BRPI0713730A2

BRPI0713730A2 - combinações compreendendo estaurosporinas

combinações compreendendo estaurosporinas Download PDF

Info

Publication number: BRPI0713730A2
Authority: BR; Brazil
Prior art keywords: mcl; formula; typically; lower alkyl; phenyl
Prior art date: 2006-06-23

Application number

BRPI0713730-3A

Other languages

English (en)

Portuguese (pt)

Inventor

Peter Valent

Original Assignee

Novartis Ag

Priority date

2006-06-23

Filing date

2007-06-22

Publication date

2012-10-30

2007-06-22 Application filed by Novartis Ag filed Critical Novartis Ag

2012-10-30 Publication of BRPI0713730A2 publication Critical patent/BRPI0713730A2/pt

Links

101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 claims abstract description 243
102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 claims abstract description 235
238000012230 antisense oligonucleotides Methods 0.000 claims abstract description 81
239000000074 antisense oligonucleotide Substances 0.000 claims abstract description 80
239000003814 drug Substances 0.000 claims abstract description 44
108091034117 Oligonucleotide Proteins 0.000 claims abstract description 43
FSPQCTGGIANIJZ-UHFFFAOYSA-N 2-[[(3,4-dimethoxyphenyl)-oxomethyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC1=C(C(N)=O)C(CCCC2)=C2S1 FSPQCTGGIANIJZ-UHFFFAOYSA-N 0.000 claims abstract description 42
102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims abstract description 42
101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims abstract description 42
230000009368 gene silencing by RNA Effects 0.000 claims abstract description 39
238000000034 method Methods 0.000 claims abstract description 32
206010028980 Neoplasm Diseases 0.000 claims abstract description 24
201000003793 Myelodysplastic syndrome Diseases 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
108091030071 RNAI Proteins 0.000 claims abstract 8
-1 4-methyl-1H-imidazol-1-yl Chemical group 0.000 claims description 408
125000000217 alkyl group Chemical group 0.000 claims description 104
150000007523 nucleic acids Chemical class 0.000 claims description 65
102000039446 nucleic acids Human genes 0.000 claims description 63
108020004707 nucleic acids Proteins 0.000 claims description 63
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
125000004432 carbon atom Chemical group C* 0.000 claims description 50
150000001875 compounds Chemical class 0.000 claims description 49
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
239000003112 inhibitor Substances 0.000 claims description 47
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
150000003839 salts Chemical class 0.000 claims description 43
229910052739 hydrogen Inorganic materials 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 41
125000002252 acyl group Chemical group 0.000 claims description 35
KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 35
229960002411 imatinib Drugs 0.000 claims description 33
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
239000005517 L01XE01 - Imatinib Substances 0.000 claims description 29
239000004055 small Interfering RNA Substances 0.000 claims description 29
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
125000005037 alkyl phenyl group Chemical group 0.000 claims description 26
239000002773 nucleotide Substances 0.000 claims description 24
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125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
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125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
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239000001301 oxygen Substances 0.000 claims description 19
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125000000623 heterocyclic group Chemical group 0.000 claims description 18
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 16
125000003277 amino group Chemical group 0.000 claims description 15
125000004103 aminoalkyl group Chemical group 0.000 claims description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
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125000005036 alkoxyphenyl group Chemical group 0.000 claims description 11
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 11
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
125000002883 imidazolyl group Chemical group 0.000 claims description 10
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 9
125000001931 aliphatic group Chemical group 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 5
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125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
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HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 claims description 3
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CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 claims description 3
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HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 27
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
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PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 9
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125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 7
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JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 7
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