3-((Hetero-)Aryl)-8-Amino-2-Oxo-1,3-Diaza-Spiro-[4.5]-Decane Derivatives

Patent metadata

Field	Value
Publication number	US-2018201616-A1
Application number	US-201815923948-A
Country	US
Kind code	A1
Filing date	Mar 16, 2018
Priority date	Jan 13, 2016
Publication date	Jul 19, 2018
Grant date	—

Abstract

The invention relates to 3-((hetero-)aryl)-8-amino-2-oxo-1,3 -diaza-spiro-[4.5]-decane derivatives, their preparation and their use in medicine, particularly in the treatment of pain.

First claim

1 . A compound according to general formula (I)

wherein
R 1 and R 2 independently of one another mean
—H;
—C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ;
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ;
wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OCH 3 , —CN and —CO 2 CH 3 ;
wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or
R 1 and R 2 together with the nitrogen atom to which they are attached form a ring and mean —(CH 2 ) 3-6 —; —(CH 2 ) 2 —O—(CH 2 ) 2 —; or —(CH 2 ) 2 —NR A —(CH 2 ) 2 —, wherein R A means —H or —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br and —I;
R 3 means
—C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
R 4 means
—H;
—C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said —C 1 -C 6 -alkyl is optionally connected through —C(═O)—, —C(═O)O—, or —S(═O) 2 —;
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 6-14-membered aryl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —; or
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5-14-membered heteroaryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 5-14-membered heteroaryl moiety is optionally connected through —C(═O)—, —C(═O)O—, —C(═O)O—CH 2 —, or —S(═O) 2 —;
R 5 means
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; or
a 5-14-membered heteroaryl moiety, unsubstituted, mono- or polysubstituted;
R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20 independently of one another mean —H, —F, —Cl, —Br, —I, —OH, or —C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted;
wherein “mono- or polysubstituted” means that one or more hydrogen atoms are replaced by a substituent independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —R 21 , —C(═O)R 21 , —C(═O)OR 21 , —C(═O)NR 21 R 22 , —C(═O)NH—(CH 2 CH 2 —) 1-30 —CH 3 , —O—(CH 2 CH 2 —O) 1-30 —H, —O—(CH 2 CH 2 —O) 1-30 —CH 3 , ═O, —OR 21 , —OC(═O)R 21 , —OC(═O)OR 21 , —OC(═O)NR 21 R 22 , —NO 2 , —NR 21 R 22 , —NR 21 —(CH 2 ) 1-6 —C(═O)R 22 , —NR 21 —(CH 2 ) 1-6 —C(═O)OR 22 , —NR 23 —(CH 2 ) 1-6 —C(═O)NR 21 R 22 , —NR 21 C(═O)R 22 , —NR 21 C(═O)—OR 22 , —NR 23 C(═O)NR 21 R 22 , —NR 21 S(═O) 2 R 22 , —SR 21 , —S(═O)R 21 , —S(═O) 2 R 21 , —S(═O) 2 OR 21 , and —S(═O) 2 NR 21 R 22 ;
wherein
R 21 , R 22 and R 23 independently of one another mean
—H;
—C 1 -C 6 -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —CO 2 H, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)NH 2 , —C(═O)NHC 1 -C 6 -alkyl, —C(═O)N(C 1 -C 6 -alkyl) 2 , —O—C 1 -C 6 -alkyl and —S(═O) 2 —C 1 -C 6 -alkyl;
a 3-12-membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered cycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
a 3-12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3-12-membered heterocycloalkyl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1 -C 6 -alkyl and —O—C 1 -C 6 -alkyl;
a 6-14-membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6-14-membered aryl moiety is optionally connected through —C 1 -C 6 -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —C 1

Assignees

• Gruenenthal Gmbh

Inventors

• Kuehnert Sven
• Koenigs Rene
• Kless Achim
• Wegert Anita
• Konetzki Ingo
• Ratcliffe Paul
• Jostock Ruth
• Koch Thomas
• Linz Klaus
• Schroeder Wolfgang

Classifications

• A61P25/04

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

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title