Substituted hydrophobic benzene sulfonamide thiazole compounds for use in treating cancer

Patent metadata

Field	Value
Publication number	US-10815207-B2
Application number	US-201615746630-A
Country	US
Kind code	B2
Filing date	Jul 22, 2016
Priority date	Jul 24, 2015
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

The present invention relates to compound of general formula (I) R 1 is selected from H, aryl and alkyl, R 2 is selected from H, alkyl, aryl and CO—R 6 ; R 3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7 and SR 7 ; R 4 is selected from (C 6 -C 12 ) alkyl, (C 2 -C 12 ) alkenyl, (C 2 -C 12 ) alkynyl and (C 6 -C 10 ) aryl, R 5 represents H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 6 R 7 , CONR 6 R 7 , NH 2 , NHR 6 , NH-aryl, NR 6 R 7 , NHCOR 6 or aminoacyl; R 6 is alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R 7 and R 8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

First claim

The invention claimed is:

1. A compound of general formula (I)

wherein
R 1 is selected from H, aryl and alkyl;
R 2 is selected from H, alkyl, aryl and CO-R 6 ;
R 3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7 and SR 7 ;
R 4 is (C 2 -C 12 ) alkynyl, wherein the alkynyl group is linear, branched or cyclic and wherein the alkynyl group is optionally substituted with one to three OH groups;
R 5 is selected from H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 7 R 8 , CONR 7 R 8 , NH 2 , NHR 6 , NH-aryl, NR 7 R 8 , NHCOR 6 and aminoacyl;
R 6 is alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); and
R 7 and R 8 are identical or different and are H or alkyl optionally substituted with halogen, OH, SH, NH 2 , O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl);
and pharmaceutically acceptable salts, tautomers, solvates or isotopic variations thereof;
wherein unless otherwise specified:
Alkyl denotes a straight- or branched hydrocarbon chain comprising 1 to 6 carbon atoms,
Alkenyl denotes a straight- or branched hydrocarbon chain comprising 2 to 6 carbon atoms and one or more double bonds,
Alkynyl denotes a straight- or branched hydrocarbon chain containing 2 to 6 carbon atoms and one or more triple bonds and optionally one or more double bonds, and
Aryl denotes a aromatic carbon ring comprising from 6 to 10 carbon atoms.

2. The compound according to claim 1 , wherein R 1 is H.

3. The compound according to claim 1 , wherein R 2 is selected from H, methyl or COCH 3 .

4. The compound according to claim 1 , wherein R 3 is H.

5. The compound according to claim 1 , wherein R 4 is
C≡CR 10 , wherein R 10 is selected from H, C 1 -C 8 alkyl, or hydroxy (C 1 -C 8 )alkyl.

6. The compound according to claim 1 , wherein R 4 is in the meta or para position with respect to the sulfonyl group.

7. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
N-(4-(3-(4-(oct-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide
N-(4-(3-(3-(oct-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide
N-(4-(3-(3-(3-hydroxyprop-1-ynyl)phenylsulfonamido)phenyl)thiazol-2-yl)acetamide
N-(4-(3-(3-ethynylphenylsulfonamido)phenyl)thiazol-2-yl)acetamide
N-(4-(3-((4-(3-hydroxyprop-1-yn-1-yl)phenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide and
N-(4-(3-((4-ethynylphenyl)sulfonamido)phenyl)thiazol-2-yl)acetamide.

8. A method of treating melanoma in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a
compound of general formula (I)

wherein
R 1 is selected from H, aryl and alkyl;
R 2 is selected from H, alkyl, aryl and CO-R 6 ;
R 3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR 7 , NR 7 R 8 , OR 7 , SR 7 ;
R 4 is (C 2 -C 12 ) alkynyl, wherein the alkynyl group is linear, branched or cyclic;
R 5 is selected from H, R 6 , aryl, OH, OR 6 , O-aryl, SH, SR 6 , S-aryl, CN, NO 2 , CF 3 , COOR 6 , SO 2 NR 7 R 8 , CONR 7 R 8 , NH 2 , NHR 6 , NH-aryl, NR 7 R 8 , NHCOR 6 and aminoacyl;
R 6 is alkyl optionally substituted with halogen, OH, SH, NH 2 O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); and
R 7 and R 8 are identical or different and are alkyl optionally substituted with halogen, OH, SH, NH 2 O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl);
or pharmaceutically acceptable salts, tautomers, solvates or isotopic variations thereof.

9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

10. The method of claim 8 , wherein the patient is an animal or human.

Assignees

• Inst Nat Sante Rech Med
• Univ Nice Sophia Antipolis
• Centre Nat Rech Scient

Inventors

• Rocchi Stephane
• Benhida Rachid
• Ballotti Robert
• Plaisant Magali
• Ronco Cyril
• Millet Antoine

Classifications

• A61K31/426

  1,3-Thiazoles · CPC title

• C07D277/46 Primary

  by carboxylic acids, or sulfur or nitrogen analogues thereof · CPC title

• A61P35/00

  Antineoplastic agents · CPC title