HUE059708T2 - 3-szubsztituált propionsavak mint alfa-V-integrin inhibitorok - Google Patents

3-szubsztituált propionsavak mint alfa-V-integrin inhibitorok

Info

Publication number
HUE059708T2
HUE059708T2 HUE17801230A HUE17801230A HUE059708T2 HU E059708 T2 HUE059708 T2 HU E059708T2 HU E17801230 A HUE17801230 A HU E17801230A HU E17801230 A HUE17801230 A HU E17801230A HU E059708 T2 HUE059708 T2 HU E059708T2
Authority
HU
Hungary
Prior art keywords
alpha
propionic acids
integrin inhibitors
substituted propionic
substituted
Prior art date
Application number
HUE17801230A
Other languages
English (en)
Hungarian (hu)
Inventor
Guohua Zhao
Pratik Devasthale
Xiang-Yang Ye
Kumaravel Selvakumar
Suresh Dhanusu
Palanikumar Balasubramanian
Leatte R Guernon
Rita Civiello
Xiaojun Han
Michael F Parker
Swanee E Jacutin-Porte
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of HUE059708T2 publication Critical patent/HUE059708T2/hu

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
HUE17801230A 2016-11-08 2017-11-07 3-szubsztituált propionsavak mint alfa-V-integrin inhibitorok HUE059708T2 (hu)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201662418848P 2016-11-08 2016-11-08

Publications (1)

Publication Number Publication Date
HUE059708T2 true HUE059708T2 (hu) 2022-12-28

Family

ID=60409432

Family Applications (1)

Application Number Title Priority Date Filing Date
HUE17801230A HUE059708T2 (hu) 2016-11-08 2017-11-07 3-szubsztituált propionsavak mint alfa-V-integrin inhibitorok

Country Status (30)

Country Link
US (2) US10968219B2 (https=)
EP (1) EP3538525B1 (https=)
JP (1) JP7097358B2 (https=)
KR (1) KR102505629B1 (https=)
CN (1) CN110167935B (https=)
AR (1) AR110153A1 (https=)
AU (1) AU2017359023B2 (https=)
CL (1) CL2019001264A1 (https=)
CO (1) CO2019005824A2 (https=)
CY (1) CY1125496T1 (https=)
DK (1) DK3538525T3 (https=)
EA (1) EA038164B1 (https=)
ES (1) ES2925173T3 (https=)
HR (1) HRP20220990T1 (https=)
HU (1) HUE059708T2 (https=)
IL (1) IL266473B (https=)
LT (1) LT3538525T (https=)
MA (1) MA46743A (https=)
MX (1) MX380799B (https=)
MY (1) MY199931A (https=)
NZ (1) NZ754207A (https=)
PE (1) PE20191647A1 (https=)
PL (1) PL3538525T3 (https=)
PT (1) PT3538525T (https=)
RS (1) RS63483B1 (https=)
SI (1) SI3538525T1 (https=)
SM (1) SMT202200338T1 (https=)
TW (1) TWI763733B (https=)
WO (1) WO2018089353A1 (https=)
ZA (1) ZA201903665B (https=)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109996541A (zh) 2016-09-07 2019-07-09 普利安特治疗公司 N-酰基氨基酸化合物及其使用方法
MX2019005234A (es) * 2016-11-08 2019-08-12 Squibb Bristol Myers Co Amidas y aminas de azol como inhibidores de integrina alfa v.
AU2017359025A1 (en) * 2016-11-08 2019-06-20 Bristol-Myers Squibb Company Cyclobutane- and azetidine-containing mono and spirocyclic compounds as alpha V integrin inhibitors
WO2018089353A1 (en) * 2016-11-08 2018-05-17 Bristol-Myers Squibb Company 3-substituted propionic acids as alpha v integrin inhibitors
CN110177787A (zh) 2016-12-29 2019-08-27 圣路易斯大学 整合素拮抗剂
MA47697A (fr) 2017-02-28 2020-01-08 Morphic Therapeutic Inc Inhibiteurs de l'(alpha-v)(bêta-6) intégrine
MA52117A (fr) 2017-02-28 2022-04-06 Morphic Therapeutic Inc Inhibiteurs de l'intégrine (alpha-v) (bêta-6)
EP4086254B1 (en) 2018-08-29 2024-12-18 Morphic Therapeutic, Inc. Integrin inhibitors
FI3844162T3 (fi) 2018-08-29 2025-03-27 Morphic Therapeutic Inc Alfa v beeta6 -integriinin estäjiä
WO2020047208A1 (en) 2018-08-29 2020-03-05 Morphic Therapeutic, Inc. Inhibitors of (alpha-v)(beta-6) integrin
KR102659859B1 (ko) 2018-10-30 2024-04-25 길리애드 사이언시즈, 인코포레이티드 알파4β7 인테그린의 억제를 위한 화합물
AU2019373242B2 (en) 2018-10-30 2023-07-13 Gilead Sciences, Inc. Compounds for inhibition of alpha 4 beta 7 integrin
EP4541422A3 (en) 2018-10-30 2025-06-25 Gilead Sciences, Inc. Quinoline derivatives as alpha4beta7 integrin inhibitors
CN112969700B (zh) 2018-10-30 2024-08-20 吉利德科学公司 作为α4β7整合素抑制剂的咪唑并吡啶衍生物
CN109824495B (zh) * 2019-02-02 2022-12-09 盐城师范学院 一种新型偶联反应在制备碳-碳键结构化合物中的应用
KR102908219B1 (ko) 2019-08-14 2026-01-08 길리애드 사이언시즈, 인코포레이티드 알파 4 베타 7 인테그린의 저해용 화합물
GB202010626D0 (en) 2020-07-10 2020-08-26 Univ Nottingham Compound
WO2025064802A1 (en) * 2023-09-21 2025-03-27 Morphic Therapeutic, Inc. INHIBITING HUMAN INTEGRIN α5β1

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0451790A1 (de) * 1990-04-12 1991-10-16 Hoechst Aktiengesellschaft 3,5-disubstituierte 2-Isoxazoline und Isoxazole, Verfahren zu deren Herstellung, diese enthaltende Mittel und ihre Verwendung
US5849736A (en) 1993-11-24 1998-12-15 The Dupont Merck Pharmaceutical Company Isoxazoline and isoxazole fibrinogen receptor antagonists
ZA972195B (en) 1996-03-15 1998-09-14 Du Pont Merck Pharma Spirocycle integrin inhibitors
EP1049693A1 (en) 1997-11-26 2000-11-08 Du Pont Pharmaceuticals Company 1,3,4-THIADIAZOLES AND 1,3,4-OXADIAZOLES AS $g(a) v?$g(b) 3? ANTAGONISTS
WO1999030709A1 (en) * 1997-12-17 1999-06-24 Merck & Co., Inc. Integrin receptor antagonists
WO2000009503A1 (en) * 1998-08-13 2000-02-24 Merck & Co., Inc. Integrin receptor antagonists
NZ539682A (en) 2001-01-29 2006-03-31 Dimensional Pharm Inc Substituted indoles and their use as integrin antagonists
BR0317600A (pt) * 2002-12-20 2005-11-29 Pharmacia Corp ácidos heteroarilalcanóicos como derivados de antagonistas de receptor de integrina
JP2006513218A (ja) * 2002-12-20 2006-04-20 ファルマシア・コーポレーション インテグリン受容体アンタゴニスト誘導体としてのピラゾール化合物
WO2006108040A1 (en) 2005-04-05 2006-10-12 Janssen Pharmaceutica, N.V. Substituted indoles and their use as integrin antagonists
TW200800999A (en) * 2005-09-06 2008-01-01 Astrazeneca Ab Novel compounds
US7592461B2 (en) 2005-12-21 2009-09-22 Bristol-Myers Squibb Company Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
AR059224A1 (es) * 2006-01-31 2008-03-19 Jerini Ag Compuestos para la inhibicion de integrinas y uso de estas
EP2049490A1 (en) 2006-06-09 2009-04-22 Astra Zeneca AB N-(benzoyl)-o- [2- (pyridin- 2 -ylamino) ethyl]-l-tyrosine derivatives and related compounds as a5b1 antagonists for the treatment of solid tumors
WO2008125811A1 (en) * 2007-04-11 2008-10-23 Astrazeneca Ab N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS
JP2013503834A (ja) 2009-09-04 2013-02-04 ビーエーエスエフ ソシエタス・ヨーロピア １−フェニルピラゾールの製造方法
US9556201B2 (en) 2009-10-29 2017-01-31 Glaxosmithkline Llc Bicyclic pyridines and analogs as sirtuin modulators
ITFI20100019A1 (it) 2010-02-12 2011-08-13 Univ Firenze Inibitori peptidomimetici di integrine basati sull'1,2,3-triazolo per la diagnosi e terapia dei tumori.
GB201305668D0 (en) 2013-03-28 2013-05-15 Glaxosmithkline Ip Dev Ltd Avs6 Integrin Antagonists
TWI667233B (zh) 2013-12-19 2019-08-01 德商拜耳製藥公司 新穎吲唑羧醯胺，其製備方法、含彼等之醫藥製劑及其製造醫藥之用途
GB201417011D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417002D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compound
GB201417094D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417018D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
KR102647026B1 (ko) 2015-02-19 2024-03-12 사이플루어 라이프 사이언시즈, 인크 플루오르화 테트라히드로나프티리디닐 노난산 유도체 및 이의 용도
CA2981371A1 (en) 2015-03-10 2016-09-15 The Regents Of The University Of California Anti-alphavbeta1 integrin inhibitors and methods of use
WO2018089353A1 (en) * 2016-11-08 2018-05-17 Bristol-Myers Squibb Company 3-substituted propionic acids as alpha v integrin inhibitors

Also Published As

Publication number Publication date
CN110167935B (zh) 2022-05-27
PT3538525T (pt) 2022-08-16
EP3538525B1 (en) 2022-06-22
ZA201903665B (en) 2022-12-21
EP3538525A1 (en) 2019-09-18
MY199931A (en) 2023-11-29
CA3042707A1 (en) 2018-05-17
TW201823244A (zh) 2018-07-01
LT3538525T (lt) 2022-09-26
US10968219B2 (en) 2021-04-06
ES2925173T3 (es) 2022-10-14
AR110153A1 (es) 2019-02-27
MX380799B (es) 2025-03-12
PL3538525T3 (pl) 2022-09-12
PE20191647A1 (es) 2019-11-07
CL2019001264A1 (es) 2019-09-13
US20190263808A1 (en) 2019-08-29
CY1125496T1 (el) 2026-02-25
IL266473B (en) 2022-06-01
WO2018089353A1 (en) 2018-05-17
JP7097358B2 (ja) 2022-07-07
US11884661B2 (en) 2024-01-30
SI3538525T1 (sl) 2022-09-30
TWI763733B (zh) 2022-05-11
MX2019005244A (es) 2019-08-05
EA038164B1 (ru) 2021-07-16
DK3538525T3 (da) 2022-08-29
NZ754207A (en) 2025-09-26
CO2019005824A2 (es) 2019-06-11
IL266473A (en) 2019-07-31
RS63483B1 (sr) 2022-09-30
EA201991122A1 (ru) 2019-10-31
MA46743A (fr) 2019-09-18
US20210188847A1 (en) 2021-06-24
KR102505629B1 (ko) 2023-03-02
KR20190073554A (ko) 2019-06-26
JP2019537594A (ja) 2019-12-26
HRP20220990T1 (hr) 2022-11-11
CN110167935A (zh) 2019-08-23
AU2017359023B2 (en) 2021-12-09
SMT202200338T1 (it) 2022-09-14
AU2017359023A1 (en) 2019-06-20

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