CR20190261A - Inhibidores de la tirosina quinasa de bruton - Google Patents

Inhibidores de la tirosina quinasa de bruton

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Publication number
CR20190261A
CR20190261A CR20190261A CR20190261A CR20190261A CR 20190261 A CR20190261 A CR 20190261A CR 20190261 A CR20190261 A CR 20190261A CR 20190261 A CR20190261 A CR 20190261A CR 20190261 A CR20190261 A CR 20190261A
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CR
Costa Rica
Prior art keywords
independently
alkyl
hal
fragment
group
Prior art date
Application number
CR20190261A
Other languages
English (en)
Inventor
Pavel Andreevich Iakovlev
Svetlana Leonidovna Gorbunova
Leonid Evgen´Evich Mikhaylov
Alexander Moldavsky
Anna Aleksandrovna Kukushkina
Anna Sergeevna Kushakova
Aleksey Sergeevich Gavrilov
Sergey Aleksandrovich Silonov
Svetlana Sergeevna Smirnova
Natalia Vladimirovna Kozhemyakina
Pavel Aleksandrovich Aleshunin
Aleksandra Vladimirovna Popkova
Mikhail Vladimirovich Rekharsky
Original Assignee
Biocad Joint Stock 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 Biocad Joint Stock Co filed Critical Biocad Joint Stock Co
Publication of CR20190261A publication Critical patent/CR20190261A/es

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    • 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
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • 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
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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

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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)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente invención se refiere a un nuevo compuesto de la Fórmula I: V2 V1 N N R1 R6 R4 R11 LR 3 n k Fórmula I o un estereoisómero, solvato o sal farmacéuticamente aceptable de este, en donde: 5 V1 es C o N, V2 es C (R2) o N, de manera que si V1 es C entonces V2 es N, si V1 es C entonces V2 es C (R2), o si V1 es N entonces V2 es C (R2); 10 cada n, k es independientemente 0, 1; cada R2, R11 es independientemente H, D, Hal, CN, NR¿R¿¿, C (O)NR¿R¿¿, alcoxi C1-C6; R3 es H, D, hidroxi, alquilo C (O)C1-C6, alquenilo C (O) C2-C6, alquinilo C (O) C2-C6, alquilo C1-C6; R4 es H, Hal, CN, CONR¿R¿¿, hidroxi, alquilo C1-C6, alcoxi C1-C6; L es CH2, NH, O o enlace químico; 15 R1 se selecciona del grupo de los fragmentos, que comprende: A1 A2 A4 A3 N O R5 R5 Fragmento 1, A1 A2 A4 A3 O A9 A8 A7 A6 A5 R5 Fragmento 2, 175 A1 A2 A4 A3 N H O A9 A8 A7 A6 A5 R5 Fragmento 3 cada A1, A2, A3, A4 es independientemente CH, N, CHal; cada A5, A6, A7, A8, A9 es independientemente C, CH o N; R5 es H, CN, Hal, CONR¿R¿¿, alquilo C1-C6, sin sustituir o sustituido por uno o más halógenos; cada R¿ y R¿¿ se selecciona independientemente a partir del grupo, que comprende H, alquilo C1-5 C6, cicloalquilo C1-C6, arilo; R6 se selecciona del grupo: N R7 O , N O R8 , N O R9, N O R10 ; cada R7, R8, R9, R10 es independientemente vinilo, metilacetilenilo; Hal es Cl, Br, I, F, 10 que tiene propiedades de inhibidor de la tirosina quinasa de Bruton (Btk), a composiciones farmacéuticas que contienen dichos compuestos, y su uso como productos farmacéuticos para el tratamiento de enfermedades y trastornos.The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.
CR20190261A 2016-11-18 2017-11-16 Inhibidores de la tirosina quinasa de bruton CR20190261A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662424041P 2016-11-18 2016-11-18
PCT/IB2017/057154 WO2018092047A1 (en) 2016-11-18 2017-11-16 Inhibitors of bruton's tyrosine kinase

Publications (1)

Publication Number Publication Date
CR20190261A true CR20190261A (es) 2019-09-02

Family

ID=60574666

Family Applications (1)

Application Number Title Priority Date Filing Date
CR20190261A CR20190261A (es) 2016-11-18 2017-11-16 Inhibidores de la tirosina quinasa de bruton

Country Status (19)

Country Link
US (1) US20190352276A1 (es)
EP (1) EP3541811A1 (es)
JP (1) JP2019537611A (es)
KR (1) KR20190104516A (es)
CN (1) CN110177781A (es)
AU (1) AU2017362066A1 (es)
BR (1) BR112019009945A2 (es)
CA (1) CA3043297A1 (es)
CL (1) CL2019001330A1 (es)
CR (1) CR20190261A (es)
EA (1) EA201990902A1 (es)
EC (1) ECSP19043231A (es)
JO (1) JOP20190113A1 (es)
MA (1) MA45888A1 (es)
MX (1) MX2019005706A (es)
PE (1) PE20191082A1 (es)
PH (1) PH12019550083A1 (es)
WO (1) WO2018092047A1 (es)
ZA (1) ZA201903694B (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10793566B2 (en) * 2016-01-21 2020-10-06 Zibo Biopolar Changsheng Pharmaceutical Co. Ltd. Bruton's tyrosine kinase inhibitors
KR102384924B1 (ko) 2017-07-12 2022-04-08 주식회사 대웅제약 신규한 1h-피라졸로피리딘 유도체 및 이를 포함하는 약학 조성물
WO2019013562A1 (ko) * 2017-07-12 2019-01-17 주식회사 대웅제약 신규한 1h-피라졸로피리딘 유도체 및 이를 포함하는 약학 조성물
US20210330643A1 (en) 2018-07-31 2021-10-28 Loxo Oncology, Inc. Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide
MX2022003707A (es) * 2019-09-26 2022-06-23 Jumbo Drug Bank Co Ltd Compuestos de pirazolopiridina como inhibidores selectivos de quinasa btk.
CN114478519A (zh) * 2020-10-23 2022-05-13 上海辉启生物医药科技有限公司 吡唑并吡啶类化合物或其盐及其制备方法和用途
US20240100172A1 (en) 2020-12-21 2024-03-28 Hangzhou Jijing Pharmaceutical Technology Limited Methods and compounds for targeted autophagy
CN116348453A (zh) * 2021-04-25 2023-06-27 烨辉医药科技(上海)有限公司 杂芳族甲酰胺化合物及其用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10201508035TA (en) * 2007-03-28 2015-10-29 Pharmacyclics Inc Inhibitors of bruton's tyrosine kinase
EP2789615B1 (en) * 2009-08-11 2017-05-03 Bristol-Myers Squibb Company Azaindazoles as Btk kinase modulators and use thereof
US7741330B1 (en) * 2009-10-12 2010-06-22 Pharmacyclics, Inc. Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase
EP2548877A1 (en) * 2011-07-19 2013-01-23 MSD Oss B.V. 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors
MA37830B1 (fr) * 2012-08-10 2018-09-28 Boehringer Ingelheim Int Composés hétéroromatiques en tant qu'inhibiteurs de la tyrosine kinase de bruton (btk)
WO2015095099A1 (en) * 2013-12-20 2015-06-25 Merck Sharp & Dohme Corp. Btk inhibitors
NZ721617A (en) * 2014-02-03 2018-01-26 Cadila Healthcare Ltd Heterocyclic compounds
AU2015296215A1 (en) * 2014-08-01 2017-03-23 Pharmacyclics Llc Inhibitors of bruton's tyrosine kinase
US10662187B2 (en) * 2016-01-21 2020-05-26 Zibo Biopolar Changsheng Pharmaceutical Co. Ltd. Bruton's tyrosine kinase inhibitors
CN109071455B (zh) * 2016-03-11 2022-08-02 嘉兴和剂药业有限公司 用于调节布鲁顿酪氨酸激酶的化合物及方法

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WO2018092047A1 (en) 2018-05-24
ECSP19043231A (es) 2019-06-30
CA3043297A1 (en) 2018-05-24
JOP20190113A1 (ar) 2019-05-15
ZA201903694B (en) 2021-04-28
AU2017362066A1 (en) 2019-05-30
CL2019001330A1 (es) 2019-09-27
MX2019005706A (es) 2019-07-08
KR20190104516A (ko) 2019-09-10
MA45888A1 (fr) 2020-06-30
BR112019009945A2 (pt) 2019-08-13
US20190352276A1 (en) 2019-11-21
CN110177781A (zh) 2019-08-27
JP2019537611A (ja) 2019-12-26
PH12019550083A1 (en) 2020-03-09
EP3541811A1 (en) 2019-09-25
EA201990902A1 (ru) 2019-11-29
PE20191082A1 (es) 2019-08-20

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