Process or preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds

Patent metadata

Field	Value
Publication number	US-9862719-B2
Application number	US-201514804847-A
Country	US
Kind code	B2
Filing date	Jul 21, 2015
Priority date	Nov 11, 2002
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

Spirocyclic cyclohexane compounds corresponding to formula I

a method for producing them, pharmaceutical compositions containing them, and methods of using them.

First claim

The invention claimed is:

1. A process for preparing a spirocyclic cyclohexane compound corresponding to formula I

wherein
R 1 and R 2 independently of one another represent H, C 1-5 -alkyl, branched or unbranched, saturated or unsaturated, unsubstituted or mono- or polysubstituted, or CHO; or
R 1 and R 2 together represent CH 2 CH 2 OCH 2 CH 2 , CH 2 CH 2 NR 11 CH 2 CH 2 or (CH 2 ) 3-6 , wherein
R 11 denotes H; C 1-5 -alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; C 3-8 -cycloalkyl, in each case saturated or unsaturated, mono- or polysubstituted or unsubstituted; aryl-, or heteroaryl, in each case mono- or polysubstituted or unsubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are in each case mono- or polysubstituted or unsubstituted;

R 3 represents C 1-5 -alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; C 3-8 -cycloalkyl, in each case saturated or unsaturated, mono- or polysubstituted or unsubstituted; aryl, in each case unsubstituted or mono- or polysubstituted; aryl or C 3-8 -cycloalkyl which are bonded via a C 1-3 -alkylene group and are in each case unsubstituted or mono- or polysubstituted;
W represents NR 4 , O or S;
wherein
R 4 denotes H; C 1-5 -alkyl, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; aryl, or heteroaryl, in each case substituted or unsubstituted; aryl, heteroaryl or cycloalkyl which are bonded via a C 1-3 -alkyl group and are in each case mono- or polysubstituted or unsubstituted; COR 12 ; SO 2 R 12 , wherein
R 12 denotes H; C 1-5 -alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted; C 3-8 -cycloalkyl, in each case saturated or unsaturated, mono- or polysubstituted or unsubstituted; aryl-, or heteroaryl, in each case mono- or polysubstituted or unsubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are in each case mono- or polysubstituted or unsubstituted; OR 13 ; NR 14 R 15 ;

R 5 represents ═O; H; COOR 13 , CONR 13 , OR 13 ; C 1-5 -alkyl, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; C 3-8 -cycloalkyl, saturated or unsaturated, unsubstituted or mono- or polysubstituted; aryl-, or heteroaryl, unsubstituted or mono- or polysubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are unsubstituted or mono- or polysubstituted;
R 6 represents H; F, Cl, NO 2 , CF 3 , OR 13 , SR 13 , SO 2 R 13 , SO 2 OR 13 , CN, COOR 13 , NR 14 R 15 ; C 1-5 -alkyl, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; C 3-8 -cycloalkyl, saturated or unsaturated, unsubstituted or mono- or polysubstituted; aryl-, or heteroaryl, unsubstituted or mono- or polysubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are unsubstituted or mono- or polysubstituted; or
R 5 and R 6 together denote (CH 2 ) n , where n=2, 3, 4, 5 or 6, wherein individual hydrogen atoms can also be replaced by F, Cl, Br, I, NO 2 , CF 3 , OR 13 , CN or C 1-5 -alkyl;
R 7 , R 8 , R 9 and R 10 independently of one another represent H, F, Cl, Br, I, NO 2 , CF 3 , OR 13 , SR 13 , SO 2 R 13 , SO 2 OR 13 , SO 2 NH 2 CN, COOR 13 , NR 14 R 15 ; C 1-5 -alkyl, C 3-8 -cycloalkyl, unsubstituted or mono- or polysubstituted; aryl-, or heteroaryl, unsubstituted or mono- or polysubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are unsubstituted or mono- or polysubstituted;
wherein
R 13 denotes H; C 1-5 -alkyl in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; C 3-8 -cycloalkyl, in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted; aryl-, or heteroaryl, unsubstituted or mono- or polysubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are unsubstituted or mono- or polysubstituted;
R 14 and R 15 independently denote H; C 1-5 -alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; or C 3-8 -cycloalkyl, in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted; aryl-, or heteroaryl, unsubstituted or mono- or polysubstituted; or aryl, C 3-8 -cycloalkyl or heteroaryl which are bonded via C 1-3 -alkyl and are unsubstituted or mono- or polysubstituted; or
R 14 and R 15 together form CH 2 CH 2 OCH 2 CH 2 , CH 2 CH 2 NR 16 CH 2 CH 2 or (CH 2 ) 3-6 , wherein
R 16 denotes H; C 1-5 -alkyl saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted;

X represents O, S, SO or, SO 2 ;
wherein, with reference to alkyl, mono- or polysubstituted means substitution of one or more hydrogen radicals by F, Cl, Br, I, —CN, NH 2 , NH-alkyl, NH-aryl, NH-heteroaryl, NH-cycloalkyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-OH, N(alkyl) 2 , N(alkyl-aryl) 2 , N(alkyl-heteroaryl) 2 , N(cycloalkyl) 2 , N(alkyl-OH) 2 , NO 2 , SH, S-alkyl, S-aryl, S-heteroaryl, S-alkyl-aryl, S-alkyl-heteroaryl, S-cycloalkyl, S-alkyl-OH, S-alkyl-SH, OH, O-alkyl, O-aryl, O-heteroaryl, O-alkyl-aryl, O-alkyl-heteroaryl, O-cycloalkyl, O-alkyl-OH, CHO, C(═O)C 1-6 -alkyl, C(═S)C 1-6 -alkyl, C(═O)aryl, C(═S)aryl, C(═O)C 1-6 -alkyl-aryl, C(═S)C 1-6 -alkyl-aryl, C(═O)-heteroaryl, C(═S)-heteroaryl, C(═O)-cycloalkyl, C(═S)-cycloalkyl, CO 2 H, CO 2 -alkyl, CO 2 -alkyl-aryl, C(═O)NH 2 , C(═O)NH-alkyl, C(═O)NHaryl, C(═O)NH-cycloalkyl, C(═O)N(alkyl) 2 , C(═O)N(alkyl-aryl) 2 , C(═O)N(alkyl-heteroaryl) 2 , C(═O)N(cycloalkyl) 2 , SO-alkyl, SO 2 -alkyl, SO 2 NH 2 , SO 3 H, PO(O—C 1-6 -alkyl) 2 , Si(C 1-6 -alkyl) 3 , Si(C 3-8 -cycloalkyl) 3 , Si(CH 2 —C 3-8 -cycloalkyl) 3 , Si(phenyl) 3 , cycloalkyl, aryl or heteroaryl on one or different atoms, and
wherein, with reference to aryl, heteroaryl and cycloalkyl, mono- or polysubstituted means substitution of one or more hydrogen atoms of the ring system by F, Cl, Br, I, CN, NH 2 , NH-alkyl, NH-aryl, NH-heteroaryl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-cycloalkyl, NH-alkyl-OH, N(alkyl) 2 , N(alkyl-aryl) 2 , N(alkyl-heteroaryl) 2 , N(cycloalkyl) 2 , N(alkyl-OH) 2 , NO 2 , SH, S-alkyl, S-cycloalkyl, S-aryl, S-heteroaryl, S-alkyl-aryl, S-alkyl-heteroaryl, S-cycloalkyl, S-alkyl-OH, S-alkyl-SH, OH, O-alkyl, O-cycloalkyl, O-aryl, O-heteroaryl, O-alkyl-aryl, O-alkyl-heteroaryl, O-cycloalkyl, O-alkyl-OH, CHO, C(═O)C 1-6 -alkyl, C(═S)C 1-6 -alkyl, C(═O)aryl, C(═S)aryl, C(═O)—C 1-6 -alkyl-aryl, C(═S)C 1-6 -alkyl-aryl, C(═O)-heteroaryl, C(═S)-heteroaryl, C(═O)-cycloalkyl, C(═S)-cycloalkyl, CO 2 H, CO 2 -alkyl, CO 2 -alkyl-aryl, C(═O)NH 2 , C(═O)NH-alkyl, C(═O)NHaryl, C(═O)NH-cycloalkyl, C(═O)N(alkyl) 2 , C(═O)N(alkyl=aryl) 2 , C(═O)N(alkyl-heteroaryl) 2 , C(═O)N(cycloalkyl) 2 , S(O)-alkyl, S(O)-aryl, SO 2 -alkyl, SO 2 -aryl, SO 2 NH 2 , SO 3 H, CF 3 , ═O, ═S; alkyl, cycloalkyl, aryl or heteroaryl; on one or different atoms;

or a physiologically acceptable salt thereof
said process comprising reacting an adduct corresponding to formula A

wherein R 01 and R 02 have the meaning given for R 2 and additionally can represent a protective group, in the presence of an acid or a trimethylsilyl ester, in a suitable solvent, with an adduct corresponding to formula B

2. A process acco

Assignees

• Gruenenthal Gmbh

Inventors

• Hinze Claudia
• Aulenbacher Otto
• Sundermann Bernd
• Oberboersch Stefan
• Friderichs Elmar
• Englberger Werner
• Koegel Babette-Yvonne
• Linz Klaus
• Schick Hans
• Sonnenschein Helmut
• Henkel Birgitta
• Rose Valerie Sarah
• Lipkin Michael Jonathan

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/02

  Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title

• A61P43/00

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