3-substituted 2-amino-indole derivatives

Patent metadata

Field	Value
Publication number	US-10059713-B2
Application number	US-201515320887-A
Country	US
Kind code	B2
Filing date	Jun 24, 2015
Priority date	Jun 25, 2014
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The present invention provides compounds of formula (I) (Formula (I)) and pharmaceutically acceptable salts thereof, wherein Q, X % X 4 , X 5 X 6 , X 7 , R 1 , R 2 , R 3 and R 8 are as defined in the specification, processes for the preparation of such compounds, pharmaceutical compositions containing them and the use of such compounds in therapy.

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein
Q represents —O—, —S—, —SO—, —SO 2 —, —SO 2 NR—, —SO 2 (CH 2 ) m — or SO 2 O—;
R represents a hydrogen atom or a C 1 -C 6 alkyl group;
m is 1 or 2;
X 4 represents N;
X 5 represents CR 5 ;
X 6 represents N;
X 7 represents CR 7 ;
R 1 and R 2 each independently represent a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, or a C 1 -C 6 alkoxycarbonyl group, each of which may be optionally substituted by at least one halogen atom;
R 3 represents a saturated or unsaturated 3- to 10-membered ring system which may comprise at least one ring heteroatom independently selected from nitrogen, oxygen and sulphur, wherein the 3- to 10-membered ring system is optionally substituted by at least one substituent independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, benzyloxycarbonyl and a saturated or unsaturated 5- to 6-membered heterocyclyl group, which heterocyclyl group is itself optionally substituted by at least one C 1 -C 6 alkyl group;
R 5 represents a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group, a C 1 -C 6 alkoxy group, a C 1 -C 6 alkylthio group, a C 1 -C 6 haloalkyl group, NR 12 R 13 , a C 3 -C 8 cycloalkyl group, or a C 5 -C 8 cycloalkenyl group;
R 7 represents a hydrogen atom, a halogen atom, NR 9 R 10 , a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, a C 2 -C 6 alkenyl group, a C 5 -C 8 cycloalkenyl group, a C 1 -C 6 alkoxy group, a C 3 -C 8 cycloalkyloxy group, a 3- to 11-membered saturated heterocyclyl group, a 3- to 11-membered saturated heterocyclyloxy group, a C 6 -C 10 aryl group, or a heteroaryl group, each of which may be optionally substituted by at least one substituent independently selected from halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, phenyl and a saturated or unsaturated 5- to 6-membered heterocyclyl group wherein each C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, phenyl or saturated or unsaturated 5- to 6-membered heterocyclyl substituent group may itself be optionally substituted by at least one substituent independently selected from halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 3 -C 6 cycloalkyl;
R 8 represents a hydrogen atom;
R 9 and R 10 each independently represent a hydrogen atom, a C 1 -C 6 alkyl group, or a —(CH 2 ) p —R 11 group, each of which may be optionally substituted by at least one substituent independently selected from halogen, C 1 -C 3 alkyl and C 1 -C 3 alkoxy;
p is 0 or 1;
R 11 represents C 3 -C 6 cycloalkyl, phenyl or a saturated or unsaturated 5- to 6-membered heterocyclyl group; and
R 12 and R 13 each independently represent a hydrogen atom or a C 1 -C 6 alkyl group.

2. A compound according to claim 1 , wherein Q represents —SO 2 —.

3. A compound according to claim 1 , wherein R 1 and R 2 are both hydrogen.

4. A compound according to claim 1 , wherein R 3 represents an unsaturated 6- to 10-membered ring system which may comprise at least one ring heteroatom independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted as defined in claim 1 .

5. A compound according to claim 1 , wherein R 3 represents phenyl or pyridyl, each optionally substituted as defined in claim 1 .

6. A compound according to claim 4 , wherein optional substituents in R 3 are selected from fluorine, chlorine, methyl, trifluoromethyl, difluoromethoxy, C 1 -C 3 alkoxy and methylmorpholinyl.

7. A compound according to claim 1 , wherein R 7 is represented by a group of formula:

wherein
X A represents N or CH;
each X B independently represents a single bond or —C(R 14 ) 2 —, provided that at least one X B represents —C(R 14 ) 2 —;
each R 14 independently represents a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a phenyl group;
X C represents —O—, —S—, —C(R 15 ) 2 — or —NR 15 —;
each R 15 independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 haloalkyl group, or the two R 15 groups in —C(R 15 ) 2 — together with the carbon atom to which they are attached, form a spiro-connected cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group, optionally substituted by one or more halogen atoms;
each R 16 independently represents a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a phenyl group, or the two R 16 together with the carbon atom to which they are attached, form a spiro-connected cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group, optionally substituted by one or more halogen atoms; and
each R 17 independently represents a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a phenyl group, or the two R 17 together with the carbon atom to which they are attached, form a spiro-connected cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group, optionally substituted by one or more halogen atoms.

8. A compound according to claim 7 , wherein
X A represents N;
each X B independently represents a single bond or —C(R 14 ) 2 —, provided that at least one X B represents —C(R 14 ) 2 —;
each R 14 independently represents a hydrogen atom or a methyl group;
X C represents —O—;
each R 16 independently represents a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, or a phenyl group, or the two R 16 together with the carbon atom to which they are attached, form a spiro-connected cyclopropyl, cyclobutyl, or cyclopentyl group; and
each R 17 independently represents a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, or a phenyl group, or the two R 17 together with the carbon atom to which they are attached, form a spiro-connected cyclopropyl, cyclobutyl, or cyclopentyl group.

9. A compound according to claim 1 , selected from the group consisting of:
7-(benzenesulfonyl)-4-(cyclohex-1-en-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-cyclohexyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
4-(cyclohex-1-en-1-yl)-7-[(4-methoxybenzene)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
4-cyclohexyl-7-[(4-methoxybenzene)sulfonyl]-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-(morpholin-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-(piperidin-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(2-fluorobenzenesulfonyl)-2-methyl-4-(2,2,3-trimethylmorpholin-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-phenyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-[(E)-2-cyclopropylethenyl]-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-(prop-1-en-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-(2-cyclopropylethyl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
6-amino-4-(cyclohex-1-en-1-yl)-N-(4-methoxyphenyl)-N-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-sulfonamide;
7-(benzenesulfonyl)-4-(propan-2-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
methyl-N-[7-(benzenesulfonyl)-4-(cyclohex-1-en-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]carbamate;
7-(benzenesulfonyl)-4-(cyclohex-1-en-1-yl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
4-(cyclohex-1-en-1-yl)-7-(pyridine-2-sulfonyl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-[(4-chlorobenzene)sulfonyl]-4-(cyclohex-1-en-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-amine;
7-(benzenesulfonyl)-4-(cyc

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Barker Gregory
• Davenport Richard
• Downham Robert
• Farnaby William
• Goldby Anne
• Hannah Duncan
• Harrison David
• Willems Henriette

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title