JP2009535387A - Ｐｉ３キナーゼ阻害剤としてのチアゾール誘導体 - Google Patents

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Publication number

JP2009535387A

JP2009535387A JP2009508458A JP2009508458A JP2009535387A JP 2009535387 A JP2009535387 A JP 2009535387A JP 2009508458 A JP2009508458 A JP 2009508458A JP 2009508458 A JP2009508458 A JP 2009508458A JP 2009535387 A JP2009535387 A JP 2009535387A

Authority

JP

Japan

Prior art keywords

compound

group

compound according

alkyl

hydrogen

Prior art date

2006-05-04

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.)

Withdrawn

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• 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 title description 2
• 150000007979 thiazole derivatives Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 215
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 55
• 239000001257 hydrogen Substances 0.000 claims abstract description 40
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims abstract description 38
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims abstract description 38
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 32
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
• 230000000694 effects Effects 0.000 claims abstract description 22
• 230000003834 intracellular effect Effects 0.000 claims abstract description 16
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• 102000013392 Carboxylesterase Human genes 0.000 claims abstract description 13
• 125000004185 ester group Chemical group 0.000 claims abstract description 13
• 235000008206 alpha-amino acids Nutrition 0.000 claims abstract description 11
• 125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 11
• 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims abstract description 8
• 201000010099 disease Diseases 0.000 claims abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
• 229910052736 halogen Chemical group 0.000 claims abstract description 5
• 150000002367 halogens Chemical group 0.000 claims abstract description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 4
• 125000005550 pyrazinylene group Chemical group 0.000 claims abstract description 4
• 125000005551 pyridylene group Chemical group 0.000 claims abstract description 4
• 125000005576 pyrimidinylene group Chemical group 0.000 claims abstract description 4
• -1 1,3-phenylene, 1,4-phenylene Chemical group 0.000 claims description 72
• 238000000034 method Methods 0.000 claims description 48
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
• 239000000203 mixture Substances 0.000 claims description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
• 125000006413 ring segment Chemical group 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
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• 125000002950 monocyclic group Chemical group 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
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• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical class FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 5
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• 239000012453 solvate Substances 0.000 claims description 5
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• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
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• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 4
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
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• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 150000003568 thioethers Chemical class 0.000 claims description 4
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
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• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
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• 201000005202 lung cancer Diseases 0.000 claims description 3
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• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 201000011549 stomach cancer Diseases 0.000 claims description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
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• 210000002784 stomach Anatomy 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims 2
• 230000009702 cancer cell proliferation Effects 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 150000003254 radicals Chemical class 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 13
• 230000002757 inflammatory effect Effects 0.000 abstract description 3
• 230000002062 proliferating effect Effects 0.000 abstract description 3
• 230000001363 autoimmune Effects 0.000 abstract description 2
• 239000000543 intermediate Substances 0.000 description 76
• 238000005481 NMR spectroscopy Methods 0.000 description 67
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 50
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
• 210000004027 cell Anatomy 0.000 description 34
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• 150000002148 esters Chemical class 0.000 description 30
• 235000019439 ethyl acetate Nutrition 0.000 description 29
• 229940024606 amino acid Drugs 0.000 description 28
• 235000001014 amino acid Nutrition 0.000 description 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
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