JP2009536620A - 医薬組み合わせ物 - Google Patents

Info

Publication number

JP2009536620A

JP2009536620A JP2009507151A JP2009507151A JP2009536620A JP 2009536620 A JP2009536620 A JP 2009536620A JP 2009507151 A JP2009507151 A JP 2009507151A JP 2009507151 A JP2009507151 A JP 2009507151A JP 2009536620 A JP2009536620 A JP 2009536620A

Authority

JP

Japan

Prior art keywords

group

compound

hydrogen

hydrocarbyl

hydroxy

Prior art date

2006-04-25

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Withdrawn

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• 150000001875 compounds Chemical class 0.000 claims abstract description 476
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 28
• 150000003839 salts Chemical class 0.000 claims abstract description 28
• 239000012453 solvate Substances 0.000 claims abstract description 28
• 229940123739 Protein kinase B inhibitor Drugs 0.000 claims abstract description 5
• 239000003197 protein kinase B inhibitor Substances 0.000 claims abstract description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 261
• 239000001257 hydrogen Substances 0.000 claims description 260
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 243
• -1 hydroxy, cyano, amino, methylamino, dimethylamino, methoxy Chemical group 0.000 claims description 237
• 125000001424 substituent group Chemical group 0.000 claims description 234
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 196
• 229910052760 oxygen Inorganic materials 0.000 claims description 186
• 229910052757 nitrogen Inorganic materials 0.000 claims description 173
• 125000005647 linker group Chemical group 0.000 claims description 146
• 229910052736 halogen Inorganic materials 0.000 claims description 140
• 229910052731 fluorine Inorganic materials 0.000 claims description 137
• 125000003118 aryl group Chemical group 0.000 claims description 131
• 125000001072 heteroaryl group Chemical group 0.000 claims description 131
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 131
• 125000000623 heterocyclic group Chemical group 0.000 claims description 130
• 150000002367 halogens Chemical class 0.000 claims description 127
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 126
• 239000011737 fluorine Substances 0.000 claims description 126
• 229910052799 carbon Inorganic materials 0.000 claims description 120
• 125000004432 carbon atom Chemical group C* 0.000 claims description 120
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 109
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 109
• 229910052717 sulfur Inorganic materials 0.000 claims description 107
• 150000001721 carbon Chemical group 0.000 claims description 99
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 99
• 238000011282 treatment Methods 0.000 claims description 96
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 93
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• 125000005842 heteroatom Chemical group 0.000 claims description 90
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 90
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• 125000003545 alkoxy group Chemical group 0.000 claims description 85
• 108091008611 Protein Kinase B Proteins 0.000 claims description 84
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• 239000000460 chlorine Substances 0.000 claims description 81
• 229910052801 chlorine Inorganic materials 0.000 claims description 81
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 79
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• 238000000034 method Methods 0.000 claims description 79
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• 125000002837 carbocyclic group Chemical group 0.000 claims description 60
• 230000000694 effects Effects 0.000 claims description 60
• YQZNKYXGZSVEHI-VXKWHMMOSA-N ethyl (2s)-2-[[(2s)-2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoyl]amino]-3-(4-fluorophenyl)propanoate Chemical group C([C@@H](C(=O)OCC)NC(=O)[C@@H](N)CC=1C=CC(=CC=1)N(CCCl)CCCl)C1=CC=C(F)C=C1 YQZNKYXGZSVEHI-VXKWHMMOSA-N 0.000 claims description 60
• 125000004122 cyclic group Chemical group 0.000 claims description 59
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 51
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• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 38
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 37
• 229910052794 bromium Inorganic materials 0.000 claims description 37
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 36
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• 125000004423 acyloxy group Chemical group 0.000 claims description 31
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 30
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• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 27
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• 125000002947 alkylene group Chemical group 0.000 claims description 24
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 23
• 108091000080 Phosphotransferase Proteins 0.000 claims description 22
• 102000020233 phosphotransferase Human genes 0.000 claims description 22
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 21
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• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 19
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
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• 229920006395 saturated elastomer Polymers 0.000 claims description 11
• SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical group COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims description 11
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 10
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 10
• 125000004442 acylamino group Chemical group 0.000 claims description 10
• 125000002883 imidazolyl group Chemical group 0.000 claims description 10
• 230000001225 therapeutic effect Effects 0.000 claims description 10
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
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• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
• 230000030833 cell death Effects 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 8
• 230000035755 proliferation Effects 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
• 125000003277 amino group Chemical group 0.000 claims description 7
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
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• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
• 125000004188 dichlorophenyl group Chemical group 0.000 claims description 6
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
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