Tetraaza-cyclopenta[a]indenyl and their use as positive allosteric modulators

Patent metadata

Field	Value
Publication number	US-9403835-B2
Application number	US-201214366901-A
Country	US
Kind code	B2
Filing date	Nov 30, 2012
Priority date	Dec 22, 2011
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The present invention provides compounds of Formula (I) as M1 receptor positive allosteric modulators for the treatment of diseases mediated by the muscarinic M1 mediator.

First claim

The invention claimed is:

1. A compound of Formula (I)

wherein
R 1 , R 2 , R 3 are each independently H, linear or branched C 1 -C 6 -alkyl, linear or branched C 1 -C 6 -alkoxy, Hal, or hydroxyl;
R a , R b are each independently H, Hal, hydroxy or A;
Q denotes a 6-membered aromatic group or a 5-6-membered heteroaromatic group having 1 to 4 heteroatoms independently selected from N, O and S;
R 4 denotes G, OG, SG, OCHF 2 , OCF 2 CHF 2 , NR 5 G, —COOG, or OCOG;
each R 5 is independently H or a linear or branched alkyl having 1 to 6 carbon atoms;
each G is independently —CH 3 , —CF 3 , —CH 2 -A, Het, Cyc, Ar, —CH 2 -Het, —CH 2 -Cyc, —CH 2 —Ar, Hal, or hydroxy;
each Hal is independently F, Cl, Br or I;
each A is independently a linear or branched carbon chain having 1 to 6 carbon atoms, wherein 1 to 3 non adjacent —CH 2 -groups may be independently from each other substituted by a group selected from O, NR 5 , S, SO, SO 2 , CO, and wherein 1 to 5 hydrogen atoms may be independently from each other substituted by Het, Cyc, Ar, or Hal;
each Het is independently a saturated, unsaturated or aromatic ring, each of which is monocyclic, bicyclic, or fused-bicyclic, and having 3- to 8-members and containing 1 to 4 heteroatoms independently selected from N, NR 5 , O, S, CO, SO or SO 2 , each of which may be substituted by 1 to 3 substituents independently selected from A, Hal, OH and Het 1 ;
Het 1 denotes a 4, 5 or 6 membered carbocyclic ring wherein 1 or 2 carbon atom are replaced by Oxygen atoms;
each Ar is independently a 6-membered carbocyclic aromatic ring or a fused or non fused byclic aromatic ring, and optionally substituted by 1 to 3 substituents independently selected from A or Hal;
each Cyc is independently a saturated or unsaturated carbocyclic ring having from 3 to 8 carbon atoms and optionally substituted by 1 to 3 substituents independently selected from A or Hal;
and/or pharmaceutically acceptable derivatives, tautomers, salts, and stereoisomers thereof.

2. The compound of claim 1 wherein
Q is a phenyl ring;
R a , R b are each independently H, Hal, Hydroxy, or a linear or branched alkyl group having 1 to 6 carbon atoms and wherein 1 to 3 hydrogen atoms may be replaced by Hal; and
R 4 is G or OG.

3. The compound of claim 1 , wherein

is selected from:

4. The compound of claim 1 , selected from:

Ex
Structures

 1

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Assignees

• Merck Patent Gmbh
• Ares Trading Sa

Inventors

• Swinnen Dominique
• Montagne Cyril
• Pomel Vincent
• Quattropani Anna
• Molette Jerome
• Gerber Patrick

Classifications

• A61P43/00

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title