TWI727981B - 氧雜螺環類衍生物、其製備方法及其在醫藥上的應用 - Google Patents

氧雜螺環類衍生物、其製備方法及其在醫藥上的應用 Download PDF

Info

Publication number
TWI727981B
TWI727981B TW105133229A TW105133229A TWI727981B TW I727981 B TWI727981 B TW I727981B TW 105133229 A TW105133229 A TW 105133229A TW 105133229 A TW105133229 A TW 105133229A TW I727981 B TWI727981 B TW I727981B
Authority
TW
Taiwan
Prior art keywords
group
cycloalkyl
general formula
aryl
heteroaryl
Prior art date
Application number
TW105133229A
Other languages
English (en)
Chinese (zh)
Other versions
TW201718558A (zh
Inventor
李心
馮斌強
陳陽
劉濤
賀峰
何明勛
陶維康
孫飄揚
Original Assignee
大陸商江蘇恆瑞醫藥股份有限公司
大陸商上海恆瑞醫藥有限公司
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 大陸商江蘇恆瑞醫藥股份有限公司, 大陸商上海恆瑞醫藥有限公司 filed Critical 大陸商江蘇恆瑞醫藥股份有限公司
Publication of TW201718558A publication Critical patent/TW201718558A/zh
Application granted granted Critical
Publication of TWI727981B publication Critical patent/TWI727981B/zh

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/04Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
TW105133229A 2015-10-15 2016-10-14 氧雜螺環類衍生物、其製備方法及其在醫藥上的應用 TWI727981B (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201510665328.X 2015-10-15
CN201510665328 2015-10-15
CN201511032876 2015-12-31
CN201511032876.5 2015-12-31

Publications (2)

Publication Number Publication Date
TW201718558A TW201718558A (zh) 2017-06-01
TWI727981B true TWI727981B (zh) 2021-05-21

Family

ID=58517778

Family Applications (1)

Application Number Title Priority Date Filing Date
TW105133229A TWI727981B (zh) 2015-10-15 2016-10-14 氧雜螺環類衍生物、其製備方法及其在醫藥上的應用

Country Status (16)

Country Link
US (1) US10442793B2 (enExample)
EP (1) EP3354649B1 (enExample)
JP (1) JP6824502B2 (enExample)
KR (1) KR102703513B1 (enExample)
CN (1) CN107001347B (enExample)
AU (1) AU2016339404B2 (enExample)
CA (1) CA3000761C (enExample)
DK (1) DK3354649T3 (enExample)
ES (1) ES2772689T3 (enExample)
HU (1) HUE048032T2 (enExample)
MX (1) MX382815B (enExample)
PL (1) PL3354649T3 (enExample)
PT (1) PT3354649T (enExample)
RU (1) RU2733373C2 (enExample)
TW (1) TWI727981B (enExample)
WO (1) WO2017063509A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI891070B (zh) * 2022-09-27 2025-07-21 大陸商上海樞境生物科技有限公司 一種含螺環類衍生物的鹽、晶型及其製備方法和應用

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX388643B (es) * 2017-04-14 2025-03-20 Jiangsu Hengrui Medicine Co Composicion farmaceutica que contiene agonista de mor y agonista de kor, y sus usos
EP3610875B1 (en) * 2017-04-14 2020-10-07 Jiangsu Hengrui Medicine Co., Ltd. Opioid receptor (mor) agonist salt, fumarate salt i crystal form thereof and preparation method thereof
CN108727347B (zh) * 2017-04-14 2020-06-16 江苏恒瑞医药股份有限公司 一种阿片样物质受体(mor)激动剂的晶型及其制备方法
CN109206417B (zh) * 2017-07-04 2023-01-03 四川海思科制药有限公司 阿片受体激动剂及其应用
US11072601B2 (en) 2017-09-18 2021-07-27 Shanghai Synergy Pharmaceutical Sciences Co., Ltd. μ-opioid receptor agonist and preparation method therefor and use thereof in field of medicine
WO2019062804A1 (zh) 2017-09-28 2019-04-04 江苏恒瑞医药股份有限公司 一种氧杂螺环类衍生物的制备方法及其中间体
AU2018349930A1 (en) * 2017-10-13 2020-04-16 Shandong Luye Pharmaceutical Co., Ltd. 2,6-dioxaspiro (4,5) decane derivatives and preparation method therefor and pharmaceutical applications thereof
JP2021505547A (ja) * 2017-12-06 2021-02-18 江蘇恒瑞医薬股▲ふん▼有限公司 疼痛を治療するための薬物の製造におけるmorアゴニストと組み合わせたkorアゴニストの使用
CN111836807A (zh) * 2018-04-28 2020-10-27 四川科伦博泰生物医药股份有限公司 氧杂螺环类化合物及其制备方法和用途
CN108424372B (zh) * 2018-05-11 2021-08-10 浙江华贝药业有限责任公司 2,2,2-三氟-n-[(s)-4-羰基四氢萘-1-基]-乙酰胺的纯化工艺
CN111163778B (zh) * 2018-05-14 2023-01-24 江苏恒瑞医药股份有限公司 一种mor受体激动剂药物组合物
CN108707086B (zh) * 2018-05-15 2021-08-10 浙江华贝药业有限责任公司 一种(1s,4s)-n-(4-羟基四氢萘-1-基)叔丁氧基碳酰胺的纯化工艺
WO2020073985A1 (zh) * 2018-10-12 2020-04-16 江苏恒瑞医药股份有限公司 一种阿片样物质受体(mor)激动剂的结晶形式及制备方法
WO2020073984A1 (zh) * 2018-10-12 2020-04-16 江苏恒瑞医药股份有限公司 一种阿片样物质受体(mor)激动剂的结晶形式及制备方法
CN112334465B (zh) * 2019-01-17 2024-06-11 上海海雁医药科技有限公司 三环取代的氧杂螺环衍生物、其制法与医药上的用途
CN111662284B (zh) * 2019-03-06 2021-08-10 上海海雁医药科技有限公司 双杂环取代的氧杂螺环衍生物、其制法与医药上的用途
WO2021027304A1 (zh) * 2019-08-14 2021-02-18 上海海雁医药科技有限公司 镇痛化合物、其制法与医药上的用途
EP4092031A4 (en) * 2020-01-17 2024-02-21 Shanghai Haiyan Pharmaceutical Technology Co., Ltd. AZABICYCLIC SUBSTITUTED OXASPIRO DERIVATIVE, METHOD FOR THE PRODUCTION THEREOF AND ITS MEDICAL USE
CN118221680A (zh) 2020-01-17 2024-06-21 上海海雁医药科技有限公司 光学纯的氧杂螺环取代的吡咯并吡唑衍生物、其制法与医药上的用途
CN113214264B (zh) * 2020-01-21 2022-08-09 上海海雁医药科技有限公司 二氢吡咯并五元杂芳基取代的氧杂螺环衍生物、其制法与医药上的用途
JP7781064B2 (ja) 2020-01-22 2025-12-05 江蘇恒瑞医薬股▲ふん▼有限公司 抗trop-2抗体-エキサテカン類似体複合体及びその医薬用途
CN114075141B (zh) * 2020-08-20 2025-02-25 上海致根医药科技有限公司 阿片受体“偏向性”配体、其制备方法及其在医药上的应用
CN114539257B (zh) * 2020-11-24 2023-08-11 江苏恒瑞医药股份有限公司 嘧啶二酮类螺环衍生物、其制备方法及其在医药上的应用
JP7751645B2 (ja) 2020-12-29 2025-10-08 上海海雁医薬科技有限公司 オキシスピロ環置換ピロロピラゾール誘導体及びその中間体並びにその調製方法
WO2023284788A1 (zh) 2021-07-13 2023-01-19 上海海雁医药科技有限公司 Mor受体激动剂的药学上可接受的盐、其多晶型物及其用途
WO2023011422A1 (zh) * 2021-08-02 2023-02-09 上海枢境生物科技有限公司 氧杂螺环类衍生物、制备方法及其用途
CN117263956A (zh) * 2022-01-19 2023-12-22 天地恒一制药股份有限公司 阿片受体激动剂及其制备方法和用途
CN116589451B (zh) * 2022-02-11 2024-07-09 成都硕德药业有限公司 一种6-氧杂螺[4,5]癸烷类化合物的新晶型、用途及其制备方法
CN117624138A (zh) * 2022-08-29 2024-03-01 江苏恒瑞医药股份有限公司 一种氧杂螺环类衍生物的可药用盐、晶型及制备方法
KR20250137614A (ko) 2023-01-18 2025-09-18 상하이 센후이 메디슨 컴퍼니 리미티드 테트라히드로-1-나프틸아민 및 이의 유도체의 제조 방법
WO2026026772A1 (zh) * 2024-07-30 2026-02-05 上海枢境生物科技有限公司 氧杂螺环类衍生物的富马酸盐晶型及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012129495A1 (en) * 2011-03-23 2012-09-27 Trevena, Inc. Opioid receptor ligands and methods of using and making same

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2160534B1 (es) 1999-12-30 2002-04-16 Vita Invest Sa Nuevos esteres derivados de (rr,ss)-2-hidroxibenzoato de 3-(2-dimetilaminometil-1-hidroxiciclohexil) fenilo.
DE10044649A1 (de) 2000-09-08 2002-07-04 Gruenenthal Gmbh Substituierte 4-Phenyl-1-(1-phenyl-cyclohexyl)-1,2,3,6-tetrahydropyridine
DE102006033109A1 (de) * 2006-07-18 2008-01-31 Grünenthal GmbH Substituierte Heteroaryl-Derivate
US7999107B2 (en) * 2007-01-31 2011-08-16 Merck Sharp & Dohme Corp. Substituted pyrano[2,3-B]pyridine derivatives as cannabinoid-1 receptor modulators
US20090028873A1 (en) 2007-07-27 2009-01-29 Auspex Pharmaceuticals, Inc. Substituted cyclohexanols
AU2009308769B2 (en) 2008-10-31 2015-03-12 Pain Therapeutics, Inc. Filamin A-binding anti-inflammatory analgesic
CN102741258B (zh) 2009-06-17 2015-09-30 德州大学体系董事会 作为分离剂的环果聚糖的组成物及方法
CN104159902B (zh) 2011-12-12 2016-05-04 格吕伦塔尔有限公司 制备(1r,4r)-6’-氟-(N,N-二甲基-和N-甲基)-4-苯基-4’,9’-二氢-3’H-螺[环己烷-1,1’-吡喃并[3,4,b]吲哚]-4-胺的方法
PL2880037T3 (pl) 2012-08-03 2019-07-31 Johnson Matthey Public Limited Company Sposób wytwarzania oksykodonu
RS55593B1 (sr) 2012-11-13 2017-06-30 Array Biopharma Inc Jedinjenja biciklične uree, tiouree, guanidina i cijanoguanidina korisna za lečenje bola

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012129495A1 (en) * 2011-03-23 2012-09-27 Trevena, Inc. Opioid receptor ligands and methods of using and making same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chen et al., "Structure−Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)‑9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine(), for the Treatment of Acute Severe Pain", Journal of Medicinal Chemistry, 2013, 56, pp 8019-8031. *
Chen et al., "Structure−Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)‑9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine(TRV130), for the Treatment of Acute Severe Pain", Journal of Medicinal Chemistry, 2013, 56, pp 8019-8031.

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI891070B (zh) * 2022-09-27 2025-07-21 大陸商上海樞境生物科技有限公司 一種含螺環類衍生物的鹽、晶型及其製備方法和應用

Also Published As

Publication number Publication date
CN107001347B (zh) 2019-09-24
RU2018115569A (ru) 2019-11-18
HUE048032T2 (hu) 2020-05-28
AU2016339404A1 (en) 2018-05-24
US10442793B2 (en) 2019-10-15
TW201718558A (zh) 2017-06-01
CA3000761C (en) 2024-02-13
JP6824502B2 (ja) 2021-02-03
AU2016339404B2 (en) 2020-08-27
DK3354649T3 (da) 2020-02-24
US20180297988A1 (en) 2018-10-18
RU2018115569A3 (enExample) 2020-01-20
WO2017063509A1 (zh) 2017-04-20
KR102703513B1 (ko) 2024-09-06
CA3000761A1 (en) 2017-04-20
MX382815B (es) 2025-03-12
EP3354649B1 (en) 2019-12-04
RU2733373C2 (ru) 2020-10-01
EP3354649A1 (en) 2018-08-01
BR112018006448A2 (pt) 2018-10-16
JP2018534257A (ja) 2018-11-22
PT3354649T (pt) 2020-02-03
EP3354649A4 (en) 2018-08-08
ES2772689T3 (es) 2020-07-08
PL3354649T3 (pl) 2020-07-27
CN107001347A (zh) 2017-08-01
MX2018004175A (es) 2018-06-06
KR20180063251A (ko) 2018-06-11

Similar Documents

Publication Publication Date Title
TWI727981B (zh) 氧雜螺環類衍生物、其製備方法及其在醫藥上的應用
WO2022268230A1 (zh) 作为kif18a抑制剂的化合物
TWI617546B (zh) 咪唑啉類衍生物、其製備方法及其在醫藥上的應用
KR102204804B1 (ko) 디히드로피라졸 gpr40 조절제
CN106164076B (zh) 作为ros1抑制剂的化合物
CN117285590A (zh) 一种化合物、其制备方法、包括其的组合物及其应用
TW202110837A (zh) 氫化吡啶并嘧啶類衍生物、其製備方法及其在醫藥上的應用
CN113164409A (zh) 具有雌激素受体α降解活性的新型化合物及其用途
WO2021185256A1 (zh) 取代的嘧啶或吡啶胺衍生物、其组合物及医药上的用途
TWI882060B (zh) 三環四氫異喹啉類衍生物、其製備方法及其在醫藥上的應用
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
TW200914442A (en) Gamma secretase modulators
WO2024199108A1 (zh) 作为wrn解旋酶抑制剂的化合物
CN113056455A (zh) 异噁唑甲酰胺化合物及其用途
WO2023046214A1 (zh) 一种受体相互作用蛋白激酶1的抑制剂及其制备方法、应用
HK1238242B (zh) 氧杂螺环类衍生物、其制备方法及其在医药上的应用
WO2022237825A1 (zh) 具有egfr抑制活性的氮杂芳基衍生物、其制备方法和应用
HK1238242A1 (en) Oxa spiro derivative, preparation method therefor, and applications thereof in medicines
BR112018006448B1 (pt) Derivado de oxaespiro, seu uso e processo de preparação, e composição farmacêutica
EP4737453A1 (en) Novel selenophene derivatives
TW202510881A (zh) 一種egfr突變抑制劑及其應用
WO2025045182A1 (zh) Ulk1抑制剂及其制备方法和用途
WO2025237258A1 (zh) 一种内酰胺结构cdk抑制剂化合物
WO2024002375A1 (zh) 一种用作smarca2/4抑制剂的化合物及其应用
HK40076301A (en) Tricyclic tetrahydroisoquinoline derivative, preparation method therefor and application thereof in medicine