HRP980267A2 - Tetrazoles - Google Patents
TetrazolesInfo
- Publication number
- HRP980267A2 HRP980267A2 HR9709972.5A HRP980267A HRP980267A2 HR P980267 A2 HRP980267 A2 HR P980267A2 HR P980267 A HRP980267 A HR P980267A HR P980267 A2 HRP980267 A2 HR P980267A2
- Authority
- HR
- Croatia
- Prior art keywords
- piperazinyl
- compound
- phenyl
- dimethyl
- image
- Prior art date
Links
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 title claims description 15
- 150000003536 tetrazoles Chemical class 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 278
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 50
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 50
- -1 hydroxy, methoxy Chemical group 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 229940005605 valeric acid Drugs 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000000556 agonist Substances 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 230000036407 pain Effects 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 206010021639 Incontinence Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000006549 dyspepsia Diseases 0.000 claims description 2
- 201000000117 functional diarrhea Diseases 0.000 claims description 2
- 208000028774 intestinal disease Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 230000004899 motility Effects 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 230000028327 secretion Effects 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 230000001562 ulcerogenic effect Effects 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000025609 Urogenital disease Diseases 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000004202 respiratory function Effects 0.000 claims 1
- 230000000392 somatic effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 456
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 426
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 322
- 239000000243 solution Substances 0.000 description 197
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 180
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 156
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 128
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 121
- 235000019439 ethyl acetate Nutrition 0.000 description 107
- 238000002360 preparation method Methods 0.000 description 99
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 98
- 235000011114 ammonium hydroxide Nutrition 0.000 description 98
- 239000000908 ammonium hydroxide Substances 0.000 description 94
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 93
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
- 238000004440 column chromatography Methods 0.000 description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 74
- 239000000377 silicon dioxide Substances 0.000 description 74
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 239000000203 mixture Substances 0.000 description 66
- 239000011541 reaction mixture Substances 0.000 description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- 238000010992 reflux Methods 0.000 description 47
- 239000000284 extract Substances 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 40
- 238000010828 elution Methods 0.000 description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- 229910021529 ammonia Inorganic materials 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
- 229910052938 sodium sulfate Inorganic materials 0.000 description 33
- 235000011152 sodium sulphate Nutrition 0.000 description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- 239000010410 layer Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 239000007864 aqueous solution Substances 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- 239000007832 Na2SO4 Substances 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 17
- 229940070710 valerate Drugs 0.000 description 17
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- YZGQDNOIGFBYKF-UHFFFAOYSA-N Ethoxyacetic acid Chemical compound CCOCC(O)=O YZGQDNOIGFBYKF-UHFFFAOYSA-N 0.000 description 14
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 13
- 238000004821 distillation Methods 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 239000006260 foam Substances 0.000 description 11
- 229920005990 polystyrene resin Polymers 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000011777 magnesium Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 238000010533 azeotropic distillation Methods 0.000 description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 9
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 9
- 239000012964 benzotriazole Substances 0.000 description 9
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 229910052749 magnesium Inorganic materials 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 238000009739 binding Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 238000005932 reductive alkylation reaction Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- VKUXNUOPPQWDMV-DTWKUNHWSA-N (2r,5s)-2,5-dimethyl-1-prop-2-enylpiperazine Chemical compound C[C@H]1CN(CC=C)[C@H](C)CN1 VKUXNUOPPQWDMV-DTWKUNHWSA-N 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 5
- MARUHZGHZWCEQU-UHFFFAOYSA-N 5-phenyl-2h-tetrazole Chemical compound C1=CC=CC=C1C1=NNN=N1 MARUHZGHZWCEQU-UHFFFAOYSA-N 0.000 description 5
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 5
- PPFJUUUQXUJURU-UHFFFAOYSA-M [Br-].CC(C)(C)[Si](C)(C)OC1=CC=CC([Mg+])=C1 Chemical compound [Br-].CC(C)(C)[Si](C)(C)OC1=CC=CC([Mg+])=C1 PPFJUUUQXUJURU-UHFFFAOYSA-M 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 108700023159 delta Opioid Receptors Proteins 0.000 description 5
- 102000048124 delta Opioid Receptors Human genes 0.000 description 5
- AFRWBGJRWRHQOV-UHFFFAOYSA-N ethyl 5-bromopentanoate Chemical compound CCOC(=O)CCCCBr AFRWBGJRWRHQOV-UHFFFAOYSA-N 0.000 description 5
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- PZWWYAHWHHNCHO-FGHAYEPSSA-N (4r,7s,10s,13r,16s,19r)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-10-(3-aminopropyl)-7-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-3,3-dimethyl-6,9,12,15,18-pentaoxo-1,2-dithia Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(=O)N[C@@H](C(SSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=CC=CC=1)(C)C)C(=O)N[C@@H]([C@H](O)C)C(N)=O)[C@@H](C)O)C1=CC=C(O)C=C1 PZWWYAHWHHNCHO-FGHAYEPSSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 101100108551 Mus musculus Akr1b7 gene Proteins 0.000 description 4
- APSUXPSYBJVPPS-YAUKWVCOSA-N Norbinaltorphimine Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CC=2C=3C[C@]4(O)[C@]67CCN(CC8CC8)[C@@H]4CC=4C7=C(C(=CC=4)O)O[C@H]6C=3NC=25)O)CC1)O)CC1CC1 APSUXPSYBJVPPS-YAUKWVCOSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 108700040302 phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide Proteins 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- WPYUCWSMVJJWFI-UHFFFAOYSA-N 2-ethoxyacetonitrile Chemical compound CCOCC#N WPYUCWSMVJJWFI-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- 241000400611 Eucalyptus deanei Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
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- NARJCMDCLJDRMV-UHFFFAOYSA-N ethyl 5-[5-(4-formylphenyl)tetrazol-2-yl]pentanoate Chemical compound CCOC(=O)CCCCN1N=NC(C=2C=CC(C=O)=CC=2)=N1 NARJCMDCLJDRMV-UHFFFAOYSA-N 0.000 description 1
- JELXJZASXLHKDV-UHFFFAOYSA-N ethyl 5-aminopentanoate;hydrochloride Chemical compound Cl.CCOC(=O)CCCCN JELXJZASXLHKDV-UHFFFAOYSA-N 0.000 description 1
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- 238000002844 melting Methods 0.000 description 1
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- QAWFLJGZSZIZHO-UHFFFAOYSA-N methyl 4-bromobutanoate Chemical compound COC(=O)CCCBr QAWFLJGZSZIZHO-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- JJGVUQXLNNGWPZ-UHFFFAOYSA-N n-phenyl-2h-tetrazol-5-amine Chemical compound C=1C=CC=CC=1NC1=NN=NN1 JJGVUQXLNNGWPZ-UHFFFAOYSA-N 0.000 description 1
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- 239000002674 ointment Substances 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
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- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Surface Acoustic Wave Elements And Circuit Networks Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9709972.5A GB9709972D0 (en) | 1997-05-19 | 1997-05-19 | Tetrazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP980267A2 true HRP980267A2 (en) | 1999-02-28 |
Family
ID=10812431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR9709972.5A HRP980267A2 (en) | 1997-05-19 | 1998-05-19 | Tetrazoles |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6514975B1 (de) |
| EP (1) | EP0983251B1 (de) |
| JP (1) | JP2000513024A (de) |
| AR (1) | AR015679A1 (de) |
| AT (1) | ATE269852T1 (de) |
| AU (1) | AU7644998A (de) |
| BR (1) | BR9809648A (de) |
| CA (1) | CA2290501C (de) |
| DE (1) | DE69824724T2 (de) |
| DK (1) | DK0983251T3 (de) |
| ES (1) | ES2221985T3 (de) |
| GB (1) | GB9709972D0 (de) |
| HR (1) | HRP980267A2 (de) |
| MA (1) | MA26499A1 (de) |
| PA (1) | PA8451601A1 (de) |
| PT (1) | PT983251E (de) |
| TN (1) | TNSN98066A1 (de) |
| WO (1) | WO1998052929A1 (de) |
| ZA (1) | ZA984158B (de) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5985880A (en) | 1996-06-05 | 1999-11-16 | Delta Pharmaceuticals | Compositions and methods for reducing respiratory depression and attendant side effects of mu opioid compounds |
| GB9804734D0 (en) * | 1998-03-05 | 1998-04-29 | Pfizer Ltd | Compounds |
| US6054623A (en) | 1998-12-18 | 2000-04-25 | Alliedsignal Inc. | Hydroxythiol grignard reaction synthesis |
| US6503905B1 (en) | 1998-12-29 | 2003-01-07 | Pfizer Inc | 3,3-biarylpiperidine and 2,2-biarylmorpholine derivatives |
| US6455055B1 (en) | 1999-02-12 | 2002-09-24 | The Procter & Gamble Company | Cosmetic compositions |
| PE20010623A1 (es) * | 1999-10-05 | 2001-07-07 | Gruenenthal Chemie | Uso de (+)-tramadol y/o o-demetiltramadol para tratamiento de urgencia urinaria incrementada y/o incontinencia urinaria |
| EP1353909B1 (de) | 2000-10-31 | 2005-04-06 | Rensselaer Polytechnic Institute | 8-substituierte 2,6-methano-3-benzazocine und 3-substituierte morphinane als opioidrezeptorbindende agenzien |
| KR100898562B1 (ko) | 2001-10-15 | 2009-05-20 | 얀센 파마슈티카 엔.브이. | 신규 치환된 4-페닐-4-[1ｈ-이미다졸-2-일]-피페리딘유도체 및 선택적인 비펩타이드 델타 아편유사작용제로서의 그의 용도 |
| PL371297A1 (en) * | 2001-10-29 | 2005-06-13 | Ardent Pharmaceuticals, Inc. | Method of treating depression with delta receptor agonist compounds |
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| JPH09501156A (ja) * | 1993-07-30 | 1997-02-04 | ザ．ウェルカム．ファウンデーション．リミテッド | 治療法で使用するピペラジン化合物 |
| JPH07247274A (ja) * | 1994-03-10 | 1995-09-26 | Wakamoto Pharmaceut Co Ltd | ピバル酸 テトラゾリルフェニルエステル誘導体、それらを有効成分として含有するエラスターゼ阻害剤及び肺障害治療剤 |
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| USH2007H1 (en) * | 1996-01-19 | 2001-12-04 | Fmc Corporation | Insecticidal N-heterocyclylalkyl-or N-[(polycyclyl)alkyl]-N′substituted piperazines |
-
1997
- 1997-05-19 GB GBGB9709972.5A patent/GB9709972D0/en active Pending
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1998
- 1998-04-17 BR BR9809648-6A patent/BR9809648A/pt not_active IP Right Cessation
- 1998-04-17 WO PCT/EP1998/002277 patent/WO1998052929A1/en active IP Right Grant
- 1998-04-17 ES ES98924137T patent/ES2221985T3/es not_active Expired - Lifetime
- 1998-04-17 AU AU76449/98A patent/AU7644998A/en not_active Abandoned
- 1998-04-17 DE DE69824724T patent/DE69824724T2/de not_active Expired - Fee Related
- 1998-04-17 AT AT98924137T patent/ATE269852T1/de not_active IP Right Cessation
- 1998-04-17 DK DK98924137T patent/DK0983251T3/da active
- 1998-04-17 CA CA002290501A patent/CA2290501C/en not_active Expired - Fee Related
- 1998-04-17 PT PT98924137T patent/PT983251E/pt unknown
- 1998-04-17 EP EP98924137A patent/EP0983251B1/de not_active Expired - Lifetime
- 1998-04-17 JP JP10549851A patent/JP2000513024A/ja not_active Ceased
- 1998-04-17 US US09/367,322 patent/US6514975B1/en not_active Expired - Fee Related
- 1998-05-15 PA PA19988451601A patent/PA8451601A1/es unknown
- 1998-05-15 AR ARP980102281A patent/AR015679A1/es unknown
- 1998-05-18 MA MA25079A patent/MA26499A1/fr unknown
- 1998-05-18 TN TNTNSN98066A patent/TNSN98066A1/fr unknown
- 1998-05-18 ZA ZA9804158A patent/ZA984158B/xx unknown
- 1998-05-19 HR HR9709972.5A patent/HRP980267A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2000513024A (ja) | 2000-10-03 |
| CA2290501C (en) | 2003-07-08 |
| TNSN98066A1 (fr) | 2005-03-15 |
| AR015679A1 (es) | 2001-05-16 |
| GB9709972D0 (en) | 1997-07-09 |
| PA8451601A1 (es) | 2000-05-24 |
| BR9809648A (pt) | 2000-07-11 |
| EP0983251A1 (de) | 2000-03-08 |
| WO1998052929A1 (en) | 1998-11-26 |
| ZA984158B (en) | 1999-11-19 |
| AU7644998A (en) | 1998-12-11 |
| MA26499A1 (fr) | 2004-12-20 |
| DK0983251T3 (da) | 2004-09-27 |
| EP0983251B1 (de) | 2004-06-23 |
| DE69824724T2 (de) | 2005-08-25 |
| DE69824724D1 (de) | 2004-07-29 |
| ES2221985T3 (es) | 2005-01-16 |
| US6514975B1 (en) | 2003-02-04 |
| PT983251E (pt) | 2004-08-31 |
| ATE269852T1 (de) | 2004-07-15 |
| CA2290501A1 (en) | 1998-11-26 |
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