WO2017012559A1 - 稠环嘧啶类化合物、中间体、其制备方法、组合物和应用 - Google Patents
稠环嘧啶类化合物、中间体、其制备方法、组合物和应用 Download PDFInfo
- Publication number
- WO2017012559A1 WO2017012559A1 PCT/CN2016/090798 CN2016090798W WO2017012559A1 WO 2017012559 A1 WO2017012559 A1 WO 2017012559A1 CN 2016090798 W CN2016090798 W CN 2016090798W WO 2017012559 A1 WO2017012559 A1 WO 2017012559A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- substituted
- compound
- group
- alkyl group
- heterocycloalkyl
- Prior art date
Links
- 0 COc1ccccc1* Chemical compound COc1ccccc1* 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N CN1CCNCC1 Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N C1NCCOC1 Chemical compound C1NCCOC1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- OQXWXMMBGZZJFV-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(NC2(C)N=Cc(cccc3-c4ccccc4OC)c3N2)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(NC2(C)N=Cc(cccc3-c4ccccc4OC)c3N2)c1)=O OQXWXMMBGZZJFV-UHFFFAOYSA-N 0.000 description 1
- UCNYLDCAIZLKOJ-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c(ccc(C(F)(F)F)c2)c2OC)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c(ccc(C(F)(F)F)c2)c2OC)c1)=O UCNYLDCAIZLKOJ-UHFFFAOYSA-N 0.000 description 1
- YKHAQCODXASDOT-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c(ccc(F)c2)c2OC)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c(ccc(F)c2)c2OC)c1)=O YKHAQCODXASDOT-UHFFFAOYSA-N 0.000 description 1
- IZEUXYGNSFUKKV-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2cccc3c2OCC3)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2cccc3c2OCC3)c1)=O IZEUXYGNSFUKKV-UHFFFAOYSA-N 0.000 description 1
- XXQGFLQVQLPDRB-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2ccccc2OC)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2ccccc2OC)c1)=O XXQGFLQVQLPDRB-UHFFFAOYSA-N 0.000 description 1
- VSCFJJLHQYPYHF-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3cccc4c3OCC4)ccc3)c3cn2)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3cccc4c3OCC4)ccc3)c3cn2)c1)=O VSCFJJLHQYPYHF-UHFFFAOYSA-N 0.000 description 1
- FQEBMZPPOTZQJX-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3ccccc3OC)cc(F)c3)c3cn2)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3ccccc3OC)cc(F)c3)c3cn2)c1)=O FQEBMZPPOTZQJX-UHFFFAOYSA-N 0.000 description 1
- YGFTUYKJTLSAND-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3ccccc3OC)cnc3)c3cn2)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(-c3ccccc3OC)cnc3)c3cn2)c1)=O YGFTUYKJTLSAND-UHFFFAOYSA-N 0.000 description 1
- BOBQPXUOLBWMDR-UHFFFAOYSA-N CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(I)ccc3)c3cn2)c1)=O Chemical compound CC(C)(C)OC(N(CC1)CCC1[n]1ncc(Nc2nc(c(I)ccc3)c3cn2)c1)=O BOBQPXUOLBWMDR-UHFFFAOYSA-N 0.000 description 1
- HENLKZLWIDJRSC-UHFFFAOYSA-N CC[n]1ncc(N)c1 Chemical compound CC[n]1ncc(N)c1 HENLKZLWIDJRSC-UHFFFAOYSA-N 0.000 description 1
- QWGSRBMEWNKULF-UHFFFAOYSA-N CC[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2ccccc2OC)c1 Chemical compound CC[n]1ncc(Nc(nc2)nc3c2[s]c(C)c3-c2ccccc2OC)c1 QWGSRBMEWNKULF-UHFFFAOYSA-N 0.000 description 1
- LQPXKEBIYOXPKM-UHFFFAOYSA-N CC[n]1ncc([N+]([O-])=O)c1 Chemical compound CC[n]1ncc([N+]([O-])=O)c1 LQPXKEBIYOXPKM-UHFFFAOYSA-N 0.000 description 1
- XUEPPIJSIPEGDP-UHFFFAOYSA-N Cc([s]c(cn1)c2nc1Cl)c2-c1ccccc1OC Chemical compound Cc([s]c(cn1)c2nc1Cl)c2-c1ccccc1OC XUEPPIJSIPEGDP-UHFFFAOYSA-N 0.000 description 1
- APNWPSRCICHORT-UHFFFAOYSA-N Cc([s]c(cn1)c2nc1Cl)c2Br Chemical compound Cc([s]c(cn1)c2nc1Cl)c2Br APNWPSRCICHORT-UHFFFAOYSA-N 0.000 description 1
- XYLKDTRVIWBNAB-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1c(CO)cccc1 Chemical compound Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1c(CO)cccc1 XYLKDTRVIWBNAB-UHFFFAOYSA-N 0.000 description 1
- MDTHUOLOQQPZMC-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1ccccc1C=O Chemical compound Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1ccccc1C=O MDTHUOLOQQPZMC-UHFFFAOYSA-N 0.000 description 1
- CBHKOHQFFILGPZ-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1ccccc1CN(C)C Chemical compound Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2-c1ccccc1CN(C)C CBHKOHQFFILGPZ-UHFFFAOYSA-N 0.000 description 1
- CMJWCYBRIQVWCY-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2Br Chemical compound Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2Br CMJWCYBRIQVWCY-UHFFFAOYSA-N 0.000 description 1
- UYHDEPKUQRJZRD-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2OCCCBr Chemical compound Cc([s]c1c2nc(Nc3c[n](C)nc3)nc1)c2OCCCBr UYHDEPKUQRJZRD-UHFFFAOYSA-N 0.000 description 1
- JYZKTBKCKOTPHP-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](C4CCN(C)CC4)nc3)nc1)c2Br Chemical compound Cc([s]c1c2nc(Nc3c[n](C4CCN(C)CC4)nc3)nc1)c2Br JYZKTBKCKOTPHP-UHFFFAOYSA-N 0.000 description 1
- MGZLIOOMLZOSSM-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](CCCN4CCCC4)nc3)nc1)c2Br Chemical compound Cc([s]c1c2nc(Nc3c[n](CCCN4CCCC4)nc3)nc1)c2Br MGZLIOOMLZOSSM-UHFFFAOYSA-N 0.000 description 1
- WPNWGNOKWJHFEX-UHFFFAOYSA-N Cc([s]c1c2nc(Nc3c[n](CCO)nc3)nc1)c2Br Chemical compound Cc([s]c1c2nc(Nc3c[n](CCO)nc3)nc1)c2Br WPNWGNOKWJHFEX-UHFFFAOYSA-N 0.000 description 1
- KFTWABNMBFJZIX-UHFFFAOYSA-N Cc([s]c1cnc(Nc2c[n](C)nc2)nc11)c1OCCCN1CCN(C)CC1 Chemical compound Cc([s]c1cnc(Nc2c[n](C)nc2)nc11)c1OCCCN1CCN(C)CC1 KFTWABNMBFJZIX-UHFFFAOYSA-N 0.000 description 1
- RYYZDXAFZQSFAH-UHFFFAOYSA-N Cc([s]c1cnc(Nc2c[n](CCN3CCN(C)CC3)nc2)nc11)c1Br Chemical compound Cc([s]c1cnc(Nc2c[n](CCN3CCN(C)CC3)nc2)nc11)c1Br RYYZDXAFZQSFAH-UHFFFAOYSA-N 0.000 description 1
- XORHNJQEWQGXCN-UHFFFAOYSA-N [O-][N+](c1c[nH]nc1)=O Chemical compound [O-][N+](c1c[nH]nc1)=O XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
-
- 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
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- 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
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Dispersion Chemistry (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
化合物 | FGFR 1 | FGFR 2 | FGFR 3 |
31 | 5.1 | 10 | 16 |
34 | 3.8 | 8.9 | 15 |
化合物 | FLT3-WT | FLT3-ITD | FLT3-D835Y |
31 | 0.28 | 0.34 | 0.20 |
34 | <5 | 0.33 | 0.23 |
Claims (26)
- 一种如式I所示的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体;其中,P选自氢原子或氘原子;X选自CH或S;Y选自N或CR5;U选自化学键或CH;V选自N或CH;W选自N或CR6;R1、R2、R3和R6独立地为氢原子、氘原子、卤素、取代或未取代的烷基、 环烷基或杂环烷基;所述的R7、R8、R9、R10和R15独立地为氢原子、氘原子、卤素、羟基、氨基、取代或未取代的烷基、烷氧基、或杂环烷基;所述的R11为氢原子、氘原子或烷基;或者,所述的R6、R2及与它们相连的环上的两个原子共同形成“取代或未取代的5-7元的碳杂环”;或者,所述的R6、R3及与它们相连的环上的两个原子共同形成“取代或未取代的5-7元的碳杂环”;所述的“取代或未取代的5-7元的碳杂环”中杂原子为氮、氧和硫中的一种或多种;R4为氢原子、氘原子、取代或未取代的烷基、烷氧基、环烷基,或取代或未取代的杂环烷基;R5为氢原子、氘原子、卤素或烷基;所述的R1、R2、R3和R6中,所述的“取代或未取代的烷基”中所述的“取代”为被一个或多个以下基团所取代,当存在多个取代基时,所述的取代基相同或不同:卤素、羟基、氨基、烷基、烷氧基、和杂环烷基;所述所的述R12的为R7氢、原R8子、、R9、氘R原10子和或R烷15基中;,所述的“取代或未取代的烷基”中所述的“取代”为被一个或多个以下基团所取代,当存在多个取代基时,所述的取代基相同或不同:氘原子、卤素、羟基、氨基、烷基、烷氧基、 和杂环烷基;所述的R13为氢原子或烷基;所述的R4中,“取代或未取代的烷基”和“取代或未取代的杂环烷基”中所述的“取代”为被一个或多个下述基团所取代,当存在多个取代基时,所述的取代基相同或不同:羟基、烷基、或杂环烷基;所述的R14为氢原子、烷基、羟甲基或烷氧基;所述的“取代或未取代的5-7元的碳杂环”中所述的“取代”为被一个或多个烷基所取代。
- 如权利要求1所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,其特征在于,当所述的R1、R2、R3和R6独立地为卤素时,所述的卤素为氟或氯;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为C1-4的烷基;和/或,当所述的R1、R2、R3和R6独立地为杂环烷基时,所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R1、R2、R3和R6独立地为杂环烷基时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-8个碳原子的杂环烷基”;和/或,当所述的R7、R8、R9、R10和R15独立地为卤素时,所述的卤素为氟;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为C1-10的烷基;和/或,当所述的R7、R8、R9、R10和R15独立地为烷氧基时,所述的烷氧基为C1-10的烷氧基;和/或,所述的R7、R8、R9、R10和R15独立地为杂环烷基时,所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R7、R8、R9、R10和R15独立地为杂环烷基时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-8个碳原子的杂环烷基”;和/或,当所述的R4为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为C1-4的烷基;和/或,当所述的R4为烷氧基时,所述的烷氧基为C1-4的烷氧基;和/或,所述的R4为“取代或未取代的杂环烷基”时,所述的“取代或未取代的杂环烷基”中所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R4为“取代或未取代的杂环烷基”时,所述的“取代或未取代的杂环烷基”中所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个,含有3-8个碳原子的杂环烷基”;和/或,当所述的R5为卤素时,所述的卤素为氟;和/或,当所述的R5为烷基时,所述的烷基为C1-4的烷基;和/或,所述的“取代或未取代的5-7元的碳杂环”中所述的“5-7元的碳杂环”为“杂原子为氧和/或氮,杂原子数为1-4个,含有2-6个碳原子的5-7元的碳杂环”;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被卤素所取代时,所述的卤素为氟;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为C1-10的烷基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被烷氧基所取代时,所述的烷氧基为C1-10的烷氧基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为 被杂环烷基所取代时,所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被杂环烷基所取代时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-8个碳原子的杂环烷基”;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被卤素所取代时,所述的卤素为氟;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为C1-10的烷基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷氧基所取代时,所述的烷氧基为C1-10的烷氧基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被杂环烷基所取代时,所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被杂环烷基所取代时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-8个碳原子的杂环烷基”;和/或,当所述的R4为“取代或未取代的烷基”或“取代或未取代的杂环烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为C1-4的烷基;和/或,当所述的R4为“取代或未取代的烷基”或“取代或未取代的杂环烷基”,所述的取代为被杂环烷基所取代时,所述的“为被杂环烷基所取代”中所述的杂环烷基经其中的碳原子或者杂原子和其他基团进行连接;和/或,当所述的R4为“取代或未取代的烷基”或“取代或未取代的杂环烷基”,所述的取代为被杂环烷基所取代时,所述的“为被杂环烷基所取代”中所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个,含有3-6个碳原子的杂环烷基”;和/或,当所述的“取代或未取代的5-7元的碳杂环”中所述的取代为被烷基所取代时,所述的烷基为C1-4的烷基。
- 如权利要求2所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,其特征在于,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为甲基;和/或,当所述的R1、R2、R3和R6独立地为杂环烷基时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-6个碳原子的杂环烷基”;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为C1-4的烷基;和/或,当所述的R7、R8、R9、R10和R15独立地为烷氧基时,所述的烷氧基为C1-4的烷氧基;和/或,当所述的R7、R8、R9、R10和R15独立地为杂环烷基时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-6个碳原子的杂环烷基”;和/或,当所述的R4为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为甲基、乙基、丙基或异丙基;和/或,当所述的R4为“取代或未取代的杂环烷基”时,所述的“取代或未取代的杂环烷基”中所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个,含有3-6个碳原子的杂环烷基”;和/或,当所述的R5为烷基时,所述的烷基为甲基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为C1-4的烷基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被烷氧基所取代时,所述的烷氧基为C1-4的烷氧基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被杂环烷基所取代时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-6个碳原子的杂环烷基”;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为C1-4的烷基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷氧基所取代时,所述的烷氧基为C1-4的烷氧基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被杂环烷基所取代时,所述的杂环烷基为“杂原子为氧和/或氮,杂原子数为1-4个含有3-6个碳原子的杂环烷基”;和/或,当所述的R4为“取代或未取代的烷基”或“取代或未取代的杂环烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为甲基;和/或,当所述的“取代或未取代的5-7元的碳杂环”中所述的取代为被烷基所取代时,所述的烷基为甲基、乙基或丙基。
- 如权利要求3所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,其特征在于,当所述的R1、R2、R3和R6独立地为杂环烷基时,所述的杂环烷基为和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”时,所述的“取代或未取代的烷基”中所述的烷基为甲基、三氘代甲基、乙基、丙基或异丙基;和/或,当所述的R7、R8、R9、R10和R15独立地为烷氧基时,所述的烷氧基为甲氧基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为甲基;和/或,当所述的R1、R2、R3和R6独立地为“取代或未取代的烷基”,所述的取代为 被烷氧基所取代时,所述的烷氧基为甲氧基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷基所取代时,所述的“为被烷基所取代”中所述的烷基为甲基;和/或,当所述的R7、R8、R9、R10和R15独立地为“取代或未取代的烷基”,所述的取代为被烷氧基所取代时,所述的烷氧基为甲氧基;
- 如权利要求1-4中任一项所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,其特征在于,在所述的化合物I中,所述的Y为CR5;和/或,在所述的化合物I中,所述的R5为氢原子或烷基;和/或,在所述的化合物I中,所述的W为CR6;和/或,在所述的化合物I中,所述的R6为氢原子;和/或,在所述的化合物I中,所述的R6和R2,及与它们相连的环上的两个原子共同形成“取代或未取代的5-7元的碳杂环”;和/或,在所述的化合物I中,所述的R1或R2为氢原子;和/或,在所述的化合物I中,所述的R4为“取代或未取代的烷基”或“取代或未取代的杂环烷基”。
- 如权利要求1所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,其特征在于,所含原子的各同位素按自然界中各同位素丰度分布存在。
- 如权利要求1-10中任一项所述的稠环嘧啶类化合物的制备方法,其为方法1-13中任一项,方法1包括下述步骤:在有机溶剂中,在碱的存在下,将化合物1-a与甲基化试剂进行取代反应,制得化合物1即可;方法2包括下述步骤:在有机溶剂中,在催化剂的存在下,将化合物II和化合物VI进行取代反应,得到化合物I即可;(请核实下列方程式是否正确,若不正确请修改)确认方法3包括下述步骤:在有机溶剂和水中,在碱和钯催化剂的存在下,将化合物III和化合物VII进行偶联反应,得到化合物I即可;其中,A为Br或I;方法4包括下述步骤:在有机溶剂中,在碱的存在下,将化合物9-a和2-(4-哌啶基)-2-丙醇进行取代反应,得到化合物9即可;方法5包括下述步骤:在有机溶剂中,在碱的存在下,将化合物17-a和吗啉进行取代反应,得到化合物17即可;方法6包括下述步骤:在有机溶剂中,在碱的存在下,将化合物17-a和吡咯烷进行取代反应,得到化合物18即可;方法7包括下述步骤:在有机溶剂中,在碱的存在下,将化合物17-a和N-甲基哌嗪 进行取代反应,得到化合物19即可;方法8包括下述步骤:在有机溶剂中,在碱、N-羟基苯并三氮唑和1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐的存在下,将化合物23-b和氮杂环丁烷进行缩合反应,得到化合物23即可;方法10包括下述步骤:在有机溶剂中,在碱存在的条件下,将化合物31和2-卤代乙醇进行取代反应,得到化合物34即可;方法11包括下述步骤:在有机溶剂中,在碱、1-羟基苯并三唑和1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐存在的条件下,将化合物32和2-羟基乙酸进行缩合反应,得到化合物36即可;方法12包括下述步骤:在有机溶剂中,在酸存在的条件下,将化合物40-a和二甲胺、三乙酰基硼氢化钠进行还原氨化反应,得到化合物40即可;方法13包括下述步骤:在有机溶剂中,在碱存在的条件下,将化合物31和氯甲酸乙酯进行缩合反应,得到化合物50即可;
- 如权利要求1-10中任一项所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体在制备药物中的应用,所述的药物用于预防、缓解或治疗,免疫系统疾病、自身免疫性疾病、细胞增殖类疾病、变应性病症和心血管系统疾病中的一种或多种。
- 如权利要求19所述的应用,其特征在于,所述的免疫系统疾病为器官移植排斥;和/或,所述的自身免疫性疾病为类风湿性关节炎、银屑病、克罗恩氏病和多发性硬化症中的一种或多种;和/或,所述的细胞增殖类疾病为骨髓纤维化、血液瘤和实体瘤中的一种或多种;和/或,所述的变应性病症为支气管哮喘;和/或,所述的心血管系统疾病为缺血性心肌病、心力衰竭和心肌梗死中的一种或多种。
- 如权利要求20所述的应用,其特征在于,所述的血液瘤为白血病和/或淋巴瘤;和/或,所述的实体瘤为肾癌、肝癌、胃癌、肺癌、乳腺癌、前列腺癌、胰腺癌、甲状腺癌、卵巢癌、胶质母细胞癌、皮肤癌和黑色素瘤中的一种或多种。
- 如权利要求1-10中任一项所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体在制备药物中的应用,所述的药物用于抑制Janus激酶、FGFR激酶、FLT3激酶和/或Src家族激酶。
- 如权利要求22所述的应用,其特征在于,所述的Janus激酶为JAK1、JAK2和JAK3中的一种或多种;所述的FGFR激酶为FGFR1、FGFR2和FGFR3中的一种或多种;所述的FLT3激酶为FLT3-WT、FLT3-ITD和FLT3-D835Y中的一种或多种;所述的Src家族激酶为c-Src、Lyn、Fyn、Lck、Hck、Fgr、Blk、Yes和Yrk中的一种或多种。
- 一种药物组合物,其包含权利要求1-10中任一项所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体,和药学上可接受的一种或多种载体和/或稀释剂。
- 如权利要求24所述的药物组合物,其特征在于,所述的稠环嘧啶类化合物、其互变异构体、其对映异构体、其非对映异构体、其药学上可接受的盐、其代谢产物、其代谢前体或其药物前体的剂量,为治疗有效量;和/或,所述的药物组合物与一种或者多种临床使用的化疗药联用。
- 如权利要求25所述的药物组合物,其特征在于,当所述的药物组合物与一种或者多种临床使用的化疗药联用时,制剂剂型为脂质体剂型。
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
RU2018103332A RU2732576C2 (ru) | 2015-07-21 | 2016-07-21 | Пиримидиновое соединение с конденсированными кольцами, его промежуточное соединение, способ получения, композиция и применение |
BR112018001209-2A BR112018001209B1 (pt) | 2015-07-21 | 2016-07-21 | Composto de pirimidina de anel fundido, intermediário, e método de preparação, composição e uso do mesmo |
EP16827250.8A EP3354653B1 (en) | 2015-07-21 | 2016-07-21 | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof |
NZ739940A NZ739940B2 (en) | 2016-07-21 | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof | |
US15/746,254 US10494378B2 (en) | 2015-07-21 | 2016-07-21 | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof |
CA2993096A CA2993096C (en) | 2015-07-21 | 2016-07-21 | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof |
AU2016295594A AU2016295594B2 (en) | 2015-07-21 | 2016-07-21 | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof |
KR1020187004890A KR102591886B1 (ko) | 2015-07-21 | 2016-07-21 | 축합고리 피리미딘계 화합물, 중간체, 이의 제조 방법, 조성물 및 응용 |
MX2018000945A MX2018000945A (es) | 2015-07-21 | 2016-07-21 | Compuesto pirimidina de anillo fusionado, intermedio y metodo de preparacion, composicion y uso del mismo. |
JP2018503190A JP6875372B2 (ja) | 2015-07-21 | 2016-07-21 | 縮合環ピリミジン系化合物、中間体、その製造方法、組成物及び応用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510430641 | 2015-07-21 | ||
CN201510430641.5 | 2015-07-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2017012559A1 true WO2017012559A1 (zh) | 2017-01-26 |
Family
ID=57833793
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2016/090798 WO2017012559A1 (zh) | 2015-07-21 | 2016-07-21 | 稠环嘧啶类化合物、中间体、其制备方法、组合物和应用 |
Country Status (10)
Country | Link |
---|---|
US (1) | US10494378B2 (zh) |
EP (1) | EP3354653B1 (zh) |
JP (1) | JP6875372B2 (zh) |
KR (1) | KR102591886B1 (zh) |
CN (1) | CN106366093B (zh) |
AU (1) | AU2016295594B2 (zh) |
CA (1) | CA2993096C (zh) |
MX (1) | MX2018000945A (zh) |
RU (1) | RU2732576C2 (zh) |
WO (1) | WO2017012559A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021175155A1 (zh) * | 2020-03-06 | 2021-09-10 | 广州再极医药科技有限公司 | 噻吩并嘧啶类衍生物及其制备方法 |
WO2021180032A1 (en) * | 2020-03-13 | 2021-09-16 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd. | Novel Therapeutic Methods |
JP2021525747A (ja) * | 2018-05-31 | 2021-09-27 | グアンジョウ マキシノベル ファーマシューティカルズ カンパニー リミテッド | 縮合環ピリミジン系化合物の塩、結晶形並びにその製造方法と使用 |
WO2024020380A1 (en) * | 2022-07-18 | 2024-01-25 | Iambic Therapeutics, Inc. | Quinazoline compounds and methods of use |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109305944B (zh) * | 2017-07-28 | 2022-09-02 | 深圳睿熙生物科技有限公司 | 布鲁顿酪氨酸激酶的抑制剂 |
CN111978331B (zh) * | 2019-05-21 | 2023-06-20 | 上海再极医药科技有限公司 | 一种flt3和fgfr激酶抑制剂的制备方法 |
WO2021148010A1 (zh) * | 2020-01-22 | 2021-07-29 | 南京明德新药研发有限公司 | 吡唑并杂芳环类化合物及其应用 |
WO2024041633A1 (zh) * | 2022-08-25 | 2024-02-29 | 广州再极医药科技有限公司 | 一种稠环嘧啶类化合物的用途 |
CN116836171A (zh) * | 2023-06-30 | 2023-10-03 | 凌科药业(杭州)有限公司 | 一种磺酰胺类化合物及其应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009062258A1 (en) * | 2007-11-15 | 2009-05-22 | Cytopia Research Pty Ltd | N-containing heterocyclic compounds |
WO2011049332A2 (en) * | 2009-10-22 | 2011-04-28 | Korea Institute Of Science And Technology | 2,7-substituted thieno[3,2-d]pyrimidine compounds as protein kinase inhibitors |
WO2011079231A1 (en) * | 2009-12-23 | 2011-06-30 | Gatekeeper Pharmaceutical, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
WO2014023385A1 (en) * | 2012-08-07 | 2014-02-13 | Merck Patent Gmbh | Pyridopyrimidine derivatives as protein kinase inhibitors |
WO2014037750A1 (en) * | 2012-09-07 | 2014-03-13 | Cancer Research Technology Limited | Inhibitor compounds |
WO2015027222A2 (en) * | 2013-08-23 | 2015-02-26 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5110347A (en) * | 1990-11-26 | 1992-05-05 | E. I Du Pont De Nemours And Company | Substituted fused heterocyclic herbicides |
US5633218A (en) * | 1995-05-24 | 1997-05-27 | E. I. Du Pont De Nemours And Company | Herbicidal benzodioxoles and benzodioxanes |
WO2001021598A1 (en) * | 1999-09-23 | 2001-03-29 | Astrazeneca Ab | Therapeutic quinazoline compounds |
PT1951684T (pt) * | 2005-11-01 | 2016-10-13 | Targegen Inc | Inibidores de cinases de tipo biaril-meta-pirimidina |
AR060358A1 (es) * | 2006-04-06 | 2008-06-11 | Novartis Vaccines & Diagnostic | Quinazolinas para la inhibicion de pdk 1 |
CL2007001165A1 (es) * | 2006-04-26 | 2008-01-25 | Hoffmann La Roche | 2-(1h-indazol-4-il)-6-(4-metanosulfonil-piperazin-1-ilmetil)-4-morfolin-4-il-tieno[3,2-d]pirimidina; procedimiento de preparacion; composicion farmaceutica; proceso de preparacion de dicha composicion; kit farmaceutico; y uso para tratar enfermedades tales como cancer, desordenes inmunes y enfermedades cardiovasculares. |
CA2748943A1 (en) * | 2009-02-09 | 2010-08-12 | Supergen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
TWI468402B (zh) * | 2009-07-31 | 2015-01-11 | 必治妥美雅史谷比公司 | 降低β-類澱粉生成之化合物 |
US20130317045A1 (en) | 2010-09-01 | 2013-11-28 | Ambit Biosciences Corporation | Thienopyridine and thienopyrimidine compounds and methods of use thereof |
TW201309655A (zh) * | 2011-01-28 | 2013-03-01 | 必治妥美雅史谷比公司 | 降低β-類澱粉生成之化合物 |
TWI659021B (zh) * | 2013-10-10 | 2019-05-11 | 亞瑞克西斯製藥公司 | Kras g12c之抑制劑 |
JO3556B1 (ar) * | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
US10947201B2 (en) * | 2015-02-17 | 2021-03-16 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
EP3275867B1 (en) * | 2015-03-24 | 2020-06-10 | Shanghai Yingli Pharmaceutical Co. Ltd. | Pyrido-fused bicyclic compounds as urat1 inhibitors for treating hyperuricemia |
CN106220644B (zh) * | 2015-04-24 | 2020-07-31 | 广州再极医药科技有限公司 | 稠环嘧啶氨基衍生物﹑其制备方法、中间体、药物组合物及应用 |
-
2016
- 2016-07-21 AU AU2016295594A patent/AU2016295594B2/en active Active
- 2016-07-21 US US15/746,254 patent/US10494378B2/en active Active
- 2016-07-21 WO PCT/CN2016/090798 patent/WO2017012559A1/zh active Application Filing
- 2016-07-21 JP JP2018503190A patent/JP6875372B2/ja active Active
- 2016-07-21 KR KR1020187004890A patent/KR102591886B1/ko active IP Right Grant
- 2016-07-21 RU RU2018103332A patent/RU2732576C2/ru active
- 2016-07-21 CA CA2993096A patent/CA2993096C/en active Active
- 2016-07-21 MX MX2018000945A patent/MX2018000945A/es unknown
- 2016-07-21 EP EP16827250.8A patent/EP3354653B1/en active Active
- 2016-07-21 CN CN201610579459.0A patent/CN106366093B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009062258A1 (en) * | 2007-11-15 | 2009-05-22 | Cytopia Research Pty Ltd | N-containing heterocyclic compounds |
WO2011049332A2 (en) * | 2009-10-22 | 2011-04-28 | Korea Institute Of Science And Technology | 2,7-substituted thieno[3,2-d]pyrimidine compounds as protein kinase inhibitors |
WO2011079231A1 (en) * | 2009-12-23 | 2011-06-30 | Gatekeeper Pharmaceutical, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
WO2014023385A1 (en) * | 2012-08-07 | 2014-02-13 | Merck Patent Gmbh | Pyridopyrimidine derivatives as protein kinase inhibitors |
WO2014037750A1 (en) * | 2012-09-07 | 2014-03-13 | Cancer Research Technology Limited | Inhibitor compounds |
WO2015027222A2 (en) * | 2013-08-23 | 2015-02-26 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021525747A (ja) * | 2018-05-31 | 2021-09-27 | グアンジョウ マキシノベル ファーマシューティカルズ カンパニー リミテッド | 縮合環ピリミジン系化合物の塩、結晶形並びにその製造方法と使用 |
JP7351061B2 (ja) | 2018-05-31 | 2023-09-27 | グアンジョウ マキシノベル ファーマシューティカルズ カンパニー リミテッド | 縮合環ピリミジン系化合物の塩、結晶形並びにその製造方法と使用 |
WO2021175155A1 (zh) * | 2020-03-06 | 2021-09-10 | 广州再极医药科技有限公司 | 噻吩并嘧啶类衍生物及其制备方法 |
WO2021180032A1 (en) * | 2020-03-13 | 2021-09-16 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd. | Novel Therapeutic Methods |
WO2024020380A1 (en) * | 2022-07-18 | 2024-01-25 | Iambic Therapeutics, Inc. | Quinazoline compounds and methods of use |
Also Published As
Publication number | Publication date |
---|---|
AU2016295594A1 (en) | 2018-03-15 |
MX2018000945A (es) | 2018-11-09 |
US10494378B2 (en) | 2019-12-03 |
RU2732576C2 (ru) | 2020-09-21 |
EP3354653A4 (en) | 2018-08-29 |
CA2993096A1 (en) | 2017-01-26 |
RU2018103332A3 (zh) | 2019-12-09 |
EP3354653B1 (en) | 2019-09-04 |
EP3354653A1 (en) | 2018-08-01 |
BR112018001209A2 (zh) | 2018-09-18 |
RU2018103332A (ru) | 2019-08-21 |
CN106366093B (zh) | 2020-08-18 |
CN106366093A (zh) | 2017-02-01 |
AU2016295594B2 (en) | 2020-04-16 |
JP2018520202A (ja) | 2018-07-26 |
KR102591886B1 (ko) | 2023-10-20 |
KR20180028521A (ko) | 2018-03-16 |
US20180208604A1 (en) | 2018-07-26 |
NZ739940A (en) | 2023-09-29 |
CA2993096C (en) | 2022-04-12 |
JP6875372B2 (ja) | 2021-05-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106366093B (zh) | 稠环嘧啶类化合物、中间体、其制备方法、组合物和应用 | |
TWI665201B (zh) | 吡唑並[1,5-a]吡嗪-4-基衍生物 | |
JP6321039B2 (ja) | 五員かつ六員複素環式化合物並びにその製造方法、医薬品組成物及びその使用 | |
TWI585088B (zh) | 作爲激酶抑制劑之咪唑并[1,2-b]嗒衍生物 | |
TWI542590B (zh) | 1,2-雙取代雜環化合物 | |
TWI666201B (zh) | 稠環衍生物、其製備方法、中間體、藥物組合物及應用 | |
CN111440189B (zh) | 稠环嘧啶氨基衍生物、其制备方法、中间体、药物组合物及应用 | |
JP2003528095A (ja) | GSK3.β阻害剤としての2−アミノ−3−(アルキル)−ピリミドン誘導体 | |
CN104876921A (zh) | 作为AKT蛋白激酶抑制剂的5H-环戊二烯并[d]嘧啶 | |
CN1882347A (zh) | Akt蛋白激酶抑制剂 | |
WO2020216190A1 (zh) | 一种喹唑啉化合物及其在医药上的应用 | |
JP2008540622A (ja) | 化合物 | |
JP2021105002A (ja) | イミダゾピリダジン化合物 | |
WO2022100623A1 (zh) | 氮取代杂环噻吩类化合物及其用途 | |
WO2021218755A1 (zh) | Shp2抑制剂及其组合物和应用 | |
CN110214138A (zh) | 嘧啶化合物及其药物用途 | |
TW202128706A (zh) | 新型雜環化合物 | |
WO2022100625A1 (zh) | 氮取代氨基碳酸酯噻吩类化合物及其用途 | |
WO2020182018A1 (zh) | 氮杂环化合物、其制备方法及用途 | |
WO2020156283A1 (zh) | 炔基嘧啶或炔基吡啶类化合物、及其组合物与应用 | |
TW201934547A (zh) | 一種嘧啶類化合物、其製備方法及其醫藥用途 | |
CN115279749B (zh) | Shp2抑制剂及其组合物和应用 | |
NZ739940B2 (en) | Fused ring pyrimidine compound, intermediate, and preparation method, composition and use thereof | |
BR112018001209B1 (pt) | Composto de pirimidina de anel fundido, intermediário, e método de preparação, composição e uso do mesmo | |
WO2023040996A1 (zh) | 氮杂吲唑大环化合物及其用途 |
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: 16827250 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2993096 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 15746254 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 2018503190 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/A/2018/000945 Country of ref document: MX |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20187004890 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2016827250 Country of ref document: EP Ref document number: 2018103332 Country of ref document: RU |
|
ENP | Entry into the national phase |
Ref document number: 2016295594 Country of ref document: AU Date of ref document: 20160721 Kind code of ref document: A |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112018001209 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112018001209 Country of ref document: BR Kind code of ref document: A2 Effective date: 20180119 |