INDOLES, DERIVATIVES AND ANALOGS THEREOF AND USES THEREFOR

1 . A compound represented by the structure of formula IV:

wherein:

X is CH or N;

R 1 is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl, O-aryl, or phenyl substituted at C3 or C5 with R 4 ,

Q is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, O-alkyl, or O-aryl;

n is 0, 1, 2 or 3;

R 2 is H, CH 3 , alkyl, benzyl, or —SO 2 Ph;

R 3 is phenyl substituted at C3 or C5 with R 4 ; R 8 R 9 ; naphthyl substituted at C5, C6, or C7 with 2-, 3- or 6-indolyl or unsubstituted, the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof; R 12 R 13 ; or 2-, 3- or 6-indolyl substituted at C1, C2, or C3 with 2-, 3- or 6-indolyl, either of the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof;

R 4 is R 5 ; C 1-3 alkylene-R 5 ; CH 2 —R 6 , CH(OH)—R 6 ; C(O)R 6 ; CH═CH—C(R 7 )—R 6 ; —C(O)—R 7 —R 6 ; —O—C(R 7 )—R 6 ; R 7 R 8 -(2-, 3-, or 6-indolyl); R 8 -(2-, 3- or 6-indolyl), the indolyl moiety independently substituted at C1 with R 2 , at C4, C5 or C6 with R 1 or with a combination thereof; R 8 R 9 or R 12 R 13 ;

R 5 is OH, NO 2 , NH 2 , —NH—C 1-3 alkyl, N═N═N, CN, or OR 6 ;

R 6 is H, C 1-3 alkyl, or a 5- or 6-membered ring independently substituted at C2, C3, C4, C5, C6 or any combination thereof with R 1 ;

R 7 is O, S or NH;

R 8 is —CH 2 , —CH 2 OH, C═O, C═S, C═CH 2 , C═NOH, C═N(NH 2 );

R 9 is H, substituted or unsubstituted indolyl, substituted or unsubstituted aryl, phenyl independently substituted at C3 with R 19 and at C4 and C5 with R 11 ; thiazolyl substituted at C4 with —C(O)OCH 3 or naphthyl substituted at C5, C6, or C7 with 2-, 3- or 6-indolyl or unsubstituted, the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof;

R 10 is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl, O-aryl, substituted or unsubstituted naphthyl or forms a dioxolyl ring with R 11 at C4;

R 11 is H, OH, or —OCH 3 ;

R 12 is pyrrolyl, furanyl, thienyl, or cyclopentadienyl;

R 13 is —C(O)-2-, 3-, or 6-indolyl, —C(O)-imidazole, —C(O)-thiazole, —C(O)-oxazole, —C(O)-isoxazole, —C(O)-benzoxazole, —C(O)-pyrrole, —C(O)-furan, —C(O)-oxazoline, —C(O)-oxazolidine, —C(O)-oxadiazole, C(O)-naphthyl or —C(O)phenyl, each independently substituted with at C2, C3, C4, C5, or C6 with R 1 ;

or its isomer, tautomer, pharmaceutically acceptable salt, pharmaceutical product, N-oxide, hydrate or any combination thereof.

2 . The compound of claim 1 , wherein said compound is represented by the structure of formula II(a):

wherein:

R 1 , R 10 , Q and Z are each independently H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl or, O-aryl;

n is 0, 1, 2 or 3;

m is 0, 1, 2, 3, or 4;

R 2 is H, CH 3 , alkyl, benzyl or —SO 2 Ph.

3 . The compound of claim 1 , wherein said compound is represented by the structure of formula IV(a):

wherein:

X is CH or N;

R 1 , R 10 , Q and Z are each independently H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl or, O-aryl;

n is 0, 1, 2 or 3;

m is 0, 1, 2, 3, or 4; and

R 2 is H, CH 3 , alkyl, benzyl or —SO 2 Ph.

4 . A compound represented by the structure of formula V:

wherein:

X is CH 2 , NH, N(R 2 ), O, S, SO or SO 2 ;

R 1 is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl, O-aryl, or phenyl substituted at C3 or C5 with R 4 ,

Q is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, O-alkyl, or O-aryl;

n is 0, 1, 2 or 3;

R 2 is H, CH 3 , alkyl, benzyl, or —SO 2 Ph;

R 3 is phenyl substituted at C3 or C5 with R 4 ; R 8 R 9 ; naphthyl substituted at C5, C6, or C7 with 2-, 3- or 6-indolyl or unsubstituted, the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof; R 12 R 13 ; or 2-, 3- or 6-indolyl substituted at C1, C2, or C3 with 2-, 3- or 6-indolyl, either of the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof;

R 4 is R 5 ; C 1-3 alkylene-R 5 ; CH 2 —R 6 , CH(OH)—R 6 ; C(O)R 6 ; CH═CH—C(R 7 )—R 6 ; —C(O)—R 7 —R 6 ; —O—C(R 7 )—R 6 ; R 7 R 8 -(2-, 3-, or 6-indolyl); R 8 -(2-, 3- or 6-indolyl), the indolyl moiety independently substituted at C1 with R 2 , at C4, C5 or C6 with R 1 or with a combination thereof; R 8 R 9 or R 12 R 13 ;

R 5 is OH, NO 2 , NH 2 , —NH—C 1-3 alkyl, N═N═N, CN, or OR 6 ;

R 6 is H, C 1-3 alkyl, or a 5- or 6-membered ring independently substituted at C2, C3, C4, C5, C6 or any combination thereof with R 1 ;

R 7 is O, S or NH;

R 8 is —CH 2 , —CH(OH), C═O, C═S, C═CH 2 , C═NOH, C═N(NH 2 );

R 9 is H, substituted or unsubstituted indolyl, substituted or unsubstituted aryl, thiazolyl substituted at C4 with —C(O)OCH 3 or naphthyl substituted at C5, C6, or C7 with 2-, 3- or 6-indolyl or unsubstituted, the indolyl moiety independently substituted at C1 with R 2 , at C4, C5, or C6 with R 1 or with a combination thereof;

R 10 is H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl, O-aryl, substituted or unsubstituted naphthyl or forms a dioxolyl ring with R 11 at C4;

R 11 is H, OH, or —OCH 3 ;

R 12 is pyrrolyl, furanyl, thienyl, or cyclopentadienyl;

R 13 is —C(O)-2-, 3-, or 6-indolyl, —C(O)-imidazole, —C(O)-thiazole, —C(O)-oxazole, —C(O)-isoxazole, —C(O)-benzoxazole, —C(O)-pyrrole, —C(O)-furan, —C(O)-oxazoline, —C(O)-oxazolidine, —C(O)-oxadiazole, C(O)-naphthyl or —C(O)phenyl, each independently substituted with at C2, C3, C4, C5, or C6 with R 1 ;

or its isomer, tautomer, pharmaceutically acceptable salt, pharmaceutical product, N-oxide, hydrate or any combination thereof.

5 . The compound of claim 4 , wherein said compound is represented by the structure of formula V(a):

wherein:

X is CH 2 , NH, N(R 2 ), O, S, SO or SO 2 ;

R 1 , R 10 , Q and Z are each independently H, F, Cl, Br, I, CF 3 , NO 2 , OH, —OCH 3 , CN, CH 3 , alkyl, alkenyl, cycloalkyl, aryl, O-alkyl or, O-aryl;

R 2 is H, CH 3 , alkyl, benzyl, or —SO 2 Ph;

n is 0, 1, 2 or 3; and

m is 0, 1, 2, 3, or 4.

6 . The compound as claimed in claim 1 , wherein X is CH, R 1 is H or F; R 2 is H or SO 2 Ph; R 3 is phenyl substituted at C3 or C5 with R 4 , R 4 is R 8 R 9 , R 8 is C═O, and R 9 is substituted or unsubstituted aryl, independently substituted at C3, C4, C5 or any combination thereof with OCH 3 , H or F.

7 . The compound according to claim 6 , wherein said compound is represented by the structure:

8 . The compound as claimed in claim 1 , wherein X is CH, R 1 is H or F; R 2 is H or SO 2 Ph; R 3 is phenyl substituted at C3 or C5 with R 4 , R 4 is R 8 R 9 , R 8 is CH(OH), R 9 is substituted or unsubstituted aryl, independently substituted at C3, C4, C5 or any combination thereof with OCH 3 or H.

9 . The compound according to claim 8 , wherein said compound is represented by the structure:

10 . The compound as claimed in claim 1 , wherein X is CH or N, R 1 is H, F, Cl, OCH 3 , or CH 3 ; R 2 is H, SO 2 Ph, CH 3 or benzyl; R 3 is R 8 R 9 ; R 8 is C═O, R 9 is substituted or unsubstituted aryl, independently substituted at C3, C4, C5 or any combination thereof with OCH 3 .

11 . The compound according to claim 10 , wherein said compound is represented by the structure:

12 . The compound as claimed in claim 4 , wherein X is S or O, R 1 is H; R 3 is R 8 R 9 ; R 8 is C═O, R 9 is substituted or unsubstituted aryl, independently substituted at C3, C4, C5 or any combination thereof with OCH 3 .

13 . The compound according to claim 12 , wherein said compound is represented by the structure:

14 . A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier, diluent or salt or any combination thereof.

15 . A method of inhibiting tubulin polymerization in a cell associated with a cell proliferative disease, comprising administering a compound according to claim 1 to a subject, in an amount effective to inhibit tubulin polymerization in said cell.

16 . The method of claim 15 , wherein said cell proliferative disease is a cancer.

17 . The method of claim 16 , wherein said cancer is prostate cancer, melanoma, colon cancer, bladder cancer or breast cancer.

18 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting prostate cancer in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regression of, or inhibit said prostate cancer.

19 . The method according to claim 18 , wherein said prostate cancer is drug resistant prostate cancer, multidrug-resistant (MDR) prostate cancer, castration-resistant prostate cancer, metastatic prostate cancer, advanced prostate cancer or any combination thereof.

20 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting melanoma in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regressions of, or inhibit said melanoma.

21 . The method according to claim 20 , wherein said melanoma is resistant melanoma, multidrug-resistant (MDR) melanoma, metastatic melanoma, or any combination thereof.

22 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting a drug-resistant tumor in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regressions of, or inhibit said drug-resistant tumor.

23 . The method according to claim 22 , wherein said drug-resistant tumor is prostate cancer tumor, melanoma tumor, breast cancer tumor, bladder cancer tumor or colon cancer tumor.

24 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting breast cancer in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regressions of, or inhibit said breast cancer.

25 . The method according to claim 24 , wherein said breast cancer is drug resistant breast cancer, multidrug-resistant (MDR) breast cancer, metastatic breast cancer, or any combination thereof.

26 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting colon cancer in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regressions of, or inhibit said colon cancer.

27 . The method according to claim 26 , wherein said colon cancer is drug resistant colon cancer, multidrug-resistant (MDR) colon cancer, metastatic colon cancer, or any combination thereof.

28 . A method of treating, halting, suppressing, reducing the severity, reducing the incidence of, reducing the risk, causing the regression of, or inhibiting bladder cancer in a subject comprising the step of administering to said subject a compound according to claim 1 , in an amount effective to treat, halt, suppress, reduce the severity, reduce the incidence of, reduce the risk of, cause the regressions of, or inhibit said bladder cancer.

29 . The method according to claim 28 , wherein said bladder cancer is drug resistant bladder cancer, multidrug-resistant (MDR) bladder cancer, metastatic bladder cancer, or any combination thereof.