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1. (WO2018040885) INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR AND USE THEREOF
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Pub. No.: WO/2018/040885 International Application No.: PCT/CN2017/096848
Publication Date: 08.03.2018 International Filing Date: 10.08.2017
IPC:
C07D 401/12 (2006.01) ,C07D 403/12 (2006.01) ,C07D 403/14 (2006.01) ,C07D 413/12 (2006.01) ,C07D 413/14 (2006.01) ,C07D 487/08 (2006.01) ,A61K 31/517 (2006.01) ,A61P 35/00 (2006.01) ,A61P 35/02 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
401
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
02
containing two hetero rings
12
linked by a chain containing hetero atoms as chain links
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
403
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/167
02
containing two hetero rings
12
linked by a chain containing hetero atoms as chain links
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
403
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/167
14
containing three or more hetero rings
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
413
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
02
containing two hetero rings
12
linked by a chain containing hetero atoms as chain links
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
413
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
14
containing three or more hetero rings
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
487
Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/-C07D477/183
02
in which the condensed system contains two hetero rings
08
Bridged systems
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
395
having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
495
having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
505
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
517
ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
02
specific for leukemia
Applicants: NANJING TRANSTHERA BIOSCIENCES CO. LTD.[CN/CN]; 3rd Floor, Building 9, Phase 2 Accelerator, No.11 Yaogu Avenue, High-tech District Nanjing, Jiangsu 210032, CN
Inventors: WU, Frank; CN
LI, Jin; CN
Agent: PATENTSINO IP FIRM; Suite 413, Shang Fang Building No.27 North Third Ring Road Middle, Xicheng District Beijing 100029, CN
Priority Data:
201610802100.501.09.2016CN
201710351160.418.05.2017CN
Title (EN) INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR AND USE THEREOF
(FR) INHIBITEURS DU RÉCEPTEUR DU FACTEUR DE CROISSANCE DES FIBROBLASTES ET LEUR UTILISATION
(ZH) 成纤维细胞生长因子受体抑制剂及其用途
Abstract:
(EN) Provided are an irreversible inhibitor of a fibroblast growth factor receptor (FGFR) as indicated by formula I, a pharmaceutically acceptable salt, a stereoisomer, a pharmaceutical preparation, a pharmaceutical composition and an application thereof. R1, R2, R3, R4, ring A, Ar, ring B and warhead are as defined in the specification. The compound has high-efficiency and high-selectivity inhibition of a fibroblast growth factor receptor and can be applied to the treatment of abnormal FGF/FGFR-mediated diseases, in particular the treatment of cancers.
(FR) L'invention concerne un inhibiteur irréversible d'un récepteur du facteur de croissance des fibroblastes (FGFR) tel qu'indiqué par la formule I, un sel pharmaceutiquement acceptable, un stéréoisomère, une préparation pharmaceutique, une composition pharmaceutique et une application de celui-ci. R1 , R2 , R3 , R4 , le cycle A, Ar, le cycle B et la charge sont tels que définis dans la description. Le composé présente une efficacité élevée et une forte inhibition de la sélectivité d'un récepteur du facteur de croissance des fibroblastes, ledit composé pouvant être appliqué au traitement de maladies à médiation par FGF/FGFR anormale, en particulier le traitement du cancer.
(ZH) 提供了一种式I所示的成纤维细胞生长因子受体(FGFR)不可逆抑制剂,其药学上可接受的盐、立体异构体,药物制剂、药物组合物及其应用。R 1、R 2、R 3、R 4、环A、Ar、环B以及warhead如说明书中所定义。所述化合物对成纤维细胞生长因子受体具有高效的和高选择性的抑制作用,可以应用于FGF/FGFR异常介导的相关疾病的治疗,尤其是在癌症疾病方面的治疗。
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: Chinese (ZH)
Filing Language: Chinese (ZH)