CN107624112B - 乳酸脱氢酶的小分子抑制剂及其使用方法 - Google Patents

乳酸脱氢酶的小分子抑制剂及其使用方法 Download PDF

Info

Publication number
CN107624112B
CN107624112B CN201580077097.9A CN201580077097A CN107624112B CN 107624112 B CN107624112 B CN 107624112B CN 201580077097 A CN201580077097 A CN 201580077097A CN 107624112 B CN107624112 B CN 107624112B
Authority
CN
China
Prior art keywords
alkyl
phenyl
radical
cycloalkyl
halo
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
CN201580077097.9A
Other languages
English (en)
Chinese (zh)
Other versions
CN107624112A (zh
Inventor
戴维·J·马洛尼
阿吉特·贾达夫
甘尼沙·雷·班图卡卢
凯勒·瑞安·布里马科姆
布赖恩·T·莫特
杨世明
丹尼尔·詹森·厄本
胡新
安顿·西梅奥诺夫
珍妮弗·L·库茨内特索瓦
亚历克斯·格雷戈里·沃特森
加里·艾伦·苏利科夫斯基
金光镐
普拉门·克里斯托夫
索姆纳特·贾纳
维克托·M·达利-乌斯马尔
威廉·J·穆尔
伦纳德·M·内克斯
希·V·丹格
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.)
UAB Research Foundation
University of Pennsylvania Penn
Vanderbilt University
US Department of Health and Human Services
Original Assignee
UAB Research Foundation
University of Pennsylvania Penn
Vanderbilt University
US Department of Health and Human Services
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 UAB Research Foundation, University of Pennsylvania Penn, Vanderbilt University, US Department of Health and Human Services filed Critical UAB Research Foundation
Publication of CN107624112A publication Critical patent/CN107624112A/zh
Application granted granted Critical
Publication of CN107624112B publication Critical patent/CN107624112B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • 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
    • 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
    • A61K31/41—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
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/422—Oxazoles 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
    • A61K31/41—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
    • A61K31/4353—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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines 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
    • A61K31/495—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
    • A61K31/495—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
    • A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
    • 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
    • A61P35/00—Antineoplastic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
    • C07D231/38—Nitrogen 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
    • C07D401/04—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
    • 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
    • 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
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
    • 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
    • C07D417/14—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 three or more hetero rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D495/14—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical 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)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CN201580077097.9A 2014-12-29 2015-12-29 乳酸脱氢酶的小分子抑制剂及其使用方法 Active CN107624112B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462097226P 2014-12-29 2014-12-29
US62/097,226 2014-12-29
PCT/US2015/067895 WO2016109559A2 (en) 2014-12-29 2015-12-29 Small molecule inhibitors of lactate dehydrogenase and methods of use thereof

Publications (2)

Publication Number Publication Date
CN107624112A CN107624112A (zh) 2018-01-23
CN107624112B true CN107624112B (zh) 2022-03-04

Family

ID=55451544

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580077097.9A Active CN107624112B (zh) 2014-12-29 2015-12-29 乳酸脱氢酶的小分子抑制剂及其使用方法

Country Status (12)

Country Link
US (5) US10351532B2 (enExample)
EP (2) EP3240785B1 (enExample)
JP (3) JP6903580B2 (enExample)
CN (1) CN107624112B (enExample)
AU (2) AU2015374118B2 (enExample)
CA (2) CA3210002A1 (enExample)
DK (1) DK3240785T3 (enExample)
ES (2) ES2883938T3 (enExample)
HU (1) HUE055662T2 (enExample)
PL (1) PL3240785T3 (enExample)
SI (1) SI3240785T1 (enExample)
WO (1) WO2016109559A2 (enExample)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016109559A2 (en) 2014-12-29 2016-07-07 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
AU2017208998B2 (en) * 2016-01-21 2021-07-15 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Bruton's tyrosine kinase inhibitors
EP3478677B1 (en) * 2016-06-29 2021-09-01 The United States of America, as represented by The Secretary, Department of Health and Human Services 1h-pyrazol-1-yl-thiazoles as inhibitors of lactate dehydrogenase and methods of use thereof
UY37557A (es) 2017-01-10 2018-07-31 Bayer Ag Derivados heterocíclicos como pesticidas
US11247987B2 (en) 2017-10-06 2022-02-15 Forma Therapeutics, Inc. Inhibiting ubiquitin specific peptidase 30
IL278291B2 (en) 2018-05-17 2023-10-01 Forma Therapeutics Inc Fused bicyclic compounds useful as ubiquitin-specific peptidase 30 inhibitors
EP3833345B1 (en) 2018-08-07 2024-07-17 Kemijski Institut Small molecule-inhibitors of 6-phosphofructo-1-kinase for reducing lactate generation by cancer cells
EP3632908A1 (en) 2018-10-02 2020-04-08 Inventiva Inhibitors of the yap/taz-tead interaction and their use in the treatment of cancer
LT3860989T (lt) 2018-10-05 2023-06-12 Forma Therapeutics, Inc. Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai
TWI820231B (zh) 2018-10-11 2023-11-01 德商拜耳廠股份有限公司 用於製備經取代咪唑衍生物之方法
MA54555A (fr) 2018-11-22 2021-09-29 Qilu Regor Therapeutics Inc Agonistes de glp-1r et leurs utilisations
AU2019387370A1 (en) 2018-11-30 2021-06-10 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
US10954221B2 (en) 2019-04-12 2021-03-23 Qilu Regor Therapeutics Inc. GLP-1R agonists and uses thereof
US20220289791A1 (en) * 2019-05-02 2022-09-15 Université Catholique de Louvain Lactate dehydrogenase inhibitor polypeptides for use in the treatment of cancer
US11725026B2 (en) * 2019-06-28 2023-08-15 The Research Foundation For The State University Of New York Compositions and methods for inhibiting lactate dehydrogenase a activity
WO2021026290A1 (en) 2019-08-07 2021-02-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services T cells having enhanced anti-tumor activity
US11752138B2 (en) 2020-05-18 2023-09-12 Vanderbilt University Treating primary or idiopathic hyperoxaluria with small molecule inhibitors of lactate dehydrogenase
US20230183228A1 (en) * 2020-05-18 2023-06-15 Chinook Therapeutics Canada, Inc. Substituted pyrazolyl compounds and methods of use thereof
US20250205203A1 (en) * 2020-05-18 2025-06-26 Chinook Therapeutics Canada, Inc. Substituted pyrazolyl compounds and methods of use thereof
WO2021251842A1 (en) * 2020-06-08 2021-12-16 Qatar Foundation For Education, Science And Community Development Targeting of lactate dehydrogenase c, methods of preparing same, and methods of using same in combination with anti-cancer treatments
KR20230039665A (ko) 2020-07-02 2023-03-21 바이엘 악티엔게젤샤프트 해충 방제제로서의 헤테로사이클 유도체
US20240066027A1 (en) * 2020-12-03 2024-02-29 Domain Therapeutics Novel par-2 inhibitors
WO2024212024A1 (en) * 2023-04-09 2024-10-17 Meta Pharmaceuticals (Hk) Limited Novel substituted pyrrole compounds, compositions comprising the substituted pyrrole compound, and methods of use thereof
WO2025011479A1 (en) * 2023-07-13 2025-01-16 Meta Pharmaceuticals (Hk) Limited Pyrazole based inhibitors of LDH and their use in immune and inflammatory diseases
WO2025026738A1 (en) 2023-07-31 2025-02-06 Bayer Aktiengesellschaft 6-[5-(ethylsulfonyl)-1-methyl-1h-imidazol-4-yl]-7-methyl-3-(pentafluoroethyl)-7h-imidazo[4,5-c]pyridazine derivatives as pesticides
WO2025241047A1 (en) * 2024-05-20 2025-11-27 Meta Pharmaceuticals (Hk) Limited Inhibitors of lactate dehydrogenase, compositions comprising the inhibitor, and methods of use thereof
WO2025241049A1 (en) * 2024-05-20 2025-11-27 Meta Pharmaceuticals (Hk) Limited Inhibitors of lactate dehydrogenase, compositions comprising the inhibitor, and methods of use thereof
WO2025241048A1 (en) * 2024-05-20 2025-11-27 Meta Pharmaceuticals (Hk) Limited Inhibitors of lactate dehydrogenase, compositions comprising the inhibitor, and methods of use thereof
CN118772058A (zh) * 2024-06-14 2024-10-15 济南尚博医药股份有限公司 一种2-氯-4-(1h-吡唑-3-基)苯甲腈的合成方法及应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008006790A1 (en) * 2006-07-14 2008-01-17 Glaxo Group Limited Indole compounds
CN102089302A (zh) * 2008-07-17 2011-06-08 旭化成制药株式会社 含氮二环性杂环化合物
CN102089303A (zh) * 2008-07-17 2011-06-08 旭化成制药株式会社 含氮杂环化合物
CN102281816A (zh) * 2008-11-20 2011-12-14 人体媒介公司 用于确定危重护理参数的方法和设备

Family Cites Families (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5182289A (en) 1988-06-14 1993-01-26 Schering Corporation Heterobicyclic compounds having antiinflammatory activity
HU217072B (hu) * 1989-01-10 1999-11-29 Pfizer Inc. 1-Heteroaril-oxindol-3-karboxamid-származékok, azok előállítása, és az azokat tartalmazó gyógyszerkészítmények
US5602113A (en) 1991-02-07 1997-02-11 Boehringer Ingelheim Pharmaceuticals, Inc. Pyridobenzo- and pyridiothieno-diazepines useful for the treatment of HIV infection
CN1071924A (zh) 1991-10-29 1993-05-12 纳幕尔杜邦公司 除草的三唑羧酸酰胺
JPH0680569A (ja) 1992-09-03 1994-03-22 Asahi Chem Ind Co Ltd 血小板凝集阻害剤
US5342851A (en) 1992-10-07 1994-08-30 Mcneil-Ppc, Inc. Substituted thiazole derivatives useful as platelet aggregation inhibitors
DE4405207A1 (de) 1994-02-18 1995-08-24 Bayer Ag N-Pyrazolylaniline und N-Pyrazolylaminopyridine
US20020028936A1 (en) * 1999-04-12 2002-03-07 Gerhard Sperl 1,3-disubstituted indolin-2-ones for neoplasia
US6136079A (en) 1999-04-30 2000-10-24 Eastman Kodak Company Dye for ink jet ink
EP1196380A2 (en) 1999-07-15 2002-04-17 NPS Allelix Corp. Indoles and indazoles for the treatment of migraine
US6407238B1 (en) 1999-10-29 2002-06-18 Boehringer Ingelheim Pharmaceuticals, Inc. Process of making substituted pyrazoles
US6436965B1 (en) 2000-03-02 2002-08-20 Merck Frosst Canada & Co. PDE IV inhibiting amides, compositions and methods of treatment
JP2002167531A (ja) 2000-11-29 2002-06-11 Fuji Photo Film Co Ltd インクジェット記録用インク組成物及び画像形成方法
PA8535601A1 (es) 2000-12-21 2002-11-28 Pfizer Derivados benzimidazol y piridilimidazol como ligandos para gabaa
TWI311133B (en) 2001-04-20 2009-06-21 Eisai R&D Man Co Ltd Carboxylic acid derivativeand the salt thereof
US7358267B2 (en) 2001-06-29 2008-04-15 Amgen Inc. Bis-aryl thiazole derivatives
IL159811A0 (en) 2001-07-13 2004-06-20 Neurogen Corp Heteroaryl substituted fused bicyclic heteroaryl compounds as gabaa receptor ligands
EP1314733A1 (en) 2001-11-22 2003-05-28 Aventis Pharma Deutschland GmbH Indole-2-carboxamides as factor Xa inhibitors
DE60309342T2 (de) 2002-08-09 2007-05-16 Eli Lilly And Co., Indianapolis Benzimidazole und benzothiazole als inhibitoren der map-kinase
WO2004016592A1 (en) 2002-08-14 2004-02-26 Ppd Discovery, Inc. Prenylation inhibitors and methods of their synthesis and use
WO2004043913A2 (en) 2002-11-08 2004-05-27 Trimeris, Inc. Hetero-substituted benzimidazole compounds and antiviral uses thereof
WO2004092140A1 (en) 2003-04-03 2004-10-28 Merck & Co., Inc. Biaryl substituted pyrazoles as sodium channel blockers
GB0323845D0 (en) 2003-10-10 2003-11-12 Angeletti P Ist Richerche Bio Chemical compounds,compositions and uses
EP1794196A2 (en) 2004-09-22 2007-06-13 Symyx Technologies, Inc. Heterocycle-amine ligands, compositions, complexes, and catalysts, and methods of making and using the same
WO2006052546A2 (en) 2004-11-04 2006-05-18 Neurogen Corporation Pyrazolylmethyl heteroaryl derivatives
US20080249091A1 (en) 2005-01-19 2008-10-09 Benjamin Pelcman Indoles Useful in the Treatment of Inflammation
EP1841766A1 (en) 2005-01-19 2007-10-10 Biolipox AB Pyrrolopyridines useful in the treatment of inflammation
JP2008527030A (ja) 2005-01-19 2008-07-24 バイオリポックス エービー 炎症の治療に有用なインドール類
MX2007008759A (es) 2005-01-19 2007-09-11 Biolipox Ab Indoles utiles en el tratamiento de la inflamacion.
JP2008527028A (ja) 2005-01-19 2008-07-24 バイオリポックス エービー 炎症の治療に有用なインドール類
WO2006078891A2 (en) 2005-01-21 2006-07-27 Neurogen Corporation Imidazolylmethyl and pyrazolylmethyl heteroaryl derivatives
GB0507198D0 (en) 2005-04-08 2005-05-18 Sb Pharmco Inc Process for preparing bicyclic compounds
US7456292B2 (en) 2005-06-30 2008-11-25 Bexel Pharmaceuticals, Inc. Hydroxamic acid-containing amino acid derivatives
WO2007018508A1 (en) 2005-07-28 2007-02-15 Glaxo Group Limited Novel m3 muscarinic acetycholine receptor antagonists
WO2007018514A1 (en) 2005-07-28 2007-02-15 Glaxo Group Limited Novel m3 muscarinic acetylcholine receptor antagonists
US7615569B2 (en) 2005-08-16 2009-11-10 Icagen, Inc. Inhibitors of ion channels
WO2007038571A2 (en) 2005-09-26 2007-04-05 Smithkline Beecham Corporation Prolyl hydroxylase antagonists
WO2007039773A1 (en) 2005-10-06 2007-04-12 Merck Sharp & Dohme Limited Use of fused pyrrole carboxylic acids for the treatment of neurodegenerative and psychiatric diseases as d-amino acid oxidase inhibitors
US20090105238A1 (en) 2005-10-17 2009-04-23 Isagro Ricerca S.R.L Compounds and Relative use for the Control of Phytopathogens
WO2007048732A1 (de) 2005-10-28 2007-05-03 Basf Aktiengesellschaft Verwendung von 5-amino-pyrazolen zur bekämpfung pflanzenpathogener schadpilze, neue 5-amino-pyrazole, verfahren zu ihrer herstellung und sie enthaltende mittel
EP1998766A2 (en) 2005-12-16 2008-12-10 Ironwood Pharmaceuticals, Inc. Useful indole compounds
ITMI20052459A1 (it) 2005-12-22 2007-06-23 Isagro Spa Sali quaternari e relativo uso per il controllo di fitopatogeni
US20080090834A1 (en) 2006-07-06 2008-04-17 Pfizer Inc Selective azole pde10a inhibitor compounds
WO2008009924A2 (en) 2006-07-18 2008-01-24 Biolipox Ab Indoles useful in the treatment of inflammation
EP2053920B1 (en) 2007-01-26 2014-04-30 North Carolina State University Inhibition of bacterial biofilms with imidazole derivatives
WO2008121861A2 (en) 2007-03-28 2008-10-09 Xenon Pharmaceuticals Inc. Pyrazole and pyrrole compounds useful in treating iron disorders
EP2197280B1 (en) 2007-08-27 2013-06-19 Basf Se Pyrazole compounds for controlling invertebrate pests
US8389567B2 (en) 2007-12-12 2013-03-05 Calcimedica, Inc. Compounds that modulate intracellular calcium
WO2009108551A2 (en) 2008-02-25 2009-09-03 H. Lundbeck A/S Heteroaryl amide analogues
ES2412779T3 (es) 2008-05-08 2013-07-12 Merck Sharp & Dohme Corp. Compuestos de espiroazaindol como inhibidores de HIF propilhidroxilasa
US9029408B2 (en) 2008-06-16 2015-05-12 Gtx, Inc. Compounds for treatment of cancer
WO2010010186A1 (en) 2008-07-25 2010-01-28 Galapagos Nv Novel compounds useful for the treatment of degenerative and inflammatory diseases
WO2010034737A1 (en) 2008-09-24 2010-04-01 Basf Se Pyrazole compounds for controlling invertebrate pests
US10167263B2 (en) * 2008-11-20 2019-01-01 Northwestern University Treatment of amyotrophic lateral sclerosis
CN101747276B (zh) 2008-11-28 2011-09-07 中国中化股份有限公司 具有含氮五元杂环的醚类化合物及其应用
WO2010063610A1 (en) 2008-12-04 2010-06-10 F. Hoffmann-La Roche Ag Pyridazinone derivatives
ES2567047T3 (es) 2008-12-23 2016-04-19 Abbvie Inc. Derivados de pirimidina anti-virales
WO2010111060A1 (en) 2009-03-23 2010-09-30 Merck Sharp & Dohme Corp. P2x3, receptor antagonists for treatment of pain
CN102448951B (zh) 2009-04-06 2017-05-10 安吉奥斯医药品有限公司 丙酮酸激酶m2调节剂、治疗组合物和相关使用方法
WO2011057942A1 (en) 2009-11-12 2011-05-19 Basf Se Insecticidal methods using pyridine compounds
WO2011076744A1 (en) 2009-12-21 2011-06-30 Novartis Ag Disubstituted heteroaryl-fused pyridines
WO2011091410A1 (en) 2010-01-25 2011-07-28 Glaxos Smithkline Llc Trpv4 antagonists
WO2012064631A1 (en) 2010-11-10 2012-05-18 Boehringer Ingelheim International Gmbh Pyridyl ureas as mineralocorticoid receptor antagonists
WO2012074022A1 (ja) 2010-12-01 2012-06-07 旭硝子株式会社 イリジウムカチオン錯体および発光組成物
AR084515A1 (es) 2010-12-22 2013-05-22 Merz Pharma Gmbh & Co Kgaa Derivados heterociclicos nitrogenados, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de enfermedades asociadas al sistema nervioso central tales como parkinson y alzheimer, entre otras
US20120225061A1 (en) 2011-03-04 2012-09-06 Matthew Burger Tetrasubstituted cyclohexyl compounds as kinase inhibitors
JP5985611B2 (ja) 2011-05-03 2016-09-06 シンタ ファーマシューティカルズ コーポレーション 炎症および免疫関連用途のための化合物
US9181231B2 (en) 2011-05-03 2015-11-10 Agios Pharmaceuticals, Inc Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia
WO2012154880A1 (en) 2011-05-09 2012-11-15 Proteostasis Therapeutics, Inc. Proteostasis regulators for treating cystic fibrosis and other protein misfolding diseases
JP2013040240A (ja) 2011-08-11 2013-02-28 Fujifilm Corp アゾ化合物、アゾ顔料、顔料分散物、着色組成物、カラーフィルター用着色組成物、カラーフィルター、カラーフィルター用着色組成物の調製方法、インクジェット記録用インク、印刷インク、塗料、染料、及び、レジストインク
EP2749562A4 (en) 2011-08-24 2015-01-07 Kissei Pharmaceutical CONDENSED HETEROCYCLIC DERIVATIVE AND ITS PHARMACEUTICAL USE
ITPI20110143A1 (it) 2011-12-20 2013-06-21 Univ Pisa Agenti terapeutici in grado di ridurre la produzione cellulare di acido lattico e composizioni farmaceutiche che comprendono tali composti
WO2013109882A1 (en) 2012-01-20 2013-07-25 Genosco Substituted pyrimidine compounds and their use as syk inhibitors
AU2013297601B2 (en) 2012-07-30 2017-02-16 Taisho Pharmaceutical Co., Ltd. Partially saturated nitrogen-containing heterocyclic compound
US10035790B2 (en) 2012-10-19 2018-07-31 Exelixis, Inc. RORγ modulators
EP2934527A4 (en) 2012-12-20 2016-07-13 Merck Sharp & Dohme 2-pyridyloxy-4-ESTER-orexin receptor antagonists
US9643955B2 (en) 2012-12-20 2017-05-09 Merck Sharp & Dohme Corp. 2-pyridyloxy-3-nitrile-4-substituted orexin receptor antagonists
WO2014099697A1 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. 3-ester-4-substituted orexin receptor antagonists
FR3001219A1 (fr) 2013-01-22 2014-07-25 Centre Nat Rech Scient Inhibiteurs de kinases
MY174813A (en) 2013-03-15 2020-05-16 Zymeworks Inc Cytotoxic and anti-mitotic compounds, and methods of using the same
KR20150121107A (ko) 2013-03-29 2015-10-28 코니카 미놀타 가부시키가이샤 이성체 혼합 금속 착체 조성물, 유기 일렉트로루미네센스 소자, 조명 장치 및 표시 장치
WO2014173880A1 (en) 2013-04-22 2014-10-30 Syngenta Participations Ag Novel microbiocides
WO2014176475A2 (en) 2013-04-26 2014-10-30 The Regents Of The University Of Michigan Egfr inhibitors and uses thereof
US9169221B2 (en) 2013-04-29 2015-10-27 Comsats Institute Of Information Technology Dihydro 1,4-benzoxazines and method of synthesizing the same using sulfonium salts
WO2016109559A2 (en) * 2014-12-29 2016-07-07 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Small molecule inhibitors of lactate dehydrogenase and methods of use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008006790A1 (en) * 2006-07-14 2008-01-17 Glaxo Group Limited Indole compounds
CN102089302A (zh) * 2008-07-17 2011-06-08 旭化成制药株式会社 含氮二环性杂环化合物
CN102089303A (zh) * 2008-07-17 2011-06-08 旭化成制药株式会社 含氮杂环化合物
CN102281816A (zh) * 2008-11-20 2011-12-14 人体媒介公司 用于确定危重护理参数的方法和设备

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Discovery of 2-(1H-indazol-1-yl)-thiazole derivatives as selective EP1 receptor antagonists for treatment of overactive bladder by core structure replacement";Masakazu Atobe等，;《Bioorg. Med. Chem. Lett.》;20140128;第24卷;第1327–1333页 *
"Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping";Adrian Hall等，;《Bioorganic & Medicinal Chemistry Letters》;20080310;第2684–2690页 *
"Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists";Masakazu Atobe等，;《Bioorg. Med. Chem. Lett.》;20130919;第6064-6067页 *

Also Published As

Publication number Publication date
US12365653B2 (en) 2025-07-22
JP7771139B2 (ja) 2025-11-17
PL3240785T3 (pl) 2021-12-06
AU2015374118A1 (en) 2017-07-20
US10961200B2 (en) 2021-03-30
EP3954685A1 (en) 2022-02-16
JP2021152064A (ja) 2021-09-30
US11897845B2 (en) 2024-02-13
JP7337883B2 (ja) 2023-09-04
US20200002285A1 (en) 2020-01-02
US20180273488A1 (en) 2018-09-27
AU2020257163B2 (en) 2022-06-30
AU2020257163A1 (en) 2020-11-19
WO2016109559A3 (en) 2016-08-25
US10351532B2 (en) 2019-07-16
EP3240785B1 (en) 2021-07-07
ES2883938T3 (es) 2021-12-09
HUE055662T2 (hu) 2021-12-28
EP3954685B1 (en) 2025-08-27
AU2015374118B2 (en) 2020-07-23
CA3210002A1 (en) 2016-07-07
CN107624112A (zh) 2018-01-23
CA2978823A1 (en) 2016-07-07
US11247971B2 (en) 2022-02-15
ES3042832T3 (en) 2025-11-24
US20210323928A1 (en) 2021-10-21
US20240368087A1 (en) 2024-11-07
DK3240785T3 (da) 2021-09-27
US20220220078A1 (en) 2022-07-14
EP3240785A2 (en) 2017-11-08
SI3240785T1 (sl) 2021-11-30
WO2016109559A2 (en) 2016-07-07
JP2023153302A (ja) 2023-10-17
JP6903580B2 (ja) 2021-07-14
CA2978823C (en) 2023-10-10
JP2018503631A (ja) 2018-02-08

Similar Documents

Publication Publication Date Title
CN107624112B (zh) 乳酸脱氢酶的小分子抑制剂及其使用方法
JP6741825B2 (ja) Ｄｎａ−ｐｋ阻害剤
JP7017521B2 (ja) アクチビン受容体様キナーゼの阻害剤
JP6374959B2 (ja) Ｄｎａ−ｐｋ阻害剤
JP6109969B2 (ja) 新規なピリミジン及びピリジン化合物並びにその利用
CN115485278A (zh) 通过缀合btk抑制剂与e3连接酶配体降解布鲁顿氏酪氨酸激酶(btk)及其使用方法
EP2124951A1 (en) 5-cyan0-4- (pyrrolo ý2, 3b¨pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors
CN112055709A (zh) 吡嗪化合物和其用途
CN119923385A (zh) Rna解旋酶dhx9的抑制剂和其用途
CN120476117A (zh) Gpr17调节剂及其用途
CN115605477B (zh) 一种吡唑并[1,5-a]吡啶类衍生物及其制备方法，组合物以及用途
CN112279837B (zh) 吡嗪化合物和其用途
CN111747954B (zh) 吡嗪化合物和其用途
HK40067410A (en) Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
HK40045062B (en) Pyrazine compounds and uses thereof
HK40045062A (en) Pyrazine compounds and uses thereof
HK40037929B (en) Pyrazine compounds and uses thereof
HK40037929A (en) Pyrazine compounds and uses thereof
HK40038625A (en) Pyrazine compounds and uses thereof

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