DE60129298T2 - Kondensierte Azepine als Vasopressinagonisten - Google Patents
Kondensierte Azepine als Vasopressinagonisten Download PDFInfo
- Publication number
- DE60129298T2 DE60129298T2 DE60129298T DE60129298T DE60129298T2 DE 60129298 T2 DE60129298 T2 DE 60129298T2 DE 60129298 T DE60129298 T DE 60129298T DE 60129298 T DE60129298 T DE 60129298T DE 60129298 T2 DE60129298 T2 DE 60129298T2
- Authority
- DE
- Germany
- Prior art keywords
- acceptable salt
- compound according
- pharmaceutically acceptable
- methyl
- proline
- 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.)
- Expired - Lifetime
Links
- 150000001538 azepines Chemical class 0.000 title claims description 4
- 229940083335 Vasopressin agonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 62
- -1 benzylcarbamoyl Chemical group 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 208000003450 Neurogenic Diabetes Insipidus Diseases 0.000 claims description 8
- 201000010064 diabetes insipidus Diseases 0.000 claims description 8
- 201000005119 neurohypophyseal diabetes insipidus Diseases 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 206010029446 nocturia Diseases 0.000 claims description 6
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 208000028235 central diabetes insipidus Diseases 0.000 claims description 5
- 230000000422 nocturnal effect Effects 0.000 claims description 5
- 208000005346 nocturnal enuresis Diseases 0.000 claims description 5
- RUOLFWZIFNQQGH-DEOSSOPVSA-N (2s)-2-n,2-n-dimethyl-1-n-[[2-methyl-4-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)phenyl]methyl]pyrrolidine-1,2-dicarboxamide Chemical compound CN(C)C(=O)[C@@H]1CCCN1C(=O)NCC1=CC=C(C(=O)N2C3=CC=CC=C3CCCC2)C=C1C RUOLFWZIFNQQGH-DEOSSOPVSA-N 0.000 claims description 4
- 208000004880 Polyuria Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000031169 hemorrhagic disease Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229960002429 proline Drugs 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- ULTFFZFLGBBBSP-VEEOACQBSA-N (2s,4r)-2-n,2-n-dimethyl-1-n-[[2-methyl-4-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)phenyl]methyl]-4-phenylmethoxypyrrolidine-1,2-dicarboxamide Chemical compound O([C@@H]1C[C@H](N(C1)C(=O)NCC=1C(=CC(=CC=1)C(=O)N1C2=CC=CC=C2CCCC1)C)C(=O)N(C)C)CC1=CC=CC=C1 ULTFFZFLGBBBSP-VEEOACQBSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 6
- CRRQPFBCZDWGNN-UHFFFAOYSA-N (methylsulfanylamino)sulfanylmethane Chemical compound CSNSC CRRQPFBCZDWGNN-UHFFFAOYSA-N 0.000 claims 1
- 208000008967 Enuresis Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000009736 wetting Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 44
- 239000012634 fragment Substances 0.000 description 26
- 239000000203 mixture Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 108010004977 Vasopressins Proteins 0.000 description 15
- 102000002852 Vasopressins Human genes 0.000 description 15
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 15
- 229960003726 vasopressin Drugs 0.000 description 15
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 description 14
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 229960004281 desmopressin Drugs 0.000 description 13
- NFLWUMRGJYTJIN-NXBWRCJVSA-N desmopressin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 NFLWUMRGJYTJIN-NXBWRCJVSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 210000002700 urine Anatomy 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 206010021639 Incontinence Diseases 0.000 description 4
- 230000002686 anti-diuretic effect Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 108010047303 von Willebrand Factor Proteins 0.000 description 4
- 102100036537 von Willebrand factor Human genes 0.000 description 4
- 229960001134 von willebrand factor Drugs 0.000 description 4
- PIWGJGUGARXIRP-VWNXMTODSA-N (2s,4r)-4-hydroxy-2-n,2-n-dimethyl-1-n-[[2-methyl-4-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)phenyl]methyl]pyrrolidine-1,2-dicarboxamide Chemical compound CN(C)C(=O)[C@@H]1C[C@@H](O)CN1C(=O)NCC1=CC=C(C(=O)N2C3=CC=CC=C3CCCC2)C=C1C PIWGJGUGARXIRP-VWNXMTODSA-N 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
- 102100026735 Coagulation factor VIII Human genes 0.000 description 3
- 108010054218 Factor VIII Proteins 0.000 description 3
- 102000001690 Factor VIII Human genes 0.000 description 3
- 201000003542 Factor VIII deficiency Diseases 0.000 description 3
- 208000009292 Hemophilia A Diseases 0.000 description 3
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229960000301 factor viii Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical compound N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 description 2
- ZUNRWCIMDCYBIQ-UHFFFAOYSA-N 3-chloro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(C(O)=O)C=C1Cl ZUNRWCIMDCYBIQ-UHFFFAOYSA-N 0.000 description 2
- LTRYUAZFLOGRLJ-UHFFFAOYSA-N 4-cyano-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1C#N LTRYUAZFLOGRLJ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical class O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 235000011941 Tilia x europaea Nutrition 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 102000004136 Vasopressin Receptors Human genes 0.000 description 2
- 108090000643 Vasopressin Receptors Proteins 0.000 description 2
- 208000027276 Von Willebrand disease Diseases 0.000 description 2
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229940124538 antidiuretic agent Drugs 0.000 description 2
- 239000003160 antidiuretic agent Substances 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000004571 lime Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- XTZCVWDSGCVDFI-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-chlorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(Cl)=C1 XTZCVWDSGCVDFI-UHFFFAOYSA-N 0.000 description 2
- 150000002829 nitrogen Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000813 peptide hormone Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 2
- BENKAPCDIOILGV-RQJHMYQMSA-N (2s,4r)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(O)=O BENKAPCDIOILGV-RQJHMYQMSA-N 0.000 description 1
- AWOLMGJLKPNBDY-NOZRDPDXSA-N (2s,4r)-4-methoxy-2-n,2-n-dimethyl-1-n-[[2-methyl-4-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)phenyl]methyl]pyrrolidine-1,2-dicarboxamide Chemical compound C1[C@H](OC)C[C@@H](C(=O)N(C)C)N1C(=O)NCC1=CC=C(C(=O)N2C3=CC=CC=C3CCCC2)C=C1C AWOLMGJLKPNBDY-NOZRDPDXSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- WQADWIOXOXRPLN-AZXPZELESA-N 1,3-dithiane Chemical group C1CS[13CH2]SC1 WQADWIOXOXRPLN-AZXPZELESA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- XDYHDIYQYUGFBR-UHFFFAOYSA-N 1h-1-benzazepine-2-carbonitrile Chemical compound N1C(C#N)=CC=CC2=CC=CC=C21 XDYHDIYQYUGFBR-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- LPEBMDFRIKYFCF-UHFFFAOYSA-N 4-bromo-2-methylbenzonitrile Chemical compound CC1=CC(Br)=CC=C1C#N LPEBMDFRIKYFCF-UHFFFAOYSA-N 0.000 description 1
- SKXUZFJOLNNWIG-UHFFFAOYSA-N 4-bromo-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1Br SKXUZFJOLNNWIG-UHFFFAOYSA-N 0.000 description 1
- NIDKGLRXRBFGEN-UHFFFAOYSA-N 4-cyano-2-methylbenzoic acid Chemical compound CC1=CC(C#N)=CC=C1C(O)=O NIDKGLRXRBFGEN-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- 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 description 1
- 206010069632 Bladder dysfunction Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 0 CSSC[C@@](C(N[C@@](Cc(cc1)ccc1O)C([N-][C@]1Cc2ccccc2)=*([C@@](CCC(N=I)=O)C(N[C@@](CC(N)=O)C(NCC(N(CCC2)[C@@]2C(N[C@@](CCCNC(N)=N)C(NCC(N)=O)=O)=O)=O)=O)=O)C1=*)=O)N Chemical compound CSSC[C@@](C(N[C@@](Cc(cc1)ccc1O)C([N-][C@]1Cc2ccccc2)=*([C@@](CCC(N=I)=O)C(N[C@@](CC(N)=O)C(NCC(N(CCC2)[C@@]2C(N[C@@](CCCNC(N)=N)C(NCC(N)=O)=O)=O)=O)=O)=O)C1=*)=O)N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 206010069645 Reduced bladder capacity Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010066218 Stress Urinary Incontinence Diseases 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- GUCRYITVDZGANG-UHFFFAOYSA-N [4-(aminomethyl)-3-methylphenyl]-(2,3,4,5-tetrahydro-1-benzazepin-1-yl)methanone;hydrochloride Chemical compound Cl.C1=C(CN)C(C)=CC(C(=O)N2C3=CC=CC=C3CCCC2)=C1 GUCRYITVDZGANG-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- YNKFCNRZZPFMEX-XHPDKPNGSA-N desmopressin acetate trihydrate Chemical compound O.O.O.CC(O)=O.C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 YNKFCNRZZPFMEX-XHPDKPNGSA-N 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- KTFQDZCNPGFKAH-UHFFFAOYSA-N methyl 3-chloro-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(Cl)=C1 KTFQDZCNPGFKAH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229940028441 minirin Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- QGCXDVIAGVEYLT-UHFFFAOYSA-N n-benzylpyrrolidine-1-carboxamide Chemical class C1CCCN1C(=O)NCC1=CC=CC=C1 QGCXDVIAGVEYLT-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 150000003017 phosphorus Chemical class 0.000 description 1
- 230000007084 physiological dysfunction Effects 0.000 description 1
- 210000001883 posterior pituitary gland Anatomy 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000003805 procoagulant Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 208000022170 stress incontinence Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Cephalosporin Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0000079 | 2000-01-05 | ||
| GBGB0000079.4A GB0000079D0 (en) | 2000-01-05 | 2000-01-05 | Novel antidiuretic agents |
| PCT/GB2001/000023 WO2001049682A1 (en) | 2000-01-05 | 2001-01-04 | Condensed azepines as vasopressin agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60129298D1 DE60129298D1 (de) | 2007-08-23 |
| DE60129298T2 true DE60129298T2 (de) | 2008-01-03 |
Family
ID=9883168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60129298T Expired - Lifetime DE60129298T2 (de) | 2000-01-05 | 2001-01-04 | Kondensierte Azepine als Vasopressinagonisten |
Country Status (34)
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5803659A (en) | 1995-12-08 | 1998-09-08 | Chattey; Nigel | Modular caissons for use in constructing, expanding and modernizing ports and harbors. |
| US7138393B2 (en) | 1998-07-24 | 2006-11-21 | Wyeth | Biologically active vasopressin agonist metabolites |
| GB0000079D0 (en) * | 2000-01-05 | 2000-02-23 | Ferring Bv | Novel antidiuretic agents |
| US7018988B2 (en) * | 2000-03-27 | 2006-03-28 | Applied Research Systems Ars Holding N.V. | Pharmaceutically active pyrrolidine derivatives as Bax inhibitors |
| HRP20020705A2 (en) * | 2000-03-27 | 2004-12-31 | Applied Research Systems | Pharmaceutically active pyrrolidine derivatives |
| GB0015601D0 (en) | 2000-06-26 | 2000-08-16 | Ferring Bv | Novel antidiuretic agents |
| GB0115515D0 (en) * | 2001-06-25 | 2001-08-15 | Ferring Bv | Oxytocin agonisys |
| GB0210397D0 (en) * | 2002-05-07 | 2002-06-12 | Ferring Bv | Pharmaceutical formulations |
| SI1619185T1 (sl) | 2003-04-28 | 2011-09-30 | Astellas Pharma Inc | 4,4-difluoro-1,2,3,4-tetrahidro-5H-1-benzazepinski derivat ali njegova sol |
| PT1530967E (pt) * | 2003-11-13 | 2006-09-29 | Ferring Bv | Embalagem blister e uma forma de dosagem solida que compreende desmopressina. |
| CA2588768A1 (en) * | 2004-11-17 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | Aromatic amide derivatives, medicinal compositions containing the same, medical uses of both |
| EP1867639A1 (en) * | 2005-03-25 | 2007-12-19 | Kissei Pharmaceutical Co., Ltd. | Urea derivative, medicinal composition containing the same, and medicinal use of these |
| WO2007052517A1 (ja) * | 2005-10-31 | 2007-05-10 | Sumitomo Chemical Company, Limited | ヒドロキシ－２－ピロリジンカルボキシアミド化合物の製法 |
| JP5220611B2 (ja) * | 2006-09-25 | 2013-06-26 | キッセイ薬品工業株式会社 | １，４−ベンゾジアゼピン誘導体、それを含有する医薬組成物およびそれらの医薬用途 |
| BRPI0811204A8 (pt) * | 2007-05-10 | 2015-09-22 | Bristol Myers Squibb Co | Tetra-hidroibenzo-1,4-diazepinas substituídas por arila e heteroarila e uso das mesmas para bloquear a recaptação de norepinefrina, dopamina e serotonina |
| WO2009021007A1 (en) | 2007-08-06 | 2009-02-12 | Serenity Pharmaceuticals Corporation | Methods and devices for desmopressin drug delivery |
| US11963995B2 (en) | 2008-05-21 | 2024-04-23 | Ferring B.V. | Methods comprising desmopressin |
| US20100286045A1 (en) | 2008-05-21 | 2010-11-11 | Bjarke Mirner Klein | Methods comprising desmopressin |
| NO3085381T3 (enExample) * | 2008-05-21 | 2018-09-15 | ||
| GB201005623D0 (en) | 2010-04-01 | 2010-05-19 | Vantia Ltd | New polymorph |
| GB201105537D0 (en) * | 2011-03-31 | 2011-05-18 | Vantia Ltd | New process |
| WO2020154581A1 (en) | 2019-01-24 | 2020-07-30 | Assia Chemical Industries Ltd | Solid state forms of fedovapagon-salicyclic acid co-crystal |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3960886A (en) * | 1968-07-03 | 1976-06-01 | Sterling Drug Inc. | Substituted N-arylanilines |
| CH599752A5 (enExample) * | 1973-04-18 | 1978-05-31 | Ciba Geigy Ag | |
| CA1047490A (en) * | 1973-04-18 | 1979-01-30 | Friedrich Karrer | Ethers |
| DE2355454A1 (de) | 1973-11-07 | 1976-10-07 | Paul Geisslinger | Lochmaschine |
| CA1265798A (en) | 1984-12-10 | 1990-02-13 | Motoo Mutsukado | 3(2h)pyridazinone, process for its preparation and anti-allergic agent containing it |
| KR0167349B1 (ko) | 1989-10-20 | 1999-02-18 | 오스카 아끼히꼬 | 벤조헤테로 고리 화합물 |
| US5753677A (en) * | 1989-10-20 | 1998-05-19 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| TW198715B (enExample) | 1991-04-19 | 1993-01-21 | Dtsuka Seiyaku Kk | |
| JPH05320135A (ja) * | 1992-05-19 | 1993-12-03 | Yamanouchi Pharmaceut Co Ltd | テトラヒドロベンズアゼピン誘導体 |
| TW250481B (enExample) * | 1992-08-20 | 1995-07-01 | Otsuka Pharma Co Ltd | |
| TW270927B (enExample) * | 1992-10-16 | 1996-02-21 | Otsuka Pharma Co Ltd | |
| AU5533894A (en) * | 1992-11-25 | 1994-06-22 | Yamanouchi Pharmaceutical Co., Ltd. | Benzanilide derivative |
| WO1994020473A1 (fr) * | 1993-03-11 | 1994-09-15 | Yamanouchi Pharmaceutical Co., Ltd. | Compose avec action antagoniste de la vasopressine |
| GB9307527D0 (en) | 1993-04-13 | 1993-06-02 | Fujisawa Pharmaceutical Co | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| US5516774A (en) | 1993-07-29 | 1996-05-14 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| US5760031A (en) * | 1993-07-29 | 1998-06-02 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5968930A (en) * | 1993-07-29 | 1999-10-19 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| US5843952A (en) * | 1993-07-29 | 1998-12-01 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US6403577B1 (en) * | 1993-11-17 | 2002-06-11 | Eli Lilly And Company | Hexamethyleneiminyl tachykinin receptor antagonists |
| FI1215U1 (fi) * | 1993-12-03 | 1994-02-21 | Valmet Paper Machinery Inc | Anlaeggning i samband med styrningen av en vira |
| FR2716194B1 (fr) * | 1994-02-14 | 1996-05-31 | Sanofi Elf | Dérivés de 3-acylamino-5-phényl-1,4-benzodiazépin-2-one polysubstitués, leur procédé de préparation et les compositions pharmaceutiques les contenant. |
| DE69514191T2 (de) * | 1994-05-06 | 2000-08-17 | Koninklijke Philips Electronics N.V., Eindhoven | Mikrowellenübertragungssystem |
| ATE360617T1 (de) | 1994-06-15 | 2007-05-15 | Otsuka Pharma Co Ltd | Benzoheterocyclische verbindungen verwendbar als vasopressin- oder oxytocin-modulatoren |
| JP2926335B2 (ja) * | 1997-06-13 | 1999-07-28 | 大塚製薬株式会社 | 医薬組成物 |
| ES2229523T3 (es) * | 1997-07-30 | 2005-04-16 | Wyeth | Agonistas triciclicos de la vasopresina. |
| IL133788A0 (en) * | 1997-07-30 | 2001-04-30 | American Home Prod | Tricyclic vasopressin agonists |
| EP1119568B1 (en) * | 1998-10-09 | 2004-02-18 | Janssen Pharmaceutica N.V. | 4,5-dihydro-isoxazole derivatives and their pharmaceutical use |
| GB2355454A (en) * | 1999-10-20 | 2001-04-25 | Ferring Bv | Antidiuretic agents |
| GB0000079D0 (en) | 2000-01-05 | 2000-02-23 | Ferring Bv | Novel antidiuretic agents |
| GB0015601D0 (en) * | 2000-06-26 | 2000-08-16 | Ferring Bv | Novel antidiuretic agents |
| DE10033337A1 (de) | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| GB0120051D0 (en) | 2001-08-16 | 2001-10-10 | Ferring Bv | Oxytocin agonists |
| GB0224557D0 (en) | 2002-10-22 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| EP1449844A1 (en) * | 2003-02-14 | 2004-08-25 | Ferring B.V. | benzamide derivatives as oxytocin agonists and vasopressin antagonists |
| EP1627876A1 (en) * | 2004-08-20 | 2006-02-22 | Ferring B.V. | Heterocyclic condensed compounds useful as antidiuretic agents |
| US7341963B2 (en) * | 2005-05-17 | 2008-03-11 | Milliken & Company | Non-woven material with barrier skin |
-
2000
- 2000-01-05 GB GBGB0000079.4A patent/GB0000079D0/en not_active Ceased
-
2001
- 2001-01-04 AR ARP010100035A patent/AR035327A1/es active IP Right Grant
- 2001-01-04 CZ CZ20022305A patent/CZ303444B6/cs not_active IP Right Cessation
- 2001-01-04 DK DK01900169T patent/DK1248784T3/da active
- 2001-01-04 DE DE60129298T patent/DE60129298T2/de not_active Expired - Lifetime
- 2001-01-04 JP JP2001550222A patent/JP3869723B2/ja not_active Expired - Fee Related
- 2001-01-04 WO PCT/GB2001/000023 patent/WO2001049682A1/en not_active Ceased
- 2001-01-04 EP EP01900169A patent/EP1248784B1/en not_active Expired - Lifetime
- 2001-01-04 ES ES01900169T patent/ES2288923T3/es not_active Expired - Lifetime
- 2001-01-04 HR HR20020481A patent/HRP20020481B1/xx not_active IP Right Cessation
- 2001-01-04 IL IL14952801A patent/IL149528A0/xx active IP Right Grant
- 2001-01-04 AT AT01900169T patent/ATE366730T1/de active
- 2001-01-04 PL PL355808A patent/PL211341B1/pl unknown
- 2001-01-04 US US10/130,749 patent/US7074781B2/en not_active Expired - Lifetime
- 2001-01-04 KR KR1020027006382A patent/KR100605466B1/ko not_active Expired - Fee Related
- 2001-01-04 BR BRPI0107414-8A patent/BR0107414B1/pt not_active IP Right Cessation
- 2001-01-04 EE EEP200200367A patent/EE200200367A/xx unknown
- 2001-01-04 NZ NZ518803A patent/NZ518803A/xx not_active IP Right Cessation
- 2001-01-04 PT PT01900169T patent/PT1248784E/pt unknown
- 2001-01-04 HK HK02108525.5A patent/HK1046910B/en not_active IP Right Cessation
- 2001-01-04 RU RU2002120798/04A patent/RU2259367C2/ru not_active IP Right Cessation
- 2001-01-04 CA CA2396277A patent/CA2396277C/en not_active Expired - Lifetime
- 2001-01-04 MY MYPI20010027A patent/MY140467A/en unknown
- 2001-01-04 CN CNB018031323A patent/CN1183129C/zh not_active Expired - Fee Related
- 2001-01-04 HU HU0203917A patent/HU229937B1/hu not_active IP Right Cessation
- 2001-01-04 UY UY26521A patent/UY26521A1/es not_active IP Right Cessation
- 2001-01-04 MX MXPA02006546A patent/MXPA02006546A/es active IP Right Grant
- 2001-01-04 AU AU23846/01A patent/AU777538B2/en not_active Ceased
- 2001-01-04 SK SK911-2002A patent/SK287005B6/sk not_active IP Right Cessation
- 2001-01-04 SI SI200130766T patent/SI1248784T1/sl unknown
- 2001-04-01 UA UA2002075517A patent/UA73152C2/uk unknown
-
2002
- 2002-06-27 ZA ZA200205180A patent/ZA200205180B/en unknown
- 2002-06-27 NO NO20023137A patent/NO322571B1/no not_active IP Right Cessation
-
2005
- 2005-12-20 JP JP2005366100A patent/JP3813629B2/ja not_active Expired - Fee Related
-
2006
- 2006-03-09 US US11/370,861 patent/US7560454B2/en not_active Expired - Fee Related
-
2007
- 2007-10-04 CY CY20071101261T patent/CY1108034T1/el unknown
-
2008
- 2008-06-23 US US12/213,651 patent/US20080261951A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60129697T2 (de) | Kondensierte azepinderivate und ihre verwendung als antidiuretisches mittel | |
| RU2259367C2 (ru) | Конденсированные азепины, фармацевтическая композиция, содержащая их, способ лечения с использованием указанной композиции | |
| DE69911259T2 (de) | Tricyclische benzodiazepine als vasopressin antagonisten | |
| DE60203290T2 (de) | Oxytocin agonisten | |
| DE68929455T2 (de) | Thieno 3,2-f 1,2,4 triazolo 4,3-a 1,4 diazepinderivate als PAF-Antagonisten | |
| EP0156191B1 (de) | Kondensierte Diazepinone, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| EP0417631A2 (de) | Kondensierte Diazepinone, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE60016786T2 (de) | Bicyclische vasopressin-agoniste | |
| DD282457A5 (de) | Verfahren zur herstellung neuer heterocyclischer derivate | |
| DE69512419T2 (de) | IMIDAZO[1,2-a]INDENO[1,2-e]PYRAZIN-2-CARBONSÄURE DERIVATE, IHRE HERSTELLUNG UND SIE ENTHALTENDE ARZNEIMITTEL | |
| JPH05213957A (ja) | 新規なスピロピロリジンイミダゾリン誘導体および新規なアミノピロリジンカルボン酸誘導体並びに該化合物を有効成分とする鎮けい剤 | |
| DE60220305T2 (de) | Verbrückte bicyclische (1,4) benzodiazepine als vasopressinrezeptorantagonisten | |
| DE3303616A1 (de) | Mutterkornalkaloide, verfahren zu deren herstellung sowie diese verbindungen enthaltende pharmazeutische zubereitungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: VANTIA LTD., CHILWORTH, GB |