AU2012209295B2 - Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same - Google Patents

Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same Download PDF

Info

Publication number
AU2012209295B2
AU2012209295B2 AU2012209295A AU2012209295A AU2012209295B2 AU 2012209295 B2 AU2012209295 B2 AU 2012209295B2 AU 2012209295 A AU2012209295 A AU 2012209295A AU 2012209295 A AU2012209295 A AU 2012209295A AU 2012209295 B2 AU2012209295 B2 AU 2012209295B2
Authority
AU
Australia
Prior art keywords
compound
bcl
nmr
cd3od
phenyl
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
AU2012209295A
Other languages
English (en)
Other versions
AU2012209295A1 (en
Inventor
Angelo AGUILAR
Longchuan Bai
Jianfang Chen
Xiaoqin LI
Liu Liu
Donna MCEACHERM
Jennifer Lynn Meagher
Jeanne STUCKEY
Duxin Sun
Shaomeng Wang
Chao-Yie Yang
Haibin Zhou
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.)
University of Michigan System
Original Assignee
University of Michigan System
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 University of Michigan System filed Critical University of Michigan System
Publication of AU2012209295A1 publication Critical patent/AU2012209295A1/en
Application granted granted Critical
Publication of AU2012209295B2 publication Critical patent/AU2012209295B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • 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
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/335Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic 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
    • C07D231/12Heterocyclic 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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic 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
    • C07D231/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
    • C07D233/90Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom 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
    • C07D307/68Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/06Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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 aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU2012209295A 2011-01-25 2012-01-24 Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same Active AU2012209295B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161436077P 2011-01-25 2011-01-25
US61/436,077 2011-01-25
PCT/US2012/022315 WO2012103059A2 (en) 2011-01-25 2012-01-24 Bcl-2/bcl-xl inhibitors and therapeutic methods using the same

Publications (2)

Publication Number Publication Date
AU2012209295A1 AU2012209295A1 (en) 2013-08-08
AU2012209295B2 true AU2012209295B2 (en) 2016-06-30

Family

ID=46544312

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2012209295A Active AU2012209295B2 (en) 2011-01-25 2012-01-24 Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same

Country Status (11)

Country Link
US (1) US8691184B2 (https=)
EP (2) EP2668180B1 (https=)
JP (1) JP5998152B2 (https=)
KR (1) KR101762724B1 (https=)
CN (1) CN103562202B (https=)
AU (1) AU2012209295B2 (https=)
CA (1) CA2825306C (https=)
ES (1) ES2693107T3 (https=)
SG (1) SG192126A1 (https=)
WO (1) WO2012103059A2 (https=)
ZA (1) ZA201305571B (https=)

Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102318204B1 (ko) * 2013-01-16 2021-10-26 더 리젠츠 오브 더 유니버시티 오브 미시간 Bcl-2bcl-xl 억제제 및 그를 사용하는 치료 방법
CN105377289A (zh) 2013-04-21 2016-03-02 耶达研究及发展有限公司 用于下调Bcl-xL和/或Bcl-w的活性和/或量的试剂
US20170216286A1 (en) 2014-01-28 2017-08-03 Mayo Foundation For Medical Education And Research Killing senescent cells and treating senescence-associated conditions using a src inhibitor and a flavonoid
US20190269675A1 (en) 2014-01-28 2019-09-05 Buck Institute for Research and Aging Treatment of parkinson's disease and other conditions caused or mediated by senescent astrocytes using small molecule senolytic agents
AU2015211021B2 (en) 2014-01-28 2020-07-02 Buck Institute For Research On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
US10328058B2 (en) 2014-01-28 2019-06-25 Mayo Foundation For Medical Education And Research Treating atherosclerosis by removing senescent foam cell macrophages from atherosclerotic plaques
CN105753814A (zh) * 2015-01-01 2016-07-13 成都贝斯凯瑞生物科技有限公司 取代氮杂环衍生物及其应用
CA2981753A1 (en) * 2015-02-06 2016-08-11 Unity Biotechnology, Inc. Compounds and uses in treatment of senescence-associated conditions
EP3261612A1 (en) 2015-02-26 2018-01-03 Yeda Research and Development Co. Ltd Method of promoting hair growth
AU2016304856B8 (en) 2015-08-10 2021-02-18 Dana-Farber Cancer Institute, Inc. Mechanism of resistance to BET bromodomain inhibitors
JP6936498B2 (ja) 2016-04-21 2021-09-15 バイオベンチャーズ・リミテッド・ライアビリティ・カンパニーBioVentures, LLC 抗アポトーシス性Bcl−2ファミリータンパク質の分解を誘導する化合物及びその使用
CN106177955B (zh) * 2016-08-18 2018-03-16 广州威溶特医药科技有限公司 Bcl‑xL抑制剂和溶瘤病毒在制备抗肿瘤药物中的应用
BR102018007822A2 (pt) 2017-04-20 2018-11-06 Gilead Sciences, Inc. composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição
EP3441069B1 (en) 2017-08-11 2023-04-05 Unity Biotechnology, Inc. Treatment of diabetic retinopathy using pharmaceutical agents that eliminate senescent cells
WO2019033122A1 (en) * 2017-08-11 2019-02-14 Unity Biotechnology, Inc. TREATMENT OF PULMONARY DISEASES USING PHARMACEUTICAL AGENTS THAT ELIMINATE SENESCENT CELLS
US20200354336A9 (en) 2017-08-11 2020-11-12 Unity Biotechnology, Inc. Treatment of Lung Diseases Using Pharmaceutical Agents that Eliminate Senescent Cells
CN107573256B (zh) * 2017-09-26 2020-02-21 安徽国星生物化学有限公司 一种对氯苯肼盐酸盐连续化生产方法及其装置
US10588916B2 (en) 2017-10-31 2020-03-17 Unity Biotechnology, Inc. Technology to inhibit vascular changes that lead to vision loss in the eye
CN109718377B (zh) * 2017-10-31 2021-03-26 中国科学院脑科学与智能技术卓越创新中心 KPNB1抑制剂和Bcl-xL抑制剂在制备抗肿瘤药物中的应用
CA3043103C (en) 2017-12-30 2021-02-09 Unity Biotechnology Peptide-based proteasome inhibitors for treating conditions mediated by senescent cells and for treating cancer
EP3737681A4 (en) 2018-01-10 2022-01-12 Recurium IP Holdings, LLC BENZAMIDE COMPOUNDS
US10111873B1 (en) 2018-01-17 2018-10-30 King Saud University Dihydropyrimidinone derivatives
EP3743069B1 (en) 2018-01-22 2025-08-06 BioVentures, LLC Bcl-2 proteins degraders for cancer treatment
TWI707849B (zh) 2018-02-13 2020-10-21 美商基利科學股份有限公司 Pd‐1/pd‐l1抑制劑
KR102591947B1 (ko) 2018-04-19 2023-10-25 길리애드 사이언시즈, 인코포레이티드 Pd-1/pd-l1 억제제
SI3788042T1 (sl) 2018-04-29 2025-06-30 Beigene Switzerland Gmbh Zaviralci BCL-2
JP7080346B2 (ja) 2018-04-30 2022-06-03 ユニティ バイオテクノロジー インコーポレイテッド 老化細胞によって引き起こされるかまたは媒介される状態の臨床管理における使用のためおよびがんを治療するための、Bclファミリーアンタゴニストであるホスホノアミダート
CA3056878C (en) 2018-04-30 2021-03-30 Unity Biotechnology Phospholidines that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
US10738042B2 (en) 2018-04-30 2020-08-11 Unity Biotechnology, Inc. Phosphonamidates that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
US10717722B2 (en) 2018-06-13 2020-07-21 Unity Biotechnology, Inc. Acyl sulfonamides that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
EP3820572B1 (en) 2018-07-13 2023-08-16 Gilead Sciences, Inc. Pd-1/pd-l1 inhibitors
CA3094449C (en) 2018-07-31 2023-02-28 Ascentage Pharma (Suzhou) Co., Ltd. Combination product of bcl-2 inhibitor and mdm2 inhibitor and use thereof in the prevention and/or treatment of diseases
CN110772521A (zh) 2018-07-31 2020-02-11 苏州亚盛药业有限公司 Bcl-2抑制剂或Bcl-2/Bcl-xL抑制剂与BTK抑制剂的组合产品及其用途
US12083136B2 (en) * 2018-07-31 2024-09-10 Ascentage Pharma (Suzhou) Co., Ltd Combination of BCL-2/BCL-XL inhibitors and chemotherapeutic agent and use thereof
JP2021516262A (ja) 2018-07-31 2021-07-01 アセンテージ ファーマ(スーチョウ)カンパニー,リミティド リツキシマブ及び/若しくはベンダムスチンと組み合わされたBcl−2阻害剤又はCHOPと組み合わされたBcl−2阻害剤の相乗的な抗腫瘍効果
TWI725488B (zh) 2018-07-31 2021-04-21 大陸商蘇州亞盛藥業有限公司 Bcl-2抑制劑與化療藥的組合產品及其在預防及/或治療疾病中的用途
US12220419B2 (en) 2018-08-22 2025-02-11 Newave Pharmaceutical Inc. BCL-2 inhibitors
JP2021535113A (ja) * 2018-08-22 2021-12-16 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司Jiangsu Hengrui Medicine Co., Ltd. ピロロ−アミノ−ピリダジノン化合物およびその中間体の調製方法
US11236085B2 (en) 2018-10-24 2022-02-01 Gilead Sciences, Inc. PD-1/PD-L1 inhibitors
WO2020140005A2 (en) 2018-12-29 2020-07-02 Newave Pharmaceutical Inc. Bcl-2 inhibitors
EP3906235B1 (en) * 2019-01-04 2023-03-15 Ascentage Pharma (Suzhou) Co., Ltd. Method for preparing sulfonamides drugs
US11370807B2 (en) 2019-01-04 2022-06-28 Ascentage Pharma (Suzhou) Co., Ltd. Process for preparing sulfonamide compounds
TWI770503B (zh) * 2019-05-13 2022-07-11 大陸商蘇州亞盛藥業有限公司 用於預測bcl-2/bcl-xl抑制劑對癌症的功效的方法和組合物
WO2021066873A1 (en) 2019-10-03 2021-04-08 Newave Pharmaceutical Inc. Condensed heterocycles as bcl-2 inhibitors
WO2021083135A1 (en) 2019-10-28 2021-05-06 Beigene, Ltd. Bcl-2 INHIBITORS
WO2021110102A1 (en) * 2019-12-02 2021-06-10 Beigene, Ltd. Methods of cancer treatment using bcl-2 inhibitor
WO2021133862A1 (en) * 2019-12-24 2021-07-01 The Regents Of The University Of California Targeting the intrinsic apoptotic machinery in glioblastoma
US12552784B2 (en) 2019-12-27 2026-02-17 Newave Pharmaceutical Inc. 1H-pyrrolo[2,3-b]pyridine derivatives as BCL-2 inhibitors for the treatment of neoplastic and autoimmune diseases
EP3914257B1 (en) * 2020-04-10 2023-12-27 Ascentage Pharma (Suzhou) Co., Ltd. Combination of a bcl-2/bcl-xl inhibitor with osimertinib
JP7839962B2 (ja) 2020-04-15 2026-04-03 ビーワン メディシンズ ワン ゲーエムベーハー Bcl-2阻害剤
EP4146649A4 (en) * 2020-05-08 2024-09-11 Fochon Biosciences, Ltd. COMPOUNDS AS BCL-2 INHIBITORS
US20250319183A1 (en) 2021-04-07 2025-10-16 David Avigan Compositions and methods for the treatment of cancer
CA3230314A1 (en) * 2021-08-31 2023-03-09 Beigene Switzerland Gmbh Solid forms of bcl-2 inhibitors, method of preparation, and use thereof
WO2023122000A1 (en) * 2021-12-20 2023-06-29 Newave Pharmaceutical Inc. Bcl-2 inhibitors
WO2024051741A1 (zh) * 2022-09-06 2024-03-14 西藏海思科制药有限公司 一种抑制Bcl-2或Bcl-xL的化合物及其在医药上的应用
CN115557846B (zh) * 2022-10-17 2023-11-10 成都道合尔医药技术有限公司 8-氨基辛酸的合成方法
EP4719408A1 (en) * 2023-05-30 2026-04-08 Ascentage Pharma (Suzhou) Co., Ltd. Bcl-2/bcl-xl protein degrader and use thereof
CN117756811A (zh) * 2023-12-29 2024-03-26 贵州民族大学 一种合成多取代基吡咯化合物的方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010010154A1 (en) * 2008-07-24 2010-01-28 Nerviano Medical Sciences S.R.L. 3,4-diarylpyrazoles as protein kinase inhibitors

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0201475A2 (hu) * 1999-02-09 2003-10-28 3-Dimensional Pharmaceuticals, Inc. Heteroarilamidin-, metilamidin- és guanidinszármazékok, előállításuk és alkalmazásuk, valamint e vegyületeket tartalmazó gyógyászati készítmények
US7432304B2 (en) 2001-05-30 2008-10-07 The Regents Of The University Of Michigan Small molecule antagonists of Bcl-2 family proteins
JP4898458B2 (ja) * 2004-02-12 2012-03-14 トランス テック ファーマ,インコーポレイテッド 置換アゾール誘導体、組成物及び使用方法
WO2005090297A1 (en) * 2004-03-19 2005-09-29 Biotie Therapies Corporation Sulphonamide derivatives
EP1778206A4 (en) * 2004-08-20 2009-08-05 Univ Michigan SMALL MOLECULE INHIBITORS FROM MEMBERS OF THE ANTIOPTOTIC BCL-2 FAMILY AND USES THEREOF
CA2577752A1 (en) * 2004-08-20 2006-03-02 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic bcl-2 family members and the uses thereof
EP1888550B1 (en) * 2005-05-12 2014-06-25 AbbVie Bahamas Ltd. Apoptosis promoters
JP5193861B2 (ja) * 2005-07-07 2013-05-08 アボット・ラボラトリーズ アポトーシス促進剤
JP2009515997A (ja) 2005-11-18 2009-04-16 タケダ サン ディエゴ インコーポレイテッド グルコキナーゼ活性剤
WO2007087441A2 (en) * 2006-01-25 2007-08-02 Synta Pharmaceuticals Corp. Substituted aromatic compounds for inflammation and immune-related uses
MX2009000395A (es) * 2006-07-14 2009-01-29 Chemocentryx Inc Triazolil fenil bencenosulfonamidas.
PE20080948A1 (es) * 2006-07-25 2008-09-10 Irm Llc Derivados de imidazol como moduladores de la senda de hedgehog
EP2120580B1 (en) * 2007-02-02 2017-12-27 Baylor College Of Medicine Compositions and methods for the treatment of metabolic disorders
US7776877B2 (en) * 2007-06-22 2010-08-17 Chemocentryx, Inc. N-(2-(hetaryl)aryl) arylsulfonamides and N-(2-(hetaryl) hetaryl arylsulfonamides
UA103319C2 (en) * 2008-05-06 2013-10-10 Глаксосмитклайн Ллк Thiazole- and oxazole-benzene sulfonamide compounds
US20110319392A1 (en) * 2009-03-12 2011-12-29 George Adjabeng Thiazole Sulfonamide And Oxazole Sulfonamide Kinase Inhibitors
US20100278921A1 (en) 2009-04-30 2010-11-04 Fischer Cristina M Solid oral formulation of abt-263
WO2011029842A1 (en) * 2009-09-10 2011-03-17 Novartis Ag Sulfonamides as inhibitors of bcl-2 family proteins for the treatment of cancer

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010010154A1 (en) * 2008-07-24 2010-01-28 Nerviano Medical Sciences S.R.L. 3,4-diarylpyrazoles as protein kinase inhibitors

Also Published As

Publication number Publication date
SG192126A1 (en) 2013-09-30
EP2668180A4 (en) 2014-08-13
JP5998152B2 (ja) 2016-09-28
WO2012103059A2 (en) 2012-08-02
CA2825306C (en) 2019-02-26
NZ613504A (en) 2015-03-27
KR20140005984A (ko) 2014-01-15
EP2668180A2 (en) 2013-12-04
WO2012103059A3 (en) 2012-10-18
EP3459945A1 (en) 2019-03-27
EP2668180B1 (en) 2018-08-01
US8691184B2 (en) 2014-04-08
US20120189539A1 (en) 2012-07-26
CA2825306A1 (en) 2012-08-02
CN103562202B (zh) 2016-09-14
JP2014507421A (ja) 2014-03-27
CN103562202A (zh) 2014-02-05
ES2693107T3 (es) 2018-12-07
KR101762724B1 (ko) 2017-07-28
ZA201305571B (en) 2014-10-29

Similar Documents

Publication Publication Date Title
AU2012209295B2 (en) Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same
AU2012209295A1 (en) Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same
AU2014207716B2 (en) Bcl-2Bcl-xL inhibitors and therapeutic methods using the same
AU2013306087B2 (en) Bivalent inhibitors of IAP proteins and therapeutic methods using the same
US20110319362A1 (en) Stat3 ligands and therapeutic uses thereof
HK40025523A (en) Bcl-2/bcl-xl inhibitors and their use in the treatment of cancer
NZ613504B2 (en) Bcl-2/bcl-xl inhibitors and therapeutic methods using the same
HK40008279A (en) Medical use of bcl-2/bcl-xl inhibitors and pharmaceutical compositions thereof
HK40008279B (en) Medical use of bcl-2/bcl-xl inhibitors and pharmaceutical compositions thereof

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)