AR091981A1 - Dihidropiridona p1 como inhibidores del factor xia - Google Patents
Dihidropiridona p1 como inhibidores del factor xiaInfo
- Publication number
- AR091981A1 AR091981A1 ARP130102764A ARP130102764A AR091981A1 AR 091981 A1 AR091981 A1 AR 091981A1 AR P130102764 A ARP130102764 A AR P130102764A AR P130102764 A ARP130102764 A AR P130102764A AR 091981 A1 AR091981 A1 AR 091981A1
- Authority
- AR
- Argentina
- Prior art keywords
- independently selected
- optionally substituted
- alkyl
- heterocycle
- carbocycle
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 12
- 229910052736 halogen Inorganic materials 0.000 abstract 7
- 150000002367 halogens Chemical class 0.000 abstract 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- 125000003118 aryl group Chemical group 0.000 abstract 6
- 150000001875 compounds Chemical class 0.000 abstract 5
- 229910052731 fluorine Inorganic materials 0.000 abstract 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 4
- 125000003545 alkoxy group Chemical group 0.000 abstract 4
- -1 -CH2OH Chemical group 0.000 abstract 3
- 125000004450 alkenylene group Chemical group 0.000 abstract 3
- 125000002947 alkylene group Chemical group 0.000 abstract 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 3
- 229910052801 chlorine Inorganic materials 0.000 abstract 3
- 125000001188 haloalkyl group Chemical group 0.000 abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 3
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 abstract 2
- 229910052794 bromium Inorganic materials 0.000 abstract 2
- 229910052799 carbon Inorganic materials 0.000 abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- 108010080805 Factor XIa Proteins 0.000 abstract 1
- 102000003827 Plasma Kallikrein Human genes 0.000 abstract 1
- 108090000113 Plasma Kallikrein Proteins 0.000 abstract 1
- 229940124639 Selective inhibitor Drugs 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- 150000001721 carbon Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 230000009977 dual effect Effects 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000009424 thromboembolic effect Effects 0.000 abstract 1
Classifications
-
- 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
- C07D471/08—Bridged 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
- A61K31/435—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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further 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
- A61K31/435—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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
- C07C53/16—Halogenated acetic acids
- C07C53/18—Halogenated acetic acids containing fluorine
-
- 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
- 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
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Estos compuestos son inhibidores selectivos del factor XIa o inhibidores duales de FXIa y calicreína plasmática. También composiciones farmacéuticas que comprenden estos compuestos y a métodos para tratar trastornos tromboembólicos y/o inflamatorios mediante su uso. Reivindicación 1: Un compuesto caracterizado por la fórmula (1) o un estereoisómero, un tautómero o una sal de aquel aceptable desde el punto de vista farmacéutico, en donde: el anillo A se selecciona independientemente de un arilo de 6 miembros y un heterociclo de 5 a 6 miembros, en donde el arilo y el heterociclo se sustituyen opcionalmente, cuando la valencia lo permite, con uno o más R⁴; el anillo B se selecciona independientemente de un arilo de 6 miembros y un heterociclo de 5 a 10 miembros, en donde el arilo y el heterociclo se sustituyen opcionalmente, cuando la valencia lo permite, con uno o más R³; el anillo C se selecciona independientemente de los compuesto de fórmula (2) y (3); - - - - es un enlace opcional; G¹ se selecciona independientemente de carbociclo C₃₋₁₀ y un heterociclo de 5 a 10 miembros, en donde el carbociclo y el heterociclo se sustituyen opcionalmente, cuando la valencia lo permite, con uno o más R⁸; X se selecciona independientemente de alquileno C₄₋₈ y alquenileno C₄₋₈, en donde el alquileno y el alquenileno se sustituyen con R¹ y R²; de manera alternativa, uno o más de los átomos de carbono del alquileno y alquenileno se pueden reemplazar por O, C=O, S(O)ₚ, S(O)ₚNH, NH y N(alquilo C₁₋₄); X¹ se selecciona independientemente de CR⁷ y N; Y se selecciona independientemente de -NH-C(O)- y -C(O)-NH-; R¹ y R² se seleccionan independientemente de H, halógeno, haloalquilo, alquilo C₁₋₆ (opcionalmente sustituido con R⁶), hidroxilo y alcoxi (opcionalmente sustituido con R⁶), y cicloalquilo C₃₋₆ opcionalmente sustituido con R⁶; opcionalmente, cuando R¹ y R² se unen al mismo átomo de carbono, forman juntos un grupo oxo o cicloalquilo C₃₋₆; opcionalmente, cuando R¹ y R² se unen a átomos de carbono adyacentes entre sí, forman juntos un enlace o un carbociclo; R³ se selecciona independientemente de H, NO₂, =O, halógeno, haloalquilo, alquilo C₁₋₄ (opcionalmente sustituido con R⁶), alquenilo C₂₋₄ (opcionalmente sustituido con R⁶), alquinilo C₂₋₄ (opcionalmente sustituido con R⁶), CN, -(CH₂)ₙ-OR⁵, -(CH₂)ₙ-NR⁵R⁵, -(CH₂)ₙ-C(O)OR⁵, -(CH₂)ₙ-NR⁹C(O)OR⁵, -(CH₂)ₙ-NR⁹C(O)R⁵, -(CH₂)ₙ-NR⁹C(N-CN)NHR⁵, -(CH₂)ₙ-NR⁹C(NH)NHR⁵, -(CH₂)ₙ-N=CR⁹NR⁵R⁵, -(CH₂)ₙ-NR⁹C(O)NR⁵R⁵, -(CH₂)ₙ-C(O)NR⁵R⁵, (CH₂)ₙ-NR⁹C(S)NR⁹C(O)R⁵, -(CH₂)ₙ-S(O)ₚR¹², -(CH₂)ₙ-S(O)ₚNR⁵R⁵, -(CH₂)ₙ-NR⁹S(O)ₚNR⁵R⁵, -(CH₂)ₙ-NR⁹S(O)ₚR¹², -(CH₂)ₙ-carbociclo C₃₋₁₀ y -(CH₂)ₙ-heterociclo de 4 a 10 miembros, en donde el carbociclo y el heterociclo se sustituyen opcionalmente con R⁶; opcionalmente, dos grupos R³ adyacentes en el carbociclo y heterociclo pueden formar un anillo opcionalmente sustituido con R⁶; R⁴ se selecciona independientemente de H, OH, NH₂, halógeno, CN, alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄, -CH₂OH, -CO₂H, -CH₂CO₂H, -CO₂(alquilo C₁₋₄), -C(O)NH₂, -C(O)NH(alquilo C₁₋₄), -C(O)N(alquilo C₁₋₄)₂, S(O)₂NH₂, cicloalquilo C₃₋₆, arilo y un heterociclo de 5 a 6 miembros, en donde el cicloalquilo, arilo y heterociclo se sustituyen opcionalmente con R⁶; R⁵ se selecciona independientemente de H, alquilo C₁₋₄ (opcionalmente sustituido con halógeno, hidroxilo, alcoxi, carboxi, alcoxicarbonilo, amino, amino sustituido), -(CH₂)ₙ-carbociclo C₃₋₁₀ y -(CH₂)ₙ-heterociclo de 4 a 10 miembros, en donde el carbociclo y el heterociclo se sustituyen opcionalmente con R⁶; de manera alternativa, R⁵ y R⁵, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico opcionalmente sustituido con R⁶; R⁶ se selecciona independientemente de -(CH₂)ₙ-OH, =O, -(CH₂)ₙNH₂, -(CH₂)ₙCN, halógeno, alquilo C₁₋₆, -(CH₂)ₙ-C(=O)OH, -(CH₂)ₙ-C(=O)O-alquilo C₁₋₄, -(CH₂)ₙ-O-alquilo C₁₋₄, -(CH₂)ₙ-carbociclo C₃₋₁₀, -(CH₂)ₙ-heterociclo de 4 a 10 miembros y -O-heterociclo de 4 a 10 miembros, en donde el carbociclo y el heterociclo se sustituyen opcionalmente con R¹⁰; R⁷ se selecciona independientemente de H, hidroxilo, alcoxi, halógeno, alquilo C₁₋₃; R⁸ se selecciona independientemente de H, halógeno, CN, NH₂, alquilo C₁₋₆, haloalquilo, haloalquilcarbonilamina, alquilcarbonilo, alcoxi, haloalcoxi, -(CH₂)ₙ-arilo, -(CH₂)ₙ-cicloalquilo C₃₋₆ y -(CH₂)ₙ-heterociclo de 4 - 6 miembros; opcionalmente, dos grupos R⁸ adyacentes en el carbociclo y heterociclo pueden formar un anillo opcionalmente sustituido con R¹⁰; R⁹ es H o alquilo C₁₋₆; R¹⁰ se selecciona independientemente de alquilo C₁₋₆ (opcionalmente sustituido con R¹¹), alquenilo C₂₋₆, alquinilo C₂₋₆, -(CH₂)ₙ-cicloalquilo C₃₋₆ (opcionalmente sustituido con R¹¹), -O-heterociclo de 4 a 10 miembros (opcionalmente sustituido con R¹¹), F, Cl, Br, CN, NO₂, =O, CO₂H, -(CH₂)ₙ-O-alquilo C₁₋₅, -(CH₂)ₙ-OR¹¹ y -(CH₂)ₙ-NR¹¹R¹¹; R¹¹, en cada caso, se selecciona independientemente de H, alquilo C₁₋₅, -(CH₂)ₙ-OH, cicloalquilo C₃₋₆ y fenilo, o R¹¹ y R¹¹, junto con el átomo de nitrógeno al que están unidos, forman un anillo heterocíclico opcionalmente sustituido con alquilo C₁₋₄; R¹² es alquilo C₁₋₆ opcionalmente sustituido con R¹¹; m es un entero seleccionado independientemente de 0 y 1; n, en cada caso, es un entero seleccionado independientemente de 0, 1, 2, 3 y 4; p, en cada caso, es un entero seleccionado independientemente de 0, 1 y 2; siempre que se excluyan los compuestos de fórmula (4) en donde el anillo A se selecciona independientemente del grupo de fórmulas (5); - - - - es un enlace opcional; R¹ se selecciona independientemente de H, hidroxilo y alquilo C₁₋₄; R², en cada caso, se selecciona independientemente de H e hidroxilo; R⁴ se selecciona independientemente de H, OH, F, O-alquilo C₁₋₄ y CN; R⁸ᵃ se selecciona independientemente de H, F, Cl y Br; R⁸ᵇ se selecciona independientemente de H y F; y R⁸ᶜ se selecciona independientemente de H, F y Cl.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261679197P | 2012-08-03 | 2012-08-03 | |
| US201361787081P | 2013-03-15 | 2013-03-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR091981A1 true AR091981A1 (es) | 2015-03-11 |
Family
ID=48949290
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP130102764A AR091981A1 (es) | 2012-08-03 | 2013-08-02 | Dihidropiridona p1 como inhibidores del factor xia |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US9409908B2 (es) |
| EP (1) | EP2880026B1 (es) |
| JP (1) | JP6082463B2 (es) |
| KR (1) | KR20150038372A (es) |
| CN (2) | CN108250199B (es) |
| AR (1) | AR091981A1 (es) |
| AU (1) | AU2013296259A1 (es) |
| BR (1) | BR112015002081A2 (es) |
| CA (1) | CA2880866A1 (es) |
| CY (1) | CY1119004T1 (es) |
| DK (1) | DK2880026T3 (es) |
| EA (1) | EA028581B1 (es) |
| ES (1) | ES2623175T3 (es) |
| HR (1) | HRP20170506T1 (es) |
| HU (1) | HUE032622T2 (es) |
| IL (1) | IL237011A0 (es) |
| LT (1) | LT2880026T (es) |
| MX (1) | MX361759B (es) |
| PL (1) | PL2880026T3 (es) |
| PT (1) | PT2880026T (es) |
| RS (1) | RS55975B1 (es) |
| SG (1) | SG11201500271UA (es) |
| SI (1) | SI2880026T1 (es) |
| SM (1) | SMT201700240T1 (es) |
| TW (1) | TW201410667A (es) |
| UY (1) | UY34960A (es) |
| WO (1) | WO2014022767A1 (es) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| PL2766346T3 (pl) | 2011-10-14 | 2017-09-29 | Bristol-Myers Squibb Company | Podstawione związki tetrahydroizochinoliny jako inhibitory czynnika XIA |
| IN2014CN02806A (es) | 2011-10-14 | 2015-07-03 | Bristol Myers Squibb Co | |
| JP6033318B2 (ja) | 2011-10-14 | 2016-11-30 | 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テトラヒドロイソキノリン化合物 |
| EP2906541B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9315519B2 (en) | 2012-10-12 | 2016-04-19 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor XIa inhibitors |
| EA032092B1 (ru) | 2012-10-12 | 2019-04-30 | Бристол-Майерс Сквибб Компани | Кристаллические формы ингибитора фактора 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 |
| FR3010076B1 (fr) * | 2013-09-02 | 2016-12-23 | Centre Nat De La Rech Scient - Cnrs - | Inhibiteurs de metalloproteases, leurs procedes de preparation et leurs utilisations therapeutiques |
| ES2687498T3 (es) * | 2014-01-31 | 2018-10-25 | Bristol-Myers Squibb Company | Macrociclos con grupos P2¿ heterocíclicos como inhibidores del factor XIa |
| NO2760821T3 (es) * | 2014-01-31 | 2018-03-10 | ||
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| NO2721243T3 (es) | 2014-10-01 | 2018-10-20 | ||
| US10160750B2 (en) * | 2015-06-19 | 2018-12-25 | Bristol-Myers Squibb Company | Diamide macrocycles as factor XIa inhibitors |
| JO3703B1 (ar) * | 2015-07-09 | 2021-01-31 | Bayer Pharma AG | مشتقات أوكسوبيريدين مستبدلة |
| CN107849026B (zh) * | 2015-07-29 | 2021-01-01 | 百时美施贵宝公司 | 携带烷基或环烷基p2′部分的因子xia大环抑制剂 |
| 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 |
| US10336730B2 (en) | 2015-08-05 | 2019-07-02 | Bristol-Myers Squibb Company | Substituted glycine derived FXIA inhibitors |
| 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 |
| CA2998902C (en) * | 2015-10-29 | 2024-03-26 | Merck Sharp & Dohme Corp. | Macrocyclic compounds as factor xia inhibitors |
| WO2017151746A1 (en) | 2016-03-02 | 2017-09-08 | Bristol-Myers Squibb Company | Diamide macrocycles having factor xia inhibiting activity |
| WO2018039094A1 (en) | 2016-08-22 | 2018-03-01 | Merck Sharp & Dohme Corp. | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| CN110062757B (zh) * | 2017-01-18 | 2022-03-04 | 广东东阳光药业有限公司 | 凝血因子XIa抑制剂及其用途 |
| WO2019011166A1 (zh) * | 2017-07-14 | 2019-01-17 | 四川科伦博泰生物医药股份有限公司 | 大环酰胺化合物及其药物组合物和用途 |
| CN113677682B (zh) | 2019-04-16 | 2023-05-30 | 华润生物医药有限公司 | 作为XIa因子抑制剂的大环衍生物 |
| WO2021013209A1 (zh) | 2019-07-23 | 2021-01-28 | 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 |
| CN113004286B (zh) * | 2019-12-20 | 2022-08-12 | 成都康弘药业集团股份有限公司 | 作为血浆激肽释放酶抑制剂的三环类化合物及其用途 |
| CN113004284B (zh) * | 2019-12-20 | 2022-08-12 | 成都康弘药业集团股份有限公司 | 作为血浆激肽释放酶抑制剂的四环类化合物及其用途 |
| US20230312560A1 (en) * | 2020-07-22 | 2023-10-05 | Janssen Pharmaceutica Nv | Compounds useful as factor xia inhibitors |
| WO2022164735A1 (en) | 2021-01-28 | 2022-08-04 | Merck Sharp & Dohme Llc | Factor xia inhibitors |
| WO2025002297A1 (zh) * | 2023-06-30 | 2025-01-02 | 深圳信立泰药业股份有限公司 | 一种多取代的大环化合物及其制备方法与应用 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028489B1 (en) | 1979-11-05 | 1983-10-05 | 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 |
| GEP20074098B (en) | 2001-09-21 | 2007-05-10 | Bristol Myers Squibb Co | Lactam-containing compounds and derivatives thereof as factor xa inhibitors |
| 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 |
| 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 |
| CN101137412B (zh) | 2005-01-13 | 2012-11-07 | 布里斯托尔-迈尔斯·斯奎布公司 | 用作凝血因子XIa抑制剂的取代的二芳基化合物 |
| 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 |
| WO2007070816A2 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Thiophene derivatives as factor xia inhibitors |
| WO2007070826A1 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| EP1966141A1 (en) | 2005-12-14 | 2008-09-10 | Brystol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| WO2008076805A2 (en) | 2006-12-15 | 2008-06-26 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| PE20081775A1 (es) * | 2006-12-20 | 2008-12-18 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| JP5318094B2 (ja) | 2007-06-13 | 2013-10-16 | ブリストル−マイヤーズ スクイブ カンパニー | 凝固因子阻害剤としてのジペプチド類似体 |
| CN102026996B (zh) | 2008-03-13 | 2015-01-07 | 百时美施贵宝公司 | 作为凝血因子xia抑制剂的哒嗪衍生物 |
| US8828983B2 (en) | 2010-02-11 | 2014-09-09 | Bristol-Myers Squibb Company | Macrocycles as factor XIa 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 |
| IN2014CN02806A (es) | 2011-10-14 | 2015-07-03 | Bristol Myers Squibb Co | |
| JP6033318B2 (ja) | 2011-10-14 | 2016-11-30 | 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テトラヒドロイソキノリン化合物 |
| PL2766346T3 (pl) | 2011-10-14 | 2017-09-29 | Bristol-Myers Squibb Company | Podstawione związki tetrahydroizochinoliny jako inhibitory czynnika XIA |
| DK2794597T3 (en) | 2011-12-21 | 2018-01-15 | Ono Pharmaceutical Co | PYRIDINON AND PYRIMIDINON DERIVATIVES AS FACTOR XIA 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 |
| GB201209138D0 (en) | 2012-05-24 | 2012-07-04 | Ono Pharmaceutical Co | Compounds |
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