CZ2003237A3 - N-(5-{[(5-Alkyl-2-oxazolyl)methyl]thio}-2-thiazolyl) karboxamidy jako inhibitory cyklin-dependentních kináz - Google Patents

Info

Publication number

CZ2003237A3

CZ2003237A3 CZ2003237A CZ2003237A CZ2003237A3 CZ 2003237 A3 CZ2003237 A3 CZ 2003237A3 CZ 2003237 A CZ2003237 A CZ 2003237A CZ 2003237 A CZ2003237 A CZ 2003237A CZ 2003237 A3 CZ2003237 A3 CZ 2003237A3

Authority

CZ

Czechia

Prior art keywords

hydrochloride

compound

trifluoroacetate

pharmaceutically acceptable

group

Prior art date

2000-07-26

Links

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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title claims description 14
• 125000000446 sulfanediyl group Chemical group *S* 0.000 title claims description 5
• 150000003857 carboxamides Chemical class 0.000 title 1
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 title 1
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 161
• 150000003839 salts Chemical class 0.000 claims abstract description 71
• 239000012453 solvate Substances 0.000 claims abstract description 21
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
• 201000010099 disease Diseases 0.000 claims abstract description 11
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
• 201000011510 cancer Diseases 0.000 claims abstract description 8
• 206010003246 arthritis Diseases 0.000 claims abstract description 6
• 230000002062 proliferating effect Effects 0.000 claims abstract description 6
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• 230000004054 inflammatory process Effects 0.000 claims abstract description 4
• 208000022605 chemotherapy-induced alopecia Diseases 0.000 claims abstract description 3
• 239000003909 protein kinase inhibitor Substances 0.000 claims abstract description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 90
• 239000000203 mixture Substances 0.000 claims description 77
• -1 diastereomers Substances 0.000 claims description 70
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 55
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 50
• 125000000217 alkyl group Chemical group 0.000 claims description 45
• 238000000034 method Methods 0.000 claims description 43
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 30
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 28
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 27
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 27
• 229940095064 tartrate Drugs 0.000 claims description 27
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• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 26
• SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 claims description 26
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• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
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• NASKBLMGBFRGIF-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-(2-hydroxyethyl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(CCO)CC1 NASKBLMGBFRGIF-UHFFFAOYSA-N 0.000 claims description 4
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• PNZXMIKHJXIPEK-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1CCCCC1 PNZXMIKHJXIPEK-UHFFFAOYSA-N 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• BMJRSDXYHRHHKI-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-cyclopropylpiperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(C2CC2)CC1 BMJRSDXYHRHHKI-UHFFFAOYSA-N 0.000 claims description 3
• USAKOZCUIYTREA-NSHDSACASA-N (3s)-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CNCCC1 USAKOZCUIYTREA-NSHDSACASA-N 0.000 claims description 2
• 108091007914 CDKs Proteins 0.000 claims description 2
• 101100495324 Caenorhabditis elegans cdk-7 gene Proteins 0.000 claims description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 2
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• 201000002364 leukopenia Diseases 0.000 claims description 2
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• LURBGHNXFQSPMM-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-(2,3-dihydroxypropyl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(CC(O)CO)CC1 LURBGHNXFQSPMM-UHFFFAOYSA-N 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 claims description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
• 206010043554 thrombocytopenia Diseases 0.000 claims description 2
• 101150073031 cdk2 gene Proteins 0.000 claims 2
• 229910021653 sulphate ion Inorganic materials 0.000 claims 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
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