MAGL 억제제로서 헤테로환형 스피로 화합물

• Main Authors: BRODNEY MICHAEL AARON, O'NEIL STEVEN VICTOR, MCALLISTER LAURA, BUTLER CHRISTOPHER RYAN
• Format: Patent
• Language: Korean
• Published: 26.03.2021
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

본 발명은 1,1,1,3,3,3-헥사플루오로프로판-2-일 (3R)-3-{[(사이클로프로필메틸)설폰일]아미노}-1-옥사-8-아자스피로[4.5]데칸-8-카복시레이트; 1,1,1,3,3,3-헥사플루오로프로판-2-일 (3R)-3-[(사이클로프로필설폰일)아미노]-1-옥사-8-아자스피로[4.5]데칸-8-카복시레이트; 1,1,1,3,3,3-헥사플루오로프로판-2-일 3-{[(사이클로프로필메틸)설폰일]아미노}-1-옥사-9-아자스피로[5.5]운데칸-9-카복시레이트; 1,1,1,3,3,3-헥사플루오로프로판-2-일 3-{[(사이클로프로필메틸)설폰일]아미노}-1-옥사-9-아자스피로[5.5]운데칸-9-카복시레이트, ENT-1; 및 1,1,1,3,3,3-헥사플루오로프로판-2-일 3-{[(사이클로프로필메틸)설폰일]아미노}-1-옥사-9-아자스피로[5.5]운데칸-9-카복시레이트, ENT-2 로 이루어진 군으로부터 선택된 화합물 또는 이의 약학적으로 허용되는 염; 이의 제조 방법; 이의 제조를 위한 중간체; 및 상기 화합물 또는 이의 염을 함유하는 조성물, 및 예를 들어 통증, 염증성 장애, 우울증, 불안, 알츠하이머병, 대사 장애, 지방간염[예를 들어 비알코올성 지방간염(NASH)], 뇌졸중 또는 암을 포함하는 MAGL-매개된 질병 및 장애를 치료하기 위한 이의 용도를 부분적으로 제공한다. The present invention provides, in part, a compound selected from the group consisting of:1,1,1,3,3,3-hexafluoropropan-2-yl (3R)-3-{[(cyclopropylmethyl)sulfonyl]amino}-1-oxa-8-azaspiro[4.5]decane-8-carboxylate;1,1,1,3,3,3-hexafluoropropan-2-yl (3R)-3-[(cyclopropylsulfonyl)amino]-1-oxa-8-azaspiro[4.5]decane-8-carboxylate;1,1,1,3,3,3-hexafluoropropan-2-yl 3-{[(cyclopropylmethyl)sulfonyl]amino}-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate;1,1,1,3,3,3-hexafluoropropan-2-yl 3-{[(cyclopropylmethyl)sulfonyl]amino}-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate, ENT-1; and1,1,1,3,3,3-hexafluoropropan-2-yl 3-{[(cyclopropylmethyl)sulfonyl]amino}-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate, ENT-2,and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, steatohepatitis [e.g. nonalcoholic Steatohepatitis (NASH)], stroke, or cancer.