Fused heterocyclic or carbocyclic compounds carrying a substituted cycloaliphatic radical and use thereof for treating vasopressin-related diseases

Patent metadata

Field	Value
Publication number	US-9617226-B2
Application number	US-201514845727-A
Country	US
Kind code	B2
Filing date	Sep 4, 2015
Priority date	Sep 5, 2014
Publication date	Apr 11, 2017
Grant date	Apr 11, 2017

Abstract

The present invention relates to novel fused heterocyclic or carbocyclic compounds of formula I

wherein the variables are as defined in the claims and the description. The invention further relates to pharmaceutical compositions comprising these compounds, and to their use for the treatment of vasopressin-related disorders.

First claim

We claim:

1. A compound of the formula (I)

wherein
X 1 , X 2 , X 3 , X 4 and X 5 , independently of each other, are N or CH;
R 1 is C 1 -C 4 -alkyl which carries a group —C(═O)R 4 or fluorinated C 1 -C 4 -alkyl which carries a group —C(═O)R 4 ;
R 2 is phenyl or a 5- or 6-membered heteroaromatic ring with 1, 2 or 3 heteroatoms selected from the group consisting of O, S and N as ring members, where phenyl or the 5- or 6-membered heteroaromatic ring may carry 1, 2 or 3 substituents R 5 ;
R 3 is a 3-, 4-, 5- or 6-membered saturated or partially unsaturated carbocyclic ring which carries one substituent R 6 and which may additionally carry 1 or 2 substituents R 7 ;
R 4 is OR 8 or —NR 9 R 10 ;
each R 5 is independently halogen, cyano, nitro, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, where the 8 last-mentioned aliphatic and cycloaliphatic radicals may carry one or more radicals R 15 ; C 3 -C 8 -cycloalkoxy, fluorinated C 3 -C 8 -cycloalkoxy, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, amino, C 1 -C 6 -alkylamino, di-(C 1 -C 6 -alkyl)-amino, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, carboxyl, C 1 -C 6 -alkoxycarbonyl, fluorinated C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylcarbonyloxy, fluorinated C 1 -C 6 -alkylcarbonyloxy, aminocarbonyl, C 1 -C 6 -alkylaminocarbonyl, di-(C 1 -C 6 -alkyl)-aminocarbonyl, phenyl, phenyl-C 1 -C 2 -alkyl, or a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO and SO 2 as ring members, where phenyl, phenyl-C 1 -C 2 -alkyl and the heterocyclic ring may carry one or more radicals R 13 ; or
two radicals R 5 , bound on adjacent ring atoms, form together with the ring atoms to which they are bound a saturated or unsaturated 3-, 4-, 5-, 6-, 7-, 8- or 9-membered ring, wherein the ring may contain 1 or 2 heteroatoms or heteroatom groups selected from the group consisting of O, S, N, NO, SO and SO 2 and/or 1 or 2 C═O groups as ring members, and wherein the ring may be substituted by one or more radicals R 13 ;

R 6 is C 1 -C 4 -alkyl which carries a radical —NR 11 R 12 or fluorinated C 1 -C 4 -alkyl, which carries a radical —NR 11 R 12 ;
each R 7 is independently halogen, cyano, hydroxyl, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, or fluorinated C 1 -C 4 -alkoxy, or two radicals R 7 bound on the same carbon ring atom form together a group ═O (oxo);
R 8 is hydrogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, where the 8 last-mentioned aliphatic and cycloaliphatic radicals may carry one or more radicals R 15 ; phenyl, phenyl-C 1 -C 2 -alkyl, or a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO and SO 2 as ring members, where phenyl, phenyl-C 1 -C 2 -alkyl and the heterocyclic ring may carry one or more radicals R 13 ;
R 9 and R 10 , independently of each other, are hydrogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, where the 8 last-mentioned aliphatic and cycloaliphatic radicals may carry one or more radicals R 15 ; C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, phenyl, phenyl-C 1 -C 2 -alkyl, or a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO and SO 2 as ring members, where phenyl, phenyl-C 1 -C 2 -alkyl and the heterocyclic ring may carry one or more radicals R 13 ; or
R 9 and R 10 , together with the nitrogen atom they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring, where the heterocyclic ring may additionally contain 1 or 2 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO, SO 2 and C═O as ring members, and where the heterocyclic ring may carry 1, 2, 3 or 4 radicals R 13 ;

R 11 and R 12 , independently of each other, are hydrogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, where the 8 last-mentioned aliphatic and cycloaliphatic radicals may carry one or more radicals R 15 ; C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, phenyl, phenyl-C 1 -C 2 -alkyl, or a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO and SO 2 as ring members, where phenyl, phenyl-C 1 -C 2 -alkyl and the heterocyclic ring may carry one or more radicals R 13 ; or
R 11 and R 12 , together with the nitrogen atom they are bound to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring, where the heterocyclic ring may additionally contain 1 or 2 heteroatoms or heteroatom groups selected from the group consisting of: O, S, N, NO, SO, SO 2 and C═O as ring members, and where the heterocyclic ring may carry 1, 2, 3 or 4 radicals R 13 ;

each R 13 is independently halogen, cyano, hydroxyl, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, fluorinated C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, amino, C 1 -C 6 -alkylamino, di-(C 1 -C 6 -alkyl)-amino, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, carboxyl, C 1 -C 6 -alkoxycarbonyl, fluorinated C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylcarbonyloxy, fluorinated C 1 -C 6 -alkylcarbonyloxy, aminocarbonyl, C 1 -C 6 -alkylaminocarbonyl, di-(C 1 -C 6 -alkyl)-aminocarbonyl, phenyl, or phenyl-C 1 -C 2 -alkyl; or two radicals R 13 bound to the same carbon ring atom together a group ═O or ═S; or
two radicals R 13 bound to the same carbon ring atom may form together with this carbon ring atom a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring, where the ring may contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from the group consisting of O, S, N, NO, SO, SO 2 and C═O as ring members, and where the ring may be substituted with one or more substituents R 14 ; or
two non-geminal radicals R 13 form together a group —(CH 2 ) k —, where k is 1, 2, 3 or 4, where 1 or 2 hydrogen atoms in this group may be replaced by a methyl group; or
two vicinal radicals R 13 form together a group —CH═CH—CH═CH—;

each R 14 is indepe

Assignees

• Abbvie Deutschland

Inventors

• Braje Wilfried
• Froggett Jayne
• Geneste Hervé
• Hornberger Wilfried
• Jantos Katja
• Kling Andreas
• Van Gaalen Marcel

Classifications

• C07D455/02

  containing not further condensed quinolizine ring systems · CPC title

• C07D491/107

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D239/91 Primary

  with aryl or aralkyl radicals attached in position 2 or 3 · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title