MX2008015955A - Aminopirazolopiridinas sustituidas y sus sales, sus preparaciones y composiciones farmacecuticas que las comprenden. - Google Patents

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Publication number

MX2008015955A

MX2008015955A MX2008015955A MX2008015955A MX2008015955A MX 2008015955 A MX2008015955 A MX 2008015955A MX 2008015955 A MX2008015955 A MX 2008015955A MX 2008015955 A MX2008015955 A MX 2008015955A MX 2008015955 A MX2008015955 A MX 2008015955A

Authority

MX

Mexico

Prior art keywords

group

alkyl

phenyl

preferably consists

heterocycloalkyl

Prior art date

2006-06-13

Links

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• 150000003839 salts Chemical class 0.000 title claims abstract description 23
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 16
• 238000002360 preparation method Methods 0.000 title claims description 136
• MJEPPEQNLZSPAP-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridin-3-amine Chemical class C1=CN=C2C(N)=NNC2=C1 MJEPPEQNLZSPAP-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 210
• 238000000034 method Methods 0.000 claims abstract description 82
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 69
• 201000010099 disease Diseases 0.000 claims abstract description 68
• 238000011282 treatment Methods 0.000 claims abstract description 35
• 230000006444 vascular growth Effects 0.000 claims abstract description 26
• 238000004519 manufacturing process Methods 0.000 claims abstract description 3
• -1 hydroxy, amino Chemical group 0.000 claims description 252
• 229910052739 hydrogen Inorganic materials 0.000 claims description 206
• 239000001257 hydrogen Substances 0.000 claims description 201
• 150000002431 hydrogen Chemical class 0.000 claims description 140
• 238000006243 chemical reaction Methods 0.000 claims description 123
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 99
• 229910052736 halogen Inorganic materials 0.000 claims description 89
• 150000002367 halogens Chemical class 0.000 claims description 88
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 71
• 239000004202 carbamide Substances 0.000 claims description 61
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 58
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 55
• 206010028980 Neoplasm Diseases 0.000 claims description 38
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 38
• 125000003118 aryl group Chemical group 0.000 claims description 35
• 230000033115 angiogenesis Effects 0.000 claims description 32
• 229910052760 oxygen Inorganic materials 0.000 claims description 32
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
• 239000001301 oxygen Substances 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 29
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 28
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
• 125000001072 heteroaryl group Chemical group 0.000 claims description 27
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 25
• 239000002253 acid Substances 0.000 claims description 25
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 23
• 150000001412 amines Chemical class 0.000 claims description 23
• 239000000460 chlorine Substances 0.000 claims description 22
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 229910052801 chlorine Inorganic materials 0.000 claims description 19
• 229910052731 fluorine Inorganic materials 0.000 claims description 16
• 206010030113 Oedema Diseases 0.000 claims description 15
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
• 125000005549 heteroarylene group Chemical group 0.000 claims description 10
• 208000027866 inflammatory disease Diseases 0.000 claims description 10
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
• 201000004681 Psoriasis Diseases 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 230000001419 dependent effect Effects 0.000 claims description 9
• 150000002429 hydrazines Chemical class 0.000 claims description 9
• 239000012948 isocyanate Substances 0.000 claims description 9
• 150000002513 isocyanates Chemical class 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 239000011593 sulfur Substances 0.000 claims description 9
• 206010027476 Metastases Diseases 0.000 claims description 8
• 125000000732 arylene group Chemical group 0.000 claims description 8
• 125000004429 atom Chemical group 0.000 claims description 8
• 125000004494 ethyl ester group Chemical group 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• 125000001153 fluoro group Chemical group F* 0.000 claims description 8
• 208000014674 injury Diseases 0.000 claims description 8
• 230000008733 trauma Effects 0.000 claims description 8
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 8
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
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• 208000006673 asthma Diseases 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
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• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 208000037803 restenosis Diseases 0.000 claims description 7
• 230000036573 scar formation Effects 0.000 claims description 7
• 150000001204 N-oxides Chemical class 0.000 claims description 6
• 208000022873 Ocular disease Diseases 0.000 claims description 6
• 208000017442 Retinal disease Diseases 0.000 claims description 6
• 206010038923 Retinopathy Diseases 0.000 claims description 6
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• 201000009273 Endometriosis Diseases 0.000 claims description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
• 208000019693 Lung disease Diseases 0.000 claims description 5
• 208000001344 Macular Edema Diseases 0.000 claims description 5
• 206010025415 Macular oedema Diseases 0.000 claims description 5
• 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 claims description 5
• 206010055870 Postmenopausal haemorrhage Diseases 0.000 claims description 5
• 206010037423 Pulmonary oedema Diseases 0.000 claims description 5
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
• 125000002947 alkylene group Chemical group 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 230000009615 deamination Effects 0.000 claims description 5
• 238000006481 deamination reaction Methods 0.000 claims description 5
• 208000037824 growth disorder Diseases 0.000 claims description 5
• 201000010230 macular retinal edema Diseases 0.000 claims description 5
• 210000005036 nerve Anatomy 0.000 claims description 5
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 5
• 201000011461 pre-eclampsia Diseases 0.000 claims description 5
• 230000002062 proliferating effect Effects 0.000 claims description 5
• 208000005333 pulmonary edema Diseases 0.000 claims description 5
• 230000008929 regeneration Effects 0.000 claims description 5
• 238000011069 regeneration method Methods 0.000 claims description 5
• 208000006386 Bone Resorption Diseases 0.000 claims description 4
• 206010048962 Brain oedema Diseases 0.000 claims description 4
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
• 230000024279 bone resorption Effects 0.000 claims description 4
• 208000006752 brain edema Diseases 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
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• 229910052740 iodine Inorganic materials 0.000 claims description 4
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• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
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• 210000001367 artery Anatomy 0.000 claims description 3
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• 229940047889 isobutyramide Drugs 0.000 claims description 3
• 230000009401 metastasis Effects 0.000 claims description 3
• 230000002093 peripheral effect Effects 0.000 claims description 3
• SROYUQLUYMEPGP-UHFFFAOYSA-N 1-[4-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[2-fluoro-3-(trifluoromethyl)phenyl]urea Chemical compound C=12C=NN(C)C2=NC(C)=CC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CC(C(F)(F)F)=C1F SROYUQLUYMEPGP-UHFFFAOYSA-N 0.000 claims description 2
• BYBSGHVXSJFZCS-UHFFFAOYSA-N 1-[4-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-phenylurea Chemical compound C=12C=NN(C)C2=NC(C)=CC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 BYBSGHVXSJFZCS-UHFFFAOYSA-N 0.000 claims description 2
• PCLDEOPUBVOTMW-UHFFFAOYSA-N 1-[4-[1-methyl-6-(morpholin-4-ylmethyl)pyrazolo[3,4-b]pyridin-4-yl]phenyl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C=2C=3C=NN(C)C=3N=C(CN3CCOCC3)C=2)=C1 PCLDEOPUBVOTMW-UHFFFAOYSA-N 0.000 claims description 2
• WLWUADABAAOKCE-UHFFFAOYSA-N 1-[4-[1-methyl-6-(morpholin-4-ylmethyl)pyrazolo[3,4-b]pyridin-4-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(C)N=CC2=C(C=2C=CC(NC(=O)NC=3C=CC=CC=3)=CC=2)C=C1CN1CCOCC1 WLWUADABAAOKCE-UHFFFAOYSA-N 0.000 claims description 2
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
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• 206010020718 hyperplasia Diseases 0.000 claims description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
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• 208000008445 altitude sickness Diseases 0.000 claims 2
• 238000006193 diazotization reaction Methods 0.000 claims 2
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 2
• 125000006456 halo alkyl cycloalkyl group Chemical group 0.000 claims 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
• MUXXBBUGTINDOI-UHFFFAOYSA-N 1-(2-fluoro-5-methylphenyl)-3-[4-(1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]urea Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)C=2C=3C=NN(C)C=3N=CC=2)=C1 MUXXBBUGTINDOI-UHFFFAOYSA-N 0.000 claims 1
• AJVQQDDBJULLHT-UHFFFAOYSA-N 1-(2-fluoro-5-methylphenyl)-3-[4-(1h-pyrazolo[3,4-b]pyridin-4-yl)phenyl]urea Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)C=2C=3C=NNC=3N=CC=2)=C1 AJVQQDDBJULLHT-UHFFFAOYSA-N 0.000 claims 1
• VABXSELRSOOYNM-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-(1h-pyrazolo[3,4-b]pyridin-4-yl)phenyl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(C=2C=3C=NNC=3N=CC=2)C=C1 VABXSELRSOOYNM-UHFFFAOYSA-N 0.000 claims 1
• MWEMKZUFOBTGSZ-UHFFFAOYSA-N 1-[4-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C=12C=NN(C)C2=NC(C)=CC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CC(C(F)(F)F)=C1 MWEMKZUFOBTGSZ-UHFFFAOYSA-N 0.000 claims 1
• XFNWQFGHTRDOQD-UHFFFAOYSA-N 1-[4-(1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C1=CN=C2N(C)N=CC2=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC(C(F)(F)F)=C1 XFNWQFGHTRDOQD-UHFFFAOYSA-N 0.000 claims 1
• VCBBDYQEYOVQBP-UHFFFAOYSA-N 1-[4-(1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-phenylurea Chemical compound C1=CN=C2N(C)N=CC2=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 VCBBDYQEYOVQBP-UHFFFAOYSA-N 0.000 claims 1
• UBXWQHJFLDNFNR-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(C=2C=CC(NC(=O)NC=3C=C(C=CC=3)C(F)(F)F)=CC=2)C=C1C1CCC1 UBXWQHJFLDNFNR-UHFFFAOYSA-N 0.000 claims 1
• QMUABAXRSAMJOL-UHFFFAOYSA-N 1-[4-(6-cyclohexyl-1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(C=2C=CC(NC(=O)NC=3C=C(C=CC=3)C(F)(F)F)=CC=2)C=C1C1CCCCC1 QMUABAXRSAMJOL-UHFFFAOYSA-N 0.000 claims 1
• HRJAFLDQXNTASV-UHFFFAOYSA-N 1-[4-(6-cyclopropyl-1-methylpyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(C=2C=CC(NC(=O)NC=3C=C(C=CC=3)C(F)(F)F)=CC=2)C=C1C1CC1 HRJAFLDQXNTASV-UHFFFAOYSA-N 0.000 claims 1
• FDNGYLCQEAECIB-UHFFFAOYSA-N 1-[4-(6-tert-butyl-1h-pyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-(2-methylphenyl)urea Chemical compound CC1=CC=CC=C1NC(=O)NC1=CC=C(C=2C=3C=NNC=3N=C(C=2)C(C)(C)C)C=C1 FDNGYLCQEAECIB-UHFFFAOYSA-N 0.000 claims 1
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