Indolyl or indolinyl hydroxamate compounds

Patent metadata

Field	Value
Publication number	US-9598364-B2
Application number	US-201414468408-A
Country	US
Kind code	B2
Filing date	Aug 26, 2014
Priority date	Mar 29, 2010
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

Indolyl or indolinyl compounds of formula (I):

wherein bond, n, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 , are defined herein. Also disclosed is a method for treating cancer with these compounds.

First claim

What is claimed is:

1. A method for treating pancreatic cancer, colorectal cancer, lung cancer, lymphoma, brain tumors, melanoma, ovarian cancer, renal cancer, and prostate cancer, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I):

wherein
is a single bond or a double bond;
n is 0, 1, or 2;
R 1 is SO 2 R a , in which R a is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
R 2 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halo, cyano, nitro, OR b , SR b , S(O)R b , NHC(O)—CH═CH—C(O)R b , NHC(O)—CH═CH—C(O)NR c R d , SO 2 NR c R d , OC(O)R b , C(O)NR c R d , NR c R d , NHC(O)R b , NHC(O)NR c R d , or NHC(S)R c , in which each of R b , R c , and R d , independently, is H, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl; and
each of R 3 , R 4 , R 5 , and R 6 , independently is, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, halo, cyano, nitro, OR b , SR b , S(O)R b , CH═CH—C(O)NR c R d , NHC(O)—CH═CH—C(O)R b , NHC(O)—CH═CH—C(O)NR c R d , SO 2 NR c R d , OC(O)R b , C(O)NR c R d , NR c R d , NHC(O)R b , NHC(O)NR c R d , or NHC(S)R c , in which each of R b , R c , and R d , independently, is H, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
provided that at least one of R 2 , R 3 , R 4 , R 5 , and R 6 has the following definitions: R 2 is NHC(O)—CH═CH—C(O)R b or NHC(O)—CH═CH—C(O)NR c R d ; or R 3 , R 5 , or R 6 is CH═CH—C(O)NR c R d , NHC(O)—CH═CH—C(O)R b , or NHC(O)—CH═CH—C(O)NR c R d ; or R 4 is C(O)NR c R d , CH═CH—C(O)NR c R d , NHC(O)—CH═CH—C(O)R b , or NHC(O)—CH═CH—C(O)NR c R d .

2. The method according to claim 1 , wherein R 4 is C(O)NR c R d , CH═CH—C(O)NR c R d , NHC(O)—CH═CH—C(O)R b , or NHC(O)—CH═CH—C(O)NR c R d .

3. The method according to claim 2 , wherein R 4 is C(O)NHOH, CH═CH—C(O)NHOH, NHC(O)—CH═CH—C(O)OH, or NHC(O)—CH═CH—C(O)NHOH.

4. The method according to claim 3 , wherein R 4 is CH═CH—C(O)NHOH.

5. The method according to claim 4 , wherein R 1 is SO 2 R a and R a is aryl or heteroaryl.

6. The method according to claim 5 , wherein R a is phenyl optionally substituted with halo, hydroxyl, alkoxyl, amino, cyano, or nitro.

7. The method according to claim 1 , wherein R 2 is NHC(O)—CH═CH—C(O)R b or NHC(O)—CH═CH—C(O)NR c R d ; or at least one of R 3 , R 5 , and R 6 is CH═CH—C(O)NR c R d , NHC(O)—CH═CH—C(O)R b , or NHC(O)—CH═CH—C(O)NR c R d .

8. The method according to claim 7 , wherein R 2 is NHC(O)—CH═CH—C(O)OH or NHC(O)—CH═CH—C(O)NHOH; or at least one of R 3 , R 5 , and R 6 is CH═CH—C(O)NHOH, NHC(O)—CH═CH—C(O)OH, or NHC(O)—CH═CH—C(O)NHOH.

9. The method according to claim 8 , wherein R 1 is SO 2 R a and R a is aryl or heteroaryl.

10. The method according to claim 9 , wherein R a is phenyl optionally substituted with halo, hydroxyl, alkoxyl, amino, cyano, or nitro.

11. The method according to claim 1 , wherein R 1 is SO 2 R a and R a is aryl or heteroaryl.

12. The method according to claim 11 , wherein R a is phenyl optionally substituted with halo, hydroxyl, alkoxyl, amino, cyano, or nitro.

13. The method according to claim 1 , wherein the compound is one of the following compounds:

14. The method according to claim 13 , wherein the compound is 3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxy-acrylamide or 3-(1-benzenesulfonyl-2,3-dihydro-1H-indol-5-yl)-N-hydroxy-acrylamide.

15. The method according to claim 1 , wherein the prostate cancer is selected from the group consisting of androgen-dependent and androgen-independent prostate cancers; the renal cancer comprises metastatic renal cell carcinoma; the lung cancer is selected from the group consisting of bronchioloalveolar carcinoma (BAC) and adenocarcinoma of the lung; the ovarian cancer is selected from the group consisting of progressive epithelial or primary peritoneal cancers; the brain tumors are selected from the group consisting of glioma, anaplastic oligodendroglioma, adult glioblastoma multiforme, and adult anaplastic astrocytoma; and the lymphoma is selected from the group consisting of non-Hodgkin's lymphoma (NHL), B-cell lymphoma and T-cell lymphoma.

16. The method according to claim 1 , wherein the non-Hodgkin's lymphoma (NHL) is selected from the group consisting of follicular lymphoma and mantle cell lymphoma.

Assignees

• Univ Taipei Medical
• Univ Ohio State
• Univ Nat Taiwan

Inventors

• Chen Ching-Shih
• Liou Jing-Ping
• Liu Hsing-Jin
• Hung Kuo-Sheng
• Shan Pei-Wen
• Chiu Wen-Ta
• Teng Che-Ming

Classifications

• C07D209/08 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D209/40

  Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone · CPC title

• C07D209/12

  Radicals substituted by oxygen atoms · CPC title

• C07D209/30 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring · CPC title

• C07D209/18

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title