-1.05 (m, 3H), 0.76 (d, J = 10.6 Hz, 2H) [M + H].sup.+ = 533.2 125 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.45 (s, 1H), 7.53 (dd, J = 8.5, 5.7 Hz, 2H), 7.37 (d, J = 4.5 Hz, 1H), 7.27 (s, 4H), 7.24 (t, J = 8.9 Hz, 2H), 7.00 (dd, J = 10.5, 9.0 Hz, 1H), 6.46 (dt, J = 8.7, 3.3 Hz, 1H), 5.14 (s, 2H), 2.34 (t, J = 7.6 Hz, 2H), 1.73-1.58 (m, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.24- 1.09 (m, 4H), 0.94-0.80 (m, 2H) [M + H].sup.+ = 533.1 126 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.8 Hz, 1H), 7.68-7.64 (m, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 6.95 (dd, J = 8.1, 1.6 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.71 (d, J = 2.9 Hz, 1H), 5.19 (s, 2H), 4.61 (t, J = 7.2 Hz, 2H), 2.11-1.99 (m, 2H), 1.96-1.85 (m, 1H), 1.68-1.55 (m, 2H), 1.28-1.21 (m, 2H), 0.96-0.85 (m, 8H), 0.68-0.60 (m, 2H) [M + H].sup.+ = 469.5 127 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 7.7 Hz, 1H), 7.32-7.26 (m, 1H), 7.26-7.22 (m, 1H), 7.20 (d, J = 8.6 Hz, 1H), 6.97 (dd, J = 7.8, 2.0 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.70 (d, J = 2.9 Hz, 1H), 5.18 (s, 2H), 2.99-2.89 (m, 2H), 1.89 (It, J = 8.4, 5.4 Hz, 1H), 1.80-1.67 (m, 3H), 0.97 (d, J = 6.4 Hz, 6H), 0.95-0.87 (m, 2H), 0.67-0.60 (m, 2H) [M + H].sup.+ = 455.5 128 .sup.1H NMR (500 MHz, DMSO-d6) δ ppm 0.57-0.64 (m, 2 H), 0.81-0.90 (m, 2 H), 1.18 (d, J = 6.6 Hz, 6 H), 1.76-1.83 (m, 1 H), 4.12 (dq, J = 13.8, 6.7 Hz, 1 H), 5.07 (s, 2 H), 6.62 (d, J = 2.7 Hz, 1 H), 6.84 (dd, J = 8.6, 2.9 Hz, 1 H), 6.90 (d, J = 8.5 Hz, 1 H), 7.08 (d, J = 8.5 Hz, 1 H), 7.11-7.16 (m, 1 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.32-7.36 (m, 1 H), 7.37-7.42 (m, 2 H), 7.42-7.47 (m, 2 H), 7.52 (s, 1 H), 8.79 (d, J = 7.7 Hz, 1 H) [M + H].sup.+ = 426.2 129 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.55-7.52 (m, 2H), 7.52-7.48 (m, 1H), 7.32-7.26 (m, 1H), 7.26-7.22 (m, 1H), 7.20 (d, J = 8.6 Hz, 1H), 6.97 (dd, J = 7.6, 2.1 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.70 (d, J = 2.9 Hz, 1H), 5.18 (s, 2H), 2.99-2.90 (m, 2H), 1.93-1.84 (m, 1H), 1.80-1.64 (m, 8H), 1.32-1.11 (m, 3H), 1.02-0.87 (m, 4H), 0.67-0.59 (m, 2H) [M + H].sup.+ = 495.5 130 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.51-7.49 (m, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.30 (t, J = 7.9 Hz, 1H), 7.27-7.21 (m, 2H), 7.19 (d, J = 8.7 Hz, 1H), 6.97 (dd, J = 8.1, 1.6 Hz, 1H), 6.81 (dd, J = 8.6, 2.9 Hz, 1H), 6.70 (d, J = 2.8 Hz, 1H), 5.19 (s, 2H), 2.94-2.88 (m, 2H), 1.95-1.84 (m, 1H), 1.72 (dt, J = 16.7, 9.3 Hz, 8H), 1.30-1.16 (m, 3H), 1.00-0.95 (t, J = 8.7 Hz, 2H), 0.93-0.88 (m, 2H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 495.4 131 .sup.1H NMR (500 MHz, DMSO-d6) δ 7.48-7.43 (m, 2H), 7.40 (dd, J = 8.1, 6.7 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 6.96-6.88 (m, 2H), 6.85 (d, J = 8.5 Hz, 1H), 6.37 (dd, J = 8.5, 2.8 Hz, 1H), 6.11 (dq, J = 5.1, 2.7, 2.3 Hz, 3H), 6.00 (t, J = 2.2 Hz, 1H), 5.05 (s, 2H), 3.80 (t, J = 6.5 Hz, 2H), 3.73 (d, J = 7.3 Hz, 4H), 2.07 (p, J = 7.2 Hz, 2H) [M + H].sup.+ = 471.2 132 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.24 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.92 (d, J = 2.2 Hz, 2H), 6.88 (d, J = 8.1 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.32 (d, J = 9.3 Hz, 1H), 5.06 (s, 2H), 2.27-2.18 (m, 2H), 2.14 (s, 3H), 1.73-1.55 (m, 5H), 1.45 (q, J = 7.0 Hz, 2H), 1.27-1.07 (m, 4H), 0.93-0.81 (m, 2H) [M + H].sup.+ = 443.2 133 .sup.1H NMR (300 MHz, DMSO) δ 8.60 (d, J = 4.5 Hz, 1H), 7.87 (t, J = 6.9 Hz, 1H), 7.55 (d, J = 7.8 Hz, 2H), 7.40-7.33 (m, 1H), 7.05 (d, J = 8.6 Hz, 1H), 7.02 (t, J = 8.0 Hz, 1H), 6.81 (dd, J = 8.7, 2.8 Hz, 1H), 6.51 (d, J = 2.8 Hz, 1H), 6.49 (s, 1H), 6.42 (t, J = 8.5 Hz, 2H), 5.15 (s, 2H), 1.96 (ddd, J = 14.4, 8.6, 5.4 Hz, 1H), 0.86 (q, J = 5.7 Hz, 2H), 0.62 (q, J = 5.7 Hz, 2H) [M + H].sup.+ = 413.4 134 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.25-7.21 (m, 2H), 7.15 (d, J = 8.7 Hz, 1H), 6.87 (dd, J = 8.1, 1.6 Hz, 1H), 6.83 (s, 1H), 6.80-6.74 (m, 2H), 6.67 (d, J = 2.9 Hz, 1H), 5.17 (s, 2H), 3.69 (bs, 2H), 3.42 (bs, 6H) 1.93- 1.82 (m, 1H), 1.47 (s, 9H), 0.94-0.87 (m, 2H), 0.65-0.58 (m, 2H) [M + H].sup.+ = 529.5 135 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.0 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.36-7.30 (m, 1H), 7.09 (d, J = 20.6 Hz, 2H), 7.02 (d, J = 8.7 Hz, 1H), 6.93 (t, J = 7.8 Hz, 1H), 6.84 (d, J = 7.3 Hz, 1H), 6.74 (dd, J = 8.6, 2.9 Hz, 1H), 6.47 (d, J = 2.8 Hz, 1H), 6.42 (d, J = 7.6 Hz, 1H), 5.04 (s, 2H), 1.97 (td, J = 8.4, 4.2 Hz, 1H), 1.90-1.80 (m, 2H), 1.67-1.53 (m, 5H), 1.19-1.02 (m, 6H), 0.88-0.72 (m, 5H), 0.65-0.56 (m, 2H) [M + H].sup.+ = 499.3 136 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 9.23 (s, 1H), 8.60 (d, J = 4.2 Hz, 1H), 7.73 (t, J = 7.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.33-7.21 (m, 3H), 7.15 (d, J = 8.5 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.78 (dd, J = 8.7, 2.8 Hz, 1H), 6.67-6.59 (m, 3H), 5.18 (s, 2H), 2.00-1.90 (m, 1H), 1.65 (dd, J = 8.2, 5.7 Hz, 2H), 1.35 (dd, J = 8.2, 5.9 Hz, 2H), 0.93 (dd, J = 13.7, 5.2 Hz, 2H), 0.62 (dd, J = 13.7, 5.2 Hz, 2H) [M + H].sup.+ = 425.3 137 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.26-7.20 (m, 1H), 7.17 (d, J = 8.7 Hz, 1H), 7.08 (t, J = 8.1 Hz, 1H), 6.77 (dd, J = 8.7, 2.9 Hz, 1H), 6.68 (d, J = 2.9 Hz, 1H), 6.44 (dd, J = 8.0, 1.5 Hz, 1H), 6.34 (t, J = 2.2 Hz, 1H), 6.28 (dd, J = 7.9, 2.0 Hz, 1H), 5.17 (s, 2H), 4.57 (p, J = 7.1 Hz, 1H), 2.44-2.33 (m, 2H), 2.22-2.06 (m, 2H), 1.91-1.85 (m, 1H), 1.70-1.57 (m, 2H), 0.95-0.86 (m, 2H), 0.65-0.55 (m, 2H) [M + H].sup.+ = 387.2 138 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.0 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.34 (d, J = 10.0 Hz, 2H), 7.06-6.99 (m, 2H), 6.83 (s, 1H), 6.77 (dd, J = 8.6, 2.8 Hz, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.53 (d, J = 7.9 Hz, 1H), 6.48 (d, J = 2.8 Hz, 1H), 5.05 (s, 2H), 3.56 (s, 3H), 2.25-2.00 (m, 2H), 1.98-1.87 (m, 2H), 1.84-1.74 (m, 1H), 1.67-1.54 (m, 5H), 1.22-1.01 (m, 6H), 0.87- 0.75 (m, 4H), 0.61 (q, J = 5.8 Hz, 2H) [M + H].sup.+ = 513.4 139 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.42 (t, J = 5.6 Hz, 1H), 7.60 (dd, J = 7.9, 1.4 Hz, 1H), 7.46 (d, J = 7.0 Hz, 2H), 7.43-7.38 (m, 2H), 7.36-7.31 (m, 1H), 7.23-7.16 (m, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.98 (d, J = 2.9 Hz, 1H), 6.85 (dd, J = 8.6, 2.9 Hz, 1H), 6.66 (dd, J = 12.9, 7.8 Hz, 2H), 5.08 (s, 2H), 3.30-3.24 (m, 2H), 2.14 (s, 3H), 1.73 (d, J = 13.0 Hz, 2H), 1.64 (dd, J = 21.4, 11.2 Hz, 3H), 1.44 (q, J = 6.9 Hz, 2H), 1.31 (ddt, J = 10.7, 7.1, 3.5 Hz, 1H), 1.19 (dt, J = 17.8, 8.5 Hz, 3H), 0.90 (q, J = 11.7 Hz, 2H) [M + H].sup.+ = 443.2 140 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 7.51 (dd, J = 8.5, 5.7 Hz, 2H), 7.26-7.19 (m, 3H), 7.05 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.95-6.90 (m, 2H), 6.87 (d, J = 8.1 Hz, 1H), 6.81 (dd, J = 8.6, 2.9 Hz, 1H), 6.32 (d, J = 9.4 Hz, 1H), 5.05 (s, 2H), 2.27-2.19 (m, 2H), 2.14 (s, 3H), 1.64 (dt, J = 18.1, 10.2 Hz, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.16 (h, J = 11.8, 11.3 Hz, 4H), 0.87 (q, J = 10.5, 9.3 Hz, 2H) [M + H].sup.+ = 461.2 141 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.2 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.22 (dd, J = 6.9, 5.2 Hz, 1H), 7.17 (d, J = 8.7 Hz, 1H), 7.05 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 8.7, 2.9 Hz, 1H), 6.69 (d, J = 2.9 Hz, 1H), 6.49 (dd, J = 8.0, 1.5 Hz, 1H), 6.36 (t, J = 2.2 Hz, 1H), 6.31 (dd, J = 8.0, 1.5 Hz, 1H), 5.57 (s, 1H), 5.17 (s, 2H), 1.95-1.82 (m, 1H), 0.95-0.87 (m, 2H), 0.65-0.57 (m, 2H), 0.24 (s, 9H) [M + H].sup.+ = 405.4 142 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.98 (s, 1H), 7.46 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.37-7.31 (m, 2H), 7.09-7.01 (m, 3H), 6.92 (dd, J = 8.1, 2.2 Hz, 1H), 6.83 (dd, J = 8.6, 2.8 Hz, 1H), 6.53 (d, J = 2.8 Hz, 1H), 5.08 (s, 2H), 3.17-3.09 (m, 2H), 1.90 (ddd, J = 13.5, 8.4, 5.3 Hz, 1H), 1.65-1.47 (m, 7H), 1.21-1.08 (m, 6H), 0.85-0.75 (m, 4H), 0.67-0.62 (m, 2H) [M + H].sup.+ = 504.3 143 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.43 (t, J = 5.6 Hz, 1H), 8.29 (s, 1H), 8.07 (d, J = 5.2 Hz, 1H), 7.59 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.7 Hz, 1H), 6.92 (d, J = 5.3 Hz, 1H), 6.87 (s, 1H), 6.81 (dd, J = 8.7, 2.8 Hz, 1H), 6.53 (d, J = 2.8 Hz, 1H), 5.12 (s, 2H), 3.23 (q, J = 6.6 Hz, 2H), 1.97-1.90 (m, 1H), 1.74-1.57 (m, 5H), 1.39 (d, J = 7.3 Hz, 2H), 1.26 (s, 1H), 1.16 (d, J = 8.8 Hz, 3H), 0.93-0.84 (m, 2H), 0.84-0.79 (m, 2H), 0.60 (d, J = 4.1 Hz, 2H) [M + H].sup.+ = 554.2 144 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.25 (s, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.1 Hz, 1H), 6.96-6.91 (m, 2H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.24 (dd, J = 8.1, 1.6 Hz, 1H), 6.20 (dd, J = 8.1, 2.1 Hz, 1H), 6.13 (t, J = 2.0 Hz, 1H), 5.07 (s, 2H), 3.82 (t, J = 5.8 Hz, 2H), 3.23 (q, J = 5.7 Hz, 2H), 2.13 (s, 3H), 1.37 (s, 9H) [M + H].sup.+ = 449.3 145 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.4 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.64 (s, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.32-7.22 (m, 3H), 7.20 (d, J = 8.8 Hz, 1H), 7.04 (dd, J = 7.9, 1.3 Hz, 1H), 6.86-6.78 (m, 2H), 6.68 (d, J = 2.8 Hz, 1H), 5.79 (s, 1H), 5.18 (s, 1H), 2.65 (d, J = 7.0 Hz, 2H), 2.03 (dq, J = 13.4, 6.7 Hz, 1H), 1.91 (It, J = 8.4, 5.6 Hz, 1H), 0.97 (d, J = 6.6 Hz, 6H), 0.95- 0.88 (m, 2H), 0.68-0.61 (m, 2H) [M + H].sup.+ = 440.5 146 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.25-7.18 (m, 2H), 7.02 (d, J = 8.6 Hz, 1H), 6.95 (dd, J = 10.4, 9.0 Hz, 1H), 6.91 (d, J = 2.8 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.35 (dt, J = 8.5, 3.3 Hz, 1H), 5.06 (s, 2H), 2.33 (t, J = 7.6 Hz, 2H), 2.13 (s, 3H), 1.65 (dt, J = 18.1, 11.1 Hz, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.17 (dq, J = 16.0, 8.5, 7.1 Hz, 4H), 0.87 (q, J = 10.6, 9.5 Hz, 2H) [M + H].sup.+ = 461.2 147 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.6, 1.7 Hz, 1H), 7.66 (t, J = 1.5 Hz, 1H), 7.58 (d, J = 7.7 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 6.95 (dd, J = 7.6, 2.2 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.71 (d, J = 2.9 Hz, 1H), 5.19 (s, 2H), 4.45 (d, J = 7.2 Hz, 2H), 1.95-1.85 (m, 1H), 1.95-1.85 (m, 1H), 0.99 (d, J = 6.7 Hz, 6H), 0.92 (dt, J = 6.0, 4.3 Hz, 2H), 0.67-0.60 (m, 2H) [M + H].sup.+ = 441.4 148 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.22 (dd, J = 4.9, 1.7 Hz, 1H), 7.83 (dd, J = 8.5, 1.7 Hz, 1H), 7.76 (dd, J = 8.5, 4.9 Hz, 1H), 7.24 (s, 1H), 7.08 (d, J = 8.6 Hz, 1H), 7.02-6.93 (m, 2H), 6.87 (dd, J = 8.6, 3.0 Hz, 1H), 6.22 (ddd, J = 10.8, 8.1, 1.9 Hz, 2H), 6.16 (t, J = 2.2 Hz, 1H), 5.37 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 2.14 (s, 3H), 1.65 (td, J = 17.0, 14.4, 7.0 Hz, 7H), 1.30-1.08 (m, 6H), 0.86 (q, J = 10.4, 9.1 Hz, 2H) [M + H].sup.+ = 432.3 149 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.47-7.43 (m, 3H), 7.40 (t, J = 7.4 Hz, 2H), 7.36-7.30 (m, 1H), 7.02 (t, J = 8.5 Hz, 2H), 6.79 (dd, J = 8.6, 2.9 Hz, 1H), 6.54 (dd, J = 4.0, 2.1 Hz, 2H), 6.50- 6.44 (m, 2H), 5.06 (s, 2H), 2.80 (t, J = 7.3 Hz, 2H), 1.94 (ddd, J = 13.7, 8.5, 5.3 Hz, 1H), 1.68- 1.58 (m, 5H), 1.54 (dt, J = 15.1, 7.5 Hz, 2H), 1.27-1.06 (m, 6H), 0.88-0.76 (m, 4H), 0.67-0.58 (m, 2H) [M + H].sup.+ = 472.4 150 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.57 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.38-7.31 (m, 1H), 7.19 (t, J = 9.2 Hz, 1H), 7.07 (s, 1H), 7.04-6.92 (m, 3H), 6.83 (dd, J = 8.8, 2.5 Hz, 1H), 6.42 (d, J = 8.0 Hz, 1H), 5.09 (s, 2H), 2.28-2.21 (m, 2H), 1.65 (dt, J = 18.4, 10.9 Hz, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.26-1.09 (m, 4H), 0.87 (q, J = 10.6, 9.5 Hz, 2H) [M + H].sup.+ = 447.2 151 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.3 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.27-7.21 (m, 1H), 7.15 (d, J = 8.6 Hz, 1H), 7.08 (t, J = 8.1 Hz, 1H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.67 (d, J = 2.9 Hz, 1H), 6.47 (dd, J = 8.0, 1.7 Hz, 1H), 6.21 (t, J = 2.2 Hz, 1H), 6.09 (dd, J = 8.0, 2.1 Hz, 1H), 5.18 (s, 2H), 5.16-5.10 (m, 1H), 4.90 (t, J = 6.8 Hz, 2H), 4.76 (t, J = 6.8 Hz, 2H), 1.94-1.83 (m, 1H), 0.95-0.87 (m, 2H), 0.66-0.59 (m, 2H) [M + H].sup.+ = 389.3 152 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.85 (d, J = 4.9 Hz, 2H), 7.47 (t, J = 4.9 Hz, 1H), 7.21 (s, 1H), 7.03 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.89 (d, J = 2.9 Hz, 1H), 6.77 (dd, J = 8.6, 3.0 Hz, 1H), 6.20 (td, J = 8.1, 2.0 Hz, 2H), 6.14 (t, J = 2.2 Hz, 1H), 5.22 (s, 2H), 3.81 (t, J = 6.5 Hz, 2H), 2.12 (s, 3H), 1.66 (td, J = 14.8, 13.2, 5.2 Hz, 7H), 1.29-1.06 (m, 6H), 0.93-0.79 (m, 2H) [M + H].sup.+ = 432.3 153 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.25 (s, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.95-6.92 (m, 2H), 6.87 (d, J = 8.0 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.33 (d, J = 7.9 Hz, 1H), 5.10 (s, 2H), 2.28-2.20 (m, 2H), 2.14 (s, 3H), 1.65 (dt, J = 18.0, 10.7 Hz, 5H), 1.44 (q, J = 7.1 Hz, 2H), 1.17 (dt, J = 17.1, 9.3 Hz, 4H), 0.87 (q, J = 10.5, 9.4 Hz, 2H) [M + H].sup.+ = 527.1 154 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 6.9 Hz, 2H), 7.42-7.36 (m, 2H), 7.36-7.30 (m, 1H), 7.11 (d, J = 8.7 Hz, 1H), 6.92 (d, J = 7.5 Hz, 1H), 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 6.74 (d, J = 3.0 Hz, 2H), 6.70-6.65 (m, 1H), 6.63 (d, J = 2.9 Hz, 1H), 6.49 (s, 1H), 5.05 (s, 2H), 4.01 (t, J = 6.4 Hz, 2H), 1.89-1.82 (m, 1H), 1.82-1.74 (m, 2H), 1.66 (q, J = 17.2, 15.6 Hz, 5H), 1.38-1.30 (m, 2H), 1.26-1.10 (m, 4H), 0.86 (ddd, J = 8.4, 6.2, 4.1 Hz, 4H), 0.65-0.59 (m, 2H) [M + H].sup.+ = 456.3 155 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.0 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.34 (d, J = 7.1 Hz, 1H), 7.21 (s, 1H), 7.06-6.97 (m, 2H), 6.84 (s, 1H), 6.76 (dd, J = 8.7, 2.9 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 6.51 (d, J = 7.9 Hz, 1H), 6.48 (d, J = 2.7 Hz, 1H), 5.05 (s, 2H), 4.52 (t, J = 5.7 Hz, 1H), 4.32 (s, 1H), 3.38 (d, J = 5.7 Hz, 2H), 1.97 (s, 1H), 1.63 (d, J = 27.6 Hz, 7H), 1.19-1.01 (m, 5H), 0.84 (d, J = 8.0 Hz, 3H), 0.78 (d, J = 11.1 Hz, 2H), 0.61 (d, J = 3.7 Hz, 2H) [M + H].sup.+ = 486.2 156 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 4.7 Hz, 1H), 7.85 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.35 (dd, J = 7.4, 4.9 Hz, 1H), 7.07-6.94 (m, 2H), 6.90-6.81 (m, 1H), 6.55 (d, J = 2.8 Hz, 1H), 6.20 (dd, J = 8.0, 1.9 Hz, 1H), 6.05 (dd, J = 8.2, 1.9 Hz, 1H), 5.97 (s, 1H), 5.16 (s, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.15 (s, 3H), 1.77 (ddd, J = 13.7, 8.5, 5.3 Hz, 1H), 1.65 (q, J = 9.3, 5.8 Hz, 6H), 1.29-1.09 (m, 7H), 0.91-0.77 (m, 4H), 0.63 (d, J = 3.6 Hz, 2H) [M + H].sup.+ = 471.1 157 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.5 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.23 (dd, J = 7.1, 5.2 Hz, 1H), 7.18-7.09 (m, 2H), 6.78 (dd, J = 8.7, 2.9 Hz, 1H), 6.71-6.59 (m, 4H), 5.17 (s, 2H), 4.25-4.14 (m, 4H), 1.94-1.81 (m, 1H), 1.33 (td, J = 7.1, 0.6 Hz, 6H), 0.95-0.87 (m, 2H), 0.65-0.57 (m, 2H) [M + H].sup.+ = 469.5 158 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.34 (t, J = 5.8 Hz, 1H), 7.27 (t, J = 7.9 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 7.00 (d, J = 2.4 Hz, 2H), 6.85-6.80 (m, 2H), 6.52 (d, J = 2.8 Hz, 1H), 5.11 (s, 2H), 2.73 (q, J = 6.7 Hz, 2H), 1.96-1.88 (m, 1H), 1.63-1.50 (m, 5H), 1.22 (t, J = 5.7 Hz, 3H), 1.17-1.03 (m, 3H), 0.87-0.81 (m, 2H), 0.80- 0.69 (m, 2H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 589.2 159 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 1.3 Hz, 1H), 8.84 (d, J = 5.2 Hz, 1H), 7.63 (dd, J = 5.2, 1.1 Hz, 1H), 7.24 (s, 1H), 7.08 (d, J = 8.7 Hz, 1H), 7.02-6.93 (m, 2H), 6.84 (dd, J = 8.6, 3.0 Hz, 1H), 6.22 (ddd, J = 12.1, 8.1, 1.9 Hz, 2H), 6.16 (t, J = 2.2 Hz, 1H), 5.19 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 2.14 (s, 3H), 1.65 (td, J = 16.9, 14.3, 6.9 Hz, 7H), 1.29-1.06 (m, 6H), 0.86 (q, J = 10.5, 9.2 Hz, 2H) [M + H].sup.+ = 432.3 160 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.6 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.23 (d, J = 6.7 Hz, 1H), 7.03-6.97 (m, 2H), 6.85 (d, J = 8.2 Hz, 1H), 6.77 (dd, J = 8.6, 2.8 Hz, 1H), 6.71 (s, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.51 (s, 1H), 5.18 (s, 2H), 4.30-4.18 (m, 4H), 2.23 (s, 3H), 1.88-1.79 (m, 1H), 1.37 (t, J = 7.1 Hz, 6H), 0.90 (dt, J = 10.0, 5.1 Hz, 2H), 0.64 (dt, J = 10.0, 5.1 Hz, 2H) 161 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.5 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.65 (t, J = 1.9 Hz, 1H), 7.56 (t, J = 8.6 Hz, 2H), 7.30 (t, J = 7.9 Hz, 1H), 7.21 (d, J = 8.6 Hz, 2H), 6.95 (dd, J = 8.1, 1.6 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.71 (d, J = 2.8 Hz, 1H), 5.54 (t, J = 7.2 Hz, 1H), 5.22 (d, J = 7.3 Hz, 2H), 5.18 (s, 2H), 1.95-1.87 (m, 1H), 1.85 (s, 3H), 1.80 (s, 3H), 0.95-0.88 (m, 2H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 453.3 162 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.7 Hz, 1H), 7.73 (td, J = 7.7, 1.6 Hz, 1H), 7.66 (t, J = 1.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 6.96 (dd, J = 7.8, 1.8 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.71 (d, J = 2.8 Hz, 1H), 5.19 (s, 2H), 4.81 (t, J = 5.5 Hz, 2H), 3.97 (t, J = 5.5 Hz, 2H), 3.36 (s, 3H), 1.96-1.84 (m, 1H), 0.96-0.88 (m, 2H), 0.64 (q, J = 5.9 Hz, 2H) [M + H].sup.+ = 443.3 163 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.73 (td, J = 7.7, 1.8 Hz, 1H), 7.68-7.65 (m, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.26-7.21 (m, 2H), 6.95 (dd, J = 8.2, 1.5 Hz, 1H), 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 6.71 (d, J = 2.9 Hz, 1H), 5.19 (s, 2H), 4.48 (d, J = 7.4 Hz, 2H), 1.96-1.85 (m, 1H), 1.53-1.45 (m, 1H), 0.97-0.86 (m, 2H), 0.71- 0.68 (m, 2H), 0.65-0.63 (m, 2H), 0.55-0.49 (m, 2H) [M + H].sup.+ = 439.4 164 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.48 (d, J = 7.1 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.35 (d, J = 7.2 Hz, 1H), 7.21 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 7.00-6.91 (m, 2H), 6.86 (dd, J = 8.6, 2.9 Hz, 1H), 6.22-6.14 (m, 2H), 6.10 (t, J = 2.1 Hz, 1H), 5.10 (s, 2H), 3.90 (dd, J = 10.8, 3.6 Hz, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.12-3.01 (m, 1H), 1.62 (ddd, J = 28.5, 24.4, 11.6 Hz, 12H), 1.30-1.08 (m, 7H), 0.93-0.82 (m, 2H) [M + H].sup.+ = 500.2 165 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.49-7.31 (m, 5H), 7.16 (s, 1H), 7.10 (d, J = 8.6 Hz, 1H), 6.99- 6.89 (m, 2H), 6.87 (d, J = 3.0 Hz, 1H), 6.26 (d, J = 7.4 Hz, 1H), 6.19 (dd, J = 4.6, 2.3 Hz, 2H), 5.78 (s, 1H), 5.09 (s, 2H), 4.11 (d, J = 2.5 Hz, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.64 (t, J = 5.3 Hz, 2H), 2.27 (s, 2H), 1.72-1.58 (m, 7H), 1.29-1.09 (m, 6H), 0.93-0.82 (m, 2H) [M + H].sup.+ = 498.2 166 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 4.8 Hz, 1H), 7.84 (td, J = 7.7, 1.5 Hz, 1H), 7.65 (d, J = 2.4 Hz, 2H), 7.56 (d, J = 2.3 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.35 (dd, J = 7.4, 4.9 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.82 (dd, J = 8.6, 2.8 Hz, 1H), 6.52 (d, J = 2.8 Hz, 1H), 6.41 (t, J = 2.1 Hz, 1H), 5.14 (s, 2H), 3.88 (t, J = 6.5 Hz, 2H), 1.92 (ddd, J = 13.7, 8.5, 5.3 Hz, 1H), 1.64 (dt, J = 21.1, 11.5 Hz, 7H), 1.29-1.11 (m, 6H), 0.87 (td, J = 9.3, 8.4, 3.8 Hz, 4H), 0.63 (q, J = 5.8 Hz, 2H) [M + H].sup.+ = 458.2 167 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 3H), 7.36-7.30 (m, 1H), 7.12-7.06 (m, 2H), 6.98 (s, 1H), 6.83 (dd, J = 8.6, 2.9 Hz, 1H), 6.73-6.64 (m, 1H), 6.62 (d, J = 2.9 Hz, 1H), 6.60 (d, J = 8.2 Hz, 1H), 5.07 (s, 2H), 2.79 (t, J = 7.2 Hz, 2H), 1.84 (ddd, J = 13.7, 8.4, 5.3 Hz, 1H), 1.63-1.55 (m, 5H), 1.54-1.47 (m, 2H), 1.28-1.21 (m, 2H), 1.19-1.05 (m, 4H), 0.85-0.73 (m, 4H), 0.67-0.61 (m, 2H) [M + H].sup.+ = 472.4 168 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.53 (d, J = 11.4 Hz, 2H), 7.50-7.45 (m, 2H), 7.45-7.38 (m, 3H), 7.38-7.32 (m, 1H), 7.31 (s, 3H), 7.05 (dd, J = 10.2, 9.0 Hz, 1H), 7.00 (dd, J = 6.1, 3.0 Hz, 1H), 6.83 (dt, J = 8.8, 4.0 Hz, 1H), 5.18 (s, 2H) [M + H].sup.+ = 405.0 169 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.34 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 7.01-6.94 (m, 2H), 6.88 (d, J = 8.1 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.51 (d, J = 2.8 Hz, 1H), 6.34 (d, J = 9.6 Hz, 1H), 5.18 (s, 2H), 2.28-2.20 (m, 2H), 1.97 (tt, J = 8.5, 5.2 Hz, 1H), 1.73-1.57 (m, 5H), 1.45 (q, J = 7.0 Hz, 2H), 1.21-1.10 (m, 4H), 0.90-0.80 (m, 4H), 0.66-0.57 (m, 2H) [M + H].sup.+ = 537.2 170 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.32 (s, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.96 (dd, J = 11.4, 8.3 Hz, 4H), 6.89 (d, J = 8.3 Hz, 1H), 6.77 (dd, J = 8.6, 2.8 Hz, 1H), 6.47 (d, J = 2.8 Hz, 1H), 6.33 (d, J = 9.1 Hz, 1H), 4.96 (s, 2H), 3.76 (s, 3H), 2.27-2.20 (m, 2H), 1.96 (ddd, J = 13.8, 8.5, 5.4 Hz, 1H), 1.72-1.57 (m, 5H), 1.45 (q, J = 7.1 Hz, 2H), 1.23- 1.09 (m, 4H), 0.92-0.80 (m, 4H), 0.66-0.57 (m, 2H) [M + H].sup.+ = 499.2 171 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.46 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.24 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.1 Hz, 1H), 6.93 (d, J = 2.7 Hz, 1H), 6.82 (dd, J = 8.6, 2.8 Hz, 1H), 6.27-6.17 (m, 2H), 6.15 (s, 1H), 5.07 (s, 2H), 4.78 (t, J = 5.6 Hz, 1H), 3.85 (t, J = 5.0 Hz, 2H), 3.65 (q, J = 5.2 Hz, 2H), 2.14 (s, 3H) [M + H].sup.+ = 350.3 172 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.06-7.00 (m, 3H), 6.94 (d, J = 8.9 Hz, 2H), 6.47 (d, J = 8.1 Hz, 1H), 6.42 (s, 1H), 6.27 (dd, J = 8.1, 1.8 Hz, 1H), 5.05 (s, 2H), 3.85 (t, J = 6.5 Hz, 2H), 1.74-1.57 (m, 7H), 1.30-1.10 (m, 6H), 0.87 (q, J = 10.3, 9.5 Hz, 2H) [M + H].sup.+ = 416.4 173 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.23 (s, 1H), 7.06 (d, J = 8.7 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.92 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.26-6.16 (m, 2H), 6.16-6.12 (m, 1H), 5.07 (s, 2H), 4.04 (q, J = 7.1 Hz, 2H), 3.85 (t, J = 5.8 Hz, 2H), 2.34 (t, J = 6.9 Hz, 2H), 2.13 (s, 3H), 1.72-1.59 (m, 4H), 1.17 (t, J = 7.1 Hz, 3H) [M + H].sup.+ = 434.2 174 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.46 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.25 (s, 1H), 7.06 (d, J = 8.7 Hz, 1H), 6.98 (t, J = 8.1 Hz, 1H), 6.93 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.26-6.19 (m, 2H), 6.14 (t, J = 2.1 Hz, 1H), 5.07 (s, 2H), 3.99- 3.92 (m, 2H), 3.64-3.57 (m, 2H), 3.28 (s, 3H), 2.14 (s, 3H) [M + H].sup.+ = 364.2 175 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.22 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.92 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.23-6.18 (m, 2H), 6.18-6.14 (m, 1H), 5.07 (s, 2H), 3.72 (d, J = 6.9 Hz, 2H), 2.24 (dt, J = 14.8, 7.4 Hz, 1H), 2.13 (s, 3H), 1.73 (dq, J = 11.8, 6.4 Hz, 2H), 1.64- 1.47 (m, 4H), 1.28 (dq, J = 14.1, 7.4, 7.0 Hz, 2H) [M + H].sup.+ = 388.2 176 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.91 (s, 2H), 7.25 (s, 1H), 7.08 (d, J = 8.6 Hz, 1H), 7.02-6.93 (m, 2H), 6.86 (dd, J = 8.6, 3.0 Hz, 1H), 6.22 (ddd, J = 10.5, 8.1, 2.0 Hz, 2H), 6.15 (t, J = 2.2 Hz, 1H), 5.16 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 2.15 (s, 3H), 1.73-1.57 (m, 7H), 1.30-1.08 (m, 6H), 0.86 (q, J = 10.3, 9.0 Hz, 2H) [M + H].sup.+ = 432.3 177 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.22 (s, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.92 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.24-6.17 (m, 2H), 6.13 (t, J = 2.1 Hz, 1H), 5.06 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 2.13 (s, 3H), 1.73-1.56 (m, 7H), 1.28-1.10 (m, 6H), 0.86 (q, J = 10.3, 9.0 Hz, 2H) [M + H].sup.+ = 430.2 178 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.8 Hz, 1H), 7.73 (td, J = 7.7, 1.7 Hz, 1H), 7.68 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.32-7.26 (m, 2H), 7.26-7.17 (m, 3H), 7.03 (dd, J = 7.9, 1.2 Hz, 1H), 6.87-6.77 (m, 2H), 6.68 (d, J = 2.8 Hz, 1H), 5.18 (s, 2H), 3.72 (t, J = 7.3 Hz, 2H), 2.90 (t, J = 7.3 Hz, 2H), 1.99 (quint, J = 7.3 Hz, 2H), 1.95-1.86 (m, 1H), 0.96-0.88 (m, 2H), 0.67-0.60 (m, 2H) [M + H].sup.+ = 442.6 179 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J = 4.2 Hz, 1H), 7.88 (s, 1H), 7.73 (td, J = 7.7, 1.8 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.29 (s, 1H), 7.28-7.22 (m, 2H), 7.19 (d, J = 8.7 Hz, 1H), 7.13-7.09 (m, 2H), 6.84-6.78 (m, 2H), 6.70 (d, J = 2.9 Hz, 1H), 5.19 (s, 2H), 1.96-1.85 (m, 1H), 0.96- 0.88 (m, 2H), 0.68-0.61 (m, 2H) [M + H].sup.+ = 384.4 180 .sup.1H NMR (500 MHz, DMSO-d6) δ ppm 0.52-0.66 (m, 2 H), 0.81-0.97 (m, 2 H), 1.14 (d, J = 6.6 Hz, 6 H), 1.78 (It, J = 8.3, 5.4 Hz, 1 H), 2.25 (s, 3 H), 4.11 (dt, J = 7.6, 6.6 Hz, 1 H), 5.05 (s, 2 H), 6.59-6.66 (m, 3 H), 6.78-6.84 (m, 2 H), 7.02-7.08 (m, 2 H), 7.31 (br d, J = 1.4 Hz, 1 H), 7.37- 7.41 (m, 2 H), 7.42-7.48 (m, 2 H), 8.36 (d, J = 7.7 Hz, 1 H) [M + H].sup.+ = 415.2 181 .sup.1H NMR (400MHz, DMSO-d6) δ 8.49 (d, J = 7.9 Hz, 1H), 7.47-7.27 (m, 6H), 7.10-7.02 (m, 2H), 6.88-6.82 (m, 2H), 6.69 (s, 1H), 6.61 (d, J = 2.9 Hz, 1H), 5.07 (s, 2H), 4.15-4.04 (m, 1H), 1.89-1.80 (m, 1H), 1.12 (d, J = 6.6 Hz, 6H), 0.88-0.81 (m, 2H), 0.64-0.57 (m, 2H) [M + H].sup.+ = 469.1 182 .sup.1H NMR (400 MHz, Methanol-d4) δ 8.56 (d, J = 4.5 Hz, 1H), 7.90 (t, J = 7.7 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.42-7.37 (m, 1H), 7.13 (d, J = 8.7 Hz, 1H), 7.02 (t, J = 8.1 Hz, 1H), 6.80 (dd, J = 8.6, 2.9 Hz, 1H), 6.64 (s, 1H), 6.59 (d, J = 3.1 Hz, 2H), 6.46 (d, J = 8.1 Hz, 1H), 5.16 (s, 2H), 3.63 (d, J = 11.1 Hz, 3H), 2.07-1.92 (m, 1H), 0.93-0.87 (m, 2H), 0.62-0.57 (m, 2H) [M + H].sup.+ = 427.0 183 .sup.1H NMR (500 MHz, DMSO-d6) δ 8.12 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.42 (s, 3H), 7.35 (t, J = 7.2 Hz, 1H), 7.30-7.24 (m, 2H), 7.09 (t, J = 8.1 Hz, 1H), 6.48 (d, J = 8.0 Hz, 1H), 6.44 (t, J = 2.1 Hz, 1H), 6.40 (dd, J = 8.1, 2.2 Hz, 1H), 5.12 (s, 2H), 3.87 (t, J = 6.5 Hz, 2H), 1.74-1.56 (m, 7H), 1.29-1.08 (m, 6H), 0.87 (q, J = 9.8, 9.4 Hz, 2H) [M + H].sup.+ = 441.1 184 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.43 (t, J = 5.5 Hz, 1H), 7.63-7.57 (m, 1H), 7.45 (s, 2H), 7.40 (s, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.24 (t, J = 7.8 Hz, 1H), 7.10 (d, J = 8.9 Hz, 2H), 7.00 (t, J = 8.9 Hz, 3H), 6.72 (t, J = 7.4 Hz, 1H), 5.08 (s, 2H), 3.27 (q, J = 6.5 Hz, 2H), 1.72 (d, J = 12.7 Hz, 2H), 1.63 (dd, J = 19.8, 11.2 Hz, 3H), 1.42 (q, J = 6.9 Hz, 2H), 1.30 (ddt, J = 10.6, 7.1, 3.5 Hz, 1H), 1.17 (h, J = 11.9 Hz, 3H), 0.91 (t, J = 11.6 Hz, 2H) [M + H].sup.+ = 429.2 185 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 7.0 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.35-7.30 (m, 1H), 7.14 (s, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.76 (dd, J = 8.6, 2.9 Hz, 1H), 6.47 (d, J = 2.8 Hz, 1H), 6.31 (d, J = 1.8 Hz, 1H), 6.16 (dd, J = 8.0, 1.9 Hz, 1H), 5.04 (s, 2H), 3.80 (t, J = 6.4 Hz, 2H), 2.00 (s, 3H), 1.95 (ddd, J = 13.7, 8.5, 5.4 Hz, 1H), 1.72-1.59 (m, 7H), 1.32- 1.10 (m, 6H), 0.92-0.82 (m, 4H), 0.63-0.58 (m, 2H) [M + H].sup.+ = 470.4 186 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.0 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.35-7.31 (m, 1H), 7.23 (s, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.78 (dd, J = 8.6, 2.8 Hz, 1H), 6.47 (d, J = 2.8 Hz, 1H), 6.08 (s, 1H), 6.02 (s, 1H), 5.97 (s, 1H), 5.05 (s, 2H), 3.79 (t, J = 6.5 Hz, 2H), 2.12 (s, 3H), 1.95 (ddd, J = 13.8, 8.5, 5.4 Hz, 1H), 1.72-1.59 (m, 7H), 1.28-1.09 (m, 6H), 0.91-0.82 (m, 4H), 0.63-0.59 (m, 2H) [M + H].sup.+ = 470.4 187 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.1 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 6.93 (dd, J = 12.8, 8.4 Hz, 2H), 6.80 (dd, J = 8.6, 2.8 Hz, 1H), 6.55-6.50 (m, 2H), 6.18 (dd, J = 8.1, 2.5 Hz, 1H), 5.90 (d, J = 2.4 Hz, 1H), 5.06 (s, 2H), 3.73 (t, J = 6.5 Hz, 2H), 2.15 (s, 3H), 1.89 (ddd, J = 13.7, 8.4, 5.3 Hz, 1H), 1.67-1.56 (m, 7H), 1.22-1.07 (m, 6H), 0.87-0.78 (m, 4H), 0.63-0.58 (m, 2H) [M + H].sup.+ = 470.4 188 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.36-7.29 (m, 2H), 7.17-7.13 (m, 1H), 7.07 (d, J = 8.6 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.49 (d, J = 2.8 Hz, 1H), 6.27 (d, J = 1.7 Hz, 1H), 6.23 (dd, J = 8.6, 1.8 Hz, 1H), 5.07 (s, 2H), 3.94 (t, J = 6.5 Hz, 2H), 1.95-1.89 (m, 1H), 1.80-1.73 (m, 2H), 1.72- 1.59 (m, 5H), 1.29-1.13 (m, 6H), 0.91-0.81 (m, 4H), 0.67-0.62 (m, 2H) [M + H].sup.+ = 499.4 189 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.73 (s, 1H), 7.49 (s, 1H), 7.45 (d, J = 7.1 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.13 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 6.78 (s, 1H), 6.69 (s, 1H), 6.49 (d, J = 2.8 Hz, 1H), 6.27 (t, J = 1.9 Hz, 1H), 5.06 (s, 2H), 3.87 (t, J = 6.5 Hz, 2H), 1.97-1.90 (m, 1H), 1.73-1.58 (m, 7H), 1.29-1.12 (m, 6H), 0.92-0.81 (m, 4H), 0.66-0.57 (m, 2H) [M + H].sup.+ = 499.4 190 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.50 (s, 1H), 7.43 (s, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.33 (d, J = 7.1 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.01 (t, J = 7.3 Hz, 1H), 6.91 (d, J = 8.7 Hz, 1H), 6.80-6.73 (m, 3H), 6.71 (s, 1H), 6.57 (d, J = 2.8 Hz, 1H), 5.04 (s, 2H), 2.39-2.34 (m, 2H), 1.88-1.80 (m, 1H), 1.68 (dd, J = 23.1, 12.0 Hz, 4H), 1.61 (s, 1H), 1.51 (d, J = 8.0 Hz, 2H), 1.25 (s, 1H), 1.15 (t, J = 11.4 Hz, 3H), 0.93-0.83 (m, 4H), 0.60 (q, J = 5.7 Hz, 2H) [M + H].sup.+ = 469.2 191 .sup.1H NMR (400 MHz, Chloroform-d) δ 9.00 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.1 Hz, 1H), 7.08-7.00 (m, 2H), 6.92 (d, J = 2.8 Hz, 1H), 6.86 (s, 1H), 6.27 (dd, J = 8.1, 1.9 Hz, 1H), 6.11 (d, J = 8.2 Hz, 1H), 6.07 (d, J = 2.1 Hz, 1H), 5.06 (s, 2H), 3.87 (dt, J = 13.5, 7.0 Hz, 4H), 2.76-2.69 (m, 2H), 2.09 (s, 3H), 1.72 (q, J = 13.3, 10.0 Hz, 7H), 1.30 (dd, J = 9.9, 4.8 Hz, 2H), 1.19 (dq, J = 21.1, 12.1, 10.8 Hz, 4H), 0.93-0.84 (m, 2H) [M + H].sup.+ = 502.2 192 .sup.1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.30 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.92 (d, J = 2.7 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.25 (d, J = 7.6 Hz, 1H), 6.19-6.13 (m, 2H), 5.07 (s, 2H), 4.52 (s, 2H), 2.14 (s, 3H) [M + H].sup.+ = 364.3 193 .sup.1H NMR (400 MHz, DMSO-d6) δ 12.00 (s, 1H), 7.45 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.23 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.92 (d, J = 2.7 Hz, 1H), 6.82 (dd, J = 8.6, 2.8 Hz, 1H), 6.25-6.17 (m, 2H), 6.15 (s, 1H), 5.07 (s, 2H), 3.85 (t, J = 6.0 Hz, 2H), 2.26 (t, J = 7.1 Hz, 2H), 2.14 (s, 3H), 1.72-1.54 (m, 4H) [M + H].sup.+ = 406.4 194 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.46 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.34 (d, J = 7.1 Hz, 1H), 7.31 (s, 1H), 7.05 (d, J = 8.6 Hz, 1H), 6.99 (t, J = 8.1 Hz, 1H), 6.93 (d, J = 2.7 Hz, 1H), 6.82 (dd, J = 8.6, 2.8 Hz, 1H), 6.27 (d, J = 8.8 Hz, 1H), 6.18 (dd, J = 8.1, 2.0 Hz, 1H), 6.12 (s, 1H), 5.07 (s, 2H), 4.64 (s, 2H), 3.67 (s, 3H), 2.13 (s, 3H) [M + H].sup.+ = 378.3 195 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 7.46 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.18 (t, J = 8.2 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 6.97 (d, J = 2.7 Hz, 1H), 6.86 (dd, J = 8.6, 2.8 Hz, 1H), 6.59 (dd, J = 8.3, 1.3 Hz, 1H), 6.53 (d, J = 8.2 Hz, 1H), 6.45 (s, 1H), 5.08 (s, 2H), 2.13 (s, 3H) [M + H].sup.+ = 374.2 196 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.36-7.31 (m, 1H), 7.23 (s, 1H), 7.06 (d, J = 8.6 Hz, 1H), 6.97 (t, J = 8.1 Hz, 1H), 6.92 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.6, 2.9 Hz, 1H), 6.25-6.18 (m, 2H), 6.18-6.14 (m, 1H), 5.07 (s, 2H), 3.86 (dd, J = 11.2, 3.5 Hz, 2H), 3.71 (d, J = 6.4 Hz, 2H), 3.35-3.27 (m, 2H), 2.13 (s, 3H), 2.00-1.88 (m, 1H), 1.63 (d, J = 12.7 Hz, 2H), 1.29 (qd, J = 11.8, 11.3, 3.8 Hz, 2H) [M + H].sup.+ = 404.2 197 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.55 (d, J = 4.5 Hz, 1H), 7.88 (s, 2H), 7.80 (d, J = 5.8 Hz, 1H), 7.43 (dd, J = 7.7, 4.8 Hz, 1H), 7.29 (d, J = 8.7 Hz, 1H), 6.92 (d, J = 2.7 Hz, 1H), 6.83 (dd, J = 8.7, 2.8 Hz, 1H), 6.23 (dd, J = 5.8, 1.9 Hz, 1H), 5.97 (d, J = 1.8 Hz, 1H), 5.13 (s, 2H), 3.89 (t, J = 6.5 Hz, 2H), 2.15 (s, 3H), 1.67 (t, J = 10.8 Hz, 6H), 1.29-1.08 (m, 7H), 0.92-0.80 (m, 2H) [M + H].sup.+ = 432.1 198 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J = 1.6 Hz, 1H), 8.55 (d, J = 4.8 Hz, 1H), 7.89 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.43 (dd, J = 7.8, 4.8 Hz, 1H), 7.36-7.30 (m, 2H), 6.93 (d, J = 2.8 Hz, 1H), 6.83 (dd, J = 8.7, 2.9 Hz, 1H), 6.02 (d, J = 7.9 Hz, 1H), 5.97 (d, J = 7.8 Hz, 1H), 5.12 (s, 2H), 4.06 (t, J = 6.7 Hz, 2H), 2.17 (s, 3H), 1.71-1.56 (m, 7H), 1.18 (dt, J = 14.7, 9.0 Hz, 6H), 0.90- 0.78 (m, 2H) [M + H].sup.+ = 432.1 199 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.86 (s, 1H), 7.80 (d, J = 5.8 Hz, 1H), 7.45 (d, J = 7.3 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.1 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H), 6.90 (d, J = 2.6 Hz, 1H), 6.81 (dd, J = 8.7, 2.8 Hz, 1H), 6.23 (dd, J = 5.8, 1.7 Hz, 1H), 5.95 (s, 1H), 5.07 (s, 2H), 3.89 (t, J = 6.5 Hz, 2H), 2.15 (s, 3H), 1.73-1.58 (m, 7H), 1.28-1.08 (m, 6H), 0.93-0.79 (m, 2H) [M + H].sup.+ = 431.1 200 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 3H), 7.38-7.26 (m, 3H), 6.90 (d, J = 2.8 Hz, 1H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.01 (d, J = 7.9 Hz, 1H), 5.96 (d, J = 7.8 Hz, 1H), 5.07 (s, 2H), 4.06 (t, J = 6.8 Hz, 2H), 2.17 (s, 3H), 1.63 (dq, J = 14.6, 8.6, 6.6 Hz, 7H), 1.27-1.09 (m, 6H), 0.91-0.79 (m, 2H) [M + H].sup.+ = 431.1 201 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.66 (dd, J = 16.8, 2.4 Hz, 2H), 7.24 (s, 1H), 7.08 (d, J = 8.6 Hz, 1H), 6.97 (t, 2H), 6.86 (dd, J = 8.6, 2.9 Hz, 1H), 6.22 (dd, J = 11.7, 8.5 Hz, 2H), 6.16 (d, J = 1.9 Hz, 1H), 5.23 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 2.14 (s, 3H), 1.73-1.57 (m, 7H), 1.31-1.07 (m, 6H), 0.86 (q, J = 10.2, 8.9 Hz, 2H) [M + H].sup.+ = 432.2 202 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.46 (s, 1H), 7.56 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.43-7.31 (m, 4H), 7.16 (t, J = 9.2 Hz, 1H), 7.03-6.95 (m, 2H), 6.81 (dd, J = 8.8, 2.4 Hz, 1H), 6.50-6.42 (m, 1H), 5.09 (s, 2H), 2.34 (t, J = 7.6 Hz, 2H), 1.74-1.56 (m, 5H), 1.46 (q, J = 7.1 Hz, 2H), 1.26- 1.08 (m, 4H), 0.94-0.81 (m, 2H) [M + H].sup.+ = 465.2 203 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.60 (d, J = 4.7 Hz, 1H), 7.81 (t, J = 3.8 Hz, 1H), 7.73 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.39 (t, J = 1.6 Hz, 1H), 7.27-7.21 (m, 2H), 7.14 (d, J = 7.7 Hz, 1H), 7.08 (d, J = 8.9 Hz, 2H), 7.00 (dd, J = 8.0, 1.5 Hz, 1H), 6.95 (d, J = 8.9 Hz, 2H), 5.19 (s, 2H), 3.66 (t, J = 9.3 Hz, 4H), 3.54 (dd, J = 11.5, 5.7 Hz, 2H), 2.53 (t, J = 5.7 Hz, 2H), 2.47 (t, J = 9.3 Hz, 4H), 1.77 (dt, J = 11.5, 5.7 Hz, 3H) [M + H].sup.+ = 447.3 204 .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.64 (d, J = 4.4 Hz, 1H), 7.83 (td, J = 7.7, 1.7 Hz, 1H), 7.58-7.50 (m, 2H), 7.36 (d, J = 7.0 Hz, 1H), 7.33-7.26 (m, 2H), 6.98 (d, J = 8.6 Hz, 1H), 6.93 (dd, J = 8.1, 1.6 Hz, 1H), 6.46 (dd, J = 8.6, 2.9 Hz, 1H), 6.37 (d, J = 2.8 Hz, 1H), 5.61 (bs, 1H), 5.11 (s, 2H), 1.83-1.74 (m, 1H), 0.83-0.76 (m, 2H), 0.49-0.43 (m, 2H) [M + H].sup.+ = 385.4 205 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.37 (d, J = 7.8 Hz, 1H), 7.46-7.42 (m, 2H), 7.42-7.36 (m, 2H), 7.35-7.29 (m, 1H), 7.09-6.99 (m, 2H), 6.80 (dd, J = 8.7, 2.9 Hz, 1H), 6.70 (s, 1H), 6.66- 6.59 (m, 2H), 6.39 (d, J = 7.7 Hz, 1H), 5.05 (s, 2H), 4.19-4.06 (m, 1H), 2.02-1.92 (m, 1H), 1.85- 1.74 (m, 1H), 1.14 (d, J = 6.6 Hz, 6H), 0.91-0.81 (m, 4H), 0.66-0.61 (m, 2H), 0.61-0.56 (m, 2H) [M + H].sup.+ = 441.2 206 .sup.1H NMR (400MHz, DMSO-d6) δ 8.51 (d, J = 7.9 Hz, 1H), 7.47-7.29 (m, 5H), 7.14-7.04 (m, 2H), 6.86-6.75 (m, 3H), 6.62-6.56 (m, 2H), 5.06 (s, 2H), 4.15-4.04 (m, 1H), 1.86-1.77 (m, 1H), 1.15 (d, J = 6.6 Hz, 6H), 0.89-0.81 (m, 2H), 0.63-0.55 (m, 2H) [M + H].sup.+ = 435.2

[0467] The following examples are provided as illustrations and in no way limit the scope of this invention.

[0468] The following examples illustrate in detail the preparation of some compounds according to the invention. The structures of the products obtained have been confirmed by NMR spectra.

Examples

Example 1: Compound (39) in Table I

[0469] According to route (I), 4-nitro-5-methylphenol (3.06 g, 20 mmoles, 1 eq.) was placed in N,N-dimethylformamide (15 mL) with K.sub.2CO.sub.3 (8.3 g, 60 mmoles, 3 eq.). Upon addition of 2-(bromomethyl)pyridine hydrobromide (5.06 g, 20 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 24 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between dichloromethane and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 2-(3-methyl-4-nitrophenoxymethyl)pyridine (4.5 g, 92%).

[0470] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.65-8.60 (m, 1H), 8.07 (d, J=9.8 Hz, 1H), 7.75 (td, J=7.7, 1.7 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.27 (t, J=6.2 Hz, 1H), 6.90-6.87 (m, 2H), 2.62 (s, 3H).

[0471] According to route (C), 2-(3-methyl-4-nitrophenoxymethyl)pyridine (4.5 g, 18.4 mmoles, 1 eq.) and tin (II) chloride dihydrate (20.8 g, 92 mmoles, 5 eq.) were placed in EtOH (184 mL). The reaction mixture was heated at 60° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a 1N NaOH aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 2-methyl-4-(pyridin-2-ylmethoxy)aniline (2.0 g, 51%).

[0472] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.58 (d, J=4.3 Hz, 1H), 7.70 (td, J=7.7, 1.7 Hz, 1H), 7.52 (d, J=7.7 Hz, 1H), 7.20 (dd, J=6.9, 5.5 Hz, 1H), 6.76 (d, J=2.7 Hz, 1H), 6.69 (dd, J=8.5, 2.7 Hz, 1H), 6.60 (d, J=8.5 Hz, 1H), 5.13 (s, 2H), 3.37 (s, 2H), 2.15 (s, 3H).

[0473] 2-Cyclopentylethan-1-amine hydrochloride (1.3 g, 8.7 mmoles, 1.1 eq.) was placed in a 3N NaOH aqueous solution (5.9 mL) and dichloromethane (1.5 mL) was added to the solution. The reaction mixture was cooled down to 0° C. with an ice bath and a solution of 3-bromobenzoyl chloride (1.0 mL, 7.9 mmoles, 1.0 eq.) in dichloromethane (2.4 mL) was added dropwise. The reaction mixture was then stirred at room temperature for 18 hours under an inert atmosphere of argon. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 3-bromo-N-(2-cyclopentylethyl)benzamide (1.8 g, 77%).

[0474] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.89 (t, J=1.7 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.65-7.58 (m, 1H), 7.31 (t, J=7.9 Hz, 1H), 6.07 (s, 1H), 3.46 (dt, J=7.4, 5.9 Hz, 2H), 1.88-1.79 (m, 3H), 1.67-1.47 (m, 6H), 1.18-1.13 (m, 2H).

[0475] According to route (A), a reaction mixture of 3-bromo-N-(2-cyclopentylethyl)benzamide (830 mg, 2.8 mmoles, 1 eq.), 2-methyl-4-(pyridin-2-ylmethoxy)aniline (600 mg, 2.8 mmoles, 1 eq.), Pd.sub.2(dba).sub.3 (258 mg, 282 μmoles, 10 mol %), XPhos (266 mg, 559 μmoles, 20 mol %) and K.sub.2CO.sub.3 (1.55 g, 11.2 mmoles, 4 eq.) in t-BuOH (11.2 mL) was heated at 90° C. and stirred for 88 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford a fraction which, after trituration in diethyl ether, gave N-(2-cyclopentylethyl)-3-{[2-methyl-4-(pyridin-2-ylmethoxy)phenyl]amino}benzamide (39) (734 mg, 61%).

[0476] .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J=4.3 Hz, 1H), 8.26 (t, J=5.5 Hz, 1H), 7.85 (td, J=7.7, 1.6 Hz, 1H), 7.54 (d, J=7.7 Hz, 1H), 7.47 (s, 1H), 7.35 (dd, J=6.9, 5.5 Hz, 1H), 7.20-7.05 (m, 4H), 6.97 (d, J=2.7 Hz, 1H), 6.85 (dd, J=8.6, 2.7 Hz, 1H), 6.75 (d, J=7.7 Hz, 1H), 5.16 (s, 2H), 3.21 (dd, J=13.4, 6.5 Hz, 2H), 2.14 (s, 3H), 1.82-1.70 (m, 2H), 1.64-1.39 (m, 6H), 1.12-1.07 (m, 3H).

[0477] .sup.13C NMR (75 MHz, d.sub.6-DMSO) δ 165.1, 155.5, 153.2, 147.6, 145.4, 135.5, 134.4, 132.7, 132.3, 127.3, 123.6, 121.5, 120.1, 115.6, 114.6, 114.2, 111.3, 111.2, 68.9, 37.1, 35.9, 34.0, 30.7, 23.2, 16.6

[0478] [M+H].sup.+=430.3

Example 2: Compound (50) in Table I

[0479] According to route (I), 4-nitrophenol (1.4 g, 10 mmoles, 1 eq.) was placed in N,N-dimethylformamide (7.7 mL) with K.sub.2CO.sub.3 (4.2 g, 30 mmoles, 3 eq.). Upon addition of 2-fluorobenzyl bromide (1.2 mL, 10 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 16 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 1-fluoro-2-(4-nitrophenoxymethyl)benzene (2.0 g, 81%).

[0480] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.22 (d, J=9.3 Hz, 2H), 7.47 (t, J=7.5 Hz, 1H), 7.37 (dd, J=13.6, 5.8 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H), 7.16-7.10 (m, 1H), 7.05 (d, J=9.3 Hz, 2H), 5.23 (s, 2H).

[0481] According to route (C), 1-[(2-fluorophenyl)methoxy]-4-nitrobenzene (1.0 g, 4.0 mmoles, 1 eq.) and tin (II) chloride dihydrate (4.6 g, 20 mmoles, 5 eq.) were placed in EtOH (40 mL). The reaction mixture was heated at 60° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a 1N NaOH aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 4-[(2-fluorophenyl)methoxy]aniline (836 mg, 95%).

[0482] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.50 (td, J=7.5, 1.0 Hz, 1H), 7.33-7.27 (m, 1H), 7.14 (td, J=7.5, 1.0 Hz, 1H), 7.10-7.03 (m, 1H), 6.82 (d, J=8.8 Hz, 2H), 6.64 (d, J=8.8 Hz, 2H), 5.06 (s, 2H), 3.43 (s, 2H).

[0483] 2-Cyclopentylethan-1-amine hydrochloride (3.0 g, 19.1 mmoles, 1.1 eq.) was placed in a 3N NaOH aqueous solution (13 mL) and dichloromethane (3.2 mL) was added to the solution. The reaction mixture was cooled down to 0° C. with an ice bath and a solution of 3-bromobenzoyl chloride (2.3 mL, 17.4 mmoles, 1 eq.) in dichloromethane (5.5 mL) was added dropwise. The reaction mixture was then stirred at room temperature for 18 hours under an inert atmosphere of argon. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 3-bromo-N-(2-cyclopentylethyl)benzamide (4.6 g, 89%).

[0484] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.89 (t, J=1.7 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.30 (t, J=7.9 Hz, 1H), 6.07 (s, 1H), 3.46 (dd, J=7.4, 5.9 Hz, 2H), 1.90-1.76 (m, 3H), 1.67-1.52 (m, 6H), 1.20-1.09 (m, 2H).

[0485] According to route (A), a reaction mixture of 3-bromo-N-(2-cyclopentylethyl)benzamide (296 mg, 1 mmole, 1 eq.), 4-[(2-fluorophenyl)methoxy]aniline (217 mg, 1 mmole, 1 eq.), Pd.sub.2(dba).sub.3 (92 mg, 100 μmoles, 10 mol %), XPhos (95 mg, 200 μmoles, 20 mol %) and K.sub.2CO.sub.3 (553 mg, 4 mmoles, 4 eq.) in t-BuOH (4 mL) was heated at 90° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford a fraction which, after trituration in diethyl ether, gave N-(2-cyclopentylethyl)-3-({4-[(2-fluorophenyl)methoxy]phenyl}amino)benzamide (50) (168 mg, 39%).

[0486] .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.31 (t, J=5.6 Hz, 1H), 8.05 (s, 1H), 7.57 (td, J=7.4, 1.5 Hz, 1H), 7.47-7.36 (m, 2H), 7.30-7.19 (m, 3H), 7.15 (d, J=7.7 Hz, 1H), 7.07 (d, J=9.0 Hz, 2H), 7.05-7.0 (m, 1H), 6.98 (d, J=9.0 Hz, 2H), 5.10 (s, 2H), 3.23 (dd, J=13.8, 6.3 Hz, 2H), 1.86-1.72 (m, 3H), 1.62-1.45 (m, 6H), 1.11-1.04 (m, 2H).

[0487] .sup.13C NMR (75 MHz, d.sub.6-DMSO) δ 164.6, 160.2, 156.9, 151.1, 143.3, 134.4, 134.2, 128.9, 128.8, 128.4, 127.1, 122.7, 122.7, 122.4, 122.2, 118.7, 117.4, 115.3, 114.9, 113.8, 113.4, 111.8, 78.0, 62.0, 35.6, 33.7, 30.4, 22.9

Example 3: Compound (60) in Table I

[0488] According to route (I), 3-bromo-4-nitrophenol (1.7 g, 7.9 mmoles, 1 eq.) was placed in N,N-dimethylformamide (6 mL) with K.sub.2CO.sub.3 (3.3 g, 23.7 mmoles, 3 eq.). Upon addition of 2-(bromomethyl)pyridine hydrobromide (2.0 g, 7.9 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 24 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between dichloromethane and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 2-(3-bromo-4-nitrophenoxymethyl)pyridine (2.4 g, 98%).

[0489] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.63 (d, J=4.8 Hz, 1H), 7.97 (d, J=9.1 Hz, 1H), 7.76 (td, J=7.7, 1.7 Hz, 1H), 7.47 (d, J=7.7 Hz, 1H), 7.35 (d, J=2.7 Hz, 1H), 7.32-7.27 (m, 1H), 7.01 (dd, J=9.1, 2.7 Hz, 1H), 5.27 (s, 2H).

[0490] According to route (J), 2-(3-bromo-4-nitrophenoxymethyl)pyridine (2.4 g, 7.8 mmoles, 1 eq.) was placed in 1,4-dioxane (28 mL) with Pd(dppf)C.sub.2.CH.sub.2Cl.sub.2 (634 mg, 0.78 mmole, 0.1 eq.). Upon addition of K.sub.3PO.sub.4 (6.6 g, 31 mmoles, 4 eq.) and cyclopropylboronic acid (2.0 g, 23.3 mmoles, 3 eq.), the reaction mixture was heated at 100° C. and stirred for 20 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel to afford 2-(3-cyclopropyl-4-nitrophenoxymethyl)pyridine (1.5 g, 71%).

[0491] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.62 (d, J=4.2 Hz, 1H), 7.94 (d, J=9.0 Hz, 1H), 7.74 (td, J=7.7, 1.7 Hz, 1H), 7.47 (d, J=7.7 Hz, 1H), 7.30-7.22 (m, 2H), 6.84 (dd, J=9.0, 2.7 Hz, 1H), 6.72 (d, J=2.7 Hz, 1H), 5.24 (s, 2H), 2.54 (tt, J=8.5, 5.5 Hz, 1H), 1.06 (q, J=4.8 Hz, 2H), 0.67 (q, J=4.8 Hz, 2H).

[0492] According to route (C), 2-(3-cyclopropyl-4-nitrophenoxymethyl)pyridine (1.5 g, 5.6 mmoles, 1 eq.) and tin (II) chloride dihydrate (6.3 g, 28 mmoles, 5 eq.) were placed in EtOH (56 mL). The reaction mixture was heated at 60° C. and stirred for 64 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a 1N NaOH aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 2-cyclopropyl-4-(pyridin-2-ylmethoxy)aniline (1.1 g, 82%).

[0493] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.58 (d, J=4.2 Hz, 1H), 7.70 (td, J=7.7, 1.7 Hz, 1H), 7.52 (d, J=7.7 Hz, 1H), 7.20 (dd, J=6.9, 5.4 Hz, 1H), 6.73 (t, J=2.7 Hz, 1H), 6.69 (d, J=2.7 Hz, 1H), 6.61 (d, J=8.3 Hz, 1H), 5.12 (s, 2H), 3.71 (s, 2H), 1.74-1.65 (m, 1H), 0.90 (q, J=4.1 Hz, 2H), 0.58 (q, J=4.1 Hz, 2H).

[0494] 2-Cyclopentylethan-1-amine hydrochloride (1.3 g, 8.7 mmoles, 1.1 eq.) was placed in a 3N NaOH aqueous solution (5.9 mL) and dichloromethane (1.5 mL) was added to the solution. The reaction mixture was cooled down to 0° C. with an ice bath and a solution of 3-bromobenzoyl chloride (1.0 mL, 7.9 mmoles, 1.0 eq.) in dichloromethane (2.4 mL) was added dropwise. The reaction mixture was then stirred at room temperature for 18 hours under an inert atmosphere of argon. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 3-bromo-N-(2-cyclopentylethyl)benzamide (1.8 g, 77%).

[0495] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.89 (t, J=1.7 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.65-7.58 (m, 1H), 7.31 (t, J=7.9 Hz, 1H), 6.07 (s, 1H), 3.46 (dt, J=7.4, 5.9 Hz, 2H), 1.88-1.79 (m, 3H), 1.67-1.47 (m, 6H), 1.18-1.13 (m, 2H).

[0496] According to route (A), a reaction mixture of 3-bromo-N-(2-cyclopentylethyl)benzamide (148 mg, 0.5 mmole, 1 eq.), 2-cyclopropyl-4-(pyridin-2-ylmethoxy)aniline (120 mg, 0.5 mmole, 1 eq.), Pd.sub.2(dba).sub.3 (46 mg, 50 μmoles, 10 mol %), XPhos (48 mg, 100 μmoles, 20 mol %) and K.sub.2CO.sub.3 (277 mg, 2.0 mmoles, 4 eq.) in t-BuOH (2 mL) was heated at 90° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford N-(2-cyclopentylethyl)-3-{[2-cyclopropyl-4-(pyridin-2-ylmethoxy)phenyl]amino}benzamide (60) (190 mg, 83%).

[0497] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.61 (d, J=4.2 Hz, 1H), 7.73 (td, J=7.7, 1.7 Hz, 1H), 7.54 (d, J=7.7 Hz, 1H), 7.26-7.19 (m, 3H), 7.16 (d, J=8.6 Hz, 1H), 7.08 (d, J=7.7 Hz, 1H), 6.95 (dd, J=7.7, 1.7 Hz, 1H), 6.78 (dd, J=8.6, 2.9 Hz, 1H), 6.68 (d, J=2.9 Hz, 1H), 6.03 (s, 1H), 5.71 (s, 1H), 5.18 (s, 2H), 3.43 (dd, J=9.8, 4.7 Hz, 2H), 1.90-1.78 (m, 5H), 1.66-1.51 (m 4H), 1.17-1.09 (m 3H), 0.94-0.87 (m 2H), 0.67-0.59 (m 2H).

[0498] .sup.13C NMR (75 MHz, CDCl.sub.3) δ 165.4, 155.1, 152.7, 146.9, 143.9, 135.4, 134.5, 133.8, 132.2, 127.0, 120.9, 120.3, 119.0, 115.3, 114.4, 111.8, 111.2, 110.0, 68.6, 37.2, 35.6, 33.6, 30.4, 22.8, 9.3, 4.9

[0499] [M+H].sup.+=456.4

Example 4: Compound (68) in Table I

[0500] According to route (I), 4-nitro-5-methylphenol (3.06 g, 20 mmoles, 1 eq.) was placed in N,N-dimethylformamide (15 mL) with K.sub.2CO.sub.3 (8.3 g, 60 mmoles, 3 eq.). Upon addition of 2-(bromomethyl)pyridine hydrobromide (5.06 g, 20 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 24 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between dichloromethane and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 2-(3-methyl-4-nitrophenoxymethyl)pyridine (4.5 g, 92%).

[0501] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.65-8.60 (m, 1H), 8.07 (d, J=9.8 Hz, 1H), 7.75 (td, J=7.7, 1.7 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.30-7.24 (m, 1H), 6.90-6.87 (m, 2H), 2.62 (s, 3H).

[0502] According to route (C), 2-(3-methyl-4-nitrophenoxymethyl)pyridine (4.5 g, 18.4 mmoles, 1 eq.) and tin (II) chloride dihydrate (20.8 g, 92 mmoles, 5 eq.) were placed in EtOH (184 mL). The reaction mixture was heated at 60° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a 1N NaOH aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to afford 2-methyl-4-(pyridin-2-ylmethoxy)aniline (2.0 g, 51%).

[0503] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.58 (d, J=4.3 Hz, 1H), 7.70 (td, J=7.7, 1.7 Hz, 1H), 7.52 (d, J=7.7 Hz, 1H), 7.23-7.17 (m, 1H), 6.76 (d, J=2.7 Hz, 1H), 6.69 (dd, J=8.5, 2.7 Hz, 1H), 6.60 (d, J=8.5 Hz, 1H), 5.13 (s, 2H), 3.37 (s, 2H), 2.15 (s, 3H).

[0504] 3-Bromophenyl isocyanate (624 μL, 5.0 mmoles, 1.0 eq.) and triethylamine (695 μL, 5.0 mmoles, 1.0 eq.) were placed in dichloromethane (5 mL) and a solution of 3-methylbutan-1-amine (580 μL, 5.0 mmoles, 1.0 eq.) in dichloromethane (2 mL) was added dropwise. The reaction mixture was then stirred at room temperature for 16 hours under an inert atmosphere of argon. The reaction mixture was concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was washed with a 1N HCl aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford 1-(3-bromophenyl)-3-(3-methylbutyl)urea (1.06 g, 74%).

[0505] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.54 (s, 1H), 7.49 (t, J=1.9 Hz, 1H), 7.18 (dt, J=7.2, 1.9 Hz, 1H), 7.13-7.03 (m, 2H), 5.56 (t, J=5.3 Hz, 1H), 3.20 (dt, J=7.5, 5.8 Hz, 2H), 1.60-1.54 (m, 1H), 1.36-1.30 (m, 2H), 0.86 (d, J=6.6 Hz, 6H).

[0506] According to route (A), a reaction mixture of 1-(3-bromophenyl)-3-(3-methylbutyl)urea (285 mg, 1.0 mmole, 1 eq.), 2-methyl-4-(pyridin-2-ylmethoxy)aniline (214 mg, 1.0 mmole, 1 eq.), Pd.sub.2(dba).sub.3 (92 mg, 100 μmoles, 10 mol %), XPhos (95 mg, 200 μmoles, 20 mol %) and K.sub.2CO.sub.3 (553 mg, 4.0 mmoles, 4 eq.) in t-BuOH (4 mL) was heated at 90° C. and stirred for 24 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford a fraction which, after trituration in diethyl ether, gave 1-isopentyl-3-(3-((2-methyl-4-(pyridin-2-ylmethoxy)phenyl)amino)phenyl)urea (68) (76 mg, 18%).

[0507] .sup.1H NMR (300 MHz, d.sub.6-DMSO) δ 8.59 (d, J=4.5 Hz, 1H), 8.15 (s, 1H), 7.85 (td, J=7.9, 1.5 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.39-7.31 (m, 1H), 7.18 (s, 1H), 7.06 (d, J=8.6 Hz, 1H), 6.96-6.90 (m, 2H), 6.82 (dd, J=8.6, 2.8 Hz, 1H), 6.73 (s, 1H), 6.67 (d, J=7.9 Hz, 1H), 6.21 (d, J=7.9 Hz, 1H), 5.92 (t, J=5.4 Hz, 1H), 5.14 (s, 2H), 3.06 (dd, J=13.3, 6.7 Hz, 2H), 2.14 (s, 3H), 1.57 (td, J=13.3, 6.7 Hz, 1H), 1.33-1.25 (m, 2H), 0.88 (d, J=6.7 Hz, 6H).

[0508] [M+H].sup.+=419.4

Example 5: Compound (73) in Table I

[0509] According to route (I), 4-nitrophenol (2.75 g, 19.8 mmoles, 1 eq.) was placed in N,N-dimethylformamide (15 mL) with K.sub.2CO.sub.3 (8.2 g, 59.3 mmoles, 3 eq.). Upon addition of 2-(bromomethyl)pyridine hydrobromide (5.0 g, 19.8 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 16 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give 2-(4-nitrophenoxymethyl)pyridine (3.1 g, 68%).

[0510] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.63 (d, J=4.8 Hz, 1H), 8.25-8.16 (m, 2H), 7.75 (td, J=7.7, 1.7 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.31-7.26 (m, 1H), 7.11-7.03 (m, 2H), 5.30 (s, 2H).

[0511] According to route (C), 2-(4-nitrophenoxymethyl)pyridine (2.0 g, 8.7 mmoles, 1 eq.) and tin (II) chloride dihydrate (9.8 g, 43 mmoles, 5 eq.) were placed in EtOH (87 mL). The reaction mixture was heated at 60° C. and stirred for 14 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with ethyl acetate. The organic phase was washed with a 1N NaOH aqueous solution then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford 4-(pyridin-2-ylmethoxy)aniline (1.1 g, 63%).

[0512] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.58 (d, J=4.3 Hz, 1H), 7.70 (td, J=7.7, 1.7 Hz, 1H), 7.52 (d, J=7.7 Hz, 1H), 7.20 (dd, J=7.2, 5.2 Hz, 1H), 6.85-6.79 (m, 2H), 6.67-6.61 (m, 2H), 5.13 (s, 2H), 3.43 (br s, 2H).

[0513] Cyclopentanepropanol (2.0 g, 15.6 mmoles, 1 eq.) and triethylamine (2.8 mL, 20.1 mmoles, 1.3 eq.) were placed in dichloromethane (9.1 mL). The solution was cooled down to 0° C. with an ice bath and a solution of 4-toluenesulfonyl chloride (2.6 g, 13.6 mmoles, 0.9 eq.) in dichloromethane (4.6 mL) was added dropwise. The reaction mixture was then stirred at room temperature for 24 hours under an inert atmosphere of argon. The organic phase was washed with a 1N HCl aqueous solution then with a saturated aqueous solution of NaHCO.sub.3, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford 3-cyclopentylpropyl 4-methylbenzene-1-sulfonate (3.2 g, 83%).

[0514] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.79 (d, J=8.1 Hz, 2H), 7.34 (d, J=8.1 Hz, 2H), 4.02 (t, J=6.6 Hz, 1H), 2.45 (s, 2H), 1.75-1.43 (m, 11H), 1.34-1.23 (m, 2H), 1.05-0.95 (m, 2H).

[0515] 3-Bromophenol (613 mg, 3.5 mmoles, 1 eq.) was placed in N,N-dimethylformamide (25 mL) with Cs.sub.2CO.sub.3 (3.5 g, 10.7 mmoles, 3 eq.). Upon addition of 3-cyclopentylpropyl 4-methylbenzene-1-sulfonate (1.0 g, 3.5 mmoles, 1 eq.), the reaction mixture was heated at 90° C. and stirred for 14 hours under an inert atmosphere of argon. Upon cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. Upon decantation, the organic phase was washed with a saturated aqueous solution of NH.sub.4Cl and then with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 1-bromo-3-(3-cyclopentylpropoxy)benzene (716 mg, 71%).

[0516] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 7.14-7.10 (m, 1H), 7.07-7.03 (m, 2H), 6.82 (ddd, J=8.1, 2.3, 1.2 Hz, 1H), 3.92 (t, J=6.6 Hz, 2H), 1.86-1.70 (m, 6H), 1.69-1.40 (m, 7H), 1.18-1.03 (m, 2H).

[0517] According to route (A), a reaction mixture of 1-bromo-3-(3-cyclopentylpropoxy)benzene (282 mg, 1.0 mmole, 1 eq.), 4-(pyridin-2-ylmethoxy)aniline (200 mg, 1.0 mmole, 1 eq.), Pd.sub.2(dba).sub.3 (92 mg, 100 μmoles, 10 mol %), XPhos (95 mg, 200 μmoles, 20 mol %) and K.sub.2CO.sub.3 (553 mg, 4.0 mmoles, 4 eq.) in t-BuOH (4 mL) was heated at 90° C. and stirred for 64 hours under an inert atmosphere of argon. The reaction mixture was then concentrated under reduced pressure and the resulting residue was diluted with dichloromethane. The organic phase was washed with a saturated aqueous solution of brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to afford 3-(3-cyclopentylpropoxy)-N-(4-(pyridin-2-ylmethoxy)phenyl)aniline (73) (94 mg, 23%).

[0518] .sup.1H NMR (300 MHz, CDCl.sub.3) δ 8.59 (d, J=5.2 Hz, 1H), 7.71 (td, J=7.7, 1.7 Hz, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.21 (dd, J=7.0, 5.2 Hz, 1H), 7.12-7.03 (m, 3H), 6.96-6.89 (m, 2H), 6.50-6.44 (m, 2H), 6.38 (dd, J=7.7, 1.7 Hz, 1H), 5.55 (br s, 1H), 5.18 (s, 2H), 3.88 (t, J=6.6 Hz, 2H), 1.82-1.68 (m, 7H), 1.66-1.46 (m, 5H), 1.17-1.04 (m, 3H).

Example 6: Compound (93) in Table I

[0519] According to procedure (A1), a reaction mixture of N-(3-bromophenyl)-3-cyclohexylpropanamide (113 mg, 0.423 mmole, 1.2 eq.), 4-(benzyloxy)-2-(cyclopent-1-en-1-yl)aniline (100 mg, 0.351 mmole, 1.0 eq.), BrettPhos Pd G3 (6.4 mg, 7.0 μmoles, 2 mol %) and Cs.sub.2CO.sub.3 (171 mg, 0.526 mmole, 1.5 eq.) in anhydrous DMF (1.3 mL) was degassed with argon and heated at 80° C. for 75 minutes under inert atmosphere. The reaction mixture was then cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give N-(3-{[4-(benzyloxy)-2-(cyclopent-1-en-1-yl)phenyl]amino}phenyl)-3-cyclohexylpropanamide (131 mg, 76%).

[0520] .sup.1H NMR (400 MHz, d.sub.6-DMSO) δ 7.52-7.22 (m, 5H), 6.76-6.53 (m, 3H), 6.01 (s, 1H), 4.97 (s, 2H), 4.50 (s, 2H), 2.62 (t, J=6.6 Hz, 2H), 1.89 (p, J=7.5 Hz, 2H).

[0521] [M+H].sup.+=495.3

[0522] A 0.025M solution of N-(3-{[4-(benzyloxy)-2-(cyclopent-1-en-1-yl)phenyl]amino}phenyl)-3-cyclohexylpropanamide (100 mg, 0.202 mmole, 1.0 eq.) in MeOH:THF (1:1) was passed through a H-cube apparatus (cartridge Pd/C 30 mm, 30° C., 2 bars, 1 m/min). The solvent was then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give N-(3-{[4-(benzyloxy)-2-cyclopentylphenyl]amino}phenyl)-3-cyclohexylpropanamide (93) (50.0 mg, 50%).

[0523] .sup.1H NMR (400 MHz, d.sub.6-DMSO) δ 9.55 (s, 1H), 7.55-7.27 (m, 5H), 7.17 (s, 1H), 7.08-6.73 (m, 6H), 6.27 (d, J=8.9 Hz, 1H), 5.08 (s, 2H), 3.26-3.13 (m, 1H), 2.28-2.15 (m, 2H), 1.89 (d, J=6.1 Hz, 2H), 1.79-1.36 (m, 14H), 1.28-1.04 (m, 4H), 0.87 (q, J=10.4, 8.9 Hz, 2H).

[0524] [M+H].sup.+=497.3

Example 7: Compound (101) in Table I

[0525] According to route (I), 4-amino-3-tert-butylphenol (100 mg, 0.581 mmole, 1 eq.) was placed in anhydrous N,N-dimethylformamide (2 mL) with Cs.sub.2CO.sub.3 (227 mg, 0.697 mmole, 1.2 eq.). Upon addition of bromomethylbenzene (75.9 μL, 0.639 mmole, 1 eq.), the reaction mixture was stirred at room temperature for 16 hours under an inert atmosphere of argon. The reaction was quenched with 1M aqueous hydrochloric acid and extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure to afford a mixture of 0 and N poly-benzylated products. The residue was taken up in methanol (15 mL) and hydrogenated using a H-cube apparatus (Pd/C 10%, 1 bar hydrogen pressure, 1 mL/min flow). The solvent was then concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give 4-(benzyloxy)-2-tert-butylaniline (23.8 mg, 21%).

[0526] .sup.1H NMR (400 MHz, d.sub.6-DMSO) δ 7.42 (d, J=6.9 Hz, 2H), 7.37 (t, J=7.3 Hz, 2H), 7.31 (d, J=7.0 Hz, 1H), 6.72 (d, J=2.7 Hz, 1H), 6.61 (d, J=2.7 Hz, 1H), 6.58 (d, J=8.5 Hz, 1H), 4.94 (s, 2H), 4.32 (s, 2H), 1.31 (s, 9H).

[0527] According to procedure (A1), a reaction mixture of methyl 2-bromobenzoate (11.0 μL, 78.3 μmoles, 1.0 eq.), 4-(benzyloxy)-2-tert-butylaniline (20.0 mg, 78.3 μmoles, 1.0 eq.), Pd(OAc).sub.2 (0.53 mg, 2.3 μmoles, 3 mol %), rac-BINAP (0.98 mg, 1.6 μmole, 2 mol %) and K.sub.2CO.sub.3 (32.5 mg, 235 μmoles, 3 eq.) in anhydrous toluene (1.0 mL) was degassed with N.sub.2 and heated at 110° C. for 75 minutes under inert atmosphere. The reaction mixture was cooled down to room temperature, filtered over a pad of celite and the pad was washed with EtOAc. A saturated aqueous solution of brine was then added to the filtrate and the mixture was extracted with EtOAc. The combined organic phases were dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give methyl 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}benzoate (50.0 mg, 47% purity, 77%).

[0528] Methyl 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}benzoate (50.0 mg, 47% purity, 60.3 μmoles, 1 eq.) was placed in methanol (2 mL) and an aqueous solution of 2M NaOH (151 μL, 302 μmoles, 5 eq.) was added. The reaction mixture was heated at 80° C. and stirred for 3 hours. It was then concentrated under reduced pressure and, after addition of an aqueous solution of 2M HCl (10 eq.), extracted with dichloromethane. The combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure to give 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}benzoic acid (28.0 mg, 42% purity, 52%).

[0529] 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}benzoic acid (28.0 mg, 42% purity, 74.6 μmoles, 1 eq.) and 2-cyclohexylethanamine (12.5 μL, 89.5 μmoles, 1.2 eq.) were placed in anhydrous N,N-dimethylformamide (1.0 mL). HATU (44.3 mg, 112 μmoles, 1.5 eq.) and DIPEA (39.1 μL, 224 μmoles, 3 eq.) were added and the resulting reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with 1M aqueous hydrochloric acid and extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel to give 2-{[4-(benzyloxy)-2-tert-butylphenyl]amino}-N-(2-cyclohexylethyl)benzamide (101) (5.1 mg, 14%).

[0530] .sup.1H NMR (400 MHz, d.sub.6-DMSO) δ 9.47 (s, 1H), 8.40 (s, 1H), 7.61 (d, J=6.9 Hz, 1H), 7.48 (d, J=7.1 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.34 (t, J=7.2 Hz, 1H), 7.16 (t, J=7.7 Hz, 1H), 7.06 (d, J=8.6 Hz, 1H), 7.00 (d, J=2.8 Hz, 1H), 6.90 (dd, J=8.6, 2.8 Hz, 1H), 6.61 (t, J=7.4 Hz, 1H), 6.49 (d, J=8.4 Hz, 1H), 5.09 (s, 2H), 3.27 (d, J=6.8 Hz, 2H), 1.74 (d, J=12.2 Hz, 2H), 1.64 (dd, J=20.5, 11.1 Hz, 3H), 1.44 (q, J=6.9 Hz, 2H), 1.31 (s, 9H), 1.26-1.13 (m, 4H), 0.90 (q, J=13.3, 12.5 Hz, 2H).

[0531] [M+H].sup.+=485.3

Pharmacological Data

Example 8: Chikungunya Virus

[0532] The compounds of the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy and in particular for preventing, inhibiting or treating Chikungunya virus infection.

[0533] Material and Methods Inhibition of Chikungunya Virus (CHIKV) Production in Infected HEK293T Cell Line.

[0534] The ability of the compounds to inhibit viral replication was assessed with an experiment in which infected cells were treated by compounds of formula (Ie) at 1 μM. As a positive control for inhibition of Chikungunya, Ribavirin was used. Toxicity of the compounds was assessed in parallel.

[0535] Amplification of Cells

[0536] Human embryonic kidney cells 293T (HEK293T, CRL-11268) were maintained in Dulbecco's modified Eagle's Medium (DMEM, 31966-021, Thermo Fisher Scientific) supplemented with 10% of fetal bovine serum (FBS), penicillin and streptomycin. After removal of the medium, cells were washed with Ca.sup.2+ and Mg.sup.2+-free salt solution to remove all traces of serum. After aspiration of wash solution, cells were dissociated with 0.25% Trypsin-EDTA solution and incubated 30 s at least in 37° C. incubator. Concentration of cell suspension was determined by an automatic cell counter (EVE, NanoEntek) and, if needed, adjusted to 0.33×10.sup.6 cells/mL with DMEM medium supplemented with 10% FBS.

[0537] Preparation of the Compounds

[0538] 100 μL of the cell suspension were dispatched in a ViewPlate-96 Black (6005182, PerkinElmer) and in a transparent 96-well cell culture plate (655180, Greiner bio-one). After an incubation for 24 h at 37° C. under 5% of CO.sub.2, compounds were added at the proper concentration.

[0539] Screen at 1 μM

[0540] An intermediate dilution was prepared with DMSO (D8418, Sigma) at 2 mM in a 96-well V-bottom microplate from the stock solution:

[0541] Mix 1 μL of the 50 mM stock library in 25 μL of DMSO.

[0542] Mix 2 μL of the 25 mM stock library in 25 μL of DMSO.

[0543] Determination of IC.sub.50 Values

[0544] An intermediate dilution was prepared with DMSO (D8418, Sigma) at 25 mM in a 96-well V-bottom microplate from the stock solution:

[0545] Mix 2 μL of the 50 mM stock library in 2 μL of DMSO.

[0546] Perform serial dilution in 2 μL of DMSO 13 times to reach 0.0015 mM. Proceed as follows in table III:

TABLE-US-00003 TABLE III Volume Con- of DMSO centration 100% (mM) (μL) Volume of solution A 12.5 2 2 μL of 50 mM solution B 6.25 2 2 μL of solution A C 3.125 2 2 μL of solution B D 1.56 2 2 μL of solution C E 0.78 2 2 μL of solution D F 0.39 2 2 μL of solution E G 0.195 2 2 μL of solution F H 0.0976 2 2 μL of solution G I 0.0488 2 2 μL of solution H J 0.0244 2 2 μL of solution I K 0.0122 2 2 μL of solution J L 0.0061 2 2 μL of solution K M 0.0030 2 2 μL of solution L N 0.0015 2 2 μL of solution M

[0547] For both screen and determination of IC.sub.50, 1 μL of each solution was added in a 1 mL Masterblock 96 wells (Greiner bio-one, 780261) containing 1 mL of DMEM medium. As a positive control, 5 μL of a 80 mM Ribavirin solution (R9644, Sigma) is added to 1 mL of DMEM. On the other hand, DMSO is used as a negative control.

[0548] Infection

[0549] Cells were infected with 30 μL of CHIKV strain of La Réunion outbreak (LR2006-OPY1) with GFP modification in 5′ (CHIK 5′LR) (Tsetsarkin K, Higgs S, McGee C E, De Lamballerie X, Charrel R N, Vanlandingham D L. Infectious Clones of Chikungunya Virus (La Réunion Isolate—Ref-SKU: 001N-EVA249 (PMID: 17187566) available at the following address: https://www.european-virus-archive.com/nucleic-acid/chikv-lr-5gfp-infectious-clone) for Vector Competence Studies. Vector Borne Zoonotic Dis. 2006; 6(4)). This modified virus was used to infect cells at MOI 0.1. The LR2006-OPY1 strain of CHIKV (CHIKV-LR) was obtained from the World Reference Center for Arboviruses at the University of Texas Medical Branch, Galveston, Tex. This strain was originally isolated from the serum of a febrile French patient returning from La Réunion Island.

[0550] Cell Lysis

[0551] Medium was removed after 22 h at 37° C. under 5% of CO.sub.2 and cells were washed as described above. 60 μL of RIPA buffer (50 mM Tris-HCl pH8, 100 mM NaCl, 1 mM MgCl.sub.2, 1% Triton X-100) was added to cells and incubated for at least 20 min before reading fluorescence signal. Pierce 660 nm Protein Assay Reagent (22660, Thermo scientific) was used to normalize fluorescence signal by protein quantity.

[0552] CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) (G3581, Promega) was used to check the toxicity of the compounds. We added 20 μL of MTS solution and read absorbance at 492 nm one hour later.

[0553] Results [0554] A first round of experiments has been performed wherein the results are expressed as inhibition percentage, which is calculated as follows, through the following steps:

[0555] 1. Fluorescence intensity (FI)/Absorbance 660 nm (A660)=A

[0556] This ratio allows considering the infection (GFP virus) to the protein amount.

[0557] 2. A′=A−background noise of non-infected plate,

[0558] 3. B=Fluorescence intensity (FI)/Absorbance 660 nm (A660) of infected but non treated plates,

[0559] 4. C=A′/B, which is then converted as the percentage of infection after treatment, compared to non-treated sample, and subsequently as the infection percentage. For instance, a value of 100 in Table IV here below means that, after treatment, the signal attributed to GFP fluorescence is abolished, which is correlated to the absence of infection.

[0560] 5. C′=100−C

[0561] This value corresponds to the inhibition's percentage.

[0562] The following Table IV encompasses said C′ value for some compounds, as calculated above with a mean of 2 experiments, and corresponding standard deviation.

[0563] Some values were originally above 100. In these cases, the value has been lowered to 100. This means that some molecules also have an impact on the viability of the cells. In other words, the A value may be lower than the background noise.

[0564] Moreover, for each measure, the test was performed with Ribavirin as control. The value of the inhibition percentage was checked, giving 100%.

TABLE-US-00004 TABLE IV % CHIKV Inhibition Ex Mean (n = 2) Standard deviation (n = 2) 36 99 0 37 100 0 38 99 2 39 98 1 40 99 1 41 99 1 43 100 0 45 99 2 46 99 2 47 96 1 48 98 1 49 98 3 50 100 0 51 100 0 52 99 1 73 100 0 [0565] A second round of experiments has been performed, giving the results as IC.sub.50 values.

[0566] The IC.sub.50 values range between 0.1 nM and 1 μM, in particular between 0.5 and 500 nM and even more particularly between 1 and 400 nM, for example between 1 and 200 nM. For example, compounds (36)-(41), (53), (54), (57), (58), (60)-(62), (64), (68), (70) and (71) have an IC.sub.50 value ranging between 1 and 400 nM.

[0567] Conclusion

[0568] Based on the previous results, it can be concluded that the compounds of formula (Ie) are suitable chemical compounds for treating and/or preventing RNA virus infections caused by RNA viruses of group IV, more particularly, Alphavirus infections, and most particularly Chikungunya virus infections.

Example 9: RSV Virus

[0569] The compounds of the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy and in particular for preventing, inhibiting or treating RSV virus infection.

[0570] Material and Methods

[0571] Protocol for Screening Antiviral Compounds for RSV Inhibition and Cytotoxicity Using Viral ToxGlo Assay

[0572] HEp-2 cells were maintained in Eagle's minimum essential medium (EMEM) with Earle's BSS adjusted to contain 2 mM L-glutamine, 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin. For the purposes of the screening assay they were grown to 90% confluency, trypsinized and recovered. The trypsin was neutralised with cell culture media and cells were centrifuged at 150×g for 5 minutes before discarding the supernatant and resuspending cell pellet in assay media (EMEM with Earle's BSS adjusted to contain 2 mM L-glutamine, 2% fetal bovine serum and 100 U/ml penicillin and 100 μg/ml streptomycin). The cells were seeded into white clear-bottomed cell culture plates at a density of 1.5×10.sup.4 cells/well in 50 μl and 4×10.sup.3 cells/well in 25 μl for 96 well plates and 384 well plates respectively. For the media/background control column assay media only was added. Cell plates were placed in a humid chamber and incubated overnight at 37° C./5% CO.sub.2. After overnight incubation cells were checked for confluency and healthy appearance.

[0573] Test articles were made up at 10× test concentration in a maximum DMSO concentration of 10% (final assay concentration maximal 1% DMSO) and added to the cell plates in volumes of 10 μl for 96 well plates and 5 μl for 384 well plates. For cell control and virus control wells the test article solvent only was added. Virus or assay media for cytotoxicity test wells and media/cell control wells was added immediately after test articles at an MOI of 0.5, 40 or 20 μl for 96 and 384 well plates respectively. Virus suspension was prepared by thawing RSV A2 frozen stocks and diluting to the required concentration of plaque forming units in assay media on ice.

[0574] Cell plates were further incubated inside a humid chamber for 72 h p.i at 37° C./5% CO.sub.2. After the incubation period cells were observed under the microscope to check for characteristic cytopathic effect in virus control wells and healthy cells in the cell control wells. After plates were adjusted to room temperature 20/40 μl Viral ToxGlo (Promega) was added to each well of the 384/96 well cell plates. Plates were incubated at room temperature, protected from light on a plate rocker for 20 minutes before measuring the luminescence on a spectrophotometer (Biotek Synergy HTX).

[0575] RSV inhibition was calculated as percentage of cytopathic effect inhibition relative to the virus control and cytotoxicity as percentage of cell survival relative to cell control wells. This allowed EC.sub.50 values to be calculated for each test article where a virus inhibition or cytotoxic dose response was identified. EC.sub.50 values ranging between 0.001 μM and 2.5 μM were found, and more particularly for compounds (36), (38), (39), (45), (46), (47), (54), (57), (60), (61), (64), (68), (70), (71), (72), (75)-(80), (82)-(86), (88)-(142), (147)-(156), (164)-(166) and (179).

TABLE-US-00005 TABLE V Ex EC.sub.50 (nM) 36 232 38 281 39 185 45 280 46 199 47 182 54 177 57 26 60 67 61 54 64 341 68 144 70 660 71 185 72 158 75 25 76 14 77 124 78 58 79 33 80 21 82 4 83 9 84 637 85 8 86 567 88 461 89 140 90 92 91 2 92 4 93 4 94 7 95 8 96 10 97 10 98 12 99 13 100 16 101 21 102 22 103 24 104 29 105 31 106 33 107 36 108 41 109 48 110 59 111 62 112 67 113 69 114 71 115 83 116 93 117 98 118 103 119 107 120 110 121 116 122 116 123 120 124 126 125 130 126 133 127 148 128 156 129 175 130 198 131 204 132 228 133 230 134 281 135 292 136 295 137 300 138 312 139 329 140 349 141 352 142 370 147 414 148 532 149 555 150 597 151 671 152 802 153 809 154 810 155 1031 156 1059 164 1325 165 2357 166 2490 179 721

[0576] Conclusion

[0577] Based on the previous results, it can be concluded that the compounds of formula (Ie) are suitable chemical compounds for treating and/or preventing RNA virus infections caused by RNA viruses of group V, more particularly, pneumovirus infections, and most particularly RSV virus infections.

Example 10: Dengue 2 Virus

[0578] The compounds of the invention have been the subject of pharmacological tests which have demonstrated their relevance as active substances in therapy and in particular for preventing, inhibiting or treating Dengue 2 virus infection.

[0579] Material and Methods

[0580] Protocol for Screening Antiviral Compounds for DENV-2 Inhibition and Cytotoxicity Using Viral ToxGlo Assay

[0581] A549 cells were maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin. For the purposes of the screening assay they were grown to 90% confluency, trypsinized and recovered. The trypsin was neutralised with cell culture media and cells were centrifuged at 150×g for 5 minutes before discarding the supernatant and resuspending cell pellet in assay media (DMEM supplemented with 2% fetal bovine serum and 100 U/ml penicillin and 100 μg/ml streptomycin). The cells were seeded into 96-well white clear-bottomed cell culture plates at a density of 1.0×10 4 cells/well in 50 μl. For the media/background control column assay media only was added. Cell plates were placed in a humid chamber and incubated overnight at 37° C./5% CO2. After overnight incubation cells were checked for confluency and healthy appearance.

[0582] Test compounds were prepared at a final concentration of 10 μM in a maximum DMSO concentration of 1% (final assay concentration maximal 0.1% DMSO) and added to the cell plates in volumes of 10 μl. For cell control and virus control wells the test article solvent only was added. As a positive inhibition control, 7-Deaza-2′-C-methyladenosine was added at 100 μM in 3 wells. Virus (DENV-2 strain 16681) or assay media for cytotoxicity test wells and media/cell control wells was added immediately after test articles at an MOI of 0.5, 40 for 96 well plates respectively. Virus suspension was prepared by thawing DENV-2 frozen stocks and diluting to the required concentration of plaque forming units in assay media.

[0583] Cell plates were further incubated inside a humid chamber for 5 days p.i at 37° C./5% CO2. After the incubation period cells were observed under the microscope to check for characteristic cytopathic effect in virus control wells and healthy cells in the cell control wells. After plates were adjusted to room temperature 20 μl Viral ToxGlo (Promega) was added to each well of the 96-well cell plates. Plates were incubated at room temperature for 5 minutes before measuring the luminescence on a spectrophotometer (Envision, PerkinElmer).

[0584] DENV-2 inhibition was calculated as percentage of cytopathic effect inhibition relative to the virus control and cytotoxicity as percentage of cell survival relative to cell control wells.

TABLE-US-00006 TABLE VI % DENV-2 Inhibition Ex Mean (n = 3) 38 65 40 71 43 71 45 89 46 71 48 110 49 111 61 55 62 55 64 93 65 77 68 70 82 64 98 60 119 104 121 59 132 71 140 74 150 78 151 63 156 82 169 59 175 60 176 85 192 66

[0585] Conclusion

[0586] Based on the previous results, it can be concluded that the compounds of formula (Ie) are suitable chemical compounds for treating and/or preventing RNA virus infections caused by RNA viruses of group IV, more particularly, Flavivirus infections, and most particularly Dengue 2 virus infections.

[0587] The present invention further relates to a pharmaceutical composition comprising at least one new compound as defined above or any of its pharmaceutically acceptable salts, or at least any of compounds (36) to (206) as defined above or any of its pharmaceutically acceptable salts and also at least one pharmaceutically acceptable excipient.

[0588] Pharmaceutical compositions of the invention can contain one or more compound(s) of the invention in any form described herein.

[0589] Still a further object of the present invention consists of the use of at least one compound of formula (Ie), as defined above, and compounds (36) to (206) as defined above, or one of their pharmaceutically acceptable salts according to the present invention for preparing a drug to prevent or treat, in a subject, a RNA virus infection caused by a RNA virus from group IV or Group V according to the Baltimore classification, and for example a Chikungunya infection, a Dengue infection, an Influenza infection or a RSV infection.

[0590] Therefore, the present invention relates to one compound of formula (Ie), as defined above, and compounds (36) to (206) or one of their acceptable salts as an agent for inhibiting, preventing or treating a RNA virus infection, and most preferably a RNA virus infection from group IV or V, and for example a Chikungunya infection, a Dengue infection, an Influenza infection or a RSV infection.

[0591] According to a particular embodiment, the treatment is continuous or non-continuous.

[0592] A “continuous treatment” means a long-term treatment which can be implemented with various administration frequencies, such as once every day, every three days, once a week, or once every two weeks or once every month.

[0593] According to one embodiment, the compound of formula (Ie), or anyone of its pharmaceutically acceptable salts, is administered at a dose varying from 0.1 to 1000 mg, in particular varying from 0.1 to 10 mg, or for example varying from 10 to 200 mg, or for example varying from 200 to 1000 mg.

[0594] Another object of the invention relates to a therapeutic method for treating and/or preventing a subject from a RNA virus infection, and most preferably a RNA virus infection caused by a virus belonging to group IV or V of the Baltimore classification comprising the administration of a therapeutically effective quantity of a compound of formula (Ie), compounds (36) to (206), as defined above, or one of their acceptable salts.

[0595] In a specific embodiment, the invention provides a use of a compound of formula (Ie) according to the invention or a pharmaceutically acceptable salt thereof or a pharmaceutically active derivative thereof or a method according to the invention wherein the compound of formula (Ie) is to be administered in combination with a co-agent useful in the treatment of said RNA virus infection, and most preferably said RNA virus infection from group IV or V, and for example Chikungunya infection, Dengue infection, Influenza infection or RSV infection.

[0596] The compounds can be administered through any mode of administration such as, for example, intramuscular, intravenous, intranasal or oral route, etc.

[0597] Compounds of the present invention may, in appropriate cases, be administered as prodrugs, such as esters, of compounds with which the invention is concerned. “Prodrug” means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis, reduction or oxidation) to a compound of the present invention. For example, an ester prodrug of a compound of the present invention may be convertible by hydrolysis in vivo to the parent molecule. Suitable esters of compounds of the present invention are for example acetates, citrates, lactates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-β-hydroxynaphthoates, gentisates, isethionates, di-p-toluoyltartrates, methanesulphonates, ethanesulphonates, benzenesulphonates, p-toluenesulphonates, cyclohexylsulfamates and quinates. Examples of ester prodrugs are those described by F. J. Leinweber, Drug Metab. Res., 1987, 18, 379. As used herein, references to the compounds of the present invention are meant to also include any prodrug or metabolite forms.

[0598] The inventive composition can further include one or more additives such as diluents, excipients, stabilizers and preservatives. Such additives are well known to those skilled in the art and are described notably in “Ullmann's Encyclopedia of Industrial Chemistry, 6.sup.th Ed.” (various editors, 1989-1998, Marcel Dekker) and in “Pharmaceutical Dosage Forms and Drug Delivery Systems” (ANSEL et al., 1994, WILLIAMS & WILKINS).

[0599] The aforementioned excipients are selected according to the dosage form and the desired mode of administration.

[0600] Compositions of this invention may be administered in any manner, including, but not limited to, orally, parenterally, sublingually, transdermally, vaginally, rectally, transmucosally, topically, intranasally via inhalation, via buccal or intranasal administration, or combinations thereof. Parenteral administration includes, but is not limited to, intravenous, intra-arterial, intra-peritoneal, subcutaneous, intramuscular, intra-thecal, and intra-articular. The compositions of this invention may also be administered in the form of an implant, which allows slow release of the compositions as well as a slow controlled i.v. infusion.

[0601] According to another embodiment, pharmaceutically acceptable compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the infection being treated.

[0602] Compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term “parenteral” as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium.

[0603] For example, a compound of formula (Ie) can be present in any pharmaceutical form which is suitable for enteral or parenteral administration, in association with appropriate excipients, for example in the form of plain or coated tablets, hard gelatine, soft shell capsules and other capsules, suppositories, or drinkable, such as suspensions, syrups, or injectable solutions or suspensions, in doses which enable the daily administration of from 0.1 to 1000 mg of active substance.

[0604] In a particular embodiment, a compound of formula (Ie) according to the invention is administered orally.

[0605] Oral route of administration is in particular preferred in the prophylaxis or treatment aspect of the invention.