CN114605404B - 一种新型含噻唑类化合物、中间体及其应用 - Google Patents
一种新型含噻唑类化合物、中间体及其应用 Download PDFInfo
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- CN114605404B CN114605404B CN202210290561.4A CN202210290561A CN114605404B CN 114605404 B CN114605404 B CN 114605404B CN 202210290561 A CN202210290561 A CN 202210290561A CN 114605404 B CN114605404 B CN 114605404B
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- 239000010452 phosphate Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
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- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
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- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
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- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000008467 subacute bacterial endocarditis Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- CTCGRXDGXGUOTE-SECBINFHSA-N tert-butyl (2r)-2-ethylpiperazine-1-carboxylate Chemical compound CC[C@@H]1CNCCN1C(=O)OC(C)(C)C CTCGRXDGXGUOTE-SECBINFHSA-N 0.000 description 1
- OKUCEQDKBKYEJY-MRVPVSSYSA-N tert-butyl (3r)-3-(methylamino)pyrrolidine-1-carboxylate Chemical compound CN[C@@H]1CCN(C(=O)OC(C)(C)C)C1 OKUCEQDKBKYEJY-MRVPVSSYSA-N 0.000 description 1
- JHOWHSGOBPRECA-UHFFFAOYSA-N tert-butyl 2-fluorobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1F JHOWHSGOBPRECA-UHFFFAOYSA-N 0.000 description 1
- LBAIYWWWORXVEQ-UHFFFAOYSA-N tert-butyl 3,3-dimethylpiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(C)(C)C1 LBAIYWWWORXVEQ-UHFFFAOYSA-N 0.000 description 1
- WISSYVQCTVUYOV-UHFFFAOYSA-N tert-butyl 3-[3-[(2-amino-1,3-thiazol-5-yl)sulfanyl]-2-fluoro-6-methoxy-4-methylbenzoyl]-2-methylpiperazine-1-carboxylate Chemical compound CC(C(C(C(C(OC)=CC(C)=C1SC2=CN=C(N)S2)=C1F)=O)NCC1)N1C(OC(C)(C)C)=O WISSYVQCTVUYOV-UHFFFAOYSA-N 0.000 description 1
- HMJIVFVFSJCVTO-UHFFFAOYSA-N tert-butyl 3-[[3-[(2-amino-1,3-thiazol-5-yl)sulfanyl]-2-fluoro-6-methoxy-4-methylbenzoyl]-methylamino]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(N(CC1)CC1N(C)C(C(C(OC)=CC(C)=C1SC2=CN=C(N)S2)=C1F)=O)=O HMJIVFVFSJCVTO-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 208000009174 transverse myelitis Diseases 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- 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
-
- 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
- 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
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
化合物编号 | ITK |
对照例 | E |
1 | C |
2 | A |
3 | A |
4 | A |
5 | B |
6 | B |
7 | C |
Claims (9)
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Citations (6)
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---|---|---|---|---|
EP1671969A2 (en) * | 2000-12-21 | 2006-06-21 | Bristol-Myers Squibb Company | Thiazolyl inhibitors of tec family tyrosine kinases |
WO2010106016A1 (en) * | 2009-03-17 | 2010-09-23 | Glaxo Group Limited | Pyrimidine derivatives used as itk inhibitors |
WO2015054612A1 (en) * | 2013-10-11 | 2015-04-16 | University Of Massachusetts | Treating organ-specific t cell mediated autoimmune diseases |
WO2016001341A1 (en) * | 2014-07-03 | 2016-01-07 | F. Hoffmann-La Roche Ag | Sulfonylaminopyridine compounds, compositions and methods of use |
CN110099684A (zh) * | 2016-11-03 | 2019-08-06 | 科尔沃斯制药股份有限公司 | 用于调节白介素-2诱导性t细胞激酶的化合物和方法 |
CN112638910A (zh) * | 2018-08-27 | 2021-04-09 | 株式会社大熊制药 | 新的杂环胺衍生物及包含其的药物组合物 |
-
2022
- 2022-03-23 CN CN202210290561.4A patent/CN114605404B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1671969A2 (en) * | 2000-12-21 | 2006-06-21 | Bristol-Myers Squibb Company | Thiazolyl inhibitors of tec family tyrosine kinases |
WO2010106016A1 (en) * | 2009-03-17 | 2010-09-23 | Glaxo Group Limited | Pyrimidine derivatives used as itk inhibitors |
WO2015054612A1 (en) * | 2013-10-11 | 2015-04-16 | University Of Massachusetts | Treating organ-specific t cell mediated autoimmune diseases |
WO2016001341A1 (en) * | 2014-07-03 | 2016-01-07 | F. Hoffmann-La Roche Ag | Sulfonylaminopyridine compounds, compositions and methods of use |
CN110099684A (zh) * | 2016-11-03 | 2019-08-06 | 科尔沃斯制药股份有限公司 | 用于调节白介素-2诱导性t细胞激酶的化合物和方法 |
CN112638910A (zh) * | 2018-08-27 | 2021-04-09 | 株式会社大熊制药 | 新的杂环胺衍生物及包含其的药物组合物 |
Non-Patent Citations (3)
Title |
---|
"A three-dimensional pharmacophore modelling of ITK inhibitors and virtual screening for novel inhibitors";V. Bagga et al.;《SAR and QSAR in Environmental Research 》;第22卷;第171-190页 * |
"Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors";Jagabandhu Das et al.;《Bioorganic & Medicinal Chemistry Letters》;第16卷;第3706–3712页 * |
"Discovery of potent inhibitors for interleukin-2-inducible T-cell kinase: structure-based virtual screening and molecular dynamics simulation approaches",;Chandrasekaran Meganathan et al.;《J Mol Model》;第19卷;第715–726页 * |
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