CN109963836A - 氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用 - Google Patents

氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用 Download PDF

Info

Publication number
CN109963836A
CN109963836A CN201880004431.1A CN201880004431A CN109963836A CN 109963836 A CN109963836 A CN 109963836A CN 201880004431 A CN201880004431 A CN 201880004431A CN 109963836 A CN109963836 A CN 109963836A
Authority
CN
China
Prior art keywords
atom
alkyl
heterocycle
hydroxyl
halogen
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
CN201880004431.1A
Other languages
English (en)
Other versions
CN109963836B (zh
Inventor
刘�东
陈磊
陆标
刘苏星
张儒民
贺峰
陶维康
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.)
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
Original Assignee
Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
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 Jiangsu Hengrui Medicine Co Ltd, Shanghai Hengrui Pharmaceutical Co Ltd filed Critical Jiangsu Hengrui Medicine Co Ltd
Publication of CN109963836A publication Critical patent/CN109963836A/zh
Application granted granted Critical
Publication of CN109963836B publication Critical patent/CN109963836B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • 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
    • C07D401/06—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 only aliphatic carbon atoms
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Indole Compounds (AREA)

Abstract

一种涉及氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用。特别地，涉及通式(I)所示的氘原子取代的吲哚甲酰胺类衍生物、其制备方法、含有该衍生物的药物组合物，其作为ROR激动剂的用途以及其用于预防和/或治疗肿瘤或癌症的用途，其中通式(I)中的各取代基与说明书中的定义相同。

Description

PCT国内申请，说明书已公开。

Claims (22)

  1. PCT国内申请，权利要求书已公开。
CN201880004431.1A 2017-09-12 2018-09-11 氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用 Active CN109963836B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201710817140 2017-09-12
CN2017108171401 2017-09-12
PCT/CN2018/105008 WO2019052440A1 (zh) 2017-09-12 2018-09-11 氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用

Publications (2)

Publication Number Publication Date
CN109963836A true CN109963836A (zh) 2019-07-02
CN109963836B CN109963836B (zh) 2022-11-22

Family

ID=65723209

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201880004431.1A Active CN109963836B (zh) 2017-09-12 2018-09-11 氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用

Country Status (9)

Country Link
US (1) US20200277278A1 (zh)
EP (1) EP3683206A4 (zh)
JP (1) JP2020533337A (zh)
CN (1) CN109963836B (zh)
AU (1) AU2018331125A1 (zh)
BR (1) BR112020004611A2 (zh)
CA (1) CA3075324A1 (zh)
TW (1) TW201912627A (zh)
WO (1) WO2019052440A1 (zh)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW202043197A (zh) * 2019-01-04 2020-12-01 大陸商江蘇恒瑞醫藥股份有限公司 吲哚甲醯胺類衍生物的晶型及其製備方法
TW202100513A (zh) * 2019-03-11 2021-01-01 大陸商江蘇恒瑞醫藥股份有限公司 氘原子取代的吲哚甲酰胺類衍生物的晶型及其製備方法
CN112745268B (zh) * 2019-10-31 2022-09-16 江苏恒瑞医药股份有限公司 苯并咪唑衍生物的晶型及制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160122318A1 (en) * 2014-11-05 2016-05-05 Vitae Pharmaceuticals, Inc. Isoindoline inhibitors of ror-gamma
WO2017024018A1 (en) * 2015-08-05 2017-02-09 Vitae Pharmaceuticals, Inc. Modulators of ror-gamma
WO2017157332A1 (zh) * 2016-03-18 2017-09-21 江苏恒瑞医药股份有限公司 芳香酰胺类衍生物、其制备方法及其在医药上的应用
CN109952298A (zh) * 2017-07-06 2019-06-28 江苏恒瑞医药股份有限公司 吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19847943A1 (de) 1998-10-09 2000-04-13 Deutsche Telekom Ag Verfahren zum Generieren von digitalen Wasserzeichen für elekronische Dokumente
ES2317076T3 (es) 2003-12-08 2009-04-16 GALDERMA RESEARCH & DEVELOPMENT Derivados bifenilicos utiles como ligandos que activan receptores rar, procedimiento para prepararlos y su utilizacion en medicina humana y en cosmeticos.
FR2863266B1 (fr) 2003-12-08 2006-01-27 Galderma Res & Dev NOUVEAUX LIGANDS ACTIVATEURS DES RECEPTEURS RARs, UTILISATION EN MEDECINES HUMAINE AINSI QU'EN COSMETIQUE
US7476673B2 (en) 2003-12-30 2009-01-13 Allergan, Inc. Disubstituted chalcone oximes as selective agonists of RARγ retinoid receptors
FR2894960B1 (fr) 2005-12-15 2008-02-29 Galderma Res & Dev Derives biphenyliques agonistes selectifs du recepteurs rar-gamma
FR2894959B1 (fr) 2005-12-15 2008-02-29 Galderma Res & Dev Derives biphenyliques agonistes selectifs du recepteur rar-gamma
TW200815384A (en) 2006-08-25 2008-04-01 Viropharma Inc Combination therapy method for treating hepatitis C virus infection and pharmaceutical compositions for use therein
FR2915993B1 (fr) 2007-05-11 2009-07-03 Galderma Res & Dev Nouveaux ligands agonistes des recepteurs pars, utilisation en medecine humaine ainsi qu'en cosmetique.
JP2011037803A (ja) 2009-08-18 2011-02-24 Central Glass Co Ltd ホルミル基置換芳香族化合物の製造方法
EP2722329A1 (en) 2012-10-18 2014-04-23 F. Hoffmann-La Roche AG Indol-amide compounds as beta-amyloid inhbitors
WO2015171558A2 (en) 2014-05-05 2015-11-12 Lycera Corporation BENZENESULFONAMIDO AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORγ AND THE TREATEMENT OF DISEASE
WO2015176267A1 (en) 2014-05-22 2015-11-26 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
US9481674B1 (en) 2016-06-10 2016-11-01 Vitae Pharmaceuticals, Inc. Dihydropyrrolopyridine inhibitors of ROR-gamma

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160122318A1 (en) * 2014-11-05 2016-05-05 Vitae Pharmaceuticals, Inc. Isoindoline inhibitors of ror-gamma
WO2017024018A1 (en) * 2015-08-05 2017-02-09 Vitae Pharmaceuticals, Inc. Modulators of ror-gamma
WO2017157332A1 (zh) * 2016-03-18 2017-09-21 江苏恒瑞医药股份有限公司 芳香酰胺类衍生物、其制备方法及其在医药上的应用
CN109952298A (zh) * 2017-07-06 2019-06-28 江苏恒瑞医药股份有限公司 吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用

Also Published As

Publication number Publication date
AU2018331125A1 (en) 2020-03-05
CA3075324A1 (en) 2019-03-21
BR112020004611A2 (pt) 2020-09-24
TW201912627A (zh) 2019-04-01
EP3683206A1 (en) 2020-07-22
WO2019052440A1 (zh) 2019-03-21
CN109963836B (zh) 2022-11-22
US20200277278A1 (en) 2020-09-03
JP2020533337A (ja) 2020-11-19
EP3683206A4 (en) 2021-01-13

Similar Documents

Publication Publication Date Title
CN111647000B (zh) 吡嗪类衍生物及其在抑制shp2中的应用
EP2358371B1 (en) P2x3, receptor antagonists for treatment of pain
CN106660974B (zh) 含氨磺酰基的1,2,5-噁二唑类衍生物、其制备方法及其在医药上的应用
KR101159034B1 (ko) 혈관신생 억제제로서의 6환 아미노-아미드 유도체
CN109952298A (zh) 吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用
AU2015336458B2 (en) KCNQ2-5 channel activator
CN110366555A (zh) 甾族类衍生物调节剂、其制备方法和应用
CN107531679A (zh) 芳香酰胺类衍生物、其制备方法及其在医药上的应用
CN107033097B (zh) 噁二唑类衍生物、其制备方法及其在医药上的应用
CN109963836A (zh) 氘原子取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用
TW202003495A (zh) 苯並哌啶或雜芳基並哌啶類衍生物、其製備方法及其在醫藥上的應用
US20180318284A1 (en) Benzopiperidine derivative, preparation method thereof and medical use thereof
CN117597341A (zh) 磺酰胺衍生物、其制备方法及其在医药上的应用
TW201540711A (zh) 具有選擇性ｅｐ２促效劑活性的化合物
CN109485595B (zh) 亲水性基团取代的吲哚甲酰胺类衍生物、其制备方法及其在医药上的应用
TW201823231A (zh) 氮雜雙環基取代的三唑類衍生物、其製備方法及其在醫藥上的應用
EP3327018B1 (en) 2-(octahydrocyclopenta[b]pyran-2-yl)1,3-thiazole-4-carboxylic acid derivatives and related compounds as ep2 agonists with intraocular pressure lowering activity
CN110372663A (zh) 含硫杂环化合物及其作为dpp4抑制剂衍生物的应用
WO2022237780A1 (zh) 酰胺衍生物及其应用
WO2023213279A1 (zh) 一类哌啶衍生物及其制备方法和用途
TWI851921B (zh) 吡嗪類衍生物及其在抑制shp2中的應用
KR102514860B1 (ko) 5-ht7 세로토닌 수용체 활성 저해용 바이페닐 피롤리딘 및 바이페닐 다이하이드로이미다졸 유도체 및 이를 유효성분으로 포함하는 약학 조성물
TW202210488A (zh) 吡嗪類衍生物及其在抑制shp2中的應用
WO2024051795A1 (zh) 用作泛素-特异性蛋白酶抑制剂的取代嘌呤酮衍生物

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
GR01 Patent grant
GR01 Patent grant