IL122540A - History 1, 4 - Benzodioxane - 2 '- methyl methyl carboxamide, their preparation and pharmaceutical preparations containing them - Google Patents
History 1, 4 - Benzodioxane - 2 '- methyl methyl carboxamide, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL122540A IL122540A IL12254096A IL12254096A IL122540A IL 122540 A IL122540 A IL 122540A IL 12254096 A IL12254096 A IL 12254096A IL 12254096 A IL12254096 A IL 12254096A IL 122540 A IL122540 A IL 122540A
- Authority
- IL
- Israel
- Prior art keywords
- carbon atoms
- benzodioxan
- carboxamide
- methyl
- ylmethyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 title description 8
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 282
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 118
- -1 carbamoylmethyl group Chemical group 0.000 claims abstract description 68
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 56
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000003277 amino group Chemical group 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 361
- 239000000203 mixture Substances 0.000 claims description 257
- 239000002904 solvent Substances 0.000 claims description 231
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 106
- 238000006243 chemical reaction Methods 0.000 claims description 104
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 96
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 89
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 74
- 239000011570 nicotinamide Substances 0.000 claims description 64
- 235000005152 nicotinamide Nutrition 0.000 claims description 60
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 48
- 125000005843 halogen group Chemical group 0.000 claims description 46
- 150000003857 carboxamides Chemical class 0.000 claims description 21
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
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- 206010020772 Hypertension Diseases 0.000 claims description 10
- 206010033664 Panic attack Diseases 0.000 claims description 10
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 10
- 208000028017 Psychotic disease Diseases 0.000 claims description 10
- 206010041250 Social phobia Diseases 0.000 claims description 10
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 10
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 10
- 208000016620 Tourette disease Diseases 0.000 claims description 10
- 230000036506 anxiety Effects 0.000 claims description 10
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 10
- 208000019906 panic disease Diseases 0.000 claims description 10
- 201000004240 prostatic hypertrophy Diseases 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- 241000282414 Homo sapiens Species 0.000 claims description 9
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- UKWJJTFMNCHNHR-UHFFFAOYSA-N 2-amino-n-[[1-[[5-(trifluoromethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound NC1=NC=CC=C1C(=O)NCC1CCN(CC2OC3=C(C=CC=C3OC2)C(F)(F)F)CC1 UKWJJTFMNCHNHR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- FNDHZDNNKBZQJM-UHFFFAOYSA-N 2-methylsulfanyl-n-[[1-[[5-(trifluoromethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound CSC1=NC=CC=C1C(=O)NCC1CCN(CC2OC3=C(C=CC=C3OC2)C(F)(F)F)CC1 FNDHZDNNKBZQJM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 2
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- KXMLVDNWVOQZHR-UHFFFAOYSA-N n-[[1-[(5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound O1C=2C(Cl)=CC=CC=2OCC1CN(CC1)CCC1CNC(=O)C1=CC=CN=C1 KXMLVDNWVOQZHR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- DBMHTLOVZSDLFD-UHFFFAOYSA-N piperidin-1-ylmethanamine Chemical compound NCN1CCCCC1 DBMHTLOVZSDLFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- STWNGMSGPBZFMX-UHFFFAOYSA-N pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.NC(=O)C1=CC=CN=C1 STWNGMSGPBZFMX-UHFFFAOYSA-N 0.000 claims 4
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- YDYXNHSKBIZKFD-UHFFFAOYSA-N 2-methylsulfanylpyridine-3-carboxamide Chemical compound CSC1=NC=CC=C1C(N)=O YDYXNHSKBIZKFD-UHFFFAOYSA-N 0.000 claims 1
- OFPMLURSEFVZIN-UHFFFAOYSA-N 5-bromo-n-[[1-[(6-bromo-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound O1C2=CC(Br)=CC=C2OCC1CN(CC1)CCC1CNC(=O)C1=CN=CC(Br)=C1 OFPMLURSEFVZIN-UHFFFAOYSA-N 0.000 claims 1
- VRXALZRDQFUZKG-UHFFFAOYSA-N 6-pyrrol-1-yl-n-[[1-[[5-(trifluoromethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound O1C=2C(C(F)(F)F)=CC=CC=2OCC1CN(CC1)CCC1CNC(=O)C(C=N1)=CC=C1N1C=CC=C1 VRXALZRDQFUZKG-UHFFFAOYSA-N 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- IAPQPJRPOBZDNW-UHFFFAOYSA-N n-[[1-[(5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]-2-methylsulfanylpyridine-3-carboxamide Chemical compound CSC1=NC=CC=C1C(=O)NCC1CCN(CC2OC3=C(Cl)C=CC=C3OC2)CC1 IAPQPJRPOBZDNW-UHFFFAOYSA-N 0.000 claims 1
- KQBUKQALEBQTFL-UHFFFAOYSA-N n-[[1-[(5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]-6-pyrrol-1-ylpyridine-3-carboxamide Chemical compound O1C=2C(Cl)=CC=CC=2OCC1CN(CC1)CCC1CNC(=O)C(C=N1)=CC=C1N1C=CC=C1 KQBUKQALEBQTFL-UHFFFAOYSA-N 0.000 claims 1
- SJLGJRFOYYILTN-UHFFFAOYSA-N n-[[1-[(6-bromo-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]-2-methylsulfanylpyridine-3-carboxamide Chemical compound CSC1=NC=CC=C1C(=O)NCC1CCN(CC2OC3=CC(Br)=CC=C3OC2)CC1 SJLGJRFOYYILTN-UHFFFAOYSA-N 0.000 claims 1
- QBGQAEMEBMEYHW-UHFFFAOYSA-N n-[[1-[(6-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]-6-pyrrol-1-ylpyridine-3-carboxamide Chemical compound O1C2=CC(Cl)=CC=C2OCC1CN(CC1)CCC1CNC(=O)C(C=N1)=CC=C1N1C=CC=C1 QBGQAEMEBMEYHW-UHFFFAOYSA-N 0.000 claims 1
- MSKHWAXYESDGKT-UHFFFAOYSA-N n-[[1-[[5-(trifluoromethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidin-4-yl]methyl]pyridine-3-carboxamide Chemical compound O1C=2C(C(F)(F)F)=CC=CC=2OCC1CN(CC1)CCC1CNC(=O)C1=CC=CN=C1 MSKHWAXYESDGKT-UHFFFAOYSA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 abstract description 7
- 125000002541 furyl group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 239000003723 serotonin 1A agonist Substances 0.000 abstract 1
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- 239000000243 solution Substances 0.000 description 161
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 160
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
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- QFGIEMYZLHIGPV-UHFFFAOYSA-N n-[[1-[(6-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl]piperidin-4-yl]methyl]-2-methoxypyridine-3-carboxamide Chemical compound COC1=NC=CC=C1C(=O)NCC1CCN(CC2OC3=CC(Cl)=CC=C3OC2)CC1 QFGIEMYZLHIGPV-UHFFFAOYSA-N 0.000 description 1
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- PBKTXDGXABFTFS-KRWDZBQOSA-N n-[[1-[[(3s)-6-chloro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]piperidin-4-yl]methyl]pyridine-2-carboxamide Chemical compound C([C@H]1COC2=CC=C(C=C2O1)Cl)N(CC1)CCC1CNC(=O)C1=CC=CC=N1 PBKTXDGXABFTFS-KRWDZBQOSA-N 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
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- 239000012188 paraffin wax Substances 0.000 description 1
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- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
- 229950001675 spiperone Drugs 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229960004940 sulpiride Drugs 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- GGBOSIGOSXVBEF-UHFFFAOYSA-N tert-butyl 4-[(pyridine-2-carbonylamino)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)C1=CC=CC=N1 GGBOSIGOSXVBEF-UHFFFAOYSA-N 0.000 description 1
- NRMRVCISVRFNBC-UHFFFAOYSA-N tert-butyl 4-[(pyridine-3-carbonylamino)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)C1=CC=CN=C1 NRMRVCISVRFNBC-UHFFFAOYSA-N 0.000 description 1
- WXQYUMLDQSSLRJ-UHFFFAOYSA-N tert-butyl 4-[(quinoline-8-carbonylamino)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)C1=CC=CC2=CC=CN=C12 WXQYUMLDQSSLRJ-UHFFFAOYSA-N 0.000 description 1
- VRSXHQJRHIPOPU-UHFFFAOYSA-N tert-butyl 4-[[(3-aminothiophene-2-carbonyl)amino]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)C1=C(N)C=CS1 VRSXHQJRHIPOPU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9514380.6A GB9514380D0 (en) | 1995-07-13 | 1995-07-13 | Therapeutic agents |
| PCT/EP1996/002890 WO1997003071A1 (en) | 1995-07-13 | 1996-07-02 | Heterocyclylcarboxamide derivatives and their use as therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL122540A0 IL122540A0 (en) | 1998-06-15 |
| IL122540A true IL122540A (en) | 2001-10-31 |
Family
ID=10777626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12254096A IL122540A (en) | 1995-07-13 | 1996-07-02 | History 1, 4 - Benzodioxane - 2 '- methyl methyl carboxamide, their preparation and pharmaceutical preparations containing them |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US5935973A (pt) |
| EP (1) | EP0839145B1 (pt) |
| JP (1) | JPH11508599A (pt) |
| KR (1) | KR19990028918A (pt) |
| CN (1) | CN1071755C (pt) |
| AT (1) | ATE253573T1 (pt) |
| AU (1) | AU708890B2 (pt) |
| BG (1) | BG62771B1 (pt) |
| BR (1) | BR9609506A (pt) |
| CA (1) | CA2223472A1 (pt) |
| CZ (1) | CZ388497A3 (pt) |
| DE (1) | DE69630604T2 (pt) |
| GB (1) | GB9514380D0 (pt) |
| HR (1) | HRP960348A2 (pt) |
| HU (1) | HUP9901485A3 (pt) |
| IL (1) | IL122540A (pt) |
| MX (1) | MX9800084A (pt) |
| NO (1) | NO980129D0 (pt) |
| NZ (1) | NZ313164A (pt) |
| PL (1) | PL324529A1 (pt) |
| RU (1) | RU2169147C2 (pt) |
| SK (1) | SK2498A3 (pt) |
| TR (1) | TR199800041T1 (pt) |
| TW (1) | TW454006B (pt) |
| WO (1) | WO1997003071A1 (pt) |
| ZA (1) | ZA965921B (pt) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9811879D0 (en) * | 1998-06-03 | 1998-07-29 | Knoll Ag | Therapeutic agents |
| GB9915616D0 (en) * | 1999-07-05 | 1999-09-01 | Knoll Ag | Therapeutic agents |
| UA73981C2 (en) | 2000-03-10 | 2005-10-17 | Merck Patent Gmbh | (r)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane for treatment of extrapyramidal movement disorders (variants), pharmaceutical composition and kit |
| WO2001078648A2 (en) * | 2000-04-17 | 2001-10-25 | Dong Wha Pharm. Ind. Co., Ltd. | 6-methylnicotinamide derivatives as antiviral agents |
| CA2428519A1 (en) * | 2000-11-14 | 2002-05-23 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Novel uses of combined selective dopamine d2 receptor antagonists and 5-ht1a receptor agonists |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US8106074B2 (en) | 2001-07-13 | 2012-01-31 | Pierre Fabre Medicament | Pyridin-2-yl-methylamine derivatives for treating opiate dependence |
| CN1292749C (zh) | 2001-07-26 | 2007-01-03 | 默克专利股份有限公司 | 2－[5－(4－氟苯基)－3－吡啶基甲氨基甲基]苯并二氢吡喃及其生理学上可接受的盐的新用途 |
| KR101204247B1 (ko) | 2003-07-22 | 2012-11-22 | 아스텍스 테라퓨틱스 리미티드 | 3,4-이치환된 1ｈ-피라졸 화합물 및 그의 시클린 의존성키나제 (ｃｄｋ) 및 글리코겐 합성효소 키나제-3(ｇｓｋ-3) 조정제로서 용도 |
| WO2005080394A1 (en) * | 2004-02-24 | 2005-09-01 | Bioaxone Therapeutique Inc. | 4-substituted piperidine derivatives |
| JP4604583B2 (ja) * | 2004-07-20 | 2011-01-05 | ダイソー株式会社 | １−アミド−３−（２−ヒドロキシフェノキシ）−２−プロパノール誘導体、ならびに２−アミドメチル−１，４−ベンゾジオキサン誘導体の製造法 |
| WO2006077424A1 (en) | 2005-01-21 | 2006-07-27 | Astex Therapeutics Limited | Pharmaceutical compounds |
| JP5475235B2 (ja) | 2005-01-21 | 2014-04-16 | アステックス・セラピューティクス・リミテッド | 医薬化合物 |
| TWI457122B (zh) | 2007-07-20 | 2014-10-21 | Orion Corp | 作為用於治療周邊和中央神經系統疾病之alpha2C拮抗劑的2,3－二氫苯並[1,4]戴奧辛－2－基甲基衍生物 |
| AU2009242092A1 (en) * | 2008-04-29 | 2009-11-05 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Modulators of dopamine neurotransmission |
| MX356699B (es) * | 2012-06-11 | 2018-06-11 | Bristol Myers Squibb Co | Profarmacos de acido fosforamidico de 5-[5-fenil-4-(piridin-2-ilme tilamino) quinazolin-2-il]piridin-3-sulfonamida. |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8302622D0 (en) * | 1983-01-31 | 1983-03-02 | Celltech Ltd | Immunoassay |
| EP0200960A1 (en) * | 1985-05-08 | 1986-11-12 | Abbott Laboratories | Total estriol fluorescence polarization immunoassay |
| WO1991013872A1 (en) * | 1990-03-15 | 1991-09-19 | The Upjohn Company | Therapeutically useful heterocyclic indole compounds |
| US5240943A (en) * | 1991-12-19 | 1993-08-31 | G. D. Searle & Co. | Benzopyran class iii antiarrhythmic agents |
| GB9314758D0 (en) * | 1993-07-16 | 1993-08-25 | Wyeth John & Brother Ltd | Heterocyclic derivatives |
| GB9318431D0 (en) * | 1993-09-06 | 1993-10-20 | Boots Co Plc | Therapeutic agents |
| FR2724383B1 (fr) * | 1994-09-13 | 1996-10-18 | Synthelabo | Derives de 2-aminopyrimidine-4-carboxamide, leur preparation et leur application en therapeutique |
-
1995
- 1995-07-13 GB GBGB9514380.6A patent/GB9514380D0/en active Pending
-
1996
- 1996-07-02 SK SK24-98A patent/SK2498A3/sk unknown
- 1996-07-02 CZ CZ973884A patent/CZ388497A3/cs unknown
- 1996-07-02 IL IL12254096A patent/IL122540A/en not_active IP Right Cessation
- 1996-07-02 US US08/981,671 patent/US5935973A/en not_active Expired - Lifetime
- 1996-07-02 NZ NZ313164A patent/NZ313164A/xx unknown
- 1996-07-02 CN CN96195477A patent/CN1071755C/zh not_active Expired - Fee Related
- 1996-07-02 DE DE69630604T patent/DE69630604T2/de not_active Expired - Fee Related
- 1996-07-02 CA CA002223472A patent/CA2223472A1/en not_active Abandoned
- 1996-07-02 MX MX9800084A patent/MX9800084A/es not_active Application Discontinuation
- 1996-07-02 AU AU65172/96A patent/AU708890B2/en not_active Ceased
- 1996-07-02 AT AT96924847T patent/ATE253573T1/de not_active IP Right Cessation
- 1996-07-02 RU RU98102441/04A patent/RU2169147C2/ru active
- 1996-07-02 WO PCT/EP1996/002890 patent/WO1997003071A1/en not_active Application Discontinuation
- 1996-07-02 TR TR1998/00041T patent/TR199800041T1/xx unknown
- 1996-07-02 PL PL96324529A patent/PL324529A1/xx unknown
- 1996-07-02 JP JP9505471A patent/JPH11508599A/ja not_active Withdrawn
- 1996-07-02 BR BR9609506A patent/BR9609506A/pt unknown
- 1996-07-02 KR KR1019980700220A patent/KR19990028918A/ko not_active Application Discontinuation
- 1996-07-02 HU HU9901485A patent/HUP9901485A3/hu unknown
- 1996-07-02 EP EP96924847A patent/EP0839145B1/en not_active Expired - Lifetime
- 1996-07-12 HR HR9514380.6A patent/HRP960348A2/hr not_active Application Discontinuation
- 1996-07-12 ZA ZA9605921A patent/ZA965921B/xx unknown
- 1996-12-19 TW TW085115692A patent/TW454006B/zh not_active IP Right Cessation
-
1997
- 1997-12-23 BG BG102145A patent/BG62771B1/bg unknown
-
1998
- 1998-01-12 NO NO980129A patent/NO980129D0/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ313164A (en) | 1999-07-29 |
| HUP9901485A2 (en) | 2000-07-28 |
| HUP9901485A3 (en) | 2001-03-28 |
| EP0839145A1 (en) | 1998-05-06 |
| HRP960348A2 (en) | 1998-04-30 |
| IL122540A0 (en) | 1998-06-15 |
| US5935973A (en) | 1999-08-10 |
| CN1071755C (zh) | 2001-09-26 |
| TR199800041T1 (xx) | 1998-05-21 |
| DE69630604T2 (de) | 2004-09-23 |
| WO1997003071A1 (en) | 1997-01-30 |
| AU708890B2 (en) | 1999-08-12 |
| MX9800084A (es) | 1998-03-29 |
| CA2223472A1 (en) | 1997-01-30 |
| RU2169147C2 (ru) | 2001-06-20 |
| CZ388497A3 (cs) | 1998-06-17 |
| CN1190967A (zh) | 1998-08-19 |
| BR9609506A (pt) | 1999-06-01 |
| NO980129L (no) | 1998-01-12 |
| GB9514380D0 (en) | 1995-09-13 |
| ZA965921B (en) | 1998-01-12 |
| BG62771B1 (bg) | 2000-07-31 |
| TW454006B (en) | 2001-09-11 |
| BG102145A (en) | 1998-11-30 |
| SK2498A3 (en) | 1998-09-09 |
| KR19990028918A (ko) | 1999-04-15 |
| NO980129D0 (no) | 1998-01-12 |
| EP0839145B1 (en) | 2003-11-05 |
| ATE253573T1 (de) | 2003-11-15 |
| JPH11508599A (ja) | 1999-07-27 |
| AU6517296A (en) | 1997-02-10 |
| PL324529A1 (en) | 1998-06-08 |
| DE69630604D1 (de) | 2003-12-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM9K | Patent not in force due to non-payment of renewal fees |