[go: up one dir, main page]

WO2021228173A1 - Composés cycliques condensés du type azépine et utilisations médicales associées - Google Patents

Composés cycliques condensés du type azépine et utilisations médicales associées Download PDF

Info

Publication number
WO2021228173A1
WO2021228173A1 PCT/CN2021/093499 CN2021093499W WO2021228173A1 WO 2021228173 A1 WO2021228173 A1 WO 2021228173A1 CN 2021093499 W CN2021093499 W CN 2021093499W WO 2021228173 A1 WO2021228173 A1 WO 2021228173A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
cycloalkyl
alkyl
ring
heteroaryl
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/CN2021/093499
Other languages
English (en)
Chinese (zh)
Inventor
殷惠军
闫旭
沙汉明
刘国标
王国政
李斌
温俊歌
路嘉伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
National Institutes of Pharmaceutical R&D Co Ltd
Original Assignee
National Institutes of Pharmaceutical R&D Co Ltd
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 National Institutes of Pharmaceutical R&D Co Ltd filed Critical National Institutes of Pharmaceutical R&D Co Ltd
Priority to CN202180012105.7A priority Critical patent/CN115038707B/zh
Publication of WO2021228173A1 publication Critical patent/WO2021228173A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Definitions

  • R 2 and R 3 together with the atoms to which they are attached form a C 6-10 aryl group, a 6 to 10-membered heteroaryl group, a 6 to 10-membered heterocyclic group or a C 6-10 cycloalkyl group, R 1 and R 4 Each independently selected from R 6 ; or
  • R'and R" are each independently selected from hydrogen, halogen, alkyl, haloalkyl
  • n is an integer from 0 to 3.
  • Ring D is selected from C 6-10 aryl, 6-10 membered heteroaryl, 6-10 membered heterocyclic group or C 6-10 cycloalkyl, preferably phenyl, 6-8 membered heteroaryl, 6-8 Member heterocyclic group, C 6-8 cycloalkyl group, the aryl group, heteroaryl group, heterocyclic group and cycloalkyl group are optionally further selected from halogen, nitro, cyano, hydroxyl, mercapto, oxo , Alkyl, -NR a R b , -C(O)R a , -O(O)CR a , -C(O)OR a , -C(O)NR a R b , -NHC(O)R a, -S (O) m R a, -S (O) m NR a R b, a -NHS (O) m R a, and -P (O) (
  • X, Y 1 , Y 2 , Z 1 , Z 2 , L, ring A, ring B, ring C, and R 5 are as defined in the general formula (I).
  • n 0, 1 or 2;
  • X, Y 1 , Y 2 , Z 1 , Z 2 , L, ring A, ring B, ring C, and R 5 are as defined in the general formula (I).
  • R b is selected from hydrogen or C 1-6 alkyl
  • Ring B is a 6 to 10 membered aromatic ring or a 5 to 6 membered aromatic heterocyclic ring, preferably a benzene ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, a pyrrole ring, a pyrazole ring, an imidazole ring, an oxazole ring, Thiazole ring, isoxazole ring, isothiazole ring, oxadiazole ring, thiadiazole ring, triazole ring, more preferably pyrazole ring, imidazole ring, triazole ring, which are optionally further substituted by one or more R 8 replace;
  • n is an integer from 0 to 3, preferably 1;
  • the present invention further relates to the compound represented by the general formula (I) according to the present invention or its meso, racemate, enantiomer, diastereomer, or a mixture thereof, or Use of its pharmaceutically acceptable salt or pharmaceutical composition containing it in the preparation of receptor-interacting protein kinase 1 (RIP1) inhibitors.
  • RIP1 receptor-interacting protein kinase 1
  • the present invention further relates to a method for preventing or treating diseases related to the activity of receptor-interacting protein kinase 1, which comprises administering to a patient in need a preventive or therapeutically effective amount of the formula (I) according to the present invention
  • the disease is preferably an inflammatory disease, an autoimmune disease or a nervous system disease, such as rheumatoid arthritis, ulcerative colitis, Crohn’s disease, psoriasis, retinal detachment, pigment Retinitis, macular degeneration, pancreatitis, atopic dermatitis, spondyloarthritis, gout, juvenile idiopathic arthritis, systemic lupus erythematosus, Sjogren's syndrome, systemic scleroderma,
  • the compounds of the present invention can be administered in the form of suppositories for rectal administration.
  • These pharmaceutical compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid in the rectum and thus will melt in the rectum to release the drug.
  • suitable non-irritating excipient include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and mixtures of fatty acid esters of polyethylene glycol.
  • alkynyl refers to an alkyl group as defined above composed of at least two carbon atoms and at least one carbon-carbon triple bond, such as ethynyl, propynyl, butynyl, and the like.
  • the alkynyl group may be substituted or unsubstituted.
  • the spiro heterocyclic group is classified into a single spiro heterocyclic group, a dispiro heterocyclic group or a polyspiro heterocyclic group, preferably a single spiro heterocyclic group and a dispiro heterocyclic group. More preferably, it is a 4-membered/4-membered, 4-membered/5-membered, 4-membered/6-membered, 5-membered/5-membered, or 5-membered/6-membered monospiro heterocyclic group.
  • Non-limiting examples of spiroheterocyclic groups include:
  • bridged heterocyclic groups include:
  • hydroxy refers to the -OH group.
  • halogen refers to fluorine, chlorine, bromine or iodine.
  • nitro refers to -NO 2 .
  • Step 3 In the presence of a catalyst, the compound Ic undergoes an intramolecular ring-closure reaction to obtain the compound Id, and the catalyst is preferably trimethylaluminum;
  • Step 14 (S)-3-(2-Benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6 -Yl)-5-methyl 2,3,7,8,9,10-hexahydronaphtho[2,3-b][1,4]oxazepine-4(5H)-one (compound 1 ) Preparation
  • Step 1 (S)-3-(2-Benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6 -Base)-5,8-dimethyl-2,3,7,8,9,1-hexahydro-[1,4]oxazepine[2,3-g]isoquinoline-4( Preparation of 5H)-ketone (7)
  • 4,5-dimethoxy-2-nitrobenzaldehyde (5.00 g, 23.7 mmol) was dissolved in 100 mL of DCM.
  • m-CPBA m-chloroperoxybenzoic acid
  • Step 4 Preparation of N-(tert-butoxycarbonyl)-O-(4,5-dimethoxy-2-nitrophenyl)-L-serine methyl ester (12d)
  • Example 13 (8S)-8-(2-benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6pyrazolo[3,4c]pyridin-6-yl )-10-methyl-9-oxo-2,3,7,8,9,10-hexahydro-[1,4]dioxino[2',3':4,5]benzo[ Preparation of 1,2-b][1,4]oxazepine-2-carboxamide (13)
  • Step 1 (S)-3-(2-Benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6 -Yl)-N,N,1-trimethyl-2-oxo-1,2,3,4,10,11-hexahydro-[1,4]oxazepine[3,2-f ]
  • the residue was purified by high-pressure preparation liquid phase separation and purification (column model: Daisogei 30mm*250mm, C18, 10um 100A, mobile phase: acetonitrile/water, gradient: 10%-30%, 30min) to obtain the title compound as a white solid, 8.00mg , The yield is 23.5%.
  • the preparation method is the same as in Example 11, except that (S)-3-(2-benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3 ,4-c]pyridin-6-yl)-1-methyl-3,4,8,9,10,11-hexahydro-[1,4]oxazepine[3,2-f]iso Quinoline-2(1H)-one (18) instead of (S)-3-(2-benzyl-3-chloro-7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo [3,4-c]pyridin-6-yl)-5-methyl-2,3,7,8,9,10-hexahydro-[1,4]oxazepine[2,3-g ] Isoquinolin-4(5H)-one (6) to obtain the title compound 24.
  • Receptor-interacting protein kinase 1 (RIP1) activation can induce necrosis of human monocytic leukemia U937 cells. Therefore, the activity of the compounds of the present invention utilizes human monocytic leukemia U937 cells (CBP60277, CoBioer) by in vitro cell necrosis assay Experiment to test.
  • CBP60277, CoBioer human monocytic leukemia U937 cells
  • e Dilute the ATP stock solution (V915B, Promega) in the 10mM ADP-Glo kit with the above reaction buffer to 100 ⁇ M. Add 5 ⁇ L of ATP solution to each well except the negative control well, and add 5 ⁇ L of reaction buffer to each well of the negative control well. The final reaction system is 10 ⁇ L, and the final concentration of ATP is 50 ⁇ M. Incubate for 4 hours in an incubator at 25°C.
  • the compounds of the present invention inhibit RIP1 activity as shown in Table 2 below.
  • A means that the compound inhibits RIP1 with IC 50 ⁇ 10 nM; B means 10 nM ⁇ IC 50 ⁇ 100 nM; C means 100 nM ⁇ IC 50 ⁇ 500 nM; D means IC 50 > 500 nM.
  • the compound of the present invention can effectively inhibit the activity of RIP1.
  • Test Example 3 Analysis of the in vitro inhibitory activity of the compound of the present invention on L929 cell necrosis
  • X is the logarithmic value of the compound concentration
  • Y is the compound's efficacy in inhibiting cell necrosis
  • Top and Bottom are the Y values at the highest and lowest plateau of the curve
  • Hillslope is the Hill constant.
  • Test Example 5 Test of the blood-brain barrier permeability of the compound of the present invention in C57BL/6J mice
  • the blood-brain barrier permeability after oral administration of the compound of the present invention is shown in Table 5.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Oncology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Psychiatry (AREA)
  • Dermatology (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des composés cycliques condensés du type azépine et leurs utilisations médicales. La présente invention concerne plus particulièrement un composé cyclique condensé du type azépine représenté par la formule générale (I), son procédé de préparation, une composition pharmaceutique comprenant celui-ci et son utilisation en tant qu'inhibiteur de protéine kinase 1 interagissant avec le récepteur (RIP1) dans le traitement de maladies associées à l'activité de RIP1. La définition de chaque substituant dans la formule générale (I) est la même que celle donnée dans la description.
PCT/CN2021/093499 2020-05-14 2021-05-13 Composés cycliques condensés du type azépine et utilisations médicales associées Ceased WO2021228173A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202180012105.7A CN115038707B (zh) 2020-05-14 2021-05-13 氮杂卓类稠环化合物及其医药用途

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010406690 2020-05-14
CN202010406690.6 2020-05-14

Publications (1)

Publication Number Publication Date
WO2021228173A1 true WO2021228173A1 (fr) 2021-11-18

Family

ID=78525342

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/093499 Ceased WO2021228173A1 (fr) 2020-05-14 2021-05-13 Composés cycliques condensés du type azépine et utilisations médicales associées

Country Status (3)

Country Link
CN (1) CN115038707B (fr)
TW (1) TW202144353A (fr)
WO (1) WO2021228173A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022171110A1 (fr) * 2021-02-10 2022-08-18 Zai Lab (Us) Llc Composés tricycliques fusionnés en tant qu'inhibiteurs de rip1-kinase et leurs utilisations
WO2022237890A1 (fr) * 2021-05-14 2022-11-17 中国医药研究开发中心有限公司 Composé à cycle fusionné du type azépine et son utilisation pharmaceutique
CN117645579A (zh) * 2022-09-02 2024-03-05 科辉智药生物科技(深圳)有限公司 作为ripk1抑制剂的氮杂䓬类稠环化合物及其应用
WO2025153090A1 (fr) * 2024-01-19 2025-07-24 无锡奕拓医药科技有限责任公司 Composé polycyclique, composition pharmaceutique associée et utilisation associée

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108431004A (zh) * 2015-10-23 2018-08-21 武田药品工业株式会社 杂环化合物
CN109134448A (zh) * 2018-10-16 2019-01-04 中南大学湘雅医院 杂环化合物及其盐、制备方法、用途和药物
WO2019204537A1 (fr) * 2018-04-20 2019-10-24 Genentech, Inc. Dérivés de n-[4-oxo-2,3-dihydro-1,5-benzoxazépin-3-yl]-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol e-2-carboxamide et composés apparentés en tant qu'inhibiteurs de la kinase rip1 pour le traitement, par exemple, du syndrome du côlon irritable (ibs)
WO2020001420A1 (fr) * 2018-06-26 2020-01-02 中国科学院上海有机化学研究所 Inhibiteur de nécrose cellulaire, son procédé de préparation et son utilisation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115867557B (zh) * 2021-05-14 2025-02-18 中国医药研究开发中心有限公司 氮杂卓类稠环化合物及其医药用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108431004A (zh) * 2015-10-23 2018-08-21 武田药品工业株式会社 杂环化合物
WO2019204537A1 (fr) * 2018-04-20 2019-10-24 Genentech, Inc. Dérivés de n-[4-oxo-2,3-dihydro-1,5-benzoxazépin-3-yl]-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol e-2-carboxamide et composés apparentés en tant qu'inhibiteurs de la kinase rip1 pour le traitement, par exemple, du syndrome du côlon irritable (ibs)
WO2020001420A1 (fr) * 2018-06-26 2020-01-02 中国科学院上海有机化学研究所 Inhibiteur de nécrose cellulaire, son procédé de préparation et son utilisation
CN109134448A (zh) * 2018-10-16 2019-01-04 中南大学湘雅医院 杂环化合物及其盐、制备方法、用途和药物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MASATO YOSHIKAWA, MORIHISA SAITOH, TAISUKE KATOH, TOMOHIRO SEKI, SIMONE V. BIGI, YUJI SHIMIZU, TSUYOSHI ISHII, TAKURO OKAI, MASAKO: "Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H -pyrazolo[3,4- c ]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure–Kinetic Relationships", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 61, no. 6, 22 March 2018 (2018-03-22), US , pages 2384 - 2409, XP055594700, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.7b01647 *
WANG ZHANMEI, JING YU, JIE HAO, MINGHUI WANG, HONG LIAO, JINXIN WANG: "Research Progress of Receptor-interacting Protein 1 and Its Inhibitors", PROGRESS IN PHARMACEUTICAL SCIENCES, CHINA PHARMACEUTICAL UNIVERSITY, CN, vol. 42, no. 12, 31 December 2018 (2018-12-31), CN , pages 945 - 951, XP055866191, ISSN: 1001-5094 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022171110A1 (fr) * 2021-02-10 2022-08-18 Zai Lab (Us) Llc Composés tricycliques fusionnés en tant qu'inhibiteurs de rip1-kinase et leurs utilisations
WO2022237890A1 (fr) * 2021-05-14 2022-11-17 中国医药研究开发中心有限公司 Composé à cycle fusionné du type azépine et son utilisation pharmaceutique
CN117645579A (zh) * 2022-09-02 2024-03-05 科辉智药生物科技(深圳)有限公司 作为ripk1抑制剂的氮杂䓬类稠环化合物及其应用
WO2024046361A1 (fr) * 2022-09-02 2024-03-07 科辉智药生物科技（无锡）有限公司 Composé cyclique fusionné d'azépine utilisé en tant qu'inhibiteur de ripk1 et utilisation associée
WO2025153090A1 (fr) * 2024-01-19 2025-07-24 无锡奕拓医药科技有限责任公司 Composé polycyclique, composition pharmaceutique associée et utilisation associée

Also Published As

Publication number Publication date
TW202144353A (zh) 2021-12-01
CN115038707B (zh) 2024-11-22
CN115038707A (zh) 2022-09-09

Similar Documents

Publication Publication Date Title
CN111295384B (zh) 双环类衍生物抑制剂、其制备方法和应用
TWI765908B (zh) 苯並咪唑類化合物激酶抑制劑及其製備方法和應用
CN104903321B (zh) 作为激酶抑制剂的经取代三环苯并咪唑
KR102755657B1 (ko) Prmt5 억제제로서의 치환 삼환류 화합물 및 그의 응용
WO2020108590A1 (fr) Pyrimidine et dérivé hétérocycle pentagonal de nitrogène, leur procédé de préparation et applications médicales
WO2021228173A1 (fr) Composés cycliques condensés du type azépine et utilisations médicales associées
CN103664973A (zh) 螺羟吲哚化合物及其作为治疗剂的用途
WO2021249519A1 (fr) Dérivé de pyridine-pyrimidine, son procédé de préparation et son utilisation pharmaceutique
WO2020030107A1 (fr) Composition pharmaceutique contenant des dérivés amides, son procédé de préparation et application associée
WO2023072297A1 (fr) Composé tétracyclique contenant de l'azote, son procédé de préparation et son utilisation en médecine
WO2022247816A1 (fr) Composé hétérocyclique contenant de l'azote, son procédé de préparation et son application dans des médicaments
WO2021249475A1 (fr) Dérivé de quinazoline condensé, son procédé de préparation et son application en médecine
TW202128690A (zh) 吡唑并雜芳基類衍生物、其製備方法及其在醫藥上的應用
CN115594695A (zh) 大环类化合物、其制备方法及其在医药上的应用
WO2023109883A1 (fr) Composés substitués par un hétérocycle aromatique, procédé de préparation associé et leur utilisation
CN114728938A (zh) 作为prmt5抑制剂的四氢异喹啉螺环化合物
EP4365183A1 (fr) Composé stéroïde, composition pharmaceutique et utilisation associées
CN115867557B (zh) 氮杂卓类稠环化合物及其医药用途
CN120092002A (zh) 稠合杂芳烃类化合物、其组合物及用途
WO2022002243A1 (fr) Dérivé d'imidazopyrimidine, son procédé de préparation et son utilisation médicale
CN117229295A (zh) 含氮大环类化合物及其制备方法和医药用途
CN112334465B (zh) 三环取代的氧杂螺环衍生物、其制法与医药上的用途
TW202246260A (zh) 稠合的氮雜三環類衍生物、其製備方法及其在醫藥上的應用
CN116783166B (zh) 二甲酰胺类化合物、其制备方法及其在医药上的应用
HK40072076A (en) Azepine fused ring compounds and medical uses thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21804165

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21804165

Country of ref document: EP

Kind code of ref document: A1