CN109563051A - 作为pde4抑制剂的并环类化合物 - Google Patents

作为pde4抑制剂的并环类化合物 Download PDF

Info

Publication number
CN109563051A
CN109563051A CN201780046018.7A CN201780046018A CN109563051A CN 109563051 A CN109563051 A CN 109563051A CN 201780046018 A CN201780046018 A CN 201780046018A CN 109563051 A CN109563051 A CN 109563051A
Authority
CN
China
Prior art keywords
compound
pharmaceutically acceptable
acceptable salt
alkyl
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201780046018.7A
Other languages
English (en)
Other versions
CN109563051B (zh
Inventor
罗云富
杨纯道
雷茂义
孙兰宝
胡国平
黎健
陈曙辉
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medshine Discovery Inc
Original Assignee
Medshine Discovery Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medshine Discovery Inc filed Critical Medshine Discovery Inc
Publication of CN109563051A publication Critical patent/CN109563051A/zh
Application granted granted Critical
Publication of CN109563051B publication Critical patent/CN109563051B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/26—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

提供一种PDE4抑制剂，及其在制备治疗与PDE4相关疾病的药物中的应用。具体公开了式(I)所示化合物及其药学上可接受的盐。

Description

PCT国内申请，说明书已公开。

Claims (23)

  1. PCT国内申请，权利要求书已公开。
CN201780046018.7A 2016-08-22 2017-08-22 作为pde4抑制剂的并环类化合物 Active CN109563051B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201610706073 2016-08-22
CN2016107060731 2016-08-22
PCT/CN2017/098462 WO2018036470A1 (zh) 2016-08-22 2017-08-22 作为pde4抑制剂的并环类化合物

Publications (2)

Publication Number Publication Date
CN109563051A true CN109563051A (zh) 2019-04-02
CN109563051B CN109563051B (zh) 2024-06-11

Family

ID=61246426

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780046018.7A Active CN109563051B (zh) 2016-08-22 2017-08-22 作为pde4抑制剂的并环类化合物

Country Status (6)

Country Link
US (1) US10532986B2 (zh)
EP (1) EP3502099B1 (zh)
JP (1) JP7050054B2 (zh)
CN (1) CN109563051B (zh)
ES (1) ES2852098T3 (zh)
WO (1) WO2018036470A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111683949A (zh) * 2018-01-29 2020-09-18 石家庄智康弘仁新药开发有限公司 一种1H-咪唑并[4,5-b]吡啶-2(3H)-酮类化合物的晶型及其制备方法

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114072382B (zh) * 2019-07-04 2023-05-26 南京明德新药研发有限公司 一种苯并咪唑-2-酮类化合物的晶型、溶剂化物、溶剂化物的晶型及它们的制备方法
US20230141101A1 (en) * 2020-02-24 2023-05-11 Suzhou Longbotai Pharmaceuticals Co., Ltd. Pde4 inhibitor compound and medical use thereof
JP2024513538A (ja) * 2021-04-12 2024-03-25 インパクト セラピューティクス （シャンハイ）， インコーポレイテッド Ｐａｒｐ阻害剤としての置換融合二環式化合物及びその使用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002072576A1 (en) * 2001-03-09 2002-09-19 Pfizer Products Inc. Benzimidazole anti-inflammatory compounds
US20040192748A1 (en) * 2002-09-13 2004-09-30 Boehringer Ingelheim Parmaceuticals, Inc. Heterocyclic compounds
CN101528712A (zh) * 2006-08-26 2009-09-09 艾博特股份有限两合公司 取代的苯并咪唑酮衍生物、包含它们的药物以及其用途
WO2011021678A1 (ja) * 2009-08-21 2011-02-24 武田薬品工業株式会社 縮合複素環化合物
WO2012021382A1 (en) * 2010-08-12 2012-02-16 Merck Sharp & Dohme Corp. Positive allosteric modulators of mglur2
CN105407888A (zh) * 2013-06-21 2016-03-16 齐尼思表观遗传学公司 新双环溴结构域抑制剂

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150119370A (ko) 2013-02-19 2015-10-23 화이자 인코포레이티드 Cns 장애 및 다른 장애의 치료를 위한 pde4 동종효소의 억제제로서의 아자벤즈이미다졸 화합물
JP2014114308A (ja) 2014-01-31 2014-06-26 Celgene Corp （＋）−２−［１−（３−エトキシ−４−メトキシフェニル）−２−メチルスルホニルエチル］−４−アセチルアミノイソインドリン−１，３−ジオンを含む固形物形態、その組成物およびその使用
AR101196A1 (es) 2014-07-16 2016-11-30 Gruenenthal Gmbh Compuestos de pirimidina sustituidos

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002072576A1 (en) * 2001-03-09 2002-09-19 Pfizer Products Inc. Benzimidazole anti-inflammatory compounds
US20040192748A1 (en) * 2002-09-13 2004-09-30 Boehringer Ingelheim Parmaceuticals, Inc. Heterocyclic compounds
CN101528712A (zh) * 2006-08-26 2009-09-09 艾博特股份有限两合公司 取代的苯并咪唑酮衍生物、包含它们的药物以及其用途
WO2011021678A1 (ja) * 2009-08-21 2011-02-24 武田薬品工業株式会社 縮合複素環化合物
WO2012021382A1 (en) * 2010-08-12 2012-02-16 Merck Sharp & Dohme Corp. Positive allosteric modulators of mglur2
CN105407888A (zh) * 2013-06-21 2016-03-16 齐尼思表观遗传学公司 新双环溴结构域抑制剂
US20160159801A1 (en) * 2013-06-21 2016-06-09 Zenith Epigenetics Corp. Novel bicyclic bromodomain inhibitors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RAEWYN M. POOLE等: ""Apremilast: First Global Approval"", 《DRUGS》, vol. 74, pages 825 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111683949A (zh) * 2018-01-29 2020-09-18 石家庄智康弘仁新药开发有限公司 一种1H-咪唑并[4,5-b]吡啶-2(3H)-酮类化合物的晶型及其制备方法
CN111683949B (zh) * 2018-01-29 2023-03-21 南京明德新药研发有限公司 一种1H-咪唑并[4,5-b]吡啶-2(3H)-酮类化合物的晶型及其制备方法

Also Published As

Publication number Publication date
WO2018036470A1 (zh) 2018-03-01
JP7050054B2 (ja) 2022-04-07
EP3502099A4 (en) 2020-03-04
JP2019529364A (ja) 2019-10-17
EP3502099A1 (en) 2019-06-26
US20190210975A1 (en) 2019-07-11
ES2852098T3 (es) 2021-09-13
US10532986B2 (en) 2020-01-14
EP3502099B1 (en) 2020-12-09
CN109563051B (zh) 2024-06-11

Similar Documents

Publication Publication Date Title
CN109715634B (zh) Menin-mll相互作用的稠合二环抑制剂
CN109071538A (zh) 作为ask1抑制剂的吡啶衍生物及其制备方法和应用
CN104837829B (zh) 抑制剂化合物
CN110198943A (zh) 作为Wee1抑制剂的1,2-二氢-3H-吡唑[3,4-d]嘧啶-3-酮衍生物
CN113490664A (zh) Tyk2抑制剂和其用途
CN111440189B (zh) 稠环嘧啶氨基衍生物、其制备方法、中间体、药物组合物及应用
ES2614355T3 (es) Derivados de glicina N-sustituida con piridazin-diona como inhibidores de HIF hidoxilasas
TW201823250A (zh) Ｍｅｎｉｎ－ｍｌｌ相互作用之螺二環抑制劑
CN109071448A (zh) Ask1抑制剂及其制备方法和应用
CN109563051A (zh) 作为pde4抑制剂的并环类化合物
CN109689663B (zh) Menin-mll相互作用的螺二环抑制剂
CN109790159A (zh) 抗流感病毒嘧啶衍生物
CN112312904A (zh) 螺环化合物
CN106459009A (zh) 丙肝病毒抑制剂及其制药用途
CN111601807B (zh) Menin-mll相互作用的外型-氮杂螺抑制剂
CN107531711A (zh) Janus激酶抑制剂
CN109970743A (zh) 为jak抑制剂的5-氯-2-二氟甲氧基苯基吡唑并嘧啶化合物
CN109661395A (zh) Pde4抑制剂
CN111683928B (zh) 作为fgfr抑制剂的吡嗪-2(1h)-酮类化合物
CN110088101A (zh) 一种含氮杂环类化合物、其制备方法、药物组合物及应用
US10604513B2 (en) Pyridone derivative comprising heteroatomic ring butane substituent, for treating fibrosis and inflammatory diseases
BR112016019487B1 (pt) Inibidores de di-hidropiridinona mgat2 tetrazolonasubstituídos, composição farmacêutica e seus usos
WO2018228475A1 (zh) Syk抑制剂及其使用方法
TW201817724A (zh) 化合物
CN110023292A (zh) 细胞凋亡抑制剂

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB02 Change of applicant information

Country or region after: China

Address after: 210032 room 218, business office building, No.9 Gaoxin Road, Jiangbei new district, Nanjing City, Jiangsu Province

Applicant after: Nanjing Mingde New Drug Development Co.,Ltd.

Address before: Room 218, No. 9 Commercial Office Building, Gaoxin Road, Nanjing High-tech Development Zone, Jiangsu Province

Applicant before: MEDSHINE DISCOVERY Inc.

Country or region before: China

CB02 Change of applicant information
GR01 Patent grant
GR01 Patent grant