CO2017003833A2 - Pirimidinonas como inhibidores del factor xia - Google Patents
Pirimidinonas como inhibidores del factor xiaInfo
- Publication number
- CO2017003833A2 CO2017003833A2 CONC2017/0003833A CO2017003833A CO2017003833A2 CO 2017003833 A2 CO2017003833 A2 CO 2017003833A2 CO 2017003833 A CO2017003833 A CO 2017003833A CO 2017003833 A2 CO2017003833 A2 CO 2017003833A2
- Authority
- CO
- Colombia
- Prior art keywords
- factor xia
- pyrimidinones
- compounds
- xia inhibitors
- inhibitors
- Prior art date
Links
Classifications
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- 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
- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles 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
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic 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
- C07D239/28—Heterocyclic 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- 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
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Abstract
La presente invención proporciona compuestos de la Fórmula (I) o estereoisómeros, tautómeros o sales farmacéuticamente aceptables de los mismos, en donde todas las variables son como se definen en la presente. Estos compuestos son inhibidores selectivos del factor XIa o inhibidores duales de FXIa y calicreína plasmática. También se refiere a composiciones farmacéuticas que comprenden estos compuestos y a métodos para tratar trastornos tromboembólicos y/o inflamatorios mediante su uso.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462058316P | 2014-10-01 | 2014-10-01 | |
PCT/US2015/042576 WO2016053455A1 (en) | 2014-10-01 | 2015-07-29 | Pyrimidinones as factor xia inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
CO2017003833A2 true CO2017003833A2 (es) | 2017-07-11 |
Family
ID=53784023
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CONC2017/0003833A CO2017003833A2 (es) | 2014-10-01 | 2017-04-20 | Pirimidinonas como inhibidores del factor xia |
Country Status (34)
Country | Link |
---|---|
EP (4) | EP4286372A3 (es) |
JP (4) | JP6462865B2 (es) |
KR (2) | KR102269999B1 (es) |
CN (3) | CN106795161B (es) |
AR (1) | AR101367A1 (es) |
AU (3) | AU2015324530B2 (es) |
CA (1) | CA2963395C (es) |
CL (1) | CL2017000712A1 (es) |
CO (1) | CO2017003833A2 (es) |
CY (2) | CY1119678T1 (es) |
DK (2) | DK3293186T3 (es) |
EA (1) | EA031590B1 (es) |
ES (3) | ES2655884T3 (es) |
HR (2) | HRP20171950T1 (es) |
HU (2) | HUE052812T2 (es) |
IL (2) | IL251434B (es) |
LT (2) | LT3089979T (es) |
MA (1) | MA40123A1 (es) |
MX (2) | MX2017003695A (es) |
MY (1) | MY183987A (es) |
NO (1) | NO2721243T3 (es) |
NZ (2) | NZ731416A (es) |
PE (2) | PE20210922A1 (es) |
PH (2) | PH12017500580B1 (es) |
PL (1) | PL3089979T3 (es) |
PT (2) | PT3293186T (es) |
RS (2) | RS61183B1 (es) |
SG (2) | SG11201702576QA (es) |
SI (2) | SI3089979T1 (es) |
TN (2) | TN2017000112A1 (es) |
TW (2) | TWI692478B (es) |
UY (1) | UY36244A (es) |
WO (1) | WO2016053455A1 (es) |
ZA (1) | ZA201702478B (es) |
Families Citing this family (30)
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GB201116559D0 (en) | 2011-09-26 | 2011-11-09 | Univ Leuven Kath | Novel viral replication inhibitors |
NO2760821T3 (es) | 2014-01-31 | 2018-03-10 | ||
CN116987080A (zh) * | 2014-01-31 | 2023-11-03 | 百时美施贵宝公司 | 作为因子xia抑制剂的具有杂环p2′基团的大环化合物 |
JP6526796B2 (ja) | 2014-09-04 | 2019-06-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Fxia阻害剤であるジアミドマクロ環 |
US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
RU2717558C2 (ru) | 2014-10-01 | 2020-03-24 | Мерк Патент Гмбх | Производные бороновой кислоты |
NO2721243T3 (es) * | 2014-10-01 | 2018-10-20 | ||
JOP20160086B1 (ar) | 2015-05-08 | 2021-08-17 | 2 Katholieke Univ Leuven Ku Leuven Research And Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
JP6742348B2 (ja) | 2015-06-19 | 2020-08-19 | 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ジアミド大員環 |
CN114874222A (zh) | 2015-07-29 | 2022-08-09 | 百时美施贵宝公司 | 携带非芳族p2,基团的因子xia新大环 |
EP3328851B1 (en) * | 2015-07-29 | 2020-04-22 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties |
JO3633B1 (ar) | 2015-09-16 | 2020-08-27 | Katholieke Univ Leuven Ku Leuven Research & Development | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
JOP20160198B1 (ar) | 2015-09-16 | 2022-03-14 | Janssen Pharmaceuticals Inc | مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
EP3423458A1 (en) | 2016-03-02 | 2019-01-09 | Bristol-Myers Squibb Company | Diamide macrocycles having factor xia inhibiting activity |
MX2018011788A (es) | 2016-03-31 | 2019-05-20 | Janssen Pharmaceuticals Inc | Derivados de indolina sustituidos como inhibidores de la replicacion virica de dengue. |
CO2018009559A2 (es) | 2016-03-31 | 2018-09-20 | Janssen Pharmaceuticals Inc | Derivados de indol sustituidos como inhibidores de la replicación vírica del dengue |
JOP20170069B1 (ar) | 2016-04-01 | 2021-08-17 | 1 Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
CR20180494A (es) | 2016-04-01 | 2019-01-29 | Janssen Pharmaceuticals Inc | Derivados de compuestos de indol sustituidos como inhibidores de la replicación vírica del dengue |
WO2018133793A1 (zh) * | 2017-01-18 | 2018-07-26 | 广东东阳光药业有限公司 | 凝血因子XIa抑制剂及其用途 |
JOP20180025B1 (ar) | 2017-03-31 | 2021-08-17 | Janssen Pharmaceuticals Inc | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
JOP20180026A1 (ar) | 2017-03-31 | 2019-01-30 | Univ Leuven Kath | مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك |
AU2018274101C1 (en) | 2017-05-22 | 2022-09-15 | Janssen Pharmaceuticals, Inc. | Substituted indoline derivatives as dengue viral replication inhibitors |
AU2018274100B2 (en) | 2017-05-22 | 2022-06-23 | Janssen Pharmaceuticals, Inc. | Substituted indoline derivatives as dengue viral replication inhibitors |
WO2020210613A1 (en) * | 2019-04-11 | 2020-10-15 | Bristol-Myers Squibb Company | Novel synthetic options towards the manufacture of (6r,10s)-10- {4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6h)-one |
KR20210151183A (ko) * | 2019-04-11 | 2021-12-13 | 브리스톨-마이어스 스큅 컴퍼니 | 치료 혈장 농도를 달성하기 위한 무정형 고체 및 가용화된 제제의 증진된 성능 |
US20220204508A1 (en) * | 2019-04-16 | 2022-06-30 | Medshine Discovery Inc. | Macrocyclic derivatives acting as xia factor inhibitor |
CN114008047B (zh) * | 2019-07-23 | 2023-03-21 | 南京明德新药研发有限公司 | 作为XIa因子抑制剂的大环衍生物 |
EP4132930A1 (en) * | 2020-04-10 | 2023-02-15 | Bristol-Myers Squibb Company | Crystalline forms of (9, 135s)-13- {4-[5-chloro-2-(4-chloro-1h,2,3- triazol- 1 -yl)phenyl] -6-oxo- 1,6-dihydropyrimidin- 1-yl}-3-(difluoromethyl)-9-methyl-3,4,7,15- tetraazatricyclo [ 12.3.1.0] octadeca- 1(18), 2(6), 4, 14, 16-pentaen-8-one |
TW202229280A (zh) * | 2020-10-12 | 2022-08-01 | 美商必治妥美雅史谷比公司 | (6r,10s)-10-{4-[5-氯-2-(4-氯-1h-1,2,3-***-1-基)苯基]-6-側氧基-1(6h)-嘧啶基}-1-(二氟甲基)-6-甲基-1,4,7,8,9,10-六氫-11,15-(亞甲橋基)吡唑并[4,3-b][1,7]二氮雜環十四炔-5(6h)-酮之製備方法 |
CN115215867B (zh) * | 2021-04-21 | 2023-12-26 | 上海美悦生物科技发展有限公司 | FXIa抑制剂及其药物组合物、制备方法和用途 |
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ZA985247B (en) | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
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CN116987080A (zh) * | 2014-01-31 | 2023-11-03 | 百时美施贵宝公司 | 作为因子xia抑制剂的具有杂环p2′基团的大环化合物 |
NO2760821T3 (es) * | 2014-01-31 | 2018-03-10 | ||
NO2721243T3 (es) * | 2014-10-01 | 2018-10-20 |
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2012
- 2012-06-14 NO NO12801069A patent/NO2721243T3/no unknown
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2015
- 2015-07-29 SG SG11201702576QA patent/SG11201702576QA/en unknown
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- 2015-07-29 ES ES15747721.7T patent/ES2655884T3/es active Active
- 2015-07-29 EA EA201790595A patent/EA031590B1/ru not_active IP Right Cessation
- 2015-07-29 PE PE2020001966A patent/PE20210922A1/es unknown
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- 2015-07-29 JP JP2017517766A patent/JP6462865B2/ja active Active
- 2015-07-29 PT PT171899354T patent/PT3293186T/pt unknown
- 2015-07-29 PT PT157477217T patent/PT3089979T/pt unknown
- 2015-07-29 AU AU2015324530A patent/AU2015324530B2/en active Active
- 2015-07-29 TN TN2017000112A patent/TN2017000112A1/en unknown
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- 2015-07-29 MA MA40123A patent/MA40123A1/fr unknown
- 2015-07-29 LT LTEP15747721.7T patent/LT3089979T/lt unknown
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- 2015-07-29 DK DK17189935.4T patent/DK3293186T3/da active
- 2015-07-29 NZ NZ766570A patent/NZ766570A/en unknown
- 2015-07-29 ES ES20197284T patent/ES2963267T3/es active Active
- 2015-07-29 ES ES17189935T patent/ES2836270T3/es active Active
- 2015-07-29 CN CN201910882473.1A patent/CN110734435B/zh active Active
- 2015-07-29 AR ARP150102426A patent/AR101367A1/es unknown
- 2015-07-29 EP EP23185426.6A patent/EP4286372A3/en active Pending
- 2015-07-29 MX MX2017003695A patent/MX2017003695A/es active IP Right Grant
- 2015-07-29 SI SI201531423T patent/SI3293186T1/sl unknown
- 2015-07-29 RS RS20201472A patent/RS61183B1/sr unknown
- 2015-07-29 SG SG10201911652TA patent/SG10201911652TA/en unknown
- 2015-07-29 CA CA2963395A patent/CA2963395C/en active Active
- 2015-07-29 LT LTEP17189935.4T patent/LT3293186T/lt unknown
- 2015-07-29 TW TW104124664A patent/TWI692478B/zh active
- 2015-07-29 KR KR1020187033199A patent/KR102269999B1/ko active IP Right Grant
- 2015-07-29 EP EP15747721.7A patent/EP3089979B1/en active Active
- 2015-07-29 RS RS20180046A patent/RS56786B1/sr unknown
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