Substituted aminoindanes and analogs thereof, and the pharmaceutical use thereof

Patent metadata

Field	Value
Publication number	US-9550788-B2
Application number	US-201414339957-A
Country	US
Kind code	B2
Filing date	Jul 24, 2014
Priority date	Sep 2, 2008
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

The invention relates to substituted aminoindanes and analogs thereof of formula I

and the pharmaceutical use thereof. Medicaments which comprise compounds of this type are suitable for the prevention or treatment of diverse disorders such as, for example, of respiratory disorders, cystic fibrosis disorders, acute or chronic renal disorders or bowel disorders.

First claim

What is claimed is:

1. A compound of the formula I

in which
A is phenyl, where one or more hydrogen atoms in said phenyl may be replaced by one or more substituents R1;
substituents R1 are selected independently of one another from the group of F, Cl, Br, I, (C 1 -C 10 )-alkyl, (C 2 -C 10 )-alkenyl-, (C 2 -C 10 )-alkynyl-, (C 3 -C 14 )-cycloalkyl-, (C 4 -C 20 )-cycloalkylalkyl-, (C 4 -C 20 )-cycloalkylalkyloxy-, (C 1 -C 10 )-alkoxy-, (C 1 -C 10 )-alkylthio-, (C 6 -C 14 )-aryl-, (C 2 -C 13 )-heteroaryl, —CN, —NR13R14, —C(O)R12, —SF 5 , —S(O) n R12, —C(O)OR12, —C(O)NR13R14 and —S(O) n NR13R14;
where two adjacent radicals R1 may also form a saturated or partly unsaturated (C 5 -C 10 )-cycloalkyl radical or a saturated or partly unsaturated (C 2 -C 9 )-cycloheteroalkyl radical, where the cycloheteroalkyl radical has 1, 2 or 3 nitrogen, 1 or 2 oxygen, 1 or 2 sulfur, 1 or 2 nitrogen and 1 oxygen or 1 sulfur atom;

where said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, cycloheteroalkyl, alkoxy, and alkylthio radicals may be substituted independently of one another one or more times by F, OH or (C 1 -C 10 )-alkoxy;
B is a mono- or fused bicyclic radical selected from the group
of 6 to 10 membered aryl radicals,
of 5 to 10 membered heteroaryl radicals,
of 3 to 10 membered cycloalkyl radicals,
of 9 to 14 membered cycloalkylaryl radicals,
of 8 to 14 membered cycloalkyiheteroaryl radicals,
of 3 to 10 membered cycloheteroalkyl radicals,
of 9 to 14 membered cycloheteroalkylaryl radicals and
of 8 to 14 membered cycloheteroalkylheteroaryl radicals,
where the cycloalkyl or cycloheteroalkyl units may be saturated or partly unsaturated, and
where the heterocyclic groups have one or more heteroatoms selected from the group of nitrogen, oxygen and sulfur;
where one or more hydrogen atoms in the radicals B may be replaced by substituents R5;
substituents R5 are selected independently of one another from the group of (C 1 -C 10 )-alkyl radicals, (C 2 -C 10 )-alkenyl radicals, (C 2 -C 10 )-alkynyl radicals, (C 1 -C 10 )-alkoxy radicals, (C 1 -C 10 )-alkylthio radicals, (C 3 -C 14 )-cycloalkyl radicals, (C 4 -C 20 )-cycloalkylalkyl radicals, (C 4 -C 20 )-cycloalkylalkyloxy, (C 2 -C 19 )-cycloheteroalkyl radicals, (C 3 -C 19 )-cycloheteroalkylalkyl radicals, (C 3 -C 11 )-cycloalkyloxy radicals, (C 2 -C 11 )-cycloheteroalkyloxy radicals, (C 6 -C 10 )-aryl radicals, (C 1 -C 9 )-heteroaryl radicals, (C 9 -C 14 )-cycloalkylaryl radicals, (C 5 -C 13 )-cycloalkylheteroaryl radicals, (C 7 -C 13 )-cycloheteroalkylaryl radicals and (C 4 -C 12 )-cycloheteroalkylheteroaryl radicals, where

the cycloalkyl and cycloheteroalkyl units may be saturated or partly unsaturated,
and where one or more hydrogen atoms in said radicals R5 may be replaced by further radicals which are selected independently of one another from the group of R11 radicals,
it is further possible for R5 to be one or more radicals which are selected independently of one another from the group of OH, (═O), NH 2 , F, Cl, Br, I, CN, NO 2 , —NR17R18, —NR16COR17, —NR16COOR17, —NR16CONR17R18, —NR16-S(O) 2 —R17, —NR16-S(O) 2 —NR17R18, —COOR16, —COR16; —CO(NR17R18), S(O) n R16 and —S(O) 2 NR17R18,
where R16, R17 and R18 independently of one another are selected from the group of H, (C 2 -C 19 )-cycloheteroalkyl, (C 3 -C 14 )-cycloalkyl, (C 6 -C 10 )-aryl and (C 1 -C 10 )-alkyl radicals,

all of which may be substituted independently of one another by OH, (═O), F, Cl, Br, I, CN, NO 2 , —NR13R14, —NR13COR12, —NR13COOR12, —NR12CONR13R14, —NR13-S(O) 2 —R12, —NR12-S(O) 2 —NR13R14, —COOR12, —COR12; —CO(NR13R14), —S(O) n R12, —S(O) 2 NR13R14, (C 1 -C 10 )-alkoxy, (C 3 -C 14 )-cycloalkyl, (C 4 -C 20 )-cycloalkylalkyl, (C 2 -C 19 )-cycloheteroalkyl, (C 3 -C 19 )-cycloheteroalkylalkyl, (C 6 -C 10 )-aryl and (C 1 -C 9 )-heteroaryl, and where R17 and R18 can form together with the nitrogen to which they are bonded a 4-7 membered, saturated, unsaturated or partly unsaturated heterocycle which may additionally comprise one or more further heteroatoms from the group —O—, —S(O) n —, ═N— and —NR15-,
where the heterocycle formed may be substituted one or more times by F, OH, (═O), NH 2 , NH(C 1 -C 4 )alkyl, N((C 1 -C 4 )alkyl) 2 , or CN, or by (C 1 -C 10 )-alkoxy, (C 1 -C 10 )-alkyl, (C 2 -C 10 )-alkenyl, (C 2 -C 10 )-alkynyl, (C 3 -C 14 )-cycloalkyl, (C 4 -C 20 )-cycloalkylalkyl, (C 2 -C 20 )-cycloheteroalkyl, (C 3 -C 19 )-cycloheteroalkylalkyl, each of which may in turn carry independently of one another one or more radicals F, OH, (═O), NH 2 , NH(C 1 -C 4 )alkyl, N((C 1 -C 4 )alkyl) 2 , CN or (C 1 -C 10 )-alkoxy;
L is a covalent bond;
X is a group —O—;
R2 is absent or is one or more substituents which may be selected independently of one another from the group of F, (C 1 -C 10 )-alkyl and (C 1 -C 10 )-alkoxy radical, where the alkyl and alkoxy radicals may be substituted independently of one another one or more times by F;
R3 and R4 are independently of one another a hydrogen radical or a radical which is selected from the group of (C 1 -C 10 )-alkyl radicals, (C 2 -C 10 )-alkenyl radicals, (C 2 -C 10 )-alkynyl radicals, (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl- radicals, (C 3 -C 14 )-cycloalkyl radicals, (C 4 -C 20 )-cycloalkylalkyl radicals, (C 2 -C 19 )-cycloheteroalkyl radicals, (C 3 -C 19 )-cycloheteroalkylalkyl radicals, (C 6 -C 10 )-aryl radicals, (C 7 -C 20 )-arylalkyl radicals, (C 1 -C 9 )-heteroaryl radicals and (C 2 -C 19 )-heteroarylalkyl radicals, where the radicals R3 and R4 may be substituted independently of one another one or more times by a radical from the group of OH, NH 2 , (═O), F, Cl, Br, I, CN, NO 2 , —NR13R14, —NR13COR12, —NR13COOR12, —NR12CONR13R14, —NR13-S(O) 2 —R12, —NR13-S(O) 2 —NR13R14, —COOR12, —COR12; —CO(NR13R14), S(O) n R12, and —S(O) 2 NR13R14, or
R3 and R4 form together with the nitrogen to which they are bonded a 4-10 membered, saturated, unsaturated or partly unsaturated heterocycle which may additionally comprise one or more further heteroatoms from the group —O—, —S(O) n —, ═N— and —NR8-, where the heterocycle may be substituted one or more times by radicals selected from the group of R7 and R9, and where
the heterocycle formed may be bridged by a bond, by a saturated or unsaturated (C 1 -C 10 )-alkyl or (C 1 -C 9 )-heteroalkyl chain or by —NR15-, —O— or —S—, and where
the alkyl and heteroalkyl chain may also form a spirocyclic ring system with the ring system formed by R3 and R4, where the alkyl and heteroalkyl bridges may be substituted independently of one another one or more times by radicals selected from the group of R7 and R9,
and where
R8 in the group —NR8- may form with the ring which R3 and R4 may form a further saturated, unsaturated or partly unsaturated heterocycle which may be substituted independently of one another one or more times by radicals selected from the group of R7 and R9, and may additionally comprise one or more further heteroatoms from the group —O—, —S(O) n —, —N═ and —NR19-;
R7 is a (C 1 -C 10 )-alkyl radical or (C 3 -C 14 )-cycloalkyl radical, where the alkyl radical may be substituted one or more times by R9;
R8 is an H, a (C 1 -C 10 )-alkyl radical, (C 3 -C 14 )-cycloalkyl radical, COR12, —CO(NR13R14), S(O) n R12 or —S(O) 2 NR13R14, where the alkyl radical may be substituted one or more times by R10;
R9 is a radical selected from the group of OH, (═O), F, Cl, Br, I, CN, NO 2 , —NR13R14, —NR13COR12, —NR13 COOR12, —NR12CONR13R14, —NR13-S(O) 2 —R12, —NR13-S(O) 2 —NR13R14, —COOR12, —COR12, —CO(NR13R14), S(O) n R

Assignees

• Sanofi Sa

Inventors

• Rackelmann Nils
• Bialy Laurent
• Englert Heinrich
• Wirth Klaus
• Arndt Petra
• Weston John
• Heinelt Uwe
• Follmann Markus

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title