BRPI0719155A2 - Composto, composição farmacêutica, uso de um composto, e, métodos para a inibição de relaxamento do esfíncter esofágico inferior transitórios e para o tratamento ou prevenção da doença do refluxo gastroesofágico, da dor, da ansiedade e da síndrome do intestino irritável. - Google Patents

Info

Publication number

BRPI0719155A2

BRPI0719155A2 BRPI0719155-3A BRPI0719155A BRPI0719155A2 BR PI0719155 A2 BRPI0719155 A2 BR PI0719155A2 BR PI0719155 A BRPI0719155 A BR PI0719155A BR PI0719155 A2 BRPI0719155 A2 BR PI0719155A2

Authority

BR

Brazil

Prior art keywords

methyl

triazol

ethoxy

compound

pyridin

Prior art date

2006-10-05

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims description 217
• 238000000034 method Methods 0.000 title claims description 43
• 238000011282 treatment Methods 0.000 title claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 26
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
• 238000010992 reflux Methods 0.000 title claims description 11
• 230000002265 prevention Effects 0.000 title claims description 10
• 230000002401 inhibitory effect Effects 0.000 title claims description 8
• 201000010099 disease Diseases 0.000 title claims description 6
• 238000003745 diagnosis Methods 0.000 title description 5
• 208000018035 Dental disease Diseases 0.000 title 1
• 208000014151 Stomatognathic disease Diseases 0.000 title 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 107
• -1 4H-1,2,4-triazol-3-yl Chemical group 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 40
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 21
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 18
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 239000000460 chlorine Substances 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical group 0.000 claims description 12
• 208000002193 Pain Diseases 0.000 claims description 10
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 10
• 210000000111 lower esophageal sphincter Anatomy 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
• 230000036407 pain Effects 0.000 claims description 7
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 6
• 125000001188 haloalkyl group Chemical group 0.000 claims description 6
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
• 230000003287 optical effect Effects 0.000 claims description 6
• 230000001052 transient effect Effects 0.000 claims description 6
• 239000004480 active ingredient Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 229910052731 fluorine Chemical group 0.000 claims description 5
• 230000005764 inhibitory process Effects 0.000 claims description 5
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
• 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 5
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims description 4
• 208000019901 Anxiety disease Diseases 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
• 230000036506 anxiety Effects 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 239000011737 fluorine Chemical group 0.000 claims description 4
• 108010029485 Protein Isoforms Proteins 0.000 claims description 3
• 102000001708 Protein Isoforms Human genes 0.000 claims description 3
• YIPORKHUENVACK-UHFFFAOYSA-N 2-oxo-1-(2-trimethylsilylethoxymethyl)pyridine-4-carbohydrazide Chemical compound C[Si](C)(C)CCOCN1C=CC(C(=O)NN)=CC1=O YIPORKHUENVACK-UHFFFAOYSA-N 0.000 claims description 2
• OPADHMIOKMGTAZ-UHFFFAOYSA-N 5-(3-methylphenyl)-1,2-oxazole-3-carbaldehyde Chemical compound CC1=CC=CC(C=2ON=C(C=O)C=2)=C1 OPADHMIOKMGTAZ-UHFFFAOYSA-N 0.000 claims description 2
• QJVBPSHLWUDCBS-UHFFFAOYSA-N ethyl 2-oxo-1-(2-trimethylsilylethoxymethyl)pyridine-4-carboxylate Chemical compound CCOC(=O)C=1C=CN(COCC[Si](C)(C)C)C(=O)C=1 QJVBPSHLWUDCBS-UHFFFAOYSA-N 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• NQBOKVREWGZKJU-MRVPVSSYSA-N (1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethanol Chemical compound N1=C([C@H](O)C)N=NN1C1=CC=CC(C)=C1 NQBOKVREWGZKJU-MRVPVSSYSA-N 0.000 claims 1
• MOXKXNZAWFECME-SECBINFHSA-N (1r)-1-[5-(3-methylphenyl)-1,2-oxazol-3-yl]ethanol Chemical compound O1N=C([C@H](O)C)C=C1C1=CC=CC(C)=C1 MOXKXNZAWFECME-SECBINFHSA-N 0.000 claims 1
• BGBUSNJDAHNJOH-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)tetrazol-5-yl]ethanone Chemical compound N1=C(C(=O)C)N=NN1C1=CC=CC(Cl)=C1 BGBUSNJDAHNJOH-UHFFFAOYSA-N 0.000 claims 1
• MOXKXNZAWFECME-UHFFFAOYSA-N 1-[5-(3-methylphenyl)-1,2-oxazol-3-yl]ethanol Chemical compound O1N=C(C(O)C)C=C1C1=CC=CC(C)=C1 MOXKXNZAWFECME-UHFFFAOYSA-N 0.000 claims 1
• XOXMZXVWQRVRSA-UHFFFAOYSA-N 1-methyl-4-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyridin-2-one Chemical compound CN1C(SC)=NN=C1C1=CC(=O)N(C)C=C1 XOXMZXVWQRVRSA-UHFFFAOYSA-N 0.000 claims 1
• FCVJZDCOFMWIKT-UHFFFAOYSA-N 1-methyl-4-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)pyridin-2-one Chemical compound N1=C(S(C)(=O)=O)N(C)C(C2=CC(=O)N(C)C=C2)=N1 FCVJZDCOFMWIKT-UHFFFAOYSA-N 0.000 claims 1
• RBQVBOKRFWGLOH-UHFFFAOYSA-N 2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound C[Si](C)(C)CCOCN1N=CC=CC1=O RBQVBOKRFWGLOH-UHFFFAOYSA-N 0.000 claims 1
• XAKCXLMMOPJCIS-UHFFFAOYSA-N 2-methoxy-4-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)pyridine Chemical compound C1=NC(OC)=CC(C=2N(C(=NN=2)S(C)(=O)=O)C)=C1 XAKCXLMMOPJCIS-UHFFFAOYSA-N 0.000 claims 1
• CEYSPSIHSYJOCT-UHFFFAOYSA-N 3-(2-methoxypyridin-4-yl)-4-methyl-1h-1,2,4-triazole-5-thione Chemical compound C1=NC(OC)=CC(C=2N(C(S)=NN=2)C)=C1 CEYSPSIHSYJOCT-UHFFFAOYSA-N 0.000 claims 1
• XUQSZCBVPRMQRJ-UHFFFAOYSA-N 4-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)-1-(2-trimethylsilylethoxymethyl)pyridin-2-one Chemical compound CN1C(SC)=NN=C1C1=CC(=O)N(COCC[Si](C)(C)C)C=C1 XUQSZCBVPRMQRJ-UHFFFAOYSA-N 0.000 claims 1
• BMYBHKLAZPHMAP-UHFFFAOYSA-N 4-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)-1h-pyridin-2-one Chemical compound N1=C(S(C)(=O)=O)N(C)C(C2=CC(=O)NC=C2)=N1 BMYBHKLAZPHMAP-UHFFFAOYSA-N 0.000 claims 1
• QWWDUYBNUCKRGC-UHFFFAOYSA-N 4-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)-2-phenylmethoxypyridine Chemical compound N1=C(S(C)(=O)=O)N(C)C(C=2C=C(OCC=3C=CC=CC=3)N=CC=2)=N1 QWWDUYBNUCKRGC-UHFFFAOYSA-N 0.000 claims 1
• XJSVMNXUSRGOOH-UHFFFAOYSA-N 4-(4-methyl-5-sulfanylidene-1h-1,2,4-triazol-3-yl)-1-(2-trimethylsilylethoxymethyl)pyridin-2-one Chemical compound CN1C(S)=NN=C1C1=CC(=O)N(COCC[Si](C)(C)C)C=C1 XJSVMNXUSRGOOH-UHFFFAOYSA-N 0.000 claims 1
• UBBUIIAEFUPFIG-LLVKDONJSA-N 4-[4-methyl-5-[(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]-1h-pyridazin-6-one Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(C)C=CC=1)C(N1C)=NN=C1C=1C=NNC(=O)C=1 UBBUIIAEFUPFIG-LLVKDONJSA-N 0.000 claims 1
• IWNKYSQGZHRHNW-SNVBAGLBSA-N 4-[5-[(1r)-1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-1h-pyridazin-6-one Chemical compound O([C@H](C)C1=NOC(=C1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C=1C=NNC(=O)C=1 IWNKYSQGZHRHNW-SNVBAGLBSA-N 0.000 claims 1
• YGGDHMSWIMDIPD-LLVKDONJSA-N 4-[5-[(1r)-1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-1h-pyridin-2-one Chemical compound O([C@H](C)C1=NOC(=C1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C=1C=CNC(=O)C=1 YGGDHMSWIMDIPD-LLVKDONJSA-N 0.000 claims 1
• YGGDHMSWIMDIPD-UHFFFAOYSA-N 4-[5-[1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-1h-pyridin-2-one Chemical compound C1=C(C=2C=C(Cl)C=CC=2)ON=C1C(C)OC(N1C)=NN=C1C=1C=CNC(=O)C=1 YGGDHMSWIMDIPD-UHFFFAOYSA-N 0.000 claims 1
• UUPRDNMOMBWQCQ-UHFFFAOYSA-N 4-[5-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]methoxy]-4-methyl-1,2,4-triazol-3-yl]-1h-pyridin-2-one Chemical compound N=1N=C(C2=CC(=O)NC=C2)N(C)C=1OCC(=NO1)C=C1C1=CC=CC(Cl)=C1 UUPRDNMOMBWQCQ-UHFFFAOYSA-N 0.000 claims 1
• WUPDUHQGDYEYAJ-QGZVFWFLSA-N 5-(3-chlorophenyl)-3-[(1r)-1-[[4-methyl-5-(2-phenylmethoxypyridin-4-yl)-1,2,4-triazol-3-yl]oxy]ethyl]-1,2-oxazole Chemical compound O([C@H](C)C1=NOC(=C1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C(C=1)=CC=NC=1OCC1=CC=CC=C1 WUPDUHQGDYEYAJ-QGZVFWFLSA-N 0.000 claims 1
• CVBHPUUMGPIEAI-UHFFFAOYSA-N 5-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)-2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound CN1C(SC)=NN=C1C1=CC(=O)N(COCC[Si](C)(C)C)N=C1 CVBHPUUMGPIEAI-UHFFFAOYSA-N 0.000 claims 1
• KGSBBPYZHOLCIO-UHFFFAOYSA-N 5-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)-2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound N1=C(S(C)(=O)=O)N(C)C(C2=CC(=O)N(COCC[Si](C)(C)C)N=C2)=N1 KGSBBPYZHOLCIO-UHFFFAOYSA-N 0.000 claims 1
• FJYMHPBYZFTMPZ-UHFFFAOYSA-N 5-[4-methyl-5-[1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]-2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound N1=NN(C=2C=C(C)C=CC=2)N=C1C(C)OC(N1C)=NN=C1C=1C=NN(COCC[Si](C)(C)C)C(=O)C=1 FJYMHPBYZFTMPZ-UHFFFAOYSA-N 0.000 claims 1
• VFPYYCGBLZHPLK-UHFFFAOYSA-N 5-[5-[1-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound N=1OC(C=2C=C(Cl)C=CC=2)=NC=1C(C)OC(N1C)=NN=C1C=1C=NN(COCC[Si](C)(C)C)C(=O)C=1 VFPYYCGBLZHPLK-UHFFFAOYSA-N 0.000 claims 1
• XQJZSOSJQLTTAB-UHFFFAOYSA-N 6-oxo-1-(2-trimethylsilylethoxymethyl)pyridazine-4-carbohydrazide Chemical compound C[Si](C)(C)CCOCN1N=CC(C(=O)NN)=CC1=O XQJZSOSJQLTTAB-UHFFFAOYSA-N 0.000 claims 1
• HFAKLRWDIHVCSP-SECBINFHSA-N [(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethyl] acetate Chemical compound N1=C([C@H](OC(C)=O)C)N=NN1C1=CC=CC(C)=C1 HFAKLRWDIHVCSP-SECBINFHSA-N 0.000 claims 1
• WBNLDAGDJAGFGF-UHFFFAOYSA-N ethyl 6-oxo-1-(2-trimethylsilylethoxymethyl)pyridazine-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(COCC[Si](C)(C)C)C(=O)C=1 WBNLDAGDJAGFGF-UHFFFAOYSA-N 0.000 claims 1
• LTLTWPKMZBCLFK-UHFFFAOYSA-N methyl 5-(3-methylphenyl)-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OC)C=C1C1=CC=CC(C)=C1 LTLTWPKMZBCLFK-UHFFFAOYSA-N 0.000 claims 1
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