JP7080346B2 - 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 - Google Patents

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 Download PDF

Info

Publication number
JP7080346B2
JP7080346B2 JP2020560258A JP2020560258A JP7080346B2 JP 7080346 B2 JP7080346 B2 JP 7080346B2 JP 2020560258 A JP2020560258 A JP 2020560258A JP 2020560258 A JP2020560258 A JP 2020560258A JP 7080346 B2 JP7080346 B2 JP 7080346B2
Authority
JP
Japan
Prior art keywords
substituted
alkyl
compound
cells
bcl
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
JP2020560258A
Other languages
English (en)
Japanese (ja)
Other versions
JP2021522270A (ja
JP2021522270A5 (https=
JPWO2019213151A5 (https=
Inventor
アン－マリー ビューソレイユ
ライアン ハドソン
Original Assignee
ユニティ バイオテクノロジー インコーポレイテッド
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 ユニティ バイオテクノロジー インコーポレイテッド filed Critical ユニティ バイオテクノロジー インコーポレイテッド
Publication of JP2021522270A publication Critical patent/JP2021522270A/ja
Publication of JP2021522270A5 publication Critical patent/JP2021522270A5/ja
Publication of JPWO2019213151A5 publication Critical patent/JPWO2019213151A5/ja
Application granted granted Critical
Publication of JP7080346B2 publication Critical patent/JP7080346B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/36—Amides thereof
    • 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
    • C07D413/12—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 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
    • A61K31/435—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
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/505—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
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • 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
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/44—Amides thereof
    • C07F9/4403—Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4419—Amides of aromatic acids (P-C aromatic linkage)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657109—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms esters of oxyacids of phosphorus in which one or more exocyclic oxygen atoms have been replaced by (a) sulfur atom(s)
    • C07F9/657127—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms esters of oxyacids of phosphorus in which one or more exocyclic oxygen atoms have been replaced by (a) sulfur atom(s) condensed with carbocyclic or heterocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65844—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a five-membered ring which may be condensed with another ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Toxicology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
JP2020560258A 2018-04-30 2019-04-30 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 Active JP7080346B2 (ja)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201862664891P 2018-04-30 2018-04-30
US201862664850P 2018-04-30 2018-04-30
US201862664860P 2018-04-30 2018-04-30
US201862664863P 2018-04-30 2018-04-30
US62/664,860 2018-04-30
US62/664,863 2018-04-30
US62/664,850 2018-04-30
US62/664,891 2018-04-30
PCT/US2019/030023 WO2019213151A1 (en) 2018-04-30 2019-04-30 Phosphonamidates that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer

Publications (4)

Publication Number Publication Date
JP2021522270A JP2021522270A (ja) 2021-08-30
JP2021522270A5 JP2021522270A5 (https=) 2022-04-20
JPWO2019213151A5 JPWO2019213151A5 (https=) 2022-04-20
JP7080346B2 true JP7080346B2 (ja) 2022-06-03

Family

ID=66530472

Family Applications (3)

Application Number Title Priority Date Filing Date
JP2020560258A Active JP7080346B2 (ja) 2018-04-30 2019-04-30 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
JP2020561053A Active JP7204780B2 (ja) 2018-04-30 2019-04-30 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アシルホスホノアミダートおよびアシルベンジルアミン
JP2020561057A Expired - Fee Related JP7089062B2 (ja) 2018-04-30 2019-04-30 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リジン

Family Applications After (2)

Application Number Title Priority Date Filing Date
JP2020561053A Active JP7204780B2 (ja) 2018-04-30 2019-04-30 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アシルホスホノアミダートおよびアシルベンジルアミン
JP2020561057A Expired - Fee Related JP7089062B2 (ja) 2018-04-30 2019-04-30 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リジン

Country Status (5)

Country Link
US (1) US10703745B2 (https=)
EP (3) EP3787626B1 (https=)
JP (3) JP7080346B2 (https=)
CN (4) CN112513057B (https=)
WO (3) WO2019213160A1 (https=)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN113248415B (zh) * 2021-05-26 2022-08-09 苏州正永生物医药有限公司 一种abt-737关键中间体的制备方法以及abt-737的制备方法
CN118717761A (zh) * 2024-05-27 2024-10-01 复旦大学 瑞美吉泮在制备治疗/预防阿尔茨海默病药物中的应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018508569A (ja) 2015-02-06 2018-03-29 ユニティ バイオテクノロジー インコーポレイテッド 老化関連状態の治療における化合物および使用

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5807846A (en) 1996-11-14 1998-09-15 Warner-Lambert Company Phosphonamide ACAT inhibitors
HUP0200260A3 (en) * 1999-03-05 2002-11-28 Metabasis Therapeutics Inc San Novel phosphorus-containing prodrugs, their preparation and their use
WO2003000188A2 (en) 2001-06-21 2003-01-03 Ariad Pharmaceuticals, Inc. Novel quinazolines and uses thereof
EP1575591A4 (en) 2002-12-23 2007-09-12 Ariad Pharma Inc HETEROCYCLES AND ITS USE
AU2006223257A1 (en) * 2005-03-11 2006-09-21 The Regents Of The University Of Michigan Chromen-4-one inhibitors of anti-apoptotic Bcl-2 family members and the uses thereof
US7834023B2 (en) * 2006-09-20 2010-11-16 Portola Pharmaceuticals, Inc. Substituted dihydroquinazolines as platelet ADP receptor inhibitors
WO2008100423A1 (en) * 2007-02-09 2008-08-21 Sirtris Pharmaceuticals, Inc. Gut microsomal triglyceride transport protein inhibitors
US8124605B2 (en) * 2007-07-06 2012-02-28 Kinex Pharmaceuticals, Llc Compositions and methods for modulating a kinase cascade
US8563735B2 (en) 2008-12-05 2013-10-22 Abbvie Inc. Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases
TWI535712B (zh) 2010-08-06 2016-06-01 阿斯特捷利康公司 化合物
CA2822039C (en) 2010-12-16 2019-05-28 Allergan, Inc. Sulfur derivatives as chemokine receptor modulators
SG192126A1 (en) 2011-01-25 2013-09-30 Univ Michigan Bcl-2/bcl-xl inhibitors and therapeutic methods using the same
US20140189897A1 (en) 2011-06-21 2014-07-03 Mayo Foundation For Medical Education And Research Transgenic animals capable of being induced to delete senescent cells
WO2013052943A2 (en) * 2011-10-06 2013-04-11 The Regents Of The University Of Michgian Small molecule inhibitors of mcl-1 and uses thereof
US9901080B2 (en) 2012-08-23 2018-02-27 Buck Institute For Research On Aging Transgenic mouse having a transgene that converts a prodrug into a cytotoxic compound in senescent cells
EP2922544B1 (en) 2012-11-21 2018-08-01 Eutropics Pharmaceuticals, Inc. Methods and compositions useful for treating diseases involving bcl-2 family proteins with quinoline derivatives
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
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
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
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
EP3125943B1 (en) 2014-04-04 2026-04-22 Merck Sharp & Dohme LLC Phosphate based linkers for intracellular delivery of drug conjugates
EP3139942B1 (en) 2014-05-05 2019-12-18 Bioventures, Llc COMPOSITIONS AND METHODS FOR INHIBITING ANTIAPOPTOTIC Bcl-2 PROTEINS AS ANTI-AGING AGENTS
US20180000816A1 (en) * 2015-02-06 2018-01-04 Unity Biotechnology, Inc. Use of a Heterocyclic Bcl-xL Inhibitor and Related Analogs for Removing Senescent Cells in the Treatment of Eye Diseases and Other Age-Related Conditions
US10195213B2 (en) 2015-03-13 2019-02-05 Unity Biotechnology, Inc. Chemical entities that kill senescent cells for use in treating age-related disease
CN107846899A (zh) 2015-07-15 2018-03-27 拜耳农作物科学股份公司 取代的氧代四氢喹啉基次膦酰胺和‑膦酰胺或其盐及其提高植物中的胁迫耐受性的用途
CN105646587B (zh) * 2016-03-02 2018-03-23 云南中医学院 1,3,2‑氧氮磷杂环戊烷类化合物、制备方法及应用
WO2019001171A1 (zh) 2017-06-27 2019-01-03 维眸生物科技上海有限公司 一种含磷化合物及其制备和应用
WO2019033122A1 (en) 2017-08-11 2019-02-14 Unity Biotechnology, Inc. TREATMENT OF PULMONARY DISEASES USING PHARMACEUTICAL AGENTS THAT ELIMINATE SENESCENT CELLS
EP3441069B1 (en) 2017-08-11 2023-04-05 Unity Biotechnology, Inc. Treatment of diabetic retinopathy using pharmaceutical agents that eliminate senescent cells

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018508569A (ja) 2015-02-06 2018-03-29 ユニティ バイオテクノロジー インコーポレイテッド 老化関連状態の治療における化合物および使用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Ina WILKENING et al.，Synthesis of phosphonamidate peptides by Staudinger reactions of silylated phosphinic acids and esters，CHEM. COMMUN.，2011年，vol.47, no.1，p.349-351

Also Published As

Publication number Publication date
CN112513057B (zh) 2024-01-05
CN117866015A (zh) 2024-04-12
EP3787626A4 (en) 2021-06-02
EP3788054B1 (en) 2022-07-20
WO2019213160A1 (en) 2019-11-07
CN112469411B (zh) 2023-10-13
CN110662752A (zh) 2020-01-07
WO2019213151A1 (en) 2019-11-07
JP2021522270A (ja) 2021-08-30
EP3787626A1 (en) 2021-03-10
EP3788052A1 (en) 2021-03-10
CN110662752B (zh) 2022-01-14
JP7089062B2 (ja) 2022-06-21
JP2021523108A (ja) 2021-09-02
EP3787626C0 (en) 2023-06-07
WO2019213153A1 (en) 2019-11-07
US10703745B2 (en) 2020-07-07
EP3788054A1 (en) 2021-03-10
CN112513057A (zh) 2021-03-16
JP7204780B2 (ja) 2023-01-16
CN112469411A (zh) 2021-03-09
JP2021523109A (ja) 2021-09-02
EP3788052A4 (en) 2021-05-26
EP3787626B1 (en) 2023-06-07
US20190367496A1 (en) 2019-12-05

Similar Documents

Publication Publication Date Title
JP7080346B2 (ja) 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
JP6797310B2 (ja) 老化細胞が介在する疾患を治療するためのペプチド系プロテアソーム阻害物質、およびがんを治療するためのペプチド系プロテアソーム阻害物質
US20250188055A1 (en) Acyl Sulfonamides that are BCL Family Antagonists for Use in Clinical Management of Conditions Caused or Mediated by Senescent Cells and for Treating Cancer
WO2020092117A2 (en) Killing senescent cells and treating senescence-associated diseases or disorders using a combination of a bcl inhibitor and an mcl-1 inhibitor
US10738042B2 (en) Phosphonamidates that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
US10745429B2 (en) Phospholidines that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
US10717722B2 (en) Acyl sulfonamides that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
HK40053662A (en) Phospholidines that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
HK40053662B (en) Phospholidines that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
WO2021092053A1 (en) Mcl-1 inhibitor macrocycle compounds for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
HK40040329A (en) Acyl sulfonamides that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
HK40040329B (en) Acyl sulfonamides that are bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer

Legal Events

Date Code Title Description
RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20210622

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20220412

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20220412

A871 Explanation of circumstances concerning accelerated examination

Free format text: JAPANESE INTERMEDIATE CODE: A871

Effective date: 20220412

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20220509

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20220524

R150 Certificate of patent or registration of utility model

Ref document number: 7080346

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250