RU2591195C2 - Замещенные n-(1h-индазол-4-ил) имидазол [1,2-а]пиридин-3- карбоксамидные соединения в качестве ингибиторов рецепторной тирозинкиназы iii типа - Google Patents

Info

Publication number

RU2591195C2

RU2591195C2 RU2013132758/04A RU2013132758A RU2591195C2 RU 2591195 C2 RU2591195 C2 RU 2591195C2 RU 2013132758/04 A RU2013132758/04 A RU 2013132758/04A RU 2013132758 A RU2013132758 A RU 2013132758A RU 2591195 C2 RU2591195 C2 RU 2591195C2

Authority

RU

Russia

Prior art keywords

methyl

indazol

pyridin

carboxamide

imidazo

Prior art date

2010-12-13

Links

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• Global Dossier
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• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical class NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 title claims description 11
• 239000003112 inhibitor Substances 0.000 title abstract description 22
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title abstract description 3
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title abstract description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 257
• 238000000034 method Methods 0.000 claims abstract description 106
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 80
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 53
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• 241000124008 Mammalia Species 0.000 claims abstract description 39
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• 230000004761 fibrosis Effects 0.000 claims abstract description 31
• 208000020084 Bone disease Diseases 0.000 claims abstract description 29
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 29
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 28
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 28
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• -1 1 - ((6-isopropylpyridin-2-yl) methyl) -3-methyl-1H-indazol-4-yl Chemical group 0.000 claims description 313
• 125000000217 alkyl group Chemical group 0.000 claims description 265
• 125000003545 alkoxy group Chemical group 0.000 claims description 190
• 125000001424 substituent group Chemical group 0.000 claims description 74
• 229920006395 saturated elastomer Polymers 0.000 claims description 69
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 61
• 229910052757 nitrogen Inorganic materials 0.000 claims description 55
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
• 238000011282 treatment Methods 0.000 claims description 47
• 238000006243 chemical reaction Methods 0.000 claims description 45
• 125000005842 heteroatom Chemical group 0.000 claims description 28
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
• 208000035475 disorder Diseases 0.000 claims description 26
• 229910052731 fluorine Inorganic materials 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 150000002367 halogens Chemical class 0.000 claims description 25
• 229910052801 chlorine Inorganic materials 0.000 claims description 24
• 229910052736 halogen Inorganic materials 0.000 claims description 24
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 14
• 239000003153 chemical reaction reagent Substances 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
• 230000015572 biosynthetic process Effects 0.000 claims description 10
• 238000009833 condensation Methods 0.000 claims description 10
• 230000005494 condensation Effects 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• ZMBYQTGAXZOMOO-UHFFFAOYSA-N imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C1=CC=CN2C(C(=O)N)=CN=C21 ZMBYQTGAXZOMOO-UHFFFAOYSA-N 0.000 claims description 10
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 10
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 8
• 125000003386 piperidinyl group Chemical group 0.000 claims description 8
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
• 125000006239 protecting group Chemical group 0.000 claims description 7
• 210000001519 tissue Anatomy 0.000 claims description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims description 6
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• 125000002393 azetidinyl group Chemical group 0.000 claims description 5
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• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
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• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
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• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
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• 125000002619 bicyclic group Chemical group 0.000 claims description 3
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• 206010028537 myelofibrosis Diseases 0.000 claims description 3
• IQSLRRLZPUWMAU-UHFFFAOYSA-N n-(1-benzylindazol-4-yl)-6-bromoimidazo[1,2-a]pyridine-3-carboxamide Chemical compound N12C=C(Br)C=CC2=NC=C1C(=O)NC(C=1C=N2)=CC=CC=1N2CC1=CC=CC=C1 IQSLRRLZPUWMAU-UHFFFAOYSA-N 0.000 claims description 3
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• FAAFDOGSFJDJRV-UHFFFAOYSA-N n-(1-benzylindazol-4-yl)-7-cyanoimidazo[1,2-a]pyridine-3-carboxamide Chemical compound C=1N=C2C=C(C#N)C=CN2C=1C(=O)NC(C=1C=N2)=CC=CC=1N2CC1=CC=CC=C1 FAAFDOGSFJDJRV-UHFFFAOYSA-N 0.000 claims description 3
• UNEBOQFCIQVXLS-UHFFFAOYSA-N n-[3-methyl-1-[(6-methylpyridin-2-yl)methyl]indazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C12=CC=CC(NC(=O)C=3N4C=CC=CC4=NC=3)=C2C(C)=NN1CC1=CC=CC(C)=N1 UNEBOQFCIQVXLS-UHFFFAOYSA-N 0.000 claims description 3
• HAAKSVJDNRYADT-UHFFFAOYSA-N n-[5-chloro-1-[[3-(trifluoromethyl)phenyl]methyl]indazol-4-yl]-7-[2-(4-methylpiperazin-1-yl)ethoxy]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C1CN(C)CCN1CCOC1=CC2=NC=C(C(=O)NC=3C=4C=NN(CC=5C=C(C=CC=5)C(F)(F)F)C=4C=CC=3Cl)N2C=C1 HAAKSVJDNRYADT-UHFFFAOYSA-N 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 claims description 2
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• ZAJBASWHBMULBK-UHFFFAOYSA-N 7-[1-(2-hydroxyethylamino)ethyl]-n-[3-methyl-1-[(6-methylpyridin-2-yl)methyl]indazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C=1N=C2C=C(C(NCCO)C)C=CN2C=1C(=O)NC(C=1C(C)=N2)=CC=CC=1N2CC1=CC=CC(C)=N1 ZAJBASWHBMULBK-UHFFFAOYSA-N 0.000 claims description 2
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