Pentacyclic heterocycles

Patent metadata

Field	Value
Publication number	US-11358972-B2
Application number	US-202016807335-A
Country	US
Kind code	B2
Filing date	Mar 3, 2020
Priority date	Mar 5, 2019
Publication date	Jun 14, 2022
Grant date	Jun 14, 2022

Abstract

The present invention provides compounds represented by formulas (I) to (XVII) or pharmaceutically acceptable salts thereof:

First claim

What is claimed is:

1. A compound selected from the group consisting of (3aS,14aR)-5-Methyl-3,3a,5,6-tetrahydro-1H-benzofuro[3′,2′:4,5]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13(2H,14aH)-dione:

(+)-7,7,12-Trimethyl-1,2,3,6,7,10,11,12,13,15b-decahydropyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a]pyrrolo[2,1-c][1,4]diazepine-5,9-dione:

(3aS,14aR)-10-Fluoro-5-methyl-3,3a,5,6-tetrahydro-1H-benzofuro[3′,2′:4,5]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13(2H,14aH)-dione:

(3aS,14aR)-5,8,10-Trimethyl-3,3a,5,6-tetrahydro-1H-cyclopenta[f]pyrido[3″,2″:4′,5′]furo[3′,2′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13(2H,14aH)-dione:

(3aR,14aR)-10-Fluoro-5-methyl-3,3a,5,6-tetrahydro-1H-benzofuro[3′,2′:4,5]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13(2H,14aH)-dione:

(3aR,14aR)-5-Methyl-10-(trifluoromethyl)-3,3a,5,6-tetrahydro-1H-benzofuro[3′,2′:4,5]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13(2H,14aH)-dione:

(3aS,14aR)-10-(2,2-Difluoroethyl)-5-methyl-2,3,3a,5,6,9,10,11,12,14a-decahydro-1H-cyclopenta[f]pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13-dione:

(3aS,14aR)-10-(2-Methoxyethyl)-5-methyl-2,3,3a,5,6,9,10,11,12,14a-decahydro-1H-cyclopenta[f]pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13-dione:

(3aS,14aR)-10-(Difluoromethyl)-5-methyl-3,3a,5,6-tetrahydro-1H-benzofuro[3′,2′:4,5]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13(2H,14aH)-dione:

(2R,15bR)-2-Fluoro-7,7,12-trimethyl-1,2,3,6,7,10,11,12,13,15b-decahydro-5H,9H-pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a]pyrrolo[2,1-c][1,4]diazepine-5,9-dione:

(+)-(3a,14a-cis)-5,10-Dimethyl-1,3,3a,5,6,9,10,11,12,14a-decahydrofuro[3,4-f]pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13-dione:

(3aS,14aS)-5-Methyl-10-(trifluoromethyl)-2,3,3a,5,6,14a-hexahydro-1H-benzofuro[3′,2′:4,5′]pyrimido[1,2-a]cyclopenta[f][1,4]diazepine-4,13-dione:

(+12-(2-Methoxyethyl)-7,7-dimethyl-1,2,3,6,7,10,11,12,13,15b-decahydro-5H,9H-pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a]pyrrolo[2,1-c][1,4]diazepine-5,9-dione:

(3aR,14aR)-5,9-Dimethyl-2,3,3a,5,6,8,9,10,11,14a-decahydro-1H-cyclopenta[f]pyrido[3″,4″:4′,5′]thieno[3′,2′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13-dione:

(3aR, 10R,14aR)-10-Fluoro-2,5-dimethyl-2,3,3a,5,6,9,10,11,12,14a-decahydro-1H-benzo[4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a]pyrrolo[3,4-f][1,4]diazepine-4,13-dione:

(3aS,14aS)-10-(2-methoxyethyl)-5-methyl-2,3,3a,5,6,9,10,11,12,14a-decahydro-1H-cyclopenta[f]pyrido[4″,3″:4′,5′]thieno[2′,3′:4,5]pyrimido[1,2-a][1,4]diazepine-4,13-dione:

and (−)-(3a,14a-trans)-2-(2-fluoroethyl)-5-methyl-2,3,3a,5,6,14a-hexahydro-1H-benzofuro[3′,2′: 4,5]pyrimido[1,2-a]pyrrolo[3,4-f][1,4]diazepine-4,13-dione:

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 and one or more pharmaceutically acceptable excipients.

3. A method for treating cognitive dysfunction in a patient with Alzheimer's disease or dementia with Lewy bodies, comprising administering to the patient the compound or pharmaceutically acceptable salt thereof according to claim 1 .

4. The method of claim 3 , wherein the patient has Alzheimer's disease.

5. The method of claim 3 , wherein the patient has dementia with Lewy bodies.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Ohashi Yoshiaki
• Norimine Yoshihiko
• HOSHIKAWA Tamaki
• Yoshida Yu
• Kobayashi Yoshihisa
• Sato Nobuhiro
• Hagiwara Koji
• Sato Nobuaki
• Hirota Shinsuke
• Harada Takaaki
• YOSHIMURA Hikaru

Classifications

• C07D495/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title

• C07D491/22

  in which the condensed system contains four or more hetero rings · CPC title

• C07D491/147 Primary

  the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title