CA2665083A1 - Mglur5 modulators - Google Patents
Mglur5 modulators Download PDFInfo
- Publication number
- CA2665083A1 CA2665083A1 CA002665083A CA2665083A CA2665083A1 CA 2665083 A1 CA2665083 A1 CA 2665083A1 CA 002665083 A CA002665083 A CA 002665083A CA 2665083 A CA2665083 A CA 2665083A CA 2665083 A1 CA2665083 A1 CA 2665083A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- triazol
- ethoxy
- compound according
- pyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 101150087728 Grm5 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 220
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 10
- 238000011282 treatment Methods 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 19
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 17
- 230000002265 prevention Effects 0.000 claims description 17
- 210000000111 lower esophageal sphincter Anatomy 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000002193 Pain Diseases 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 230000036407 pain Effects 0.000 claims description 7
- 230000001052 transient effect Effects 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 230000003287 optical effect Effects 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 230000036506 anxiety Effects 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
- 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 description 3
- 108010029485 Protein Isoforms Proteins 0.000 claims description 3
- 102000001708 Protein Isoforms Human genes 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
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- 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 description 2
- 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 description 2
- 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 description 2
- JHJGFOZHTWQUDS-UHFFFAOYSA-N 2-methoxy-4-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyridine Chemical compound C1=NC(OC)=CC(C=2N(C(SC)=NN=2)C)=C1 JHJGFOZHTWQUDS-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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
- 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 description 2
- 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 description 2
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- 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 description 2
- 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 description 2
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- TYRVSFQDVZAMBW-GFCCVEGCSA-N 4-[5-[(1r)-1-[5-(3-chlorophenyl)-1,2-oxazol-3-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-1-methylpyridin-2-one Chemical compound O([C@H](C)C1=NOC(=C1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C=1C=CN(C)C(=O)C=1 TYRVSFQDVZAMBW-GFCCVEGCSA-N 0.000 claims description 2
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- WUPDUHQGDYEYAJ-UHFFFAOYSA-N 5-(3-chlorophenyl)-3-[1-[[4-methyl-5-(2-phenylmethoxypyridin-4-yl)-1,2,4-triazol-3-yl]oxy]ethyl]-1,2-oxazole Chemical compound C1=C(C=2C=C(Cl)C=CC=2)ON=C1C(C)OC(N1C)=NN=C1C(C=1)=CC=NC=1OCC1=CC=CC=C1 WUPDUHQGDYEYAJ-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
- 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 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
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
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- NKTIPELEHVFXSE-SNVBAGLBSA-N 4-[5-[(1r)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]-1h-pyridin-2-one Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C=1C=CNC(=O)C=1 NKTIPELEHVFXSE-SNVBAGLBSA-N 0.000 claims 1
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- 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
- JZCJAGQBCYZIIE-UHFFFAOYSA-N 5-[4-methyl-5-[1-[5-(3-methylphenyl)-1,2-oxazol-3-yl]ethoxy]-1,2,4-triazol-3-yl]-2-(2-trimethylsilylethoxymethyl)pyridazin-3-one Chemical compound C1=C(C=2C=C(C)C=CC=2)ON=C1C(C)OC(N1C)=NN=C1C=1C=NN(COCC[Si](C)(C)C)C(=O)C=1 JZCJAGQBCYZIIE-UHFFFAOYSA-N 0.000 claims 1
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| WO2012058128A2 (en) * | 2010-10-28 | 2012-05-03 | Merck Sharp & Dohme Corp. | Caprolactam mglur5 receptor modulators |
| US8703946B2 (en) | 2010-12-08 | 2014-04-22 | Vanderbilt University | Substituted pyrazolo[1,5-A]pyrazine compounds as allosteric modulators of mGluR5 receptors |
| EP2651222A4 (en) * | 2010-12-17 | 2014-04-30 | Univ Vanderbilt | BICYCLIC TRIAZOL AND PYRAZOLLACTAME AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS |
| US8471027B2 (en) | 2011-04-06 | 2013-06-25 | Hoffmann-La Roche Inc. | Adamantyl compounds |
| EP2857387A1 (en) | 2013-10-07 | 2015-04-08 | Boehringer Ingelheim International Gmbh | Process for manufacturing 1,6-dihydro-6-oxo-4-pyridazine carboxylic acid |
| EP3486235A4 (en) * | 2016-07-15 | 2020-02-12 | Oriental (Luzhou) Agrochemicals. Co., Ltd. | SYNTHETIC METHOD FOR 1,2,4-TRIAZOLE-3-THION COMPOUND AND INTERMEDIATE PRODUCT THEREOF |
| US12435078B2 (en) | 2017-09-18 | 2025-10-07 | Gfb (Abc), Llc | Pyridazinones and methods of use thereof |
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| AU2007303889A2 (en) | 2010-07-15 |
| NZ575657A (en) | 2011-03-31 |
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| RU2009111113A (ru) | 2010-11-10 |
| IL197722A0 (en) | 2009-12-24 |
| BRPI0719155A2 (pt) | 2014-02-04 |
| KR20090060328A (ko) | 2009-06-11 |
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| WO2008041075A1 (en) | 2008-04-10 |
| RU2439068C2 (ru) | 2012-01-10 |
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| TW200821305A (en) | 2008-05-16 |
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| AU2007303889A1 (en) | 2008-04-10 |
| AR062965A1 (es) | 2008-12-17 |
| CO6220935A2 (es) | 2010-11-19 |
| EP2079730A1 (en) | 2009-07-22 |
| PE20081378A1 (es) | 2008-11-12 |
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