The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

Compounds of formula (I):

##STR00001##

where

##STR00002##

n, R.sup.1, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7 and R.sup.8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window.

##STR00001##

The present invention provides a compound represented by general formula I or a pharmaceutical acceptable salt thereof, the preparation method therefor and the use thereof in preparing a medicine for treating a neurological disease, such as epilepsy, convulsion, neuropathic pain, acute ischemic stroke, and a neurodegenerative disease. The compound according to present invention has a better absorption in brain tissue when compared with RTG. In addition, the compound provided by present invention has not only a greatly enhanced efficacy, but also a neurotoxicity greatly lower than that of RTG, and thus possesses a wider safety window.

##STR00001##

This invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is H, halogen, NR.sub.5R.sub.6, NR.sub.5C(0)-R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R.sub.2 and R.sub.3 are each, independently, H, halogen, NH.sub.2, CX.sub.3, C(O)OR.sub.8, C(O)R.sub.8, C(O)NR.sub.9R.sub.10, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R.sub.8, R.sub.9 and R.sub.10 are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is Ar.sub.1Z or ZAr.sub.1Z, wherein Ar.sub.1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is O, S, CH.sub.2, C(O), NH, NHNH, NHC(O), C(O)NH, NHC(O)CH.sub.2NH, NHC(O)CH.sub.2C(O), N(OH), CH.sub.2CH.sub.2 or NHC(O)CHCH; and R.sub.4 is alkyl, OR.sub.11 or NHOR.sub.11, wherein R.sub.11 is H, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is Ar.sub.1Z, Z is absent, Ar.sub.1 is phenyl, R.sub.2 and R.sub.3 are H, n=1, and R.sub.4 is NHOH, then R.sub.1 is other than carbazole, tetrahydro--carboline, tetrahydro--carboline, C(O)NR.sub.5R.sub.6 and NR.sub.5C(0)-R.sub.6, wherein one of R.sub.5 or R.sub.6 is quinline and the other of R.sub.5 or R.sub.6 is H;
or a pharmaceutically acceptable salt thereof.

This invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is H, halogen, NR.sub.5R.sub.6, NR.sub.5C(0)-R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R.sub.2 and R.sub.3 are each, independently, H, halogen, NH.sub.2, CX.sub.3, C(O)OR.sub.8, C(O)R.sub.8, C(O)NR.sub.9R.sub.10, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R.sub.8, R.sub.9 and R.sub.10 are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is Ar.sub.1Z or ZAr.sub.1Z, wherein Ar.sub.1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is O, S, CH.sub.2, C(O), NH, NHNH, NHC(O), C(O)NH, NHC(O)CH.sub.2NH, NHC(O)CH.sub.2C(O), N(OH), CH.sub.2CH.sub.2 or NHC(O)CHCH; and R.sub.4 is alkyl, OR.sub.11 or NHOR.sub.11, wherein R.sub.11 is H, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is Ar.sub.1Z, Z is absent, Ar.sub.1 is phenyl, R.sub.2 and R.sub.3 are H, n=1, and R.sub.4 is NHOH, then R.sub.1 is other than carbazole, tetrahydro--carboline, tetrahydro--carboline, C(O)NR.sub.5R.sub.6 and NR.sub.5C(0)-R.sub.6, wherein one of R.sub.5 or R.sub.6 is quinline and the other of R.sub.5 or R.sub.6 is H;
or a pharmaceutically acceptable salt thereof.

The present invention provides a pest control agent, acaricide or fungicide that contains, as the active ingredient thereof, at least one type of compound selected from the aryloxyurea compounds represented by formula (V) (wherein R.sup.1 to R.sup.5 each independently represents an alkyl group or the like, X is a halogen atom or the like, n is an integer of 0 to 5, and Z is an oxygen atom or sulfur atom) or salts thereof. ##STR00001##

The present invention provides a pest control agent, acaricide or fungicide that contains, as the active ingredient thereof, at least one type of compound selected from the aryloxyurea compounds represented by formula (V) (wherein R.sup.1 to R.sup.5 each independently represents an alkyl group or the like, X is a halogen atom or the like, n is an integer of 0 to 5, and Z is an oxygen atom or sulfur atom) or salts thereof. ##STR00001##

Compounds of formula (I): where, n, R.sup.1, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7 and R.sup.8 are defined herein, or pharmaceutically acceptable salts thereof, are described herein. The disclosed compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of formula (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof. ##STR00001##