BENZYL PIPERAZINE COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN ANTIVIRUS

Abstract

Disclosed are a benzyl piperazine compound, a preparation method there for and an application thereof in an antivirus. The benzyl piperazine compound has a structure represented by the following general formula(I). It is proven by experiments that the benzyl piperazine compound not only has significant antiviral activity, but also has the advantages of low cytotoxicity, a high selectivity index and soon.

##STR00001##

Claims

1. A compound having the structure as shown in the general formula I or a pharmaceutically acceptable salt thereof: ##STR00143## wherein R.sub.1 is alkyl containing 1 to 4 carbons or H; R.sub.2 is H, alkyl, cycloalkyl, aryl, heteroaryl, or, aryl or heteroaryl substituted with 1, 2 or 3 substituents, wherein, the substituent is selected from the group consisting of alkyl, cycloalkyl, alkoxy, phenoxy, alkylthio, phenylthio, halogen, cyano, and haloalkyl; when being alkyl or cycloalkyl, R.sub.2 is alkyl containing 1 to 6 carbon atoms, or cycloalkyl containing 3 to 6 carbon atoms, and the alkyl and cycloalkyl are optionally substituted with halogen; R.sub.3 is cyano or trifluoromethyl; X is N or CH; Y is CH or single bond connecting X and Aryl; when Y is a single bond, R.sub.2 is absent, and R.sub.3 is trifluoromethyl; Aryl is a benzene or aza-aromatic ring, or a benzene or aza-aromatic ring containing 1-3 substituents selected from the group consisting of alkyl, cycloalkyl, alkyloxy, phenoxy or substituted phenoxy, alkylthio, phenylthio or substituted phenylthio, haloalkyl, cyano, and halogen; R.sub.4 is substituted alkyl or substituted heterocycloalkyl, and when R.sub.4 is substituted alkyl, the substituent is selected from the group consisting of alkylamino, dialkylamino, and saturated or unsaturated heterocyclyl containing one nitrogen or two nitrogens; when R.sub.4 is substituted heterocycloalkyl, the heterocycloalkyl contains at least one nitrogen atom, and the substituent is selected from the group consisting of alkyl, alkylamino and dialkylamino; R.sub.5 is hydrogen or alkyl containing 1-4 carbons; alternatively, R.sub.4, R.sub.5, and the nitrogen atom to which they are attached jointly form a cyclic structure containing 1 or 2 nitrogen atoms or cyclic structure substituted with a substituent selected from the group consisting of alkyl containing 1 to 6 carbons, alkylamino, dialkylamino, cycloalkyl, and heterocyclic groups.

2. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof having the structure shown in the general formula II: ##STR00144## wherein R.sub.1 is alkyl containing 1 to 4 carbons or H; R.sub.2 is H, alkyl, cycloalkyl, aryl, heteroaryl, or, aryl or heteroaryl substituted with 1, 2 or 3 substituents, wherein, the substituent is selected from the group consisting of alkyl, cycloalkyl, alkoxy, phenoxy, alkylthio, phenylthio, halogen, cyano, and haloalkyl; when being alkyl or cycloalkyl, R.sub.2 is alkyl containing 1 to 6 carbon atoms, or cycloalkyl containing 3 to 6 carbon atoms, or optionally substituted with halogen; R.sub.3 is cyano or trifluoromethyl; X is N or CH; Y is CH or a single bond linking X to the aromatic ring containing Z.sub.1, Z.sub.2, and Z.sub.3; when Y is a single bond, R.sub.2 is absent, and R.sub.3 is trifluoromethyl; Z.sub.1, Z.sub.2, Z.sub.3 are the same or different, Z.sub.1, Z.sub.2, Z.sub.3 are each C(R.sub.6) or N, respectively, R.sub.6 is H, alkyl, cycloalkyl, alkyloxy, phenoxy or substituted phenoxy, alkylthio, phenylthio or substituted phenylthio, haloalkyl, cyano, or halogen; R.sub.4 is ##STR00145## wherein, n=1-3, R.sub.7, R.sub.8 are each H, alkyl, or substituted alkyl, respectively, or R.sub.7 and R.sub.8, together with the nitrogen atom to which they are bonded, form a cyclic group or a substituted cyclic group substituted with 1, 2 or 3 substituents selected from the group consisting of alkyl, alkylamino, dialkylamino, and heterocyclyl, such as pyrrolidinyl, the cyclic group is a three-, four-, five-, six-, or seven-membered saturated or unsaturated cyclic group containing 1 or 2 nitrogen atoms, for example, the three-membered cyclic group is aziridinyl, the four-membered cyclic group is azetidinyl, the five membered cyclic group is selected from the group consisting of pyrrolyl, pyrrolidinyl, imidazolyl, and oxazolyl, the six-membered cyclic group is selected from the group consisting of morpholinyl, piperazinyl, piperidinyl, pyridinyl, and pyrimidinyl, and the seven-membered cyclic group is 1,4-diazepanyl; or R.sub.4 is ##STR00146## wherein R.sub.12 is alkyl containing 1-4 carbon atoms, such as methyl, ethyl; R.sub.11, the nitrogen to which R.sub.11 is bound, the carbon to which R.sub.10 is bound, the carbon to which R.sub.9 is bound, and R.sub.9 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, alkylamino, and dialkylamino, and akyl in the alkylamino and dialkylamino contains 1 to 4 carbon atoms, R.sub.10 is H; or R.sub.11 with the nitrogen to which it is bound, the carbon to which R.sub.10 is bound, and R.sub.10 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, C1-C4 alkylamino, and di-C1-C4 alkylamino, for example, dimethylamino, diethylamino, R.sub.9 is H; alternatively, R.sub.4 is alkyl which contains 1-4 carbons and is substituted by amino, alkylamino, dialkylamino, or four-, five-, or six membered saturated heterocycles containing one or two nitrogens; alternatively, R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two nitrogen atoms, the substituents are selected from the group consisting of alkyl containing 1 to 6 carbon atoms, C1-C4 alkylamino groups, di-C1-C4 alkylamino groups, cycloalkyl groups containing 3 to 5 carbon atoms or saturated heterocyclic groups containing one nitrogen, such as dimethylamino, diethylamino, cyclopropanyl or pyrrolidinyl.

3. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 1, when R.sub.4 is ##STR00147## R.sub.4 is ##STR00148## n=2 or 3, R.sub.10 is H; or R.sub.4 is ##STR00149## n=2, 3 or 4, and R.sub.9 is H.

4. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 1, wherein R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two heteroatoms, the five-membered heterocycle is selected from the group consisting of pyrrolidinyl, pyrrolyl, imidazolyl, imidazolidinyl, and oxazolyl, the six-membered heterocycle is selected from the group consisting of morpholine, piperazine, and piperidine, and the seven-membered heterocycle is selected from 1,4-diazepane; the substituents are selected from the group consisting of alkyl containing 1 to 4 carbon atoms, di-C1-C4 alkylamino groups, cycloalkyl groups containing 3 to 5 carbon atoms, and heterocyclic groups containing 3 to 5 carbon atoms and one nitrogen, such as methyl, ethyl, alkylamino, dimethylamino, diethylamino, cyclopropyl, or pyrrolidinyl.

5. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 4, wherein R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00150## wherein n=1 or 2, R.sub.13 is alkyl containing 1-4 carbons or cycloalkyl containing 3 to 5 carbons, and the alkyl containing 1-4 carbon is, such as methyl, or ethyl; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00151## wherein n=1 or 2, R.sub.14 and R.sub.15 are alkyl groups containing 1 to 4 carbons; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00152## wherein R.sub.16 is a diC1-C4 alkylamino group, such as dimethylamino, diethylamino, or a saturated five-membered heterocyclic ring containing one nitrogen, such as pyrrolidinyl. alternatively, R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00153## R.sub.16 is a diC1-C4 alkylamino, e.g., dimethylamino, diethylamino.

6. The compound as claimed in claim 1 having the structure shown in the general formula III or a pharmaceutically acceptable salt thereof: ##STR00154## .sup.1Aryl is the same as or different from .sup.2Aryl, .sup.1Aryl and .sup.2Aryl are each a benzene ring or aza aromatic ring, or a substituted benzene ring or aza aromatic ring, the aza aromatic ring is a heteroaromatic ring containing 1 to 2 nitrogen atoms, preferably pyridine rings and pyrimidine rings, the substitution is that 1 to 2 substituents are at any position on the ring, and the substituents are selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxy, phenoxy or substituted phenoxy, alkylthio, phenylthio, phenylthio or substituted phenylthio, haloalkyl, cyano and halogen; R.sub.1 is alkyl containing 1 to 4 carbons or H; R.sub.3 is cyano or trifluoromethyl; X is N or CH; R.sub.4 is substituted alkyl or substituted heterocycloalkyl, and when R.sub.4 is substituted alkyl, the substituent is selected from the group consisting of alkylamino, dialkylamino, and saturated or unsaturated heterocyclyl containing one nitrogen or two nitrogens; when R.sub.4 is a substituted heterocycloalkyl, the heterocycloalkyl contains at least one nitrogen atom, and the substituent is selected from the group consisting of alkyl, alkylamino and dialkylamino; R.sub.5 is hydrogen or an alkyl containing 1-4 carbons; or, R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two nitrogen atoms, the substituents are selected from the group consisting of alkyl containing 1 to 6 carbon atoms, alkylamino, di-C1-C4 alkylamino, cycloalkyl containing 3 to 5 carbon atoms or saturated heterocyclic groups containing one nitrogen, such as dimethylamino, diethylamino, cyclopropanyl or pyrrolidinyl.

7. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 6, wherein R.sub.4 is ##STR00155## wherein, n=1-3, R.sub.7 and R.sub.8 are H or alkyl or substituted alkyl, or R.sub.7 and R.sub.8 together with the nitrogen atom to which they are bonded form a cyclic group or substituted cyclic group, the substituent is selected from the group consisting of alkyl, alkylamino, dialkylamino and heterocyclic group, such as pyrrolidinyl, the cyclic group is three-, four-, five-, six- or seven-membered saturated or unsaturated cyclic group containing 1 or 2 nitrogen atoms, for example, the three-membered cyclic group is selected from aziridinyl, and the four-membered cyclic group is selected from azetidinyl, the five-membered cyclic group is selected from the group consisting of pyrrolyl, pyrrolidinyl, imidazolyl and oxazolyl, and the six-membered cyclic group is selected from the group consisting of morpholinyl, piperazinyl, piperidinyl, pyridinyl, and pyrimidinyl, the seven-membered cyclic group is 1,4-diazepanyl; or R.sub.4 is ##STR00156## wherein R.sub.12 is alkyl containing 1-4 carbon atoms, such as methyl, ethyl; R.sub.11, the nitrogen to which Ru is bound, the carbon to which R.sub.10 is bound, the carbon to which R.sub.9 is bound, and R.sub.9 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, alkylamino, and dialkylamino, R.sub.10 is H; or R.sub.11, the nitrogen to which R.sub.11 is bound, the carbon to which R.sub.10 is bound, and R.sub.10 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, alkylamino, and di-C1-C4 alkylamino, for example, dimethylamino, diethylamino, R.sub.9 is H; or, R.sub.4 is a substituted alkyl, the substituent is selected from the group consisting of amino, alkylamino, dialkylamino, and four-, five-, or six-membered saturated heterocycles containing one or two nitrogens.

8. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 7, when R.sub.4 is ##STR00157## R.sub.4 is ##STR00158## n=2 or 3, R.sub.10 is H; or R.sub.4 is ##STR00159## n=2, 3 or 4, and R.sub.9 is H.

9. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 6, wherein R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two heteroatoms, the five-membered heterocycle is selected from the group consisting of pyrrolidinyl, pyrrolyl, imidazolyl, imidazolidinyl, and oxazolyl, the six-membered heterocycle is selected from the group consisting of morpholine, piperazine, and piperidine, and the seven-membered heterocycle is selected from 1,4-diazepane; the substituents are selected from the group consisting of alkyl containing 1 to 4 carbon atoms, di-C1-C4 alkylamino, cycloalkyl containing 3 to 5 carbon atoms, and heterocyclic groups containing 3 to 5 carbon atoms and one nitrogen, such as methyl, ethyl, alkylamino, dimethylamino, diethylamino, cyclopropyl, or pyrrolidinyl.

10. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 9, wherein R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00160## wherein n=1 or 2, R.sub.13 is alkyl containing 1-4 carbons or cycloalkyl containing 3 to 5 carbons, and the alkyl containing 1-4 carbon is, such as methyl, ethyl; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00161## wherein n=1 or 2, R.sub.14 and R.sub.15 are alkyl groups containing 1 to 4 carbons; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00162## wherein R.sub.16 is a diC1-C4 alkylamino group, such as dimethylamino, diethylamino, or a saturated five-membered heterocyclic ring containing one nitrogen, such as pyrrolidinyl; or, R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00163## R.sub.16 is a diC1-C4 alkylamino, e.g., dimethylamino, diethylamino.

11. The compound as claimed in claim 1 having the structure shown in the general formula IV or a pharmaceutically acceptable salt thereof: ##STR00164## R.sub.1 is alkyl containing 1 to 4 carbons or H; R.sub.3 is trifluoromethyl; X is N or CH; Z.sub.1, Z.sub.2, Z.sub.3 are the same or different, Z.sub.1, Z.sub.2, Z.sub.3 are each C(R.sub.6) or N, respectively, R.sub.6 is H, alkyl, cycloalkyl, alkyloxy, phenoxy or substituted phenoxy, alkylthio, phenylthio or substituted phenylthio, haloalkyl, cyano, halogen; R.sub.4 is substituted alkyl or substituted heterocycloalkyl, and when R.sub.4 is substituted alkyl, the substituent is selected from the group consisting of alkylamino, dialkylamino, and saturated or unsaturated heterocyclyl containing one nitrogen or two nitrogens; when R.sub.4 is a substituted heterocycloalkyl, the heterocycloalkyl contains at least one nitrogen atom, and the substituent is selected from the group consisting of alkyl, alkylamino and dialkylamino; R.sub.5 is hydrogen or an alkyl containing 1-4 carbons; or, R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two nitrogen atoms, the substituents are selected from the group consisting of alkyl containing 1 to 6 carbon atoms, alkylamino, di-C1-C4 alkylamino, cycloalkyl containing 3 to 5 carbon atoms and saturated heterocyclic groups containing one nitrogen, such as dimethylamino, diethylamino, cyclopropanyl or pyrrolidinyl.

12. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 11, wherein R.sub.4 is ##STR00165## wherein, n=1-3, R.sub.7 and R.sub.8 are H or alkyl or substituted alkyl, or R.sub.7 and R.sub.8 together with the nitrogen atom to which they are bonded form a cyclic group or substituted cyclic group, the substituent is selected from the group consisting of alkyl, alkylamino, dialkylamino and heterocyclic group, such as pyrrolidinyl, such as pyrrolidin-1-yl, the cyclic group is three-, four-, five-, six- or seven-membered saturated or unsaturated cyclic group containing 1 or 2 nitrogen atoms, for example, the three-membered cyclic group is selected from aziridinyl, and the four-membered cyclic group is selected from azetidinyl, the five-membered cyclic group is selected from the group consisting of pyrrolyl, pyrrolidinyl, imidazolyl and oxazolyl, and the six-membered cyclic group is selected from the group consisting of morpholinyl, piperazinyl, piperidinyl, pyridinyl, and pyrimidinyl, the seven-membered cyclic group is 1,4-diazepanyl; or R.sub.4 is ##STR00166## wherein R.sub.12 is alkyl containing 1-4 carbon atoms, such as methyl, ethyl; R.sub.11, the nitrogen to which Ru is bound, the carbon to which R.sub.10 is bound, the carbon to which R.sub.9 is bound, and R.sub.9 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, alkylamino, or dialkylamino, R.sub.10 is H; or R.sub.11 with the nitrogen to which it is bound, the carbon to which R.sub.10 is bound, and R.sub.10 together form a saturated five-, six-, or seven-membered heterocyclic ring or a saturated five-, six-, or seven-membered heterocyclic ring substituted by 1 or 2 substituents selected from the group consisting of alkyl containing 1 to 4 carbon atoms, alkylamino, and di-C1-C4 alkylamino, for example, dimethylamino, diethylamino, R.sub.9 is H; or, R.sub.4 is a substituted alkyl, the substituent is selected from the group consisting of amino, alkylamino, dialkylamino, and four-, five-, or six-membered saturated heterocycles containing one or two nitrogens.

13. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 12, when R.sub.4 is ##STR00167## R.sub.4 is ##STR00168## n=2 or 3, R.sub.10 is H; or R.sub.4 is ##STR00169## n=2, 3 or 4, and R.sub.9 is H.

14. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 12, wherein R.sub.5, R.sub.4 and the nitrogen atom to which they are bonded together form a saturated heterocycle or a saturated heterocycle substituted by a substituent, and the heterocycle is a five-, six- or seven-membered heterocycle containing one or two heteroatoms, the five-membered heterocycle is selected from the group consisting of pyrrolidinyl, pyrrolyl, imidazolyl, imidazolidinyl, and oxazolyl, the six-membered heterocycle is selected from the group consisting of morpholine, piperazine, and piperidine, and the seven-membered heterocycle is selected from 1,4-diazepane; the substituents are selected from the group consisting of alkyl containing 1 to 4 carbon atoms, di-C1-C4 alkylamino, cycloalkyl containing 3 to 5 carbon atoms, and heterocyclic groups containing 3 to 5 carbon atoms and one nitrogen, such as methyl, ethyl, methylamino, ethylamino, dimethylamino, diethylamino, cyclopropyl, or pyrrolidinyl.

15. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 14, wherein R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00170## wherein n=1 or 2, R.sub.13 is alkyl containing 1-4 carbons or cycloalkyl containing 3 to 5 carbons, and the alkyl containing 1-4 carbon is, such as methyl, ethyl; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00171## wherein n=1 or 2, R.sub.14 and R.sub.15 are alkyl groups containing 1 to 4 carbons; or R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00172## wherein R.sub.16 is a diC1-C4 alkylamino group, such as dimethylamino, diethylamino, or a saturated five-membered heterocyclic ring containing one nitrogen, such as pyrrolidinyl; or, R.sub.5, R.sub.4 together with the nitrogen atom to which they are bonded form ##STR00173## R.sub.16 is a diC1-C4 alkylamino, e.g., dimethylamino, diethylamino.

16. The compound or the pharmaceutically acceptable salt thereof as claimed in claim 1, which is: 1-(3-((4-(1-(4-bromophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(4-chlorobenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(1-(3-chloro-4-fluorophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(4-chloro-3-methylbenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(1-(4-methoxyphenyl)butyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3,4-dichlorobenzyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine 1-(3-((4-(4-chlorobenzyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(1-(4-bromophenyl)propyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(1-(4-chlorophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1,N.sup.1, N.sup.2-trimethyl-N.sup.2-(3-((4-(4-methylbenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)ethan-1,2-diamine 2-((4-(4-chloro-3-methylbenzyl)piperazin-1-yl)methyl)-4-(4-ethylpiperazin-1-yl)benzonitrile 2-((4-(4-chlorobenzyl)piperazin-1-yl)methyl)-4-(4-cyclopropylpiperazin-1-yl)benzonitrile 2-((4-(1-(4-chlorophenyl)ethyl)piperazin-1-yl)methyl)-4-((2-(ethyl(methyl)amino)ethyl)(methyl)amino)benzonitrile 4-(3-(dimethylamino)piperidin-1-yl)-2-((4-(1-phenylethyl)piperazin-1-yl)methyl)benzonitrile 4-((2-(dimethylamino)ethyl)(methyl)amino)-2-((4-(1-(4-(trifluoromethyl)phenyl)ethyl)piperazin-1-yl)methyl)benzonitrile 2-((4-(1-(4-chlorophenyl)-2-methylpropyl)piperazin-1-yl)methyl)-4-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)benzonitrile 2-((4-(3-chloro-4-fluorobenzyl)piperazin-1-yl)methyl)-4-((2-(diethylamino)ethyl)(methyl)amino)benzonitrile 4-((3-(1H-pyrrol-1-yl)propyl)amino)-2-((4-(3,4-dichlorobenzyl)piperazin-1-yl)methyl)benzonitrile N.sup.1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(4-bromophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1, N.sup.2,N.sup.2-trimethylethan-1,2-diamine 3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpiperidin-2-yl)methyl)-4-(trifluoromethyl)aniline 1-(3-((4-(4-chlorophenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 3-((4-(4-bromophenyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpyrrolidin-2-yl)methyl)-4-(trifluoromethyl)aniline 3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-N-((1-ethylpyrrolidin-2-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline N.sup.1-(3-((4-(4-bromo-3-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N, N-dimethylpiperidin-4-amine 1-(4-chlorophenyl)-4-(5-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2-(trifluoromethyl)benzyl)piperazine 1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N, N-dimethylpyrrolidin-3-amine 1-(4-chlorophenyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine 3-((4-(4-chlorophenyl)-2-methylpiperazin-1-yl)methyl)-N-methyl-N-(piperidin-1-ylmethyl)-4-(trifluoromethyl)aniline 1-(3-((4-(4-chloro-3-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(4-bromo-3-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 1-methyl-4-(3-((2-propyl-4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-1,4-diazepane 1-(3-((4-(3-chloro-4-methylphenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-ethyl-1,4-diazepane 1-(3-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(3-chloro-4-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(4-bromo-3-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 3-((4-(4-chlorophenyl)piperidin-1-yl)methyl)-N-methyl-N-(2-(pyrrolidin-1)ethyl)-4-(trifluoromethyl)aniline 1-(3-((4-(4-chloro-3-methylphenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(4-chloro-3-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(3,4-dichlorophenyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 1-(3-((4-(4-chloro-3-methylphenyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-methylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-bromophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-isopropylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(bis(4-cyclopropylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N-(2-(azetidin-1-yl)ethyl)-3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline 1-(3-((4-((4-fluorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(bis(4-(trifluoromethyl)phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 1-(bis(4-chlorophenyl)methyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine 1-(3-((4-((4-chlorophenyl)(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-methyl-4-(3-((4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-1,4-diazepane N.sup.1-(3-((4-(bis(4-methoxyphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.2,N.sup.2-dimethyl-N.sup.1-propylethan-1,2-diamine 1-(3-((4-(bis(4-fluorophenyl)methyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 1-(3-((4-(bis(4-chlorophenyl)methyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane 3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpyrrolidin-2-yl)methyl)-4-(trifluoromethyl)aniline 3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-N-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)aniline N-(2-(aziridin-1-yl)ethyl)-3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline 1-(3-((4-(di(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-ethyl-1,4-diazepane N.sup.1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpiperidin-3-amine 1-(bis(4-bromophenyl)methyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine 1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpiperidin-4-amine N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2-dimethyl-N.sup.2-propylethan-1,2-diamine N.sup.1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.2-(2-(dimethylamino)ethyl)-N.sup.1,N.sup.2-dimethylethan-1,2-diamine N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(bis(4-bromophenyl)methyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2, N.sup.2-trimethylethan-1,2-diamine 2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-methoxyphenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 2-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 4-((2-(1H-imidazol-1-yl)ethyl)(methyl)amino)-2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)benzonitrile 2-((4-(di(pyridin-4-yl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methylpiperazin-1-yl)benzonitrile 2-((4-(bis(4-isopropylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-tert-butylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-bromophenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-cyclopropylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(3-(dimethylamino)pyrrolidin-1-yl)benzonitrile 2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)benzonitrile 4-((2-(aziridin-1-yl)ethyl)(methyl)amino)-2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)benzonitrile 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 2-((4-((4-chlorophenyl)(pyridin-4-yl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 2-((4-(bis(4-chlorophenyl)methyl)piperidin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile 2-((4-(bis(4-fluorophenyl)methyl)piperidin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile N-{3-[4-(4-chlorophenyl)piperazin-1-yl]methyl)-4-(trifluoromethyl)phenyl}-N,1-dimethylpyrrolidin-3-amine 4-[{2-[ethyl(methyl)amino]ethyl}(methyl)amino)-2-({4-[1-(pyrazin-2-yl)ethyl]piperazin-1-yl}methyl)benzonitrile N1-(3-[{4-[bis(3,4-dichlorophenyl)methyl]piperazin-1-yl}methyl]-4-(trifluoromethyl)phenyl)-N2,N2-diethyl-N1-methylethan-1,2-diamine 2-({4-[bis(4-chloro-3-methylphenyl)methyl]piperazin-1-yl}methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile 1-[3-({4-[cyclohexyl(3,4-dichlorophenyl)methyl]piperazin-1-yl}methyl)-4-(trifluoromethyl)phenyl]-4-methyl-1,4-diazepane 2-({4-[(4-chlorophenyl)(cyclobutyl)methyl]piperazin-1-yl}methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile 2-[(4-chlorophenyl){4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl]piperazin-1-yl}methyl]pyrazine 4-(4-methylpiperazin-1-yl)-2-[(4-{(pyrazin-2-yl)[(4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methyl]benzonitrile 1-methyl-4-[3-({4-[(4-phenoxyphenyl)(pyridin-2-yl)methyl]piperazin-1-yl}methyl)-4-(trifluoromethyl)phenyl]-1,4-diazepane N-{3-([4-{bis[4-(phenylthio)phenyl]methyl}piperazin-1-yl]methyl)-4-(trifluoromethyl)phenyl}-1-ethyl-N-methylpyrrolidin-3-amine 2-({4-(bis(4-(methylthio)phenyl]methyl}piperazin-1-yl)methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile 3-([4-{bis[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl]methyl)-N-methyl-N-[2-(pyrrolidin-1-yl)ethyl]-4-(trifluoromethyl)aniline 2-({4-[(4-cyanophenyl)(cyclopentyl)methyl]piperazin-1-yl}methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile 4-{1-(4-[5-{[2-(dimethylamino)ethyl](methyl)amino}-2-(trifluoromethyl)benzyl]piperazin-1-yl)ethyl}benzonitrile 4-([3-(1H-imidazol-1-yl)propyl]amino)-2-({4-[bis(4-chlorophenyl)methyl]piperazin-1-yl}methyl)benzonitrile N.sup.1-(3-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine N.sup.1-(3-((4-(3-methyl-4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine, or 1-(3-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane.

17. (canceled)

18. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds as claimed in claim 1 or a pharmaceutically acceptable salt thereof, and comprising one or more pharmaceutically acceptable excipients.

19. The pharmaceutical composition as claimed in claim 18, wherein the pharmaceutically acceptable salt refers to the product from salt forming reaction with an acid, including inorganic acid salts such as hydrochloride, hydrobromide or sulfate and the like; organic acid salts such as acetate, lactate, succinate, fumarate, maleate, citrate, benzoate, methanesulfonate, or 4-methylbenzoate salt.

20. A method for treating viral infections, which comprises administering to the patient a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof as claimed in claim 1, wherein the virus is a DNA virus and/or a RNA virus, or a hepatitis virus.

21. The method as claimed in claim 20, wherein the DNA viruses are herpes viruses, hepatotropic viruses, adenoviruses, or papilloma viruses; and the RNA viruses are mumps viruses, influenza viruses, coronaviruses, retroviruses, enterovirus or flaviviruses, or, the viruses are hepatitis C viruses.

Description

DETAILED DESCRIPTION

[0201] The present invention will be described in further detail by reference to the following specific examples, but the present invention is not limited to the following specific examples.

Example 1: Synthesis of 1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl) methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane (44)

[0202] 305 μL 5-fluoro-2-(trifluoromethyl)benzyl bromide was dissolved in 6 mL acetone, added 617 mg 1-(bis(4-fluorophenyl)methyl)piperazine and 805 mg anhydrous potassium carbonate under stirring, and reacted at room temperature for 2.5 hours. After the reaction was completed, the reaction system was filtered by suction, the solvent of the filtrate was removed by rotary distillation, and 6 mL ethyl acetate and 3 mL distilled water were added for extraction, the organic phase was washed with saturated sodium chloride solution, then anhydrous magnesium sulfate was added for drying, and then filtered, concentrated, purified by column chromatography (petroleum ether:ethyl acetate=10:1) to obtain intermediate1-(bis(4-fluorophenyl)methyl)-4-(5-fluoro-2-(trifluoromethyl)benzyl)piperazine (80% yield). 232 mg of 1-(bis(4-fluorophenyl)methyl)-4-(5-fluoro-2-(trifluoro-methyl)benzyl)piperazine was dispersed in 4 mL of anhydrous DMSO, the mixture was placed in a 15 mL pressure-resistant tube, and 187 μL N-methylhomopiperazine and 207 mg anhydrous potassium carbonate were added, the reaction was conducted at 120° C. for 96 hours under airtight conditions, and the raw materials monitored by TLC had completely disappeared. The reaction system was filtered, the filtrate was extracted with ethyl acetate and water, and the organic layer was washed with water and saturated sodium chloride solution, added anhydrous magnesium sulfate to dry and then filtered, purified by column chromatography (dichloromethane:methanol=10:1) to obtain product 1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl) phenyl)-4-methyl-1,4-diazepane (58% yield), mass spectrum (ESI.sup.+): m/z=559.3 (M+H).sup.+.

[0203] The following compounds were obtained by the methods similar to that in Example 1: [0204] (1)1-(3-((4-(1-(4-bromophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0205] mass spectrum (ESI.sup.+): m/z=539.2 (M+H).sup.+ [0206] (2)1-(3-((4-(4-chlorobenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0207] mass spectrum (ESI.sup.+): m/z=481.2 (M+H).sup.+ [0208] (3)1-(3-((4-(1-(3-chloro-4-fluorophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0209] mass spectrum (ESI.sup.+): m/z=513.2 (M+H).sup.+ [0210] (4)1-(3-((4-(4-chloro-3-methylbenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0211] mass spectrum (ESI.sup.+): m/z=495.2 (M+H).sup.+ [0212] (5)1-(3-((4-(1-(4-methoxyphenyl)butyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0213] mass spectrum (ESI.sup.+): m/z=519.3 (M+H).sup.+ [0214] (6)1-(3,4-dichlorobenzyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine [0215] mass spectrum (ESI.sup.+): m/z=501.2 (M+H).sup.+ [0216] (7)1-(3-((4-(4-chlorobenzyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0217] mass spectrum (ESI.sup.+): m/z=480.2 (M+H).sup.+ [0218] (8)N.sup.1-(3-((4-(1-(4-bromophenyl)propyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0219] mass spectrum (ESI.sup.+): m/z=541.2 (M+H).sup.+ [0220] (9)N.sup.1-(3-((4-(1-(4-chlorophenyl)ethyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0221] mass spectrum (ESI.sup.+): m/z=483.2 (M+H).sup.+ [0222] (10)N.sup.1,N.sup.1,N.sup.2-trimethyl-N.sup.2-(3-((4-(4-methylbenzyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)ethan-1,2-diamine [0223] mass spectrum (ESI.sup.+): m/z=449.3 (M+H).sup.+ [0224] (19)N.sup.1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0225] mass spectrum (ESI.sup.+): m/z=455.2 (M+H).sup.+ [0226] (20)N.sup.1-(3-((4-(4-bromophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0227] mass spectrum (ESI.sup.+): m/z=499.2 (M+H).sup.+ [0228] (21)3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpiperidin-2-yl)methyl)-4-(trifluoromethyl)aniline [0229] mass spectrum (ESI.sup.+): m/z=495.2 (M+H).sup.+ [0230] (22)1-(3-((4-(4-chlorophenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0231] mass spectrum (ESI.sup.+): m/z=481.2 (M+H).sup.+ [0232] (23)1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0233] mass spectrum (ESI.sup.+): m/z=467.2 (M+H).sup.+ [0234] (24)3-((4-(4-bromophenyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpyrrolidin-2-yl)methyl)-4-(trifluoromethyl)aniline [0235] mass spectrum (ESI.sup.+): m/z=525.2 (M+H).sup.+ [0236] (25)3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-N-((1-ethylpyrrolidin-2-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline [0237] mass spectrum (ESI.sup.+): m/z=495.2 (M+H).sup.+ [0238] (26)N.sup.1-(3-((4-(4-bromo-3-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0239] mass spectrum (ESI.sup.+): m/z=533.1 (M+H).sup.+ [0240] (27)1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpiperidin-4-amine [0241] mass spectrum (ESI.sup.+): m/z=481.2 (M+H).sup.+ [0242] (28)1-(4-chlorophenyl)-4-(5-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2-(trifluoromethyl)benzyl)piperazine [0243] mass spectrum (ESI.sup.+): m/z=507.2 (M+H).sup.+ [0244] (29)1-(3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpyrrolidin-3-amine [0245] mass spectrum (ESI.sup.+): m/z=467.2 (M+H).sup.+ [0246] (30)1-(4-chlorophenyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine [0247] mass spectrum (ESI.sup.+): m/z=453.2 (M+H).sup.+ [0248] (31)3-((4-(4-chlorophenyl)-2-methylpiperazin-1-yl)methyl)-N-methyl-N-(piperidin-1-ylmethyl)-4-(trifluoromethyl)aniline [0249] mass spectrum (ESI.sup.+): m/z=495.2 (M+H).sup.+ [0250] (32)1-(3-((4-(4-chloro-3-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0251] mass spectrum (ESI.sup.+): m/z=549.2 (M+H).sup.+ [0252] (33)N.sup.1-(3-((4-(4-bromo-3-(trifluoromethyl)phenyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0253] mass spectrum (ESI.sup.+): m/z=581.2 (M+H).sup.+ [0254] (34)1-methyl-4-(3-((2-propyl-4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-1,4-diazepane [0255] mass spectrum (ESI.sup.+): m/z=543.3. (M+H).sup.+ [0256] (35)1-(3-((4-(3-chloro-4-methylphenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-ethyl-1,4-diazepane [0257] mass spectrum (ESI.sup.+): m/z=495.2 (M+H).sup.+ [0258] (36)1-(3-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0259] mass spectrum (ESI.sup.+): m/z=451.2 (M+H).sup.+ [0260] (37)1-(3-((4-(3-chloro-4-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0261] mass spectrum (ESI.sup.+): m/z=485.2 (M+H).sup.+ [0262] (38)N.sup.1-(3-((4-(4-bromo-3-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0263] mass spectrum (ESI.sup.+): m/z=533.1 (M+H).sup.+ [0264] (39)3-((4-(4-chlorophenyl) piperidin-1-yl)methyl)-N-methyl-N-(2-pyrrolidin-1-yl) ethyl-4-(trifluoromethyl)aniline [0265] mass spectrum (ESI.sup.+): m/z=480.2 (M+H).sup.+ [0266] (40)1-(3-((4-(4-chloro-3-methylphenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0267] mass spectrum (ESI.sup.+): m/z=481.2 (M+H).sup.+ [0268] (41)N.sup.1-(3-((4-(4-chloro-3-fluorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0269] mass spectrum (ESI.sup.+): m/z=473.2 (M+H).sup.+ [0270] (42)N.sup.1-(3-((4-(3,4-dichlorophenyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0271] mass spectrum (ESI.sup.+): m/z=488.2 (M+H).sup.+ [0272] (43)1-(3-((4-(4-chloro-3-methylphenyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0273] mass spectrum (ESI.sup.+): m/z=480.2 (M+H).sup.+ [0274] (45)1-(3-((4-(bis(4-methylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0275] mass spectrum (ESI.sup.+): m/z=551.3 (M+H).sup.+ [0276] (46)1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0277] mass spectrum (ESI.sup.+): m/z=591.2 (M+H).sup.+ [0278] (47)1-(3-((4-(bis(4-bromophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0279] mass spectrum (ESI.sup.+): m/z=679.1 (M+H).sup.+ [0280] (48)1-(3-((4-(bis(4-isopropylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0281] mass spectrum (ESI.sup.+): m/z=607.4 (M+H).sup.+ [0282] (49)N.sup.1-(3-((4-(bis(4-cyclopropylphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0283] mass spectrum (ESI.sup.+): m/z=591.4 (M+H).sup.+ [0284] (50)N.sup.1-(2-(azetidin-1-yl)ethyl)-3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline [0285] mass spectrum (ESI.sup.+): m/z=591.2 (M+H).sup.+ [0286] (51)1-(3-((4-((4-fluorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0287] mass spectrum (ESI.sup.+): m/z=541.3 (M+H).sup.+ [0288] (52)N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0289] mass spectrum (ESI.sup.+): m/z=579.2 (M+H).sup.+ [0290] (53)N.sup.1-(3-((4-(bis(4-(trifluoromethyl)phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0291] mass spectrum (ESI.sup.+): m/z=647.3 (M+H).sup.+ [0292] (54)N.sup.1-(3-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0293] mass spectrum (ESI.sup.+): m/z=545.3 (M+H).sup.+ [0294] (55)1-(bis(4-chlorophenyl)methyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine [0295] mass spectrum (ESI.sup.+): m/z=577.2 (M+H).sup.+ [0296] (56)1-(3-((4-((4-chlorophenyl)(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0297] mass spectrum (ESI.sup.+): m/z=558.3 (M+H).sup.+ [0298] (57)1-methyl-4-(3-((4-(phenyl(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-1,4-diazepane [0299] mass spectrum (ESI.sup.+): m/z=524.3 (M+H).sup.+ [0300] (58)N.sup.1-(3-((4-(bis(4-methoxyphenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0301] mass spectrum (ESI.sup.+): m/z=571.3 (M+H).sup.+ [0302] (59)N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.2,N.sup.2-dimethyl-N.sup.1-propylethan-1,2-diamine [0303] mass spectrum (ESI.sup.+): m/z=607.2 (M+H).sup.+ [0304] (60)1-(3-((4-(bis(4-fluorophenyl)methyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0305] mass spectrum (ESI.sup.+): m/z=573.3 (M+H).sup.+ [0306] (61)1-(3-((4-(bis(4-chlorophenyl)methyl)-2-methylpiperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0307] mass spectrum (ESI.sup.+): m/z=605.2 (M+H).sup.+ [0308] (62)3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-N-((1-methylpyrrolidin-2-yl)methyl)-4-(trifluoromethyl)aniline [0309] mass spectrum (ESI.sup.+): m/z=605.2 (M+H).sup.+ [0310] (63)3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-N-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)aniline [0311] mass spectrum (ESI.sup.+): m/z=605.2 (M+H).sup.+ [0312] (64)N-(2-(aziridin-1-yl)ethyl)-3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-N-methyl-4-(trifluoromethyl)aniline [0313] mass spectrum (ESI.sup.+): m/z=577.2 (M+H).sup.+ [0314] (65)1-(3-((4-(di(pyridin-2-yl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-ethyl-1,4-diazepane [0315] mass spectrum (ESI.sup.+): m/z=539.3 (M+H).sup.+ [0316] (66)N.sup.1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0317] mass spectrum (ESI.sup.+): m/z=547.3 (M+H).sup.+ [0318] (67)1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpiperidin-3-amine [0319] mass spectrum (ESI.sup.+): m/z=605.2 (M+H).sup.+ [0320] (68)1-(bis(4-bromophenyl)methyl)-4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl)piperazine [0321] mass spectrum (ESI.sup.+): m/z=665.1 (M+H).sup.+ [0322] (69)1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N,N-dimethylpiperidin-4-amine [0323] mass spectrum (ESI.sup.+): m/z=573.3 (M+H).sup.+ [0324] (70)N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2-dimethyl-N.sup.2-propylethan-1,2-diamine [0325] mass spectrum (ESI.sup.+): m/z=607.2 (M+H).sup.+ [0326] (71)N.sup.1-(3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.2-(2-(dimethylamino)ethyl)-N.sup.1,N.sup.2-dimethylethan-1,2-diamine [0327] mass spectrum (ESI.sup.+): m/z=604.3 (M+H).sup.+ [0328] (72)N.sup.1-(3-((4-(bis(4-chlorophenyl)methyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0329] mass spectrum (ESI.sup.+): m/z=578.2 (M+H).sup.+ [0330] (73)N.sup.1-(3-((4-(bis(4-bromophenyl)methyl)piperidin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0331] mass spectrum (ESI.sup.+): m/z=666.1 (M+H).sup.+ [0332] (92)N-{3-[4-(4-chlorophenyl)piperazin-1-yl]methyl)-4-(trifluoromethyl)phenyl}-N,1-dimethylpyrrolidin-3-amine [0333] mass spectrum (ESI.sup.+): m/z=467.2 (M+H).sup.+ [0334] (94)N1-(3-[{4-[bis(3,4-dichlorophenyl)methyl]piperazin-1-yl}methyl]-4-(trifluoromethyl)phenyl)-N2,N2-diethyl-N1-methylethan-1,2-diamine [0335] mass spectrum (ESI.sup.+): m/z=675.2 (M+H).sup.+ [0336] (96)1-[3-({4-[cyclohexyl(3,4-dichlorophenyl)methyl]piperazin-1-yl}methyl)-4-(trifluoromethyl)phenyl]-4-methyl-1,4-diazepane [0337] mass spectrum (ESI.sup.+): m/z=597.3 (M+H).sup.+ [0338] (98)2-[(4-chlorophenyl){4-(5-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)benzyl]piperazin-1-yl}methyl]pyrazine [0339] mass spectrum (ESI.sup.+): m/z=545.2 (M+H).sup.+ [0340] (100)1-methyl-4-[3-({4-[(4-phenoxyphenyl)(pyridin-2-yl)methyl]piperazin-1-yl}methyl)-4-(trifluoromethyl)phenyl]-1,4-diazepane [0341] mass spectrum (ESI.sup.+): m/z=616.3 (M+H).sup.+ [0342] (101)N-{3-([4-{bis[4-(phenylthio)phenyl]methyl}piperazin-1-yl]methyl)-4-(trifluoromethyl)phenyl}-1-ethyl-N-methylpyrrolidin-3-amine [0343] mass spectrum (ESI.sup.+): m/z=753.3 (M+H).sup.+ [0344] (103)3-([4-{bis[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl]methyl)-N-methyl-N-[2-(pyrrolidin-1-yl)ethyl]-4-(trifluoromethyl)aniline [0345] mass spectrum (ESI.sup.+): m/z=673.3 (M+H).sup.+ [0346] (105)4-{1-(4-[5-{[2-(dimethylamino)ethyl](methyl)amino}-2-(trifluoromethyl)benzyl]piperazin-1-yl)ethyl}benzonitrile [0347] mass spectrum (ESI.sup.+): m/z=474.3 (M+H).sup.+ [0348] (107)N.sup.1-(3-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0349] mass spectrum (ESI.sup.+): m/z=489.2 (M+H).sup.+ [0350] (108)N.sup.1-(3-((4-(3-methyl-4-chlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [0351] mass spectrum (ESI.sup.+): m/z=469.2 (M+H).sup.+ [0352] (109)1-(3-((4-(3,4-dichlorophenyl)piperazin-1-yl)methyl)-4-(trifluoromethyl)phenyl)-4-methyl-1,4-diazepane [0353] mass spectrum (ESI.sup.+): m/z=501.1 (M+H).sup.+

Example 2: Synthesis of 4-((3-(1H-pyrrol-1-yl)propyl)amino)-2-((4-(3,4-dichlorobenzyl)piperazin-1-yl)methyl)benzonitrile (18)

[0354] 642 mg 5-fluoro-2-cyanobenzyl bromide (3.0 mmol) was dissolved in 10 mL acetone, added 808 mg 1-(3,4-dichlorobenzyl)piperazine (3.3 mmol) and 1242 mg anhydrous potassium carbonate (9.0 mmol) under stirring, and reacted at room temperature for 3 hours. After the reaction was completed, the reaction system was filtered by suction, the solvent of the filtrate was removed by rotary distillation, after 6 mL ethyl acetate was added to dissolve, 3 mL distilled water was added and stirred fully before standing and stratifying, the organic phase was washed again with saturated sodium chloride solution, an appropriate amount of anhydrous magnesium sulfate was added for drying, and then filtered, purified by column chromatography (petroleum ether:ethyl acetate=10:1) to obtain intermediate 2-((4-(3,4-dichlorobenzyl)piperazin-1-yl)methyl)-4-fluoro-benzonitrile (75% yield). 378 mg of 2-((4-(3,4-dichlorobenzyl) piperazin-1-yl) methyl)-4-fluoro-benzonitrile was dissolved ultrasonically in 3.0 mL anhydrous DMSO, the mixture was placed in a 15 mL pressure-resistant tube, 354 μL 3-(1H-pyrrol-1-yl)propan-1-amine (3.0 mmol) and 414 mg anhydrous potassium carbonate (3.0 mmol) were added under stirring, the reaction was conducted at 120° C. for 8 hours under airtight conditions, and the raw materials monitored by TLC had completely disappeared. The reaction system was filtered, the filtrate was dried to remove the solvent, and the remaining was dissolved by adding 6 mL ethyl acetate, then washed with water and saturated sodium chloride solution successively, added anhydrous magnesium sulfate to dry and then filtered, purified by column chromatography (dichloromethane:methanol=8:1) to obtain product 4-((3-(1H-pyrrol-1-yl)propyl)amino)-2-((4-(3,4-dichlorobenzyl)piperazin-1-yl)methyl)benzonitrile (47% yield), mass spectrum (ESI.sup.+): m/z=482.2 (M+H).sup.+.

[0355] The following compounds were obtained by the methods similar to that in Example 2: [0356] (11)2-((4-(4-chloro-3-methylbenzyl)piperazin-1-yl)methyl)-4-(4-ethylpiperazin-1-yl)benzonitrile [0357] mass spectrum (ESI.sup.+): m/z=452.2 (M+H).sup.+ [0358] (12)2-((4-(4-chlorobenzyl)piperazin-1-yl)methyl)-4-(4-cyclopropylpiperazin-1-yl)benzonitrile [0359] mass spectrum (ESI.sup.+): m/z=450.2 (M+H).sup.+ [0360] (13)2-((4-(1-(4-chlorophenyl)ethyl)piperazin-1-yl)methyl)-4-((2-(ethyl(methyl)amino)ethyl)(methyl)amino)benzonitrile [0361] mass spectrum (ESI.sup.+): m/z=454.3 (M+H).sup.+ [0362] (14)4-(3-(dimethylamino)piperidin-1-yl)-2-((4-(1-phenylethyl)piperazin-1-yl)methyl)benzonitrile [0363] mass spectrum (ESI.sup.+): m/z=432.3 (M+H).sup.+ [0364] (15)4-((2-(dimethylamino)ethyl)(methyl)amino)-2-((4-(1-(4-(trifluoromethyl)phenyl)ethyl)piperazin-1-yl)methyl)benzonitrile [0365] mass spectrum (ESI.sup.+): m/z=474.3 (M+H).sup.+ [0366] (16)2-((4-(1-(4-chlorophenyl)-2-methylpropyl)piperazin-1-yl)methyl)-4-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)benzonitrile [0367] mass spectrum (ESI.sup.+): m/z=494.3 (M+H).sup.+ [0368] (17)2-((4-(3-chloro-4-fluorobenzyl)piperazin-1-yl)methyl)-4-((2-(diethylamino)ethyl)(methyl)amino)benzonitrile [0369] mass spectrum (ESI.sup.+): m/z=472.3 (M+H).sup.+ [0370] (74)2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0371] mass spectrum (ESI.sup.+): m/z=536.2 (M+H).sup.+ [0372] (75)2-((4-(bis(4-methoxyphenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0373] mass spectrum (ESI.sup.+): m/z=540.3 (M+H).sup.+ [0374] (76)2-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0375] mass spectrum (ESI.sup.+): m/z=516.3 (M+H).sup.+ [0376] (77)2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0377] mass spectrum (ESI.sup.+): m/z=548.2 (M+H).sup.+ [0378] (78)4-((2-(1H-imidazol-1-yl)ethyl)(methyl)amino)-2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)benzonitrile [0379] mass spectrum (ESI.sup.+): m/z=559.2 (M+H).sup.+ [0380] (79)2-((4-(di(pyridin-4-yl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0381] mass spectrum (ESI.sup.+): m/z=470.3 (M+H).sup.+ [0382] (80)2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(4-methylpiperazin-1-yl)benzonitrile [0383] mass spectrum (ESI.sup.+): m/z=534.2 (M+H).sup.+ [0384] (81)2-((4-(bis(4-isopropylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0385] mass spectrum (ESI.sup.+): m/z=552.4 (M+H).sup.+ [0386] (82)2-((4-(bis(4-tert-butylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0387] mass spectrum (ESI.sup.+): m/z=580.4 (M+H).sup.+ [0388] (83)2-((4-(bis(4-bromophenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0389] mass spectrum (ESI.sup.+): m/z=624.1 (M+H).sup.+ [0390] (84)2-((4-(bis(4-cyclopropylphenyl)methyl)piperazin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0391] mass spectrum (ESI.sup.+): m/z=548.4 (M+H).sup.+ [0392] (85)2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(3-(dimethylamino)pyrrolidin-1-yl)benzonitrile [0393] mass spectrum (ESI.sup.+): m/z=548.2 (M+H).sup.+ [0394] (86)2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)-4-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)benzonitrile [0395] mass spectrum (ESI.sup.+): m/z=562.2 (M+H).sup.+ [0396] (87)4-((2-(aziridin-1-yl)ethyl)(methyl)amino)-2-((4-(bis(4-chlorophenyl)methyl)piperazin-1-yl)methyl)benzonitrile [0397] mass spectrum (ESI.sup.+): m/z=534.2 (M+H).sup.+ [0398] (88)2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0399] mass spectrum (ESI.sup.+): m/z=514.3 (M+H).sup.+ [0400] (89)2-((4-((4-chlorophenyl)(pyridin-4-yl)methyl)piperazin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0401] mass spectrum (ESI.sup.+): m/z=515.3 (M+H).sup.+ [0402] (90)2-((4-(bis(4-chlorophenyl)methyl)piperidin-1-yl)methyl)-4-((2-(dimethylamino)ethyl)(methyl)amino)benzonitrile [0403] mass spectrum (ESI.sup.+): m/z=535.2 (M+H).sup.+ [0404] (91)2-((4-(bis(4-fluorophenyl)methyl)piperidin-1-yl)methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0405] mass spectrum (ESI.sup.+): m/z=515.3 (M+H).sup.+ [0406] (93)4-[{2-[ethyl(methyl)amino]ethyl}(methyl)amino)-2-({4-[1-(pyrazin-2-yl)ethyl]piperazin-1-yl}methyl)benzonitrile [0407] mass spectrum (ESI.sup.+): m/z=422.3 (M+H).sup.+ [0408] (95)2-({4-[bis(4-chloro-3-methylphenyl)methyl]piperazin-1-yl}methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile [0409] mass spectrum (ESI.sup.+): m/z=564.3 (M+H).sup.+ [0410] (97)2-({4-[(4-chlorophenyl)(cyclobutyl)methyl]piperazin-1-yl}methyl)-4-(4-methyl-1,4-diazepan-1-yl)benzonitrile [0411] mass spectrum (ESI.sup.+): m/z=492.3 (M+H).sup.+ [0412] (99)4-(4-methylpiperazin-1-yl)-2-[(4-{(pyrazin-2-yl)[(4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methyl]benzonitrile [0413] mass spectrum (ESI.sup.+): m/z=536.3 (M+H).sup.+ [0414] (102)2-({4-(bis(4-(methylthio)phenyl]methyl}piperazin-1-yl)methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile [0415] mass spectrum (ESI.sup.+): m/z=560.3 (M+H).sup.+ [0416] (104)2-({4-[(4-cyanophenyl)(cyclopentyl)methyl]piperazin-1-yl}methyl)-4-{[2-(dimethylamino)ethyl](methyl)amino}benzonitrile [0417] mass spectrum (ESI.sup.+): m/z=485.3 (M+H).sup.+ [0418] (106)4-([3-(1H-imidazol-1-yl)propyl]amino)-2-({4-[bis(4-chlorophenyl)methyl]piperazin-1-yl}methyl)benzonitrile [0419] mass spectrum (ESI.sup.+): m/z=559.2 (M+H).sup.+

Example 3: Assay of the Anti-HCV Activity of the Compounds of the Present Invention

[0420] 100 μL Huh7.5 cells were seeded at a density of 1×10.sup.5/mL in a 96-well cell culture plate and incubated in an incubator at 37° C., 5% CO.sub.2 and saturated humidity for 6 hrs. Then, while infecting Huh7.5 cells with viral solution containing HCV virus particles, the compounds of the present invention (including all specific compounds listed herein) were added at a concentration of 1 μM, respectively. After continuing incubation for 96 hrs, the total intracellular RNA was extracted separately, and the content of intracellular HCV RNA was measured by one-step quantitative RT-PCR, compared with the RNA level of the viral control, and the inhibition rate of the compounds against HCV was calculated. The results of some compounds are shown in Table 1.

[0421] The results of the anti-HCV activity assay of the compounds of the present invention and synthesized in cell culture are shown in Table 1

TABLE-US-00001 TABLE 1 Activity of compounds against HCV inhib- itory molec- Num- activi- ular ber chemical name structures ties* weight.sup.# 1 1-(3-((4-(1-(4- bromophenyl)ethyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00034] +++ 539 2 1-(3-((4-(4-chlorobenzyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00035] +++ 481 3 1-(3-((4-(1-(3-chloro-4- fluorophenyl)ethyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00036] +++ 513 4 1-(3-((4-(4-chloro-3- methylbenzyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00037] +++ 495 5 1-(3-((4-(1-(4- methoxyphenyl)butyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00038] +++ 519 6 1-(3,4-dichlorobenzyl)-4-(5-(4- methylpiperazin-1-yl)-2- (trifluoromethyl)benzyl)piperazine [00039] +++ 501 7 1-(3-((4-(4-chlorobenzyl)piperidin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00040] ++ 480 8 N.sup.1-(3-((4-(1-(4- bromophenyl)propyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00041] +++ 542 9 N.sup.1-(3-((4-(1-(4- chlorophenyl)ethyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00042] +++ 483 10 N.sup.1,N.sup.1,N.sup.2-trimethyl-N.sup.2-(3-((4-(4- methylbenzyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)ethan-1,2- diamine [00043] ++ 449 11 2-((4-(4-chloro-3- methylbenzyl)piperazin-1- yl)methyl)-4-(4-ethylpiperazin-1- yl)benzonitrile [00044] ++ 452 12 2-((4-(4-chlorobenzyl)piperazin-1- yl)methyl)-4-(4- cyclopropylpiperazin-1- yl)benzonitrile [00045] ++ 450 13 2-((4-(1-(4- chlorophenyl)ethyl)piperazin-1- yl)methyl)-4-((2- (ethyl(methyl)amino)ethyl)(methyl) amino)benzonitrile [00046] +++ 454 14 4-(3-(dimethylamino)piperidin-1- yl)-2-((4-(1-phenylethyl)piperazin- 1-yl)methyl)benzonitrile [00047] ++ 432 15 4-((2- (dimethylamino)ethyl)(methyl) amino)-2-((4-(1-(4-(trifluoro- methyl)phenyl)ethyl)piperazin- 1-yl)methyl)benzonitrile [00048] +++ 474 16 2-((4-(1-(4-chlorophenyl)-2- methylpropyl)piperazin-1- yl)methyl)-4-(methyl(2-(pyrrolidin- 1-yl)ethyl)amino)benzonitrile [00049] +++ 494 17 2-((4-(3-chloro-4- fluorobenzyl)piperazin-1- yl)methyl)-4-((2- (diethylamino)ethyl)(methyl)amino) benzonitrile [00050] +++ 472 18 4-((3-(1H-pyrrol-1- yl)propyl)amino)-2-((4-(3,4- dichlorobenzyl)piperazin-1- yl)methyl)benzonitrile [00051] +++ 482 19 N.sup.1-(3-((4-(4- chlorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00052] +++ 455 20 N.sup.1-(3-((4-(4- bromophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00053] +++ 499 21 3-((4-(4-chlorophenyl)piperazin-1- yl)methyl)-N-methyl-N-((1- methylpiperidin-2-yl)methyl)-4- (trifluoromethyl)aniline [00054] +++ 495 22 1-(3-((4-(4-chlorophenyl)-2- methylpiperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00055] +++ 481 23 1-(3-((4-(4-chlorophenyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00056] +++ 467 24 3-((4-(4-bromophenyl)piperazin-1- yl)methyl)-N-methyl-N-((1- methylpyrrolidin-2-yl)methyl)-4- (trifluoromethyl)aniline [00057] +++ 525 25 3-((4-(4-chlorophenyl)piperazin-1- yl)methyl)-N-((1-ethylpyrrolidin-2- yl)methyl)-N-methyl-4- (trifluoromethyl)aniline [00058] +++ 495 26 N.sup.1-(3-((4-(4-bromo-3- chlorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00059] +++ 534 27 1-(3-((4-(4-chlorophenyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-N,N- dimethylpiperidin-4-amine [00060] +++ 481 28 1-(4-chlorophenyl)-4-(5-(4- (pyrrolidin-1-yl)piperidin-1-yl)-2- (trifluoromethyl)benzyl)piperazine [00061] +++ 507 29 1-(3-((4-(4-chlorophenyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-N,N- dimethylpyrrolidin-3-amine [00062] +++ 467 30 1-(4-chlorophenyl)-4-(5-(4- methylpiperazin-1-yl)-2- (trifluoromethyl)benzyl)piperazine [00063] +++ 453 31 3-((4-(4-chlorophenyl)-2- methylpiperazin-1-yl)methyl)-N- methyl-N-(piperidin-1-ylmethyl)-4- (trifluoromethyl)aniline [00064] +++ 495 32 1-(3-((4-(4-chloro-3- (trifluoromethyl)phenyl)-2- methylpiperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00065] +++ 549 33 N.sup.1-(3-((4-(4-bromo-3- (trifluoromethyl)phenyl)-2- methylpiperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00066] +++ 581 34 1-methyl-4-(3-((2-propyl-4-(4- (trifluoromethyl)phenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-1,4- diazepane [00067] +++ 543 35 1-(3-((4-(3-chloro-4- methylphenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-ethyl- 1,4-diazepane [00068] +++ 495 36 1-(3-((4-(4-fluorophenyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00069] +++ 451 37 1-(3-((4-(3-chloro-4- fluorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00070] +++ 485 38 N.sup.1-(3-((4-(4-bromo-3- chlorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00071] +++ 534 39 3-((4-(4-chlorophenyl)piperidin-1- yl)methyl)-N-methyl-N-(2- (pyrrolidin-1)ethyl)-4- (trifluoromethyl)aniline [00072] +++ 480 40 1-(3-((4-(4-chloro-3- methylphenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00073] +++ 481 41 N.sup.1-(3-((4-(4-chloro-3- fluorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00074] +++ 473 42 N.sup.1-(3-((4-(3,4- dichlorophenyl)piperidin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00075] +++ 488 43 1-(3-((4-(4-chloro-3- methylphenyl)piperidin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00076] +++ 480 44 1-(3-((4-(bis(4- fluorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- 4-methyl-1,4-diazepane [00077] +++ 559 45 1-(3-((4-(bis(4- methylphenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- 4-methyl-1,4-diazepane [00078] +++ 551 46 1-(3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- 4-methyl-1,4-diazepane [00079] +++ 592 47 1-(3-((4-(bis(4- bromophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- 4-methyl-1,4-diazepane [00080] +++ 680 48 1-(3-((4-(bis(4- isopropylphenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- 4-methyl-1,4-diazepane [00081] +++ 607 49 N.sup.1-(3-((4-(bis(4- cyclopropylphenyl)methyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00082] +++ 591 50 N-(2-(azetidin-1-yl)ethyl)-3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-N-methyl-4- (trifluoromethyl)aniline [00083] ++ 592 51 1-(3-((4-((4-fluoro- phenyl)(phenyl)methyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl-1,4- diazepane [00084] +++ 541 52 N.sup.1-(3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [00085] +++ 580 53 N.sup.1-(3-((4-(bis(4-(trifluoro- methyl)phenyl)methyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00086] +++ 647 54 N.sup.1-(3-((4-((4-chloro- phenyl)(phenyl)methyl)piperazin- 1-yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00087] +++ 545 55 1-(bis(4-chlorophenyl)methyl)-4-(5- (4-methylpiperazin-1-yl)-2- (trifluoromethyl)benzyl)piperazine [00088] +++ 578 56 1-(3-((4-((4-chlorophenyl)(pyridin-2- yl)methyl)piperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl-1,4- diazepane [00089] ++ 558 57 1-methyl-4-(3-((4-(phenyl(pyridin-2- yl)methyl)piperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-1,4- diazepane [00090] ++ 524 58 N.sup.1-(3-((4-(bis(4- methoxyphenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [00091] +++ 571 59 N.sup.1-(3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.2,N.sup.2-dimethyl-N.sup.1-propylethan-1,2- diamine [00092] +++ 608 60 1-(3-((4-(bis(4-fluorophenyl)methyl)- 2-methylpiperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl-1,4- diazepane [00093] +++ 573 61 1-(3-((4-(bis(4-chlorophenyl)methyl)- 2-methylpiperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl-1,4- diazepane [00094] +++ 606 62 3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-N-methyl-N-((1- methylpyrrolidin-2-yl)methyl)-4- (trifluoromethyl)aniline [00095] +++ 606 63 3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-N-methyl-N-(2-(pyrrolidin- 1-yl)ethyl)-4-(trifluoromethyl)aniline [00096] +++ 606 64 N-(2-(aziridin-1-yl)ethyl)-3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-N-methyl-4- (trifluoromethyl)aniline [00097] +++ 578 65 1-(3-((4-(di(pyridin-2- yl)methyl)piperazin-1-yl)methyl)-4- (trifluoromethyl)phenyl)-4-ethyl-1,4- diazepane [00098] ++ 539 66 N.sup.1-(3-((4-(bis(4- fluorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [00099] +++ 547 67 1-(3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N,N-dimethylpiperidin-3-amine [00100] +++ 606 68 1-(bis(4-bromophenyl)methyl)-4-(5- (4-methylpiperazin-1-yl)-2- (trifluoromethyl)benzyl)piperazine [00101] +++ 666 69 1-(3-((4-(bis(4- fluorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N,N-dimethylpiperidin-4-amine [00102] +++ 573 70 N.sup.1-(3-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2-dimethyl-N.sup.2-propylethan-1,2- diamine [00103] +++ 608 71 N.sup.1-(3-((4-(bis(4- fluorophenyl)methyl)piperazin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.2-(2-(dimethylamino)ethyl)-N.sup.1,N.sup.2- dimethylethan-1,2-diamine [00104] +++ 604 72 N.sup.1-(3-((4-(bis(4- chlorophenyl)methyl)piperidin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [00105] +++ 579 73 N.sup.1-(3-((4-(bis(4- bromophenyl)methyl)piperidin-1- yl)methyl)-4-(trifluoromethyl)phenyl)- N.sup.1,N.sup.2,N.sup.2-trimethylethan-1,2-diamine [00106] +++ 667 74 2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00107] +++ 537 75 2-((4-(bis(4- methoxyphenyl)methyl)piperazin-1- yl)methyl)-4-(4-methyl-1,4-diazepan- 1-yl)benzonitrile [00108] +++ 540 76 2-((4-(bis(4- fluorophenyl)methyl)piperazin-1- yl)methyl)-4-(4-methyl-1,4-diazepan- 1-yl)benzonitrile [00109] +++ 516 77 2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(4-methyl-1,4-diazepan- 1-yl)benzonitrile [00110] +++ 549 78 4-((2-(1H-imidazol-1- yl)ethyl)(methyl)amino)-2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)benzonitrile [00111] +++ 560 79 2-((4-(di(pyridin-4- yl)methyl)piperazin-1-yl)methyl)-4- ((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00112] ++ 470 80 2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(4-methylpiperazin-1- yl)benzonitrile [00113] +++ 535 81 2-((4-(bis(4- isopropylphenyl)methyl)piperazin-1- yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00114] +++ 552 82 2-((4-(bis(4-tert- butylphenyl)methyl)piperazin-1- yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00115] +++ 580 83 2-((4-(bis(4- bromophenyl)methyl)piperazin-1- yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00116] +++ 625 84 2-((4-(bis(4- cyclopropylphenyl)methyl)piperazin- 1-yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00117] +++ 548 85 2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(3- (dimethylamino)pyrrolidin-1- yl)benzonitrile [00118] +++ 549 86 2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)-4-(methyl(2-(pyrrolidin-1- yl)ethyl)amino)benzonitrile [00119] +++ 563 87 4-((2-(aziridin-1- yl)ethyl)(methyl)amino)-2-((4-(bis(4- chlorophenyl)methyl)piperazin-1- yl)methyl)benzonitrile [00120] ++ 535 88 2-((4-((4-chloro- phenyl)(phenyl)methyl)piperazin- 1-yl)methyl)-4-(4-methyl-1,4- diazepan-1-yl)benzonitrile [00121] +++ 514 89 2-((4-((4-chlorophenyl)(pyridin-4- yl)methyl)piperazin-1-yl)methyl)-4-(4- methyl-1,4-diazepan-1-yl)benzonitrile [00122] +++ 515 90 2-((4-(bis(4- chlorophenyl)methyl)piperidin-1- yl)methyl)-4-((2- (dimethylamino)ethyl)(methyl)amino) benzonitrile [00123] +++ 536 91 2-((4-(bis(4- fluorophenyl)methyl)piperidin-1- yl)methyl)-4-(4-methyl-1,4-diazepan- 1-yl)benzonitrile [00124] +++ 515 92 N-{3-[4-(4-chlorophenyl)piperazin-1- yl]methyl)-4-(trifluoromethyl)phenyl}- N,1-dimethylpyrrolidin-3-amine [00125] +++ 467 93 4-[{2- [ethyl(methyl)amino]ethyl}(methyl) amino)-2-({4-[1-(pyrazin-2- yl)ethyl]piperazin-1- yl}methyl)benzonitrile [00126] ++ 422 94 N1-(3-[{4-[bis(3,4- dichlorophenyl)methyl]piperazin-1- yl}methyl]-4-(trifluoromethyl)phenyl)- N2,N2-diethyl-N1-methylethan-1,2- diamine [00127] +++ 676 95 2-({4-[bis(4-chloro-3- methylphenyl)methyl]piperazin-1- yl}methyl)-4-{[2- (dimethylamino)ethyl](methyl)amino) benzonitrile [00128] +++ 565 96 1-[3-({4-[cyclohexyl(3,4- dichlorophenyl)methyl]piperazin-1- yl}methyl)-4-(trifluoromethyl)phenyl]- 4-methyl-1,4-diazepane [00129] +++ 598 97 2-({4-[(4-chloro- phenyl)(cyclobutyl)methyl]piperazin- 1-yl}methyl)-4-(4-methyl-1,4- diazepan-1-yl)benzonitrile [00130] +++ 492 98 2-[(4-chlorophenyl){4-(5-(4- methylpiperazin-1-yl)-2- (trifluoromethyl)benzyl]piperazin-1- yl}methyl]pyrazine [00131] ++ 545 99 4-(4-methylpiperazin-1-yl)-2-[(4- {(pyrazin-2-yl)[(4-(trifluoro- methyl)phenyl]methyl}piperazin- 1-yl)methyl]benzonitrile [00132] ++ 536 100 1-methyl-4-[3-({4-[(4- phenoxyphenyl)(pyridin-2- yl)methyl]piperazin-1-yl}methyl)-4- (trifluoromethyl)phenyl]-1,4- diazepane [00133] ++ 616 101 N-{3-([4-{bis[4- (phenylthio)phenyl]methyl}piperazin- 1-yl]methyl)-4- (trifluoromethyl)phenyl}-1-ethyl-N- methylpyrrolidin-3-amine [00134] +++ 753 102 2-({4-(bis(4- (methylthio)phenyl]methyl}piperazin- 1-yl)methyl)-4-{[2- (dimethylamino)ethyl](methyl)amino} benzonitrile [00135] +++ 560 103 3-([4-{bis[4-(trifluoro- methyl)phenyl]methyl}piperazin- 1-yl]methyl)-N-methyl-N-[2- (pyrrolidin-1-yl)ethyl]-4- (trifluoromethyl)aniline [00136] +++ 673 104 2-({4-[(4-cyano- phenyl)(cyclopentyl)methyl]piperazin- 1-yl}methyl)-4-{[2- (dimethylamino)ethyl](methyl)amino} benzonitrile [00137] +++ 485 105 4-{1-(4-[5-{[2-(dimethyl- amino)ethyl](methyl)amino}- 2-(trifluoromethyl)benzyl]piperazin- 1-yl)ethyl}benzonitrile [00138] +++ 474 106 4-([3-(1H-imidazol-1- yl)propyl]amino)-2-({4-[bis(4- chlorophenyl)methyl]piperazin-1- yl}methyl)benzonitrile [00139] +++ 560 107 N.sup.1-(3-((4-(3,4- dichlorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00140] +++ 489 108 N.sup.1-(3-((4-(4-chloro-3- methylphenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-N.sup.1,N.sup.2,N.sup.2- trimethylethan-1,2-diamine [00141] +++ 469 109 1-(3-((4-(3,4- dichlorophenyl)piperazin-1- yl)methyl)-4- (trifluoromethyl)phenyl)-4-methyl- 1,4-diazepane [00142] +++ 501 *Inhibitory levels of the compounds against HCV replication at an administered concentration of 1 μM, + indicates inhibition rates in the range of 25%-50%, ++ indicates inhibition rates in the range of 50%-75% and +++ indicates inhibition rates above 75%. .sup.#The effective digits of molecular weights of all compounds in the table are retained to three digits and rounded off.