MXPA04011404A - Procedimientos para el tratamiento de enfermedades y afecciones respiratorias usando un inhibidor selectivo de inos. - Google Patents

Info

Publication number

MXPA04011404A

MXPA04011404A MXPA04011404A MXPA04011404A MXPA04011404A MX PA04011404 A MXPA04011404 A MX PA04011404A MX PA04011404 A MXPA04011404 A MX PA04011404A MX PA04011404 A MXPA04011404 A MX PA04011404A MX PA04011404 A MXPA04011404 A MX PA04011404A

Authority

MX

Mexico

Prior art keywords

alkyl

optionally substituted

group

amino

halo

Prior art date

2002-05-16

Links

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• Global Dossier
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• 208000023504 respiratory system disease Diseases 0.000 title claims abstract description 18
• 239000003112 inhibitor Substances 0.000 title claims description 41
• 238000000034 method Methods 0.000 title abstract description 54
• 238000011282 treatment Methods 0.000 title abstract description 21
• 101100396994 Drosophila melanogaster Inos gene Proteins 0.000 title 1
• 229940124639 Selective inhibitor Drugs 0.000 claims abstract description 18
• 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims abstract description 14
• 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims abstract description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 168
• -1 heteroaralkoxy Chemical group 0.000 claims description 154
• 125000005843 halogen group Chemical group 0.000 claims description 151
• 125000003545 alkoxy group Chemical group 0.000 claims description 140
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 110
• 238000006243 chemical reaction Methods 0.000 claims description 107
• 229910052739 hydrogen Inorganic materials 0.000 claims description 100
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 94
• 150000001875 compounds Chemical class 0.000 claims description 87
• 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 82
• 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 82
• 239000001257 hydrogen Substances 0.000 claims description 79
• 208000006673 asthma Diseases 0.000 claims description 76
• 150000002431 hydrogen Chemical group 0.000 claims description 69
• 125000000623 heterocyclic group Chemical group 0.000 claims description 58
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 55
• 150000003839 salts Chemical class 0.000 claims description 53
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 48
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
• 125000003118 aryl group Chemical group 0.000 claims description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 206010006451 bronchitis Diseases 0.000 claims description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 125000001072 heteroaryl group Chemical group 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 230000000241 respiratory effect Effects 0.000 claims description 24
• 125000003107 substituted aryl group Chemical group 0.000 claims description 24
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• 125000001188 haloalkyl group Chemical group 0.000 claims description 22
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 150000002367 halogens Chemical class 0.000 claims description 18
• 239000004201 L-cysteine Substances 0.000 claims description 17
• 125000004429 atom Chemical group 0.000 claims description 17
• 125000000304 alkynyl group Chemical group 0.000 claims description 16
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 15
• 206010061218 Inflammation Diseases 0.000 claims description 15
• 230000004054 inflammatory process Effects 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
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• 210000004072 lung Anatomy 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
• 230000001684 chronic effect Effects 0.000 claims description 11
• 206010014561 Emphysema Diseases 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 125000004414 alkyl thio group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 9
• 239000013566 allergen Substances 0.000 claims description 9
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
• 125000004442 acylamino group Chemical group 0.000 claims description 8
• 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 8
• 125000004104 aryloxy group Chemical group 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 241000700605 Viruses Species 0.000 claims description 7
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
• 206010003557 Asthma exercise induced Diseases 0.000 claims description 6
• 208000004657 Exercise-Induced Asthma Diseases 0.000 claims description 6
• 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 6
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• 230000001939 inductive effect Effects 0.000 claims description 6
• 150000004684 trihydrates Chemical class 0.000 claims description 6
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 5
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 5
• 206010035664 Pneumonia Diseases 0.000 claims description 5
• 206010040047 Sepsis Diseases 0.000 claims description 5
• 125000001589 carboacyl group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
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• 208000011580 syndromic disease Diseases 0.000 claims description 5
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
• RFEBDZANCVHDLP-UHFFFAOYSA-N 3-[(4-cyanophenyl)methylamino]-6-(trifluoromethyl)quinoxaline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=C(C(F)(F)F)C=C2N=C1NCC1=CC=C(C#N)C=C1 RFEBDZANCVHDLP-UHFFFAOYSA-N 0.000 claims description 4
• 208000010444 Acidosis Diseases 0.000 claims description 4
• 206010001029 Acute pulmonary oedema Diseases 0.000 claims description 4
• 208000035939 Alveolitis allergic Diseases 0.000 claims description 4
• 241000272201 Columbiformes Species 0.000 claims description 4
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• 208000003241 Fat Embolism Diseases 0.000 claims description 4
• 206010021143 Hypoxia Diseases 0.000 claims description 4
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 230000007950 acidosis Effects 0.000 claims description 4
• 208000026545 acidosis disease Diseases 0.000 claims description 4
• 125000002252 acyl group Chemical group 0.000 claims description 4
• 125000005354 acylalkyl group Chemical group 0.000 claims description 4
• 125000004423 acyloxy group Chemical group 0.000 claims description 4
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
• 125000005466 alkylenyl group Chemical group 0.000 claims description 4
• 125000000539 amino acid group Chemical group 0.000 claims description 4
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
• 125000003435 aroyl group Chemical group 0.000 claims description 4
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 4
• 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 4
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
• 125000001769 aryl amino group Chemical group 0.000 claims description 4
• 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 4
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
• 125000005421 aryl sulfonamido group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 4
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
• 238000007675 cardiac surgery Methods 0.000 claims description 4
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
• 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 208000022195 farmer lung disease Diseases 0.000 claims description 4
• 125000004967 formylalkyl group Chemical group 0.000 claims description 4
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 4
• 125000004995 haloalkylthio group Chemical group 0.000 claims description 4
• 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 4
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 4
• 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 4
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 4
• 230000007954 hypoxia Effects 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
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• 208000004594 persistent fetal circulation syndrome Diseases 0.000 claims description 4
• 239000000651 prodrug Substances 0.000 claims description 4
• 229940002612 prodrug Drugs 0.000 claims description 4
• 229940048914 protamine Drugs 0.000 claims description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims description 4
• KAXFOSOXUNYWRV-CAHLUQPWSA-N (2s)-2-amino-3-[(2s)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-CAHLUQPWSA-N 0.000 claims description 3
• VQGCWTDMOOOHCH-PFPYCLJUSA-N (z,2s)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C\CC[C@H](N)C(O)=O VQGCWTDMOOOHCH-PFPYCLJUSA-N 0.000 claims description 3
• 150000004683 dihydrates Chemical class 0.000 claims description 3
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
• KAXFOSOXUNYWRV-IYSWYEEDSA-N (2s)-2-amino-3-[(2r)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-IYSWYEEDSA-N 0.000 claims description 2
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
• ZLBLGYXDADNGOG-DKCNVOGISA-N (e,2s)-2-amino-6-fluoro-7-[1-(hydroxyamino)ethylideneamino]hept-5-enoic acid Chemical compound ON=C(C)NC\C(F)=C/CC[C@H](N)C(O)=O ZLBLGYXDADNGOG-DKCNVOGISA-N 0.000 claims description 2
• LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 2
• 206010003504 Aspiration Diseases 0.000 claims description 2
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 2
• 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 2
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• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 201000004193 respiratory failure Diseases 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 13
• 229940119568 Inducible nitric oxide synthase inhibitor Drugs 0.000 claims 12
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 2
• LOBRQMHOHPDZKT-JZGIKJSDSA-N (2r)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfonyl]-2-methylpropanoic acid;dihydrochloride Chemical compound Cl.Cl.CC(=N)NCCS(=O)(=O)C[C@](C)(N)C(O)=O LOBRQMHOHPDZKT-JZGIKJSDSA-N 0.000 claims 1
• CRCVUETYUUMUHJ-GQBYOYERSA-N (E,2R)-2-amino-6-(1-aminoethylideneamino)-2-methylhex-4-enoic acid dihydrochloride Chemical compound Cl.Cl.N[C@@](C(=O)O)(C\C=C\CNC(C)=N)C CRCVUETYUUMUHJ-GQBYOYERSA-N 0.000 claims 1
• ITXXZGPTRJMLEV-FBKVPIMCSA-N (E,2R)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid dihydrochloride Chemical compound CC(=NC/C(=C\CC[C@H](C(=O)O)N)/F)N.Cl.Cl ITXXZGPTRJMLEV-FBKVPIMCSA-N 0.000 claims 1
• ITXXZGPTRJMLEV-BZOMEDCHSA-N (E,2S)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid dihydrochloride Chemical compound Cl.Cl.N[C@H](C(=O)O)CC\C=C(/CNC(C)=N)\F ITXXZGPTRJMLEV-BZOMEDCHSA-N 0.000 claims 1
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