AR118081A1 - Inhibidores de enzimas - Google Patents

Inhibidores de enzimas

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Publication number
AR118081A1
AR118081A1 ARP200100395A ARP200100395A AR118081A1 AR 118081 A1 AR118081 A1 AR 118081A1 AR P200100395 A ARP200100395 A AR P200100395A AR P200100395 A ARP200100395 A AR P200100395A AR 118081 A1 AR118081 A1 AR 118081A1
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Argentina
Prior art keywords
independently selected
halo
alkoxy
alkyl
ring
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ARP200100395A
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English (en)
Inventor
Xuezheng Yang
Joseph William Wrigglesworth
Alun John Smith
Smith Colin Peter Sambrook
Rachael Pittaway
Iain Robert Miller
Matthew Robert Conroy
Thomas Matthew Baker
Terence Aaron Panchal
Stefano Levanto
Karamjit Singh Jandu
Paul Stuart Hinchliffe
Julie Nicole Hamblin
Erica Lee Goldsmith
Emanuela Gancia
Andrew Peter Cridland
David Edward Clark
Michael John Stocks
David Philip Rooker
Alicja Stela Obara
Alessandro Mazzacani
Sally Louise Marsh
Simon Teanby Hodgson
David Michael Evans
Hannah Joy Edwards
Rebecca Louise Davie
Mitchell Lewis Childs
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Kalvista Pharmaceuticals Ltd
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Publication of AR118081A1 publication Critical patent/AR118081A1/es

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    • 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
    • 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
    • A61K31/55—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • 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
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
    • C07D471/04—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
    • C07D487/04—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
    • 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
    • C07D491/12—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 three hetero rings
    • C07D491/14—Ortho-condensed systems
    • C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
    • 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
    • C07D491/12—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 three hetero rings
    • C07D491/20—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

La presente proporciona compuestos de fórmula (1), composiciones que comprenden dichos compuestos; el uso terapéutico de dichos compuestos (por ejemplo, en el tratamiento o prevención de una enfermedad o afección en la que está implicada la actividad de la calicreína plasmática); y métodos para tratar pacientes con dichos compuestos; en donde R⁵, R⁶, R⁷, A, B, W, X, Y y Z tienen la definición proporcionada en el presente documento. Reivindicación 1: Un compuesto de fórmula (1), donde W, X, Y y Z se seleccionan independientemente de C, C(R¹⁶)-C, C(R¹⁶)=C, C=N, O y N, de modo que el anillo que contiene W, X, Y y Z es un heteroarilo de 5 ó 6 miembros; R⁵, R⁶ y R⁷ están independientemente ausentes o se seleccionan independientemente de H, alquilo, cicloalquilo, alcoxi, halo, OH, CN, CF₃, arilo, heteroariloᵃ, pirrolidinilo vinculado a N, piperidinilo vinculado a N, morfolino vinculado a N, piperazinilo vinculado a N, -NR¹³R¹⁴, -COOR¹³, -CONR¹³R¹⁴ y -NR¹³COR¹⁴; R¹⁶ se selecciona independientemente de H, alquilo, cicloalquilo, alcoxi, halo, OH, CN, CF₃, arilo, heteroariloᵃ pirrolidinilo vinculado a N, piperidinilo vinculado a N, morfolinilo vinculado a N, piperazinilo vinculado a N, -NR¹³R¹⁴, -COOR¹³, -CONR¹³R¹⁴ y -NR¹³COR¹⁴; o W, X, Y y Z se seleccionan independientemente de C, C(R¹⁶)-C, C(R¹⁶)=C, C=N y N y uno de R⁵, R⁶, R⁷ o R¹⁶ es oxo de modo que el anillo que contiene W, X, Y y Z es 2-piridona o 4-piridona en donde los otros de R⁵, R⁶, R⁷ y R¹⁶ están independientemente ausentes o se seleccionan independientemente de H, alquilo, cicloalquilo, alcoxi, halo, OH, CN, CF₃, arilo, heteroariloᵃ, pirrolidinilo vinculado a N, piperidinilo vinculado a N, morfolinilo vinculado a N, piperazinilo vinculado a N, -NR¹³R¹⁴, -COOR¹³, -CONR¹³R¹⁴ y -NR¹³COR¹⁴; B es de fórmula (2) que comprende anillos aromáticos B’ y B’’ que están unidos por un enlace; B’ es fenilo o piridilo; B’’ es pirrol, pirazol, triazol o tetrazol; n es 0, 1 ó 2; R⁹ y R¹⁰ se seleccionan independientemente de H, alquilo, cicloalquilo, alcoxi, halo, OH, CN y CF₃; cada R¹¹ se selecciona independientemente entre alquilo, cicloalquilo, alcoxi, halo, OH, -COOR¹³, -CONR¹³NR¹⁴, CN y CF₃; A es un anillo heterocíclico de la fórmula (3) que comprende un anillo aromático (A’) fusionado a un anillo no aromático (A’’); A’¹ y A’² son independientemente C o N; A’ es heteroarilo o fenilo, en donde el fenilo puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquilo, alcoxi, OH, OCF₃, halo, CN y CF₃ y en donde el heteroarilo puede estar opcionalmente sustituido según se indica más adelante; A’’ es heterocicloalquilo; en donde opcionalmente un átomo de anillo de carbono en A’’ está sustituido con un alquileno o un heteroalquileno de tal manera que el átomo de anillo de carbono en A’’ junto con el alquileno o el heteroalquileno forma un cicloalquilo o heterocicloalquiloᵃ que es espiro con respecto al anillo A’’; y/o en donde opcionalmente dos átomos del anillo en A’’ están unidos por un alquileno o heteroalquileno para formar un anillo no aromático que contiene 5, 6 ó 7 miembros del anillo; alquilo es un hidrocarburo saturado lineal que tiene hasta 10 átomos de carbono (C₁₋₁₀) o un hidrocarburo saturado ramificado de entre 3 y 10 átomos de carbono (C₃₋₁₀); el alquilo puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente entre C₁₋₆alcoxi, OH, -NR¹³R¹⁴, -COOR¹³, -CONR¹³R¹⁴, CN, CF₃, halo; un alquiloᵇ es un hidrocarburo lineal saturado que tiene hasta 10 átomos de carbono (C₁₋₁₀) o un hidrocarburo ramificado saturado de entre 3 y 10 átomos de carbono (C₃₋₁₀); el alquiloᵇ puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente entre C₁₋₆alcoxi, OH, CN, CF₃, halo; alquileno es un hidrocarburo saturado lineal bivalente que tiene de 1 a 5 átomos de carbono (C₁₋₅); el alquileno puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de alquilo, C₁₋₆alcoxi, OH, CN, CF₃, halo; arilo es fenilo, bifenilo o naftilo; el arilo puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquilo, alcoxi, metilendioxi, etilendioxi, OH, halo, CN, heteroariloᵃ, -(CH₂)₀₋₃-O-heteroariloᵃ, ariloᵇ, -O-ariloᵇ, -(CH₂)₁₋₃-ariloᵇ, -(CH₂)₁₋₃-heteroariloᵃ, -COOR¹³, -CONR¹³R¹⁴, -(CH₂)₀₋₃-NR¹³R¹⁴, OCF₃ y CF₃; ariloᵇ es fenilo, bifenilo o naftilo; el ariloᵇ puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquiloᵇ, alcoxi, OH, halo, CN y CF₃; heteroalquileno es un hidrocarburo lineal bivalente saturado que tiene de 2 a 5 átomos de carbono (C₂₋₅), en el que al menos uno de los 2 a 5 átomos de carbono se reemplaza con NR⁸, S u O; el heteroalquileno puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de alquilo C₁₋₆alcoxi, OH, CN, CF₃, halo; cicloalquilo es un anillo hidrocarburo monocíclico saturado de entre 3 y 6 átomos de carbono (C₃₋₆); el cicloalquilo puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de alquilo, C₁₋₆alcoxi, OH, CN, CF₃, halo; alcoxi es un hidrocarburo lineal con enlaces O de entre 1 y 6 átomos de carbono (C₁₋₆) o un hidrocarburo ramificado con enlaces O de entre 3 y 6 átomos de carbono (C₃₋₆); alcoxi puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de OH, CN, CF₃ y fluoro; halo es F, Cl, Br o I; heteroarilo es un anillo aromático de 5 ó 6 miembros que contiene carbono que contiene uno, dos o tres miembros de anillo que se seleccionan de N, NR⁸, S y O; el heteroarilo puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquilo, alcoxi, OH, OCF₃, halo, CN y CF₃; heteroariloᵃ es un anillo aromático mono o bicíclico de 5, 6, 9 ó 10 miembros que contiene, cuando es posible, 1, 2, 3 ó 4 miembros del anillo seleccionados independientemente de N, NR¹², S y O; el heteroariloᵃ puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquilo, alcoxi, OH, OCF₃, halo, CN, ariloᵇ, -(CH₂)₁₋₃-ariloᵇ, -(CH₂)₀₋₃-NR¹³R¹⁴, heteroariloᵇ, -COOR¹³, -CONR¹³R¹⁴ y CF₃; heteroariloᵇ es un anillo aromático mono o bicíclico de 5, 6, 9 ó 10 miembros, que contiene, cuando es posible, 1, 2 ó 3 miembros del anillo seleccionados independientemente de N, NR¹², S y O; en donde el heteroariloᵇ puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados independientemente de alquiloᵇ, alcoxi, OH, halo, CN, ariloᵇ, -(CH₂)₁₋₃-ariloᵇ y CF₃; heterocicloalquilo es un anillo monocíclico que contiene 5, 6, ó 7 miembros de anillo, en el que uno o dos miembros del anillo se seleccionan independientemente de N, NR⁸, S, que contiene carbono no aromático SO, SO₂ y O; en donde heterocicloalquilo puede estar opcionalmente sustituido con 1, 2, ó 3 sustituyentes independientemente seleccionados de alquilo, alcoxi, OH, OCF₃, halo, oxo y CN; heterocicloalquiloᵃ es un anillo monocíclico que contiene 3, 4, 5, ó 6, miembros de anillo, donde al menos un miembro del anillo se selecciona independientemente de NR⁸, que contiene carbono no aromático S, SO, SO₂ y O; heterocicloalquiloᵃ puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de alquilo C₁₋₆alcoxi, OH, CN, CF₃, halo; R⁸ se selecciona independientemente de H, alquilo, cicloalquilo o heterocicloalquiloᵇ; heterocicloalquiloᵇ es un anillo monocíclico no aromático que contiene carbono que contiene 3, 4, 5 ó 6 miembros del anillo, en el que al menos un miembro del anillo se selecciona independientemente de N, NR¹², S y O; heterocicloalquiloᵇ puede estar opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados independientemente de alquilo, C₁₋₆alcoxi, OH, CN, CF₃, halo; R¹² se selecciona independientemente de H, alquiloᵇ o cicloalquilo; R¹³ y R¹⁴ se seleccionan independientemente de H, alquiloᵇ, ariloᵇ y heteroariloᵇ o R¹³ y R¹⁴ junto con el átomo de nitrógeno al que están unidos forman un anillo heterocíclico de 4, 5, 6 ó 7 miembros que contiene carbono, que contiene opcionalmente un heteroátomo adicional seleccionado entre N, NR¹², S, SO, SO₂ y O, que puede ser saturado o insaturado con 1 ó 2 dobles enlaces y que puede estar opcionalmente mono o disustituido con sustituyentes seleccionados de oxo, alquiloᵇ, alcoxi, OH, halo y CF₃; y tautómeros, isómeros, estereoisómeros (incluidos enantiómeros, diastereoisómeros y mezclas racémicas y no racémicas de los mismos), isótopos deuterados y sus sales y/o solvatos farmacéuticamente aceptables.
ARP200100395A 2019-08-09 2020-02-13 Inhibidores de enzimas AR118081A1 (es)

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PCT/GB2019/052252 WO2021028645A1 (en) 2019-08-09 2019-08-09 Plasma kallikrein inhibitors

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EP (1) EP4010333A1 (es)
JP (1) JP2022543515A (es)
KR (1) KR20220046592A (es)
CN (1) CN114206852A (es)
AR (1) AR118081A1 (es)
AU (1) AU2020328208A1 (es)
BR (1) BR112022001025A2 (es)
CA (1) CA3147390A1 (es)
CL (1) CL2022000214A1 (es)
CO (1) CO2022000426A2 (es)
IL (1) IL289764A (es)
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GB201609607D0 (en) 2016-06-01 2016-07-13 Kalvista Pharmaceuticals Ltd Polymorphs of N-(3-Fluoro-4-methoxypyridin-2-yl)methyl)-3-(methoxymethyl)-1-({4-((2-oxopy ridin-1-yl)methyl)phenyl}methyl)pyrazole-4-carboxamide and salts
GB201719881D0 (en) 2017-11-29 2018-01-10 Kalvista Pharmaceuticals Ltd Solid forms of plasma kallikrein inhibitor and salts thereof
CN114206852A (zh) 2019-08-09 2022-03-18 卡尔维斯塔制药有限公司 血浆激肽释放酶抑制剂

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