BRPI0809867A2 - Composto, método de indução da apoptose em uma célula, método de sensibilização de uma célula para um sinal apoptótico, método para inibir a ligação de uma proteína iap a uma proteína caspase e métodos - Google Patents

Info

Publication number

BRPI0809867A2

BRPI0809867A2 BRPI0809867-0A BRPI0809867A BRPI0809867A2 BR PI0809867 A2 BRPI0809867 A2 BR PI0809867A2 BR PI0809867 A BRPI0809867 A BR PI0809867A BR PI0809867 A2 BRPI0809867 A2 BR PI0809867A2

Authority

BR

Brazil

Prior art keywords

alkyl

heterocycle

mmol

optionally substituted

amino

Prior art date

2007-04-30

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims description 193
• 238000000034 method Methods 0.000 title claims description 75
• 230000006907 apoptotic process Effects 0.000 title claims description 25
• 102000011727 Caspases Human genes 0.000 title claims description 21
• 108010076667 Caspases Proteins 0.000 title claims description 21
• 230000001640 apoptogenic effect Effects 0.000 title claims description 10
• 230000002401 inhibitory effect Effects 0.000 title claims description 9
• 206010070834 Sensitisation Diseases 0.000 title claims 2
• 230000008313 sensitization Effects 0.000 title claims 2
• 230000006698 induction Effects 0.000 title description 2
• -1 mercapto, carboxyl Chemical group 0.000 claims description 275
• 125000000217 alkyl group Chemical group 0.000 claims description 177
• 125000000623 heterocyclic group Chemical group 0.000 claims description 142
• 125000003118 aryl group Chemical group 0.000 claims description 102
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 78
• 229910052736 halogen Inorganic materials 0.000 claims description 70
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 62
• 125000003545 alkoxy group Chemical group 0.000 claims description 55
• 125000002252 acyl group Chemical group 0.000 claims description 51
• 125000001072 heteroaryl group Chemical group 0.000 claims description 46
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
• 125000001188 haloalkyl group Chemical group 0.000 claims description 40
• 150000002367 halogens Chemical group 0.000 claims description 40
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 36
• 229910052717 sulfur Inorganic materials 0.000 claims description 36
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 31
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 125000004104 aryloxy group Chemical group 0.000 claims description 18
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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 16
• 125000004043 oxo group Chemical group O=* 0.000 claims description 15
• 125000004423 acyloxy group Chemical group 0.000 claims description 14
• 238000006467 substitution reaction Methods 0.000 claims description 14
• 125000004442 acylamino group Chemical group 0.000 claims description 13
• 230000005855 radiation Effects 0.000 claims description 13
• 230000027455 binding Effects 0.000 claims description 12
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 11
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• 241000124008 Mammalia Species 0.000 claims description 9
• 125000003282 alkyl amino group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 7
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
• 125000001769 aryl amino group Chemical group 0.000 claims description 6
• 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 6
• 230000001939 inductive effect Effects 0.000 claims description 6
• 125000005647 linker group Chemical group 0.000 claims description 6
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 5
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• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
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• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
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• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
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• 230000002018 overexpression Effects 0.000 claims description 3
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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 3
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
• VTBOTOBFGSVRMA-UHFFFAOYSA-N 1-Methylcyclohexanol Chemical compound CC1(O)CCCCC1 VTBOTOBFGSVRMA-UHFFFAOYSA-N 0.000 claims description 2
• HCFRWBBJISAZNK-UHFFFAOYSA-N 4-Hydroxycyclohexylcarboxylic acid Chemical compound OC1CCC(C(O)=O)CC1 HCFRWBBJISAZNK-UHFFFAOYSA-N 0.000 claims description 2
• 108010006654 Bleomycin Proteins 0.000 claims description 2
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• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
• 229960001561 bleomycin Drugs 0.000 claims description 2
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
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• 229960004397 cyclophosphamide Drugs 0.000 claims description 2
• 229960000684 cytarabine Drugs 0.000 claims description 2
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 2
• DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims description 2
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• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 2
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• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
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