CN109790116B - Trpv4拮抗剂 - Google Patents

Trpv4拮抗剂 Download PDF

Info

Publication number
CN109790116B
CN109790116B CN201780057911.XA CN201780057911A CN109790116B CN 109790116 B CN109790116 B CN 109790116B CN 201780057911 A CN201780057911 A CN 201780057911A CN 109790116 B CN109790116 B CN 109790116B
Authority
CN
China
Prior art keywords
sulfonyl
pyrrolidin
hydroxymethyl
hydroxy
benzonitrile
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.)
Active
Application number
CN201780057911.XA
Other languages
English (en)
Chinese (zh)
Other versions
CN109790116A (zh
Inventor
E.J.伯纳迪克
C.A.布鲁克斯
B.G.拉夫霍恩
李鹏
J.M.马修斯
J.J.麦卡蒂
M.R.森德
L.R.特雷尔
J.E.佩罗
D.J.贝姆
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.)
GlaxoSmithKline LLC
Original Assignee
GlaxoSmithKline LLC
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 GlaxoSmithKline LLC filed Critical GlaxoSmithKline LLC
Publication of CN109790116A publication Critical patent/CN109790116A/zh
Application granted granted Critical
Publication of CN109790116B publication Critical patent/CN109790116B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • 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
    • 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
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not 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
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P1/10—Laxatives
    • 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
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P11/06—Antiasthmatics
    • 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
    • A61P11/14—Antitussive agents
    • 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
    • A61P11/16—Central respiratory analeptics
    • 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
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • 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
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur 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
    • C07D403/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D417/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Reproductive Health (AREA)
  • Hospice & Palliative Care (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Otolaryngology (AREA)
  • Psychiatry (AREA)
  • Transplantation (AREA)
CN201780057911.XA 2016-09-20 2017-09-20 Trpv4拮抗剂 Active CN109790116B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201662397008P 2016-09-20 2016-09-20
US62/397,008 2016-09-20
US201762482300P 2017-04-06 2017-04-06
US62/482,300 2017-04-06
PCT/IB2017/055702 WO2018055526A1 (en) 2016-09-20 2017-09-20 Trpv4 antagonists

Publications (2)

Publication Number Publication Date
CN109790116A CN109790116A (zh) 2019-05-21
CN109790116B true CN109790116B (zh) 2022-10-28

Family

ID=60084021

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780057911.XA Active CN109790116B (zh) 2016-09-20 2017-09-20 Trpv4拮抗剂

Country Status (10)

Country Link
US (1) US11260049B2 (enExample)
EP (1) EP3515888B1 (enExample)
JP (1) JP7106528B2 (enExample)
KR (1) KR20190049865A (enExample)
CN (1) CN109790116B (enExample)
AU (1) AU2017330620A1 (enExample)
CA (1) CA3036933A1 (enExample)
ES (1) ES2877763T3 (enExample)
RU (1) RU2019110821A (enExample)
WO (1) WO2018055526A1 (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3515889A1 (en) 2016-09-20 2019-07-31 GlaxoSmithKline Intellectual Property (No. 2) Limited Trpv4 antagonists
TW201825458A (zh) 2016-09-20 2018-07-16 英商葛蘭素史克智慧財產（第二）有限公司 Ｔｒｐｖ４拮抗劑
TWI878266B (zh) 2019-02-15 2025-04-01 愛爾蘭商博士倫愛爾蘭有限公司 治療眼表痛之方法
JP6994061B2 (ja) 2019-02-15 2022-01-14 ノバルティス アーゲー ４－（７－ヒドロキシ－２－イソプロピル－４－オキソ－４ｈ－キナゾリン－３－イル）－ベンゾニトリルの製剤
CN110407721A (zh) * 2019-08-13 2019-11-05 上海毕得医药科技有限公司 一种4-氰基-3-(三氟甲基)苯-1-磺酰氯的合成方法
US20230339934A1 (en) 2020-04-30 2023-10-26 Raqualia Pharma Inc. Pyrimidin-4(3h)-one derivatives as trpv4 antagonists
TW202216143A (zh) 2020-07-16 2022-05-01 日商拉夸里亞創藥股份有限公司 作為眼疾病的治療藥之ｔｒｐｖ４抑制藥
CN112500419A (zh) * 2020-11-23 2021-03-16 浙大城市学院 一种环氧稠合的2-亚甲基吡咯烷类化合物及其制备方法
CN114058694A (zh) * 2021-11-29 2022-02-18 上海市普陀区中心医院 Trpv1在筛选或制备预防、缓解和/或治疗肝脏疾病的药物中的应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007082262A2 (en) * 2006-01-11 2007-07-19 Smithkline Beecham Corporation Novel compounds

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2064336B (en) 1979-12-06 1984-03-14 Glaxo Group Ltd Device for dispensing medicaments
DE3274065D1 (de) 1981-07-08 1986-12-11 Draco Ab Powder inhalator
IT1203660B (it) 1982-10-08 1989-02-15 Glaxo Group Ltd Dispositivi per somministrare farmaci a pazienti e confezione di blister per essi
US4778054A (en) 1982-10-08 1988-10-18 Glaxo Group Limited Pack for administering medicaments to patients
GB2169265B (en) 1982-10-08 1987-08-12 Glaxo Group Ltd Pack for medicament
GB2178965B (en) 1985-07-30 1988-08-03 Glaxo Group Ltd Devices for administering medicaments to patients
US6536427B2 (en) 1990-03-02 2003-03-25 Glaxo Group Limited Inhalation device
HU213221B (en) 1990-03-02 1997-03-28 Glaxo Group Ltd Inhalation device and medicine packet for device
GB9004781D0 (en) 1990-03-02 1990-04-25 Glaxo Group Ltd Device
CN1232451A (zh) 1996-08-28 1999-10-20 普罗克特和甘保尔公司 取代的环状胺金属蛋白酶抑制剂
GB9700226D0 (en) 1997-01-08 1997-02-26 Glaxo Group Ltd Inhalation device
DK1461315T3 (da) 2001-12-06 2009-11-16 Cornell Res Foundation Inc Katalytisk carbonylering af tre- og fireleddede heterocykler
GB0201677D0 (en) 2002-01-25 2002-03-13 Glaxo Group Ltd Medicament dispenser
JP4969238B2 (ja) 2003-03-27 2012-07-04 サイトキネティクス・インコーポレーテッド 化合物、組成物および方法
GB0317374D0 (en) 2003-07-24 2003-08-27 Glaxo Group Ltd Medicament dispenser
KR101105909B1 (ko) 2004-02-16 2012-01-17 글락소 그룹 리미티드 약품 분배기에 사용되는 카운터
AR048523A1 (es) 2004-04-07 2006-05-03 Kalypsys Inc Compuestos con estructura de aril sulfonamida y sulfonilo como moduladores de ppar y metodos para tratar trastornos metabolicos
EP1755603A4 (en) 2004-04-28 2009-03-11 Merck & Co Inc 3,3-DISUBSTITUTED TETRAHYDROPYRANYL CYCLOPENTYL AMIDE MODULATORS OF CHEMOKIN RECEPTOR ACTIVITY
EP1758884A2 (en) 2004-05-20 2007-03-07 Elan Pharmaceuticals, Inc. N-cyclic sulfonamido inhibitors of gamma secretase
CN1329374C (zh) 2004-06-09 2007-08-01 上海靶点药物有限公司 作为ccr5拮抗剂的化合物
KR20070041742A (ko) 2004-07-12 2007-04-19 바이엘 크롭사이언스 아게 살진균제 및 살충제로서의 치환된 2-피롤리돈 유도체
GB0418278D0 (en) 2004-08-16 2004-09-15 Glaxo Group Ltd Medicament dispenser
DOP2006000010A (es) 2005-01-10 2006-07-31 Arena Pharm Inc Procedimiento para preparar eteres aromáticos
GB0515584D0 (en) 2005-07-28 2005-09-07 Glaxo Group Ltd Medicament dispenser
AR058289A1 (es) 2005-12-12 2008-01-30 Glaxo Group Ltd Colector para ser usado en dispensador de medicamento
JP2009521451A (ja) 2005-12-21 2009-06-04 シェーリング コーポレイション ヒスタミンｈ３アンタゴニストとして有用な置換アニリン誘導体
US7884107B2 (en) 2006-06-30 2011-02-08 Merck Substituted piperidines that increase P53 activity and the uses thereof
WO2008091863A1 (en) 2007-01-23 2008-07-31 Kalypsys, Inc. Sulfonyl-substituted bicyclic compounds as ppar modulators for the treatment of non-alcoholic steatohepatitis
US20110046199A1 (en) 2008-01-17 2011-02-24 Purdue Research Foundation Small molecule inhibitors of hiv proteases
CN102203074A (zh) 2008-06-20 2011-09-28 麦它波莱克斯股份有限公司 芳基gpr119激动剂及其用途
ES2605856T3 (es) 2012-11-16 2017-03-16 Bristol-Myers Squibb Company Moduladores GPR40 de dihidropirazol
CA2900888A1 (en) 2013-03-15 2014-09-18 AbbVie Deutschland GmbH & Co. KG Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy
TW201524952A (zh) 2013-03-15 2015-07-01 Araxes Pharma Llc Ｋｒａｓ ｇ１２ｃ之共價抑制劑
WO2014163161A1 (ja) 2013-04-04 2014-10-09 武田薬品工業株式会社 複素環化合物
WO2016016370A1 (en) 2014-07-31 2016-02-04 INSERM (Institut National de la Santé et de la Recherche Médicale) Flt3 receptor antagonists
EP3515889A1 (en) 2016-09-20 2019-07-31 GlaxoSmithKline Intellectual Property (No. 2) Limited Trpv4 antagonists
TW201825458A (zh) 2016-09-20 2018-07-16 英商葛蘭素史克智慧財產（第二）有限公司 Ｔｒｐｖ４拮抗劑

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007082262A2 (en) * 2006-01-11 2007-07-19 Smithkline Beecham Corporation Novel compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Identification of false positives in "HTS hits to lead": The application of Bayesian models in HTS triage to rapidly deliver a series of selective TRPV4 antagonists;Sarah E. Skerratt et al.;《Med. Chem. Commun.》;20121023;第4卷;第244-251页 *

Also Published As

Publication number Publication date
RU2019110821A (ru) 2020-10-22
CA3036933A1 (en) 2018-03-29
US20210299113A1 (en) 2021-09-30
JP7106528B2 (ja) 2022-07-26
BR112019005416A2 (pt) 2019-06-18
EP3515888B1 (en) 2021-03-31
AU2017330620A1 (en) 2019-03-28
CN109790116A (zh) 2019-05-21
ES2877763T3 (es) 2021-11-17
JP2019532052A (ja) 2019-11-07
KR20190049865A (ko) 2019-05-09
US11260049B2 (en) 2022-03-01
WO2018055526A1 (en) 2018-03-29
EP3515888A1 (en) 2019-07-31

Similar Documents

Publication Publication Date Title
CN109790116B (zh) Trpv4拮抗剂
US11229623B2 (en) TRPV4 antagonists
ES2952994T3 (es) Compuestos, composiciones y métodos
US10590077B2 (en) TRPV4 antagonists
TWI752963B (zh) 用於治療或預防與β-3腎上腺素受體相關病症之β-3腎上腺素受體調節劑
ES2474152T3 (es) Derivados de 6,7,8,9-tetrahidro-5H-pirimido[4,5-d]azepin-4-il]-amina como moduladores de TRPV1 para el tratamiento de dolor.
CN101528729A (zh) 作为gsk-3抑制剂的嘧啶酮化合物
JP6869176B2 (ja) Ｃｒｔｈ２アンタゴニストとしての化合物およびその使用
CN104650070A (zh) 二氢嘧啶类化合物及其在药物中的应用
CN115873000A (zh) 异喹啉酮类及喹唑啉酮类化合物及其组合物和用途
BR112019005416B1 (pt) Compostos antagonistas de trpv4, composição farmacêutica compreendendo os mesmos, processo para preparar a dita composição farmacêutica e usos terapêuticos dos compostos
BR112019005464B1 (pt) Compostos antagonistas de trpv4, composição farmacêutica compreendendo os mesmos, processo para preparar a dita composição farmacêutica e usos terapêuticos dos compostos

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
CP03 Change of name, title or address
CP03 Change of name, title or address

Address after: Steve Niki

Patentee after: GLAXOSMITHKLINE LLC

Country or region after: United Kingdom

Address before: British Meader Sykes

Patentee before: GLAXOSMITHKLINE LLC

Country or region before: United Kingdom