JP6033319B2 - 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 - Google Patents

第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 Download PDF

Info

Publication number
JP6033319B2
JP6033319B2 JP2014535924A JP2014535924A JP6033319B2 JP 6033319 B2 JP6033319 B2 JP 6033319B2 JP 2014535924 A JP2014535924 A JP 2014535924A JP 2014535924 A JP2014535924 A JP 2014535924A JP 6033319 B2 JP6033319 B2 JP 6033319B2
Authority
JP
Japan
Prior art keywords
alkyl
group
conh
alkylene
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
JP2014535924A
Other languages
English (en)
Japanese (ja)
Other versions
JP2014532070A (ja
JP2014532070A5 (US07585860-20090908-C00112.png
Inventor
マイケル・ジェイ・オーワット
ドナルド・ジェイ・ピー・ピント
レオン・エム・スミス・ザ・セカンド
シェファリ・スリヴァスタヴァ
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.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of JP2014532070A publication Critical patent/JP2014532070A/ja
Publication of JP2014532070A5 publication Critical patent/JP2014532070A5/ja
Application granted granted Critical
Publication of JP6033319B2 publication Critical patent/JP6033319B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—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 carbon chain containing aromatic 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
    • C07D401/14—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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine 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
    • A61K31/496—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
    • A61K31/535—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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • 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
    • 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
    • C07D471/10—Spiro-condensed 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
    • 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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • 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
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
JP2014535924A 2011-10-14 2012-10-12 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 Active JP6033319B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161547292P 2011-10-14 2011-10-14
US61/547,292 2011-10-14
PCT/US2012/059969 WO2013056060A1 (en) 2011-10-14 2012-10-12 Substituted tetrahydroisoquinoline compounds as factor xia inhibitors

Publications (3)

Publication Number Publication Date
JP2014532070A JP2014532070A (ja) 2014-12-04
JP2014532070A5 JP2014532070A5 (US07585860-20090908-C00112.png) 2015-12-03
JP6033319B2 true JP6033319B2 (ja) 2016-11-30

Family

ID=47080863

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2014535924A Active JP6033319B2 (ja) 2011-10-14 2012-10-12 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物

Country Status (32)

Country Link
US (6) US9000172B2 (US07585860-20090908-C00112.png)
EP (2) EP2766346B1 (US07585860-20090908-C00112.png)
JP (1) JP6033319B2 (US07585860-20090908-C00112.png)
KR (1) KR101937514B1 (US07585860-20090908-C00112.png)
CN (1) CN103974938B (US07585860-20090908-C00112.png)
AR (1) AR088456A1 (US07585860-20090908-C00112.png)
AU (1) AU2012322085B2 (US07585860-20090908-C00112.png)
BR (1) BR112014008807B1 (US07585860-20090908-C00112.png)
CA (1) CA2851810C (US07585860-20090908-C00112.png)
CL (1) CL2014000925A1 (US07585860-20090908-C00112.png)
CO (1) CO6950479A2 (US07585860-20090908-C00112.png)
CY (1) CY1118993T1 (US07585860-20090908-C00112.png)
DK (1) DK2766346T3 (US07585860-20090908-C00112.png)
EA (1) EA023649B1 (US07585860-20090908-C00112.png)
ES (1) ES2625256T3 (US07585860-20090908-C00112.png)
HR (1) HRP20170784T8 (US07585860-20090908-C00112.png)
HU (1) HUE034857T2 (US07585860-20090908-C00112.png)
IL (1) IL231574B (US07585860-20090908-C00112.png)
LT (1) LT2766346T (US07585860-20090908-C00112.png)
MX (1) MX359766B (US07585860-20090908-C00112.png)
MY (1) MY165742A (US07585860-20090908-C00112.png)
PE (1) PE20141825A1 (US07585860-20090908-C00112.png)
PL (1) PL2766346T3 (US07585860-20090908-C00112.png)
PT (1) PT2766346T (US07585860-20090908-C00112.png)
RS (1) RS56168B1 (US07585860-20090908-C00112.png)
SG (2) SG10201700328YA (US07585860-20090908-C00112.png)
SI (1) SI2766346T1 (US07585860-20090908-C00112.png)
TN (1) TN2014000155A1 (US07585860-20090908-C00112.png)
TW (2) TWI586651B (US07585860-20090908-C00112.png)
UY (1) UY34393A (US07585860-20090908-C00112.png)
WO (1) WO2013056060A1 (US07585860-20090908-C00112.png)
ZA (2) ZA201403440B (US07585860-20090908-C00112.png)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG183153A1 (en) 2010-02-11 2012-09-27 Bristol Myers Squibb Co Macrocycles as factor xia inhibitors
TW201319068A (zh) 2011-08-05 2013-05-16 必治妥美雅史谷比公司 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑
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
CN103987696B (zh) 2011-10-14 2016-12-21 百时美施贵宝公司 作为因子xia抑制剂的取代的四氢异喹啉化合物
MY165742A (en) 2011-10-14 2018-04-23 Bristol Myers Squibb Co Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
WO2013055984A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
TW201416362A (zh) 2012-07-19 2014-05-01 Dainippon Sumitomo Pharma Co １－（環烷基羰基）脯胺酸衍生物
WO2014022766A1 (en) 2012-08-03 2014-02-06 Bristol-Myers Squibb Company Dihydropyridone p1 as factor xia inhibitors
TW201410667A (zh) 2012-08-03 2014-03-16 必治妥美雅史谷比公司 二氫吡啶酮ｐ１作爲凝血因子ｘｉａ抑制劑
US9403774B2 (en) 2012-10-12 2016-08-02 Bristol-Myers Squibb Company Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
JP6154473B2 (ja) 2012-10-12 2017-06-28 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因子阻害剤の結晶形
WO2014059202A1 (en) 2012-10-12 2014-04-17 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
WO2014160668A1 (en) 2013-03-25 2014-10-02 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors
WO2014194809A1 (zh) * 2013-06-05 2014-12-11 永光制药有限公司 具有溶栓、抗栓和自由基清除三重活性的新型化合物、其合成、纳米结构和应用
EP3988549A1 (en) 2014-01-31 2022-04-27 Bristol-Myers Squibb Company Macrocycles with heterocyclic p2' groups as factor xia inhibitors
NO2760821T3 (US07585860-20090908-C00112.png) 2014-01-31 2018-03-10
KR101927114B1 (ko) 2014-02-07 2018-12-10 엑시테라 파마슈티컬스 인코퍼레이티드 치료 화합물 및 조성물
EP3104702B1 (en) 2014-02-11 2022-08-10 Merck Sharp & Dohme LLC Factor xia inhibitors
WO2015123093A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Factor xia inhibitors
WO2015160634A1 (en) * 2014-04-16 2015-10-22 Merck Sharp & Dohme Corp. Factor ixa inhibitors
EP3131897B8 (en) 2014-04-16 2022-08-03 Merck Sharp & Dohme LLC Factor ixa inhibitors
EP3134408B1 (en) * 2014-04-22 2020-08-12 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
US9868727B2 (en) 2014-07-28 2018-01-16 Merck Sharp & Dohme Corp. Factor XIa inhibitors
US10081623B2 (en) 2014-09-04 2018-09-25 Bristol-Myers Squibb Company Diamide macrocycles that are FXIa inhibitors
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
ES2803659T3 (es) 2015-07-29 2021-01-28 Bristol Myers Squibb Co Inhibidores macrocíclicos del factor xia que contienen restos alquilo o cicloalquilo p2’
CN107922393A (zh) 2015-07-29 2018-04-17 百时美施贵宝公司 携带非芳族p2,基团的因子xia新大环
WO2017074833A1 (en) 2015-10-29 2017-05-04 Merck Sharp & Dohme Corp. Macrocyclic spirocarbamate derivatives as factor xia inhibitors, pharmaceutically acceptable compositions and their use
JP6892858B2 (ja) 2015-10-29 2021-06-23 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． 第ＸＩａ因子阻害剤
CN107540659A (zh) * 2016-06-29 2018-01-05 四川科伦博泰生物医药股份有限公司 四氢异喹啉类化合物、其制备方法、药物组合物及其用途
US10143681B2 (en) 2016-08-22 2018-12-04 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2018041122A1 (zh) 2016-08-31 2018-03-08 江苏恒瑞医药股份有限公司 氧代吡啶酰胺类衍生物、其制备方法及其在医药上的应用
CN109721539B (zh) * 2017-10-27 2021-07-09 天津药物研究院有限公司 吡唑酰胺类衍生物及其制备方法和用途
CN109867660A (zh) * 2017-12-01 2019-06-11 四川科伦博泰生物医药股份有限公司 含季铵离子的四氢异喹啉酰胺化合物及其药物用途
CN111356677B (zh) * 2018-01-26 2023-08-01 四川科伦博泰生物医药股份有限公司 四氢异喹啉类衍生物及其制备方法和用途
CA3089970A1 (en) 2018-02-07 2019-08-15 eXIthera Pharmaceuticals Inc. Therapeutic compounds and compositions
CN111655686B (zh) * 2018-03-28 2024-02-09 四川科伦博泰生物医药股份有限公司 四氢异喹啉类衍生物及其制备方法和用途
WO2019218899A1 (zh) * 2018-05-17 2019-11-21 四川科伦博泰生物医药股份有限公司 含聚乙二醇醚的四氢异喹啉酰胺化合物及其药物用途
JP2021529201A (ja) 2018-07-02 2021-10-28 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司Ｊｉａｎｇｓｕ Ｈｅｎｇｒｕｉ Ｍｅｄｉｃｉｎｅ Ｃｏ．， Ｌｔｄ． オキシピリジンアミド誘導体の結晶形およびその調製方法
WO2020092594A1 (en) * 2018-10-30 2020-05-07 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
CA3117470A1 (en) * 2018-10-30 2020-05-07 Exithera Pharmaceuticals, Inc. Therapeutic compounds and compositions
CN114206854B (zh) 2019-09-27 2023-02-24 深圳信立泰药业股份有限公司 FXIa抑制剂及其制备方法和医药用途
CN115066417A (zh) * 2019-12-31 2022-09-16 上海京新生物医药有限公司 凝血因子XIa抑制剂

Family Cites Families (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1525186A (fr) 1967-03-29 1968-05-17 Roussel Uclaf Nouvelles pénicillines et procédé de préparation
EP0028489B1 (en) 1979-11-05 1983-10-05 Beecham Group Plc Enzyme derivatives, and their preparation
DE4034829A1 (de) 1990-11-02 1992-05-07 Merck Patent Gmbh Cyclopeptide
JP3190431B2 (ja) 1991-07-01 2001-07-23 三菱化学株式会社 ケトン誘導体
GB9206757D0 (en) 1992-03-27 1992-05-13 Ferring Bv Novel peptide receptor ligands
WO1996034010A2 (en) 1995-03-29 1996-10-31 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5624936A (en) 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5869682A (en) 1996-04-03 1999-02-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
AU717298B2 (en) 1996-04-03 2000-03-23 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
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.
TW557297B (en) 1997-09-26 2003-10-11 Abbott Lab Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same
HU227920B1 (en) 1998-03-19 2012-06-28 Vertex Pharma Inhibitors of caspases, pharmaceutical compositions comprising thereof and their use
NZ508268A (en) 1998-05-26 2004-02-27 Warner Lambert Co Bicyclic pyrimidines and bicyclic 3,4- dihydropyrimidines as inhibitors of cellular proliferation
US6307049B1 (en) 1998-09-30 2001-10-23 The Procter & Gamble Co. Heterocyclic 2-substituted ketoamides
JP2002534420A (ja) 1999-01-02 2002-10-15 アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 新規なマロン酸誘導体、その調製方法、その使用およびそれを含有する医薬組成物（Ｘａ因子活性阻害）
EP1016663A1 (en) 1999-01-02 2000-07-05 Aventis Pharma Deutschland GmbH Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity)
CZ20013577A3 (cs) 1999-04-09 2002-07-17 Basf Aktiengesellschaft Inhibitory komplementních proteáz s nízkou molekulovou hmotností
CA2383008A1 (en) 1999-06-14 2000-12-21 Amanda Jane Lyons Compounds
DE19962924A1 (de) 1999-12-24 2001-07-05 Bayer Ag Substituierte Oxazolidinone und ihre Verwendung
EP1125925A1 (en) 2000-02-15 2001-08-22 Applied Research Systems ARS Holding N.V. Amine derivatives for the treatment of apoptosis
CA2408486A1 (en) 2000-05-11 2001-11-15 Bristol-Myers Squibb Company Tetrahydroisoquinoline analogs useful as growth hormone secretagogues
SV2003000617A (es) 2000-08-31 2003-01-13 Lilly Co Eli Inhibidores de la proteasa peptidomimetica ref. x-14912m
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
WO2003011222A2 (en) 2001-07-27 2003-02-13 Merck & Co., Inc. Thrombin inhibitors
CA2726702A1 (en) 2001-09-21 2003-04-03 Bristol-Myers Squibb Company Lactam-containing compounds and derivatives thereof as factor xa inhibitors
AU2002357692A1 (en) * 2001-11-09 2003-05-26 Bristol-Myers Squibb Company Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity
US20040180855A1 (en) 2003-02-19 2004-09-16 Schumacher William A. Methods of treating thrombosis with reduced risk of increased bleeding times
US7138412B2 (en) 2003-03-11 2006-11-21 Bristol-Myers Squibb Company Tetrahydroquinoline derivatives useful as serine protease inhibitors
US7129264B2 (en) 2003-04-16 2006-10-31 Bristol-Myers Squibb Company Biarylmethyl indolines and indoles as antithromboembolic agents
CA2531796A1 (en) * 2003-08-08 2005-02-17 Transtech Pharma, Inc. Aryl and heteroaryl compounds, compositions, and methods of use
US7417063B2 (en) 2004-04-13 2008-08-26 Bristol-Myers Squibb Company Bicyclic 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
US7453002B2 (en) 2004-06-15 2008-11-18 Bristol-Myers Squibb Company Five-membered heterocycles useful as serine protease inhibitors
WO2006017295A2 (en) 2004-07-12 2006-02-16 Idun Pharmaceuticals, Inc. Tetrapeptide analogs
JP5236293B2 (ja) 2005-01-13 2013-07-17 ブリストル−マイヤーズ スクイブ カンパニー Ｘｉａ因子阻害剤としての置換ビアリール化合物
WO2006089005A2 (en) 2005-02-17 2006-08-24 Bristol-Myers Squibb Company Combination of selective factor viia and/or xia and plasma kallikrein inhibitors
KR20080018948A (ko) 2005-06-17 2008-02-28 바스프 악티엔게젤샤프트 표백 촉진제의 제조 방법
CA2627426A1 (en) 2005-11-11 2007-05-18 Markus Boehringer Carbocyclic fused cyclic amines as inhibitors of the coagulation factor xa
WO2007070818A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
KR20080087817A (ko) 2005-12-14 2008-10-01 브리스톨-마이어스 스큅 컴퍼니 인자 ｘｉａ 억제제로서 아릴프로피온아미드,아릴아크릴아미드, 아릴프로핀아미드 또는 아릴메틸우레아유사체
US8466295B2 (en) 2005-12-14 2013-06-18 Bristol-Myers Squibb Company Thiophene derivatives as factor XIa inhibitors
PE20071132A1 (es) 2005-12-23 2007-12-14 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
BRPI0716715B1 (pt) 2006-08-23 2021-07-06 Xenon Pharmaceuticals, Inc Derivados de 4-(n-azacicloalquil) anilidas como moduladores de canal de potássio, seus usos, produto, composição, comprimido e cápsula
ES2546815T3 (es) 2006-12-15 2015-09-28 Bristol-Myers Squibb Company Análogos de arilpropilamida, arilacrilamida, arilpropinamida o arilmetilurea como inhibidores del factor XIa
PE20081775A1 (es) 2006-12-20 2008-12-18 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
US8367709B2 (en) 2007-06-13 2013-02-05 Bristol-Myers Squibb Company Dipeptide analogs as coagulation factor inhibitors
ATE543811T1 (de) 2008-03-13 2012-02-15 Bristol Myers Squibb Co Pyridazinderivate als faktor-xia-inhibitoren
WO2010151317A1 (en) 2009-06-22 2010-12-29 Millennium Pharmaceuticals, Inc. Substituted hydroxamic acids and uses thereof
WO2011002520A2 (en) 2009-07-02 2011-01-06 Angion Biomedica Corp. Small molecule inhibitors of parp activity
AR077695A1 (es) 2009-08-04 2011-09-14 Schering Corp Derivados de pirimidina como inhibidores del factor ixa
SG183153A1 (en) 2010-02-11 2012-09-27 Bristol Myers Squibb Co Macrocycles as factor xia inhibitors
WO2013009527A2 (en) 2011-07-08 2013-01-17 Merck Sharp & Dohme Corp. Factor ixa inhibitors
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
TW201319068A (zh) 2011-08-05 2013-05-16 必治妥美雅史谷比公司 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑
MY165742A (en) 2011-10-14 2018-04-23 Bristol Myers Squibb Co Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
CN103987696B (zh) 2011-10-14 2016-12-21 百时美施贵宝公司 作为因子xia抑制剂的取代的四氢异喹啉化合物
WO2013055984A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
PT2794597T (pt) 2011-12-21 2018-01-16 Ono Pharmaceutical Co Derivados de piridinona e pirimidinona como inibidores do fator xia
US20140350034A1 (en) 2012-01-27 2014-11-27 Novartis Ag Aminopyridine derivatives as plasma kallikrein inhibitors
US20140378474A1 (en) 2012-01-27 2014-12-25 Novartis Ag 5-membered heteroarylcarboxamide derivatives as plasma kallikrein inhibitors
JP2015083542A (ja) 2012-02-08 2015-04-30 大日本住友製薬株式会社 ３位置換プロリン誘導体
PL2847228T3 (pl) 2012-05-10 2019-03-29 Bayer Pharma Aktiengesellschaft Przeciwciała zdolne do wiązania się z czynnikiem krzepnięcia XI i/lub jego aktywowaną postacią, czynnikiem Xla oraz ich zastosowanie
GB201209138D0 (en) 2012-05-24 2012-07-04 Ono Pharmaceutical Co Compounds
TW201416362A (zh) 2012-07-19 2014-05-01 Dainippon Sumitomo Pharma Co １－（環烷基羰基）脯胺酸衍生物
WO2014022766A1 (en) 2012-08-03 2014-02-06 Bristol-Myers Squibb Company Dihydropyridone p1 as factor xia inhibitors
TW201410667A (zh) 2012-08-03 2014-03-16 必治妥美雅史谷比公司 二氫吡啶酮ｐ１作爲凝血因子ｘｉａ抑制劑
US9403774B2 (en) 2012-10-12 2016-08-02 Bristol-Myers Squibb Company Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
JP6154473B2 (ja) 2012-10-12 2017-06-28 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因子阻害剤の結晶形
WO2014059202A1 (en) 2012-10-12 2014-04-17 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
US9708308B2 (en) 2012-12-19 2017-07-18 Merck Sharp Dohme Corp. Factor IXa inhibitors
GB201300304D0 (en) 2013-01-08 2013-02-20 Kalvista Pharmaceuticals Ltd Benzylamine derivatives
GB2510407A (en) 2013-02-04 2014-08-06 Kalvista Pharmaceuticals Ltd Aqueous suspensions of kallikrein inhibitors for parenteral administration
WO2014160668A1 (en) 2013-03-25 2014-10-02 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors
NO2760821T3 (US07585860-20090908-C00112.png) 2014-01-31 2018-03-10
EP3988549A1 (en) 2014-01-31 2022-04-27 Bristol-Myers Squibb Company Macrocycles with heterocyclic p2' groups as factor xia inhibitors

Also Published As

Publication number Publication date
HRP20170784T1 (hr) 2017-08-11
CA2851810A1 (en) 2013-04-18
MX359766B (es) 2018-10-10
AU2012322085B2 (en) 2017-05-04
EP2766346B1 (en) 2017-03-29
TWI586651B (zh) 2017-06-11
US9447110B2 (en) 2016-09-20
CN103974938A (zh) 2014-08-06
TW201722918A (zh) 2017-07-01
JP2014532070A (ja) 2014-12-04
NZ624874A (en) 2016-07-29
PT2766346T (pt) 2017-05-26
CN103974938B (zh) 2016-11-09
EP2766346A1 (en) 2014-08-20
US9000172B2 (en) 2015-04-07
WO2013056060A1 (en) 2013-04-18
SG10201700328YA (en) 2017-02-27
ZA201408141B (en) 2015-09-30
UY34393A (es) 2013-04-30
PE20141825A1 (es) 2014-11-29
BR112014008807A2 (pt) 2017-04-25
IL231574B (en) 2018-07-31
US20170073330A1 (en) 2017-03-16
US20160318904A1 (en) 2016-11-03
US20160075715A1 (en) 2016-03-17
US20180201603A1 (en) 2018-07-19
EA201490724A1 (ru) 2014-07-30
SI2766346T1 (sl) 2017-05-31
KR101937514B1 (ko) 2019-01-10
TWI633091B (zh) 2018-08-21
ZA201403440B (en) 2016-01-27
IL231574A0 (en) 2014-04-30
US20150157624A1 (en) 2015-06-11
CL2014000925A1 (es) 2014-07-18
US10208021B2 (en) 2019-02-19
EA023649B1 (ru) 2016-06-30
BR112014008807B1 (pt) 2021-12-14
LT2766346T (lt) 2017-06-12
PL2766346T3 (pl) 2017-09-29
ES2625256T3 (es) 2017-07-19
AR088456A1 (es) 2014-06-11
US9192607B2 (en) 2015-11-24
CO6950479A2 (es) 2014-05-20
TN2014000155A1 (en) 2015-09-30
CA2851810C (en) 2020-01-07
CY1118993T1 (el) 2018-01-10
KR20140090623A (ko) 2014-07-17
HUE034857T2 (en) 2018-03-28
AU2012322085A1 (en) 2014-05-29
DK2766346T3 (en) 2017-07-03
US20140296214A1 (en) 2014-10-02
HRP20170784T8 (hr) 2018-05-18
TW201321358A (zh) 2013-06-01
MX2014004245A (es) 2014-06-05
RS56168B1 (sr) 2017-11-30
US9944625B2 (en) 2018-04-17
EP3309148A1 (en) 2018-04-18
MY165742A (en) 2018-04-23
SG11201401384UA (en) 2014-09-26

Similar Documents

Publication Publication Date Title
JP6033319B2 (ja) 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物
EP2766347B1 (en) Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2978751B1 (en) Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors
EP2906541B1 (en) Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2906552B1 (en) Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
US8039506B2 (en) Bicyclic lactam factor VIIa inhibitors useful as anticoagulants
JP6742348B2 (ja) 第ｘｉａ因子阻害剤としてのジアミド大員環
NZ624874B2 (en) Substituted tetrahydroisoquinoline compounds as factor xia inhibitors

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20151009

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20151009

RD04 Notification of resignation of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7424

Effective date: 20160219

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20160524

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20160526

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160824

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: 20160927

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20161025

R150 Certificate of patent or registration of utility model

Ref document number: 6033319

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250