KR102729666B1 - 비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클 - Google Patents

비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클 Download PDF

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KR102729666B1
KR102729666B1 KR1020187005398A KR20187005398A KR102729666B1 KR 102729666 B1 KR102729666 B1 KR 102729666B1 KR 1020187005398 A KR1020187005398 A KR 1020187005398A KR 20187005398 A KR20187005398 A KR 20187005398A KR 102729666 B1 KR102729666 B1 KR 102729666B1
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KR20180033267A (ko
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예헹 주
앤드류 케이. 딜저
윌리엄 알. 유잉
마이클 제이. 오르와트
도널드 제이.피. 핀토
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브리스톨-마이어스 스큅 컴퍼니
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—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
    • 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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D403/14—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 three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
KR1020187005398A 2015-07-29 2016-07-28 비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클 Active KR102729666B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562198188P 2015-07-29 2015-07-29
US62/198,188 2015-07-29
PCT/US2016/044363 WO2017019821A1 (en) 2015-07-29 2016-07-28 Factor xia new macrocycle bearing a non-aromatic p2' group

Publications (2)

Publication Number Publication Date
KR20180033267A KR20180033267A (ko) 2018-04-02
KR102729666B1 true KR102729666B1 (ko) 2024-11-12

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KR1020187005398A Active KR102729666B1 (ko) 2015-07-29 2016-07-28 비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클

Country Status (7)

Country Link
US (1) US10676477B2 (enExample)
EP (2) EP3328852B1 (enExample)
JP (1) JP6816103B2 (enExample)
KR (1) KR102729666B1 (enExample)
CN (3) CN114874222B (enExample)
ES (2) ES2937156T3 (enExample)
WO (1) WO2017019821A1 (enExample)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9453018B2 (en) * 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
ES2762987T3 (es) 2015-06-19 2020-05-26 Bristol Myers Squibb Co Macrociclos de diamida como inhibidores del factor XIA
EP3328851B1 (en) 2015-07-29 2020-04-22 Bristol-Myers Squibb Company Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties
JP2019507167A (ja) 2016-03-02 2019-03-14 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ｘｉａ因子阻害活性を有するジアミド大員環
US11034669B2 (en) 2018-11-30 2021-06-15 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009114677A1 (en) 2008-03-13 2009-09-17 Bristol-Myers Squibb Company Pyridazine derivatives as factor xia inhibitors
WO2011100401A1 (en) 2010-02-11 2011-08-18 Bristol-Myers Squibb Company Macrocycles as factor xia inhibitors
WO2013022814A1 (en) 2011-08-05 2013-02-14 Bristol-Myers Squibb Company Cyclic p1 linkers as factor xia inhibitors

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3065190D1 (en) 1979-11-05 1983-11-10 Beecham Group Plc Enzyme derivatives, and their preparation
PE121699A1 (es) 1997-02-18 1999-12-08 Boehringer Ingelheim Pharma Heterociclos biciclicos disustituidos como inhibidores de la trombina
ZA985247B (en) 1997-06-19 1999-12-17 Du Pont Merck Pharma Guanidine mimics as factor Xa inhibitors.
WO2000076970A2 (en) 1999-06-14 2000-12-21 Eli Lilly And Company Serine protease inhibitors
DE19962924A1 (de) 1999-12-24 2001-07-05 Bayer Ag Substituierte Oxazolidinone und ihre Verwendung
AR035216A1 (es) 2000-12-01 2004-05-05 Astrazeneca Ab Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios
SI1427415T1 (sl) 2001-09-21 2009-12-31 Bristol Myers Squibb Co Sestavine, ki vsebujejo laktame in njihovi derivati kot inhibitorji faktorja xa
US20040180855A1 (en) 2003-02-19 2004-09-16 Schumacher William A. Methods of treating thrombosis with reduced risk of increased bleeding times
US7417063B2 (en) 2004-04-13 2008-08-26 Bristol-Myers Squibb Company Bicyclic heterocycles useful as serine protease inhibitors
US7453002B2 (en) 2004-06-15 2008-11-18 Bristol-Myers Squibb Company Five-membered heterocycles useful as serine protease inhibitors
US7429604B2 (en) 2004-06-15 2008-09-30 Bristol Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
US7459564B2 (en) 2005-01-13 2008-12-02 Bristol-Myers Squibb Company Substituted biaryl compounds as factor XIa inhibitors
US20060183771A1 (en) 2005-02-17 2006-08-17 Seiffert Dietmar A Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors
CA2633252A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors
US8466295B2 (en) 2005-12-14 2013-06-18 Bristol-Myers Squibb Company Thiophene derivatives as factor XIa inhibitors
WO2007070818A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
JP5342450B2 (ja) 2006-12-15 2013-11-13 ブリストル−マイヤーズ スクイブ カンパニー 第ＸＩａ因子インヒビターとしてのアリールプロピオンアミド、アリールアクリルアミド、アリールプロピンアミド、またはアリールメチルウレアアナログ
PE20081775A1 (es) * 2006-12-20 2008-12-18 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
CN101784516B (zh) 2007-06-13 2014-07-02 百时美施贵宝公司 作为凝血因子抑制剂的二肽类似物
TW201311689A (zh) 2011-08-05 2013-03-16 必治妥美雅史谷比公司 作為因子ｘｉａ抑制劑之新穎巨環化合物
HRP20170784T8 (hr) 2011-10-14 2018-05-18 Bristol-Myers Squibb Company Supstituirani spojevi tetrahidroizohinolina kao inhbitori xia faktora
WO2013056034A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2899183B1 (en) 2011-10-14 2018-09-19 Bristol-Myers Squibb Company Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors
WO2014022766A1 (en) 2012-08-03 2014-02-06 Bristol-Myers Squibb Company Dihydropyridone p1 as factor xia inhibitors
CN104507924B (zh) * 2012-08-03 2018-01-23 百时美施贵宝公司 二氢吡啶酮p1作为凝血因子xia抑制剂
US9315519B2 (en) 2012-10-12 2016-04-19 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor XIa inhibitors
EP2906541B1 (en) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
HRP20180465T1 (hr) 2012-10-12 2018-05-04 Bristol-Myers Squibb Company Kristalni oblici inhibitora faktora xia
JP6479763B2 (ja) 2013-03-25 2019-03-06 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ｘｉａ因子阻害剤としての置換アゾール含有のテトラヒドロイソキノリン
UY35971A (es) 2014-01-31 2015-07-31 Bristol Myers Squibb Company Una Corporación Del Estado De Delaware Macrociclos con grupos p2? aromáticos como inhibidores del factor xia
NO2760821T3 (enExample) 2014-01-31 2018-03-10
CN107074821B (zh) 2014-09-04 2020-05-22 百时美施贵宝公司 为fxia抑制剂的二酰胺大环化合物
NO2721243T3 (enExample) 2014-10-01 2018-10-20
ES2762987T3 (es) 2015-06-19 2020-05-26 Bristol Myers Squibb Co Macrociclos de diamida como inhibidores del factor XIA
EP3328851B1 (en) 2015-07-29 2020-04-22 Bristol-Myers Squibb Company Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties
WO2017023992A1 (en) 2015-08-05 2017-02-09 Bristol-Myers Squibb Company Novel substituted glycine derived fxia inhibitors
JP2019507167A (ja) 2016-03-02 2019-03-14 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ｘｉａ因子阻害活性を有するジアミド大員環

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009114677A1 (en) 2008-03-13 2009-09-17 Bristol-Myers Squibb Company Pyridazine derivatives as factor xia inhibitors
WO2011100401A1 (en) 2010-02-11 2011-08-18 Bristol-Myers Squibb Company Macrocycles as factor xia inhibitors
WO2013022814A1 (en) 2011-08-05 2013-02-14 Bristol-Myers Squibb Company Cyclic p1 linkers as factor xia inhibitors

Also Published As

Publication number Publication date
ES2937156T3 (es) 2023-03-24
EP3868753A1 (en) 2021-08-25
EP3868753B1 (en) 2022-12-21
JP2018522024A (ja) 2018-08-09
US10676477B2 (en) 2020-06-09
JP6816103B2 (ja) 2021-01-20
ES2871111T3 (es) 2021-10-28
US20190010154A1 (en) 2019-01-10
CN114874222A (zh) 2022-08-09
EP3328852B1 (en) 2021-04-28
CN107922393A (zh) 2018-04-17
CN114805365A (zh) 2022-07-29
CN114805365B (zh) 2024-07-23
EP3328852A1 (en) 2018-06-06
KR20180033267A (ko) 2018-04-02
CN114874222B (zh) 2025-06-06
WO2017019821A1 (en) 2017-02-02

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