CN1183129C - 作为加压素激动剂的稠合氮杂� - Google Patents
作为加压素激动剂的稠合氮杂� Download PDFInfo
- Publication number
- CN1183129C CN1183129C CNB018031323A CN01803132A CN1183129C CN 1183129 C CN1183129 C CN 1183129C CN B018031323 A CNB018031323 A CN B018031323A CN 01803132 A CN01803132 A CN 01803132A CN 1183129 C CN1183129 C CN 1183129C
- Authority
- CN
- China
- Prior art keywords
- compound
- pharmaceutically useful
- useful salt
- methyl
- group
- 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 - Fee Related
Links
- 239000000556 agonist Substances 0.000 title abstract description 6
- 150000001538 azepines Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 13
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 201000010064 diabetes insipidus Diseases 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 208000008967 Enuresis Diseases 0.000 claims abstract description 7
- 206010029446 nocturia Diseases 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 208000003450 Neurogenic Diabetes Insipidus Diseases 0.000 claims abstract description 5
- 208000028235 central diabetes insipidus Diseases 0.000 claims abstract description 5
- 201000005119 neurohypophyseal diabetes insipidus Diseases 0.000 claims abstract description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- -1 benzylamino formyl Chemical group 0.000 claims description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
- 229960002429 proline Drugs 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 208000032843 Hemorrhage Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 208000004880 Polyuria Diseases 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 4
- 125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 7
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 1
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000002686 anti-diuretic effect Effects 0.000 abstract description 6
- 102000004136 Vasopressin Receptors Human genes 0.000 abstract description 3
- 108090000643 Vasopressin Receptors Proteins 0.000 abstract description 3
- 229940124538 antidiuretic agent Drugs 0.000 abstract description 3
- 239000003805 procoagulant Substances 0.000 abstract description 2
- 229940083335 Vasopressin agonist Drugs 0.000 abstract 1
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- 208000005346 nocturnal enuresis Diseases 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 description 25
- 239000012634 fragment Substances 0.000 description 20
- 239000002585 base Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 229960004281 desmopressin Drugs 0.000 description 14
- 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 14
- 238000000034 method Methods 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 206010021639 Incontinence Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 230000000694 effects Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical group [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 102100022641 Coagulation factor IX Human genes 0.000 description 3
- 108010076282 Factor IX Proteins 0.000 description 3
- 201000003542 Factor VIII deficiency Diseases 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 229930182821 L-proline Natural products 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 3
- 208000027276 Von Willebrand disease Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 229960004222 factor ix Drugs 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)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
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 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 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
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 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
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-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
- 239000005864 Sulphur Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003160 antidiuretic agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical class 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 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
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 2
- 229940127264 non-peptide agonist Drugs 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 2
- 239000000813 peptide hormone Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction 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
- 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 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- WHLUQAYNVOGZST-UHFFFAOYSA-N tifenamil Chemical group C=1C=CC=CC=1C(C(=O)SCCN(CC)CC)C1=CC=CC=C1 WHLUQAYNVOGZST-UHFFFAOYSA-N 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- JLFFRYVFNZAXDK-ZETCQYMHSA-N (2S)-1-[(2-methylpropan-2-yl)oxycarbonyloxy]pyrrolidine-2-carboxylic acid Chemical compound C(=O)(OC(C)(C)C)ON1[C@H](C(=O)O)CCC1 JLFFRYVFNZAXDK-ZETCQYMHSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical group C1CCSSC1 CXWGKAYMVASWDQ-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
- 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
- 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 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
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 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
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000854350 Enicospilus group Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229940127316 Potassium Channel Antagonists Drugs 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 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 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-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
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001816 cooling 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
- 125000004093 cyano group Chemical group *C#N 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
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 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
- 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
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 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
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- TXKMVPPZCYKFAC-UHFFFAOYSA-N disulfur monoxide Inorganic materials O=S=S TXKMVPPZCYKFAC-UHFFFAOYSA-N 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000001261 hydroxy acids Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000006872 improvement 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
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229940028441 minirin Drugs 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
- 150000002829 nitrogen Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 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
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 101150078860 pho gene Proteins 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 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
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 231100000817 safety factor Toxicity 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical compound S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 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
- 206010046494 urge incontinence Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229960003726 vasopressin Drugs 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0000079.4A GB0000079D0 (en) | 2000-01-05 | 2000-01-05 | Novel antidiuretic agents |
| GB0000079.4 | 2000-01-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1392875A CN1392875A (zh) | 2003-01-22 |
| CN1183129C true CN1183129C (zh) | 2005-01-05 |
Family
ID=9883168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB018031323A Expired - Fee Related CN1183129C (zh) | 2000-01-05 | 2001-01-04 | 作为加压素激动剂的稠合氮杂� |
Country Status (34)
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| MXPA02009382A (es) * | 2000-03-27 | 2003-01-28 | Applied Research Systems | Derivados de pirrolidina farmaceuticamente activos. |
| WO2001074769A1 (en) * | 2000-03-27 | 2001-10-11 | Applied Research Systems Ars Holding N.V. | Pharmaceutically active pyrrolidine derivatives as bax inhibitors |
| 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 |
| RU2326868C2 (ru) * | 2003-04-28 | 2008-06-20 | Астеллас Фарма Инк. | Производное 4,4-дифтор-1,2,2,4-тетрагидро-5н-1-бензазепина или его соль |
| DE60305043T2 (de) * | 2003-11-13 | 2006-11-30 | Ferring B.V. | Blisterverpackung und feste Dosierungsform enthaltend Desmopressin |
| WO2006054560A1 (ja) * | 2004-11-17 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | 芳香族アミド誘導体、それを含有する医薬組成物およびそれらの医薬用途 |
| CA2602351A1 (en) * | 2005-03-25 | 2006-10-05 | 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 |
| WO2008141081A1 (en) * | 2007-05-10 | 2008-11-20 | Amr Technology, Inc. | Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| CA2988753A1 (en) | 2007-08-06 | 2009-02-12 | Serenity Pharmaceuticals, Llc | Methods and devices for desmopressin drug delivery |
| US11963995B2 (en) | 2008-05-21 | 2024-04-23 | Ferring B.V. | Methods comprising desmopressin |
| ES2462465T5 (es) * | 2008-05-21 | 2018-02-28 | Ferring B.V. | Desmopresina bucodispersable para aumentar el periodo inicial del sueño no alterado por nocturia |
| US20100286045A1 (en) | 2008-05-21 | 2010-11-11 | Bjarke Mirner Klein | Methods comprising desmopressin |
| 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 (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3960886A (en) | 1968-07-03 | 1976-06-01 | Sterling Drug Inc. | Substituted N-arylanilines |
| CH599752A5 (US20070167479A1-20070719-C00034.png) | 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 |
| EP0450097B1 (en) | 1989-10-20 | 1996-04-24 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| US5753677A (en) | 1989-10-20 | 1998-05-19 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| CA2066104C (en) * | 1991-04-19 | 2003-05-27 | Hidenori Ogawa | Benzazepine derivatives as vasopressin antagonists |
| 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 |
| EP0612319A1 (en) | 1992-08-20 | 1994-08-31 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds as oxytocin and vasopressin antagonists |
| TW270927B (US20070167479A1-20070719-C00034.png) * | 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 (en) | 1993-03-11 | 1994-09-15 | Yamanouchi Pharmaceutical Co., Ltd. | Compound with vasopressin antagonism |
| 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 |
| US5843952A (en) | 1993-07-29 | 1998-12-01 | 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 |
| US5760031A (en) | 1993-07-29 | 1998-06-02 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5516774A (en) | 1993-07-29 | 1996-05-14 | American Cyanamid Company | Tricyclic diazepine vasopressin antagonists and oxytocin antagonists |
| FI1215U1 (fi) * | 1993-12-03 | 1994-02-21 | Valmet Paper Machinery Inc | Anlaeggning i samband med styrningen av en vira |
| WO1995031034A2 (en) * | 1994-05-06 | 1995-11-16 | Philips Electronics N.V. | Microwave transmission system |
| DE69530690T2 (de) | 1994-06-15 | 2004-03-18 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclische derivate 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 |
| CN1183134C (zh) * | 1997-07-30 | 2005-01-05 | 惠氏公司 | 三环后叶加压素激动剂 |
| NZ502448A (en) * | 1997-07-30 | 2002-12-20 | Wyeth Corp | Tricyclic vasopressin agonists and medicaments containing these compounds |
| JP2002527438A (ja) | 1998-10-09 | 2002-08-27 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ４，５−ジヒドロ−イソオキサゾール誘導体及びそれらの製薬学的使用 |
| 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 KR KR1020027006382A patent/KR100605466B1/ko active IP Right Grant
- 2001-01-04 CA CA2396277A patent/CA2396277C/en not_active Expired - Lifetime
- 2001-01-04 HU HU0203917A patent/HU229937B1/hu not_active IP Right Cessation
- 2001-01-04 ES ES01900169T patent/ES2288923T3/es not_active Expired - Lifetime
- 2001-01-04 AT AT01900169T patent/ATE366730T1/de active
- 2001-01-04 DE DE60129298T patent/DE60129298T2/de not_active Expired - Lifetime
- 2001-01-04 CN CNB018031323A patent/CN1183129C/zh not_active Expired - Fee Related
- 2001-01-04 EE EEP200200367A patent/EE200200367A/xx unknown
- 2001-01-04 DK DK01900169T patent/DK1248784T3/da active
- 2001-01-04 CZ CZ20022305A patent/CZ303444B6/cs not_active IP Right Cessation
- 2001-01-04 US US10/130,749 patent/US7074781B2/en not_active Expired - Lifetime
- 2001-01-04 SK SK911-2002A patent/SK287005B6/sk not_active IP Right Cessation
- 2001-01-04 AU AU23846/01A patent/AU777538B2/en not_active Ceased
- 2001-01-04 NZ NZ518803A patent/NZ518803A/xx not_active IP Right Cessation
- 2001-01-04 IL IL14952801A patent/IL149528A0/xx active IP Right Grant
- 2001-01-04 MY MYPI20010027A patent/MY140467A/en unknown
- 2001-01-04 BR BRPI0107414-8A patent/BR0107414B1/pt not_active IP Right Cessation
- 2001-01-04 MX MXPA02006546A patent/MXPA02006546A/es active IP Right Grant
- 2001-01-04 PL PL355808A patent/PL211341B1/pl unknown
- 2001-01-04 PT PT01900169T patent/PT1248784E/pt unknown
- 2001-01-04 WO PCT/GB2001/000023 patent/WO2001049682A1/en active IP Right Grant
- 2001-01-04 UY UY26521A patent/UY26521A1/es not_active IP Right Cessation
- 2001-01-04 EP EP01900169A patent/EP1248784B1/en not_active Expired - Lifetime
- 2001-01-04 AR ARP010100035A patent/AR035327A1/es active IP Right Grant
- 2001-01-04 SI SI200130766T patent/SI1248784T1/sl unknown
- 2001-01-04 RU RU2002120798/04A patent/RU2259367C2/ru not_active IP Right Cessation
- 2001-01-04 JP JP2001550222A patent/JP3869723B2/ja not_active Expired - Fee Related
- 2001-04-01 UA UA2002075517A patent/UA73152C2/uk unknown
-
2002
- 2002-05-31 HR HR20020481A patent/HRP20020481B1/xx not_active IP Right Cessation
- 2002-06-27 NO NO20023137A patent/NO322571B1/no not_active IP Right Cessation
- 2002-06-27 ZA ZA200205180A patent/ZA200205180B/en unknown
- 2002-11-26 HK HK02108525.5A patent/HK1046910B/zh 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 |
|---|---|---|
| CN1183129C (zh) | 作为加压素激动剂的稠合氮杂� | |
| CN1187358C (zh) | 四氢杂环吖庚因基嘧啶衍生物 | |
| CN1046730C (zh) | 吡唑并[1,5-a]嘧啶衍生物 | |
| CN1150187C (zh) | 改善性功能障碍的a1b-肾上腺素能受体的选择性拮抗剂的应用 | |
| CN100347170C (zh) | 具有dpp－iv抑制活性的氮杂二环辛烷与壬烷衍生物 | |
| CN1097054C (zh) | 三环类吡唑衍生物及其组合物 | |
| CN1037439C (zh) | 制备具有神经保护作用的吲哚酮及有关衍生物的方法 | |
| CN1040985C (zh) | 苯并氮杂䓬类化合物的制备方法 | |
| CN1034176C (zh) | 用于预防和治疗糖尿病并发症的药物组合物的制备方法 | |
| CN1137794A (zh) | 5-(2-咪唑啉基氨基)苯并咪唑衍生物、其制备及作为α-肾上腺素受体激动剂的应用 | |
| CN1195741C (zh) | 嘧啶酮化合物,包含该化合物的药物组合物以及制备该化合物的方法 | |
| CN1202168A (zh) | 作为血清素拮抗剂的喹诺－2(1h)－酮衍生物 | |
| CN1455769A (zh) | 用作β－3肾上腺素能受体激动剂的环胺磺酰胺 | |
| CN1209358C (zh) | αLβ2介导细胞粘连的抑制剂 | |
| CN1387526A (zh) | 作为cgrp拮抗剂的新环丙烷、包含该化合物的药物及其生产方法 | |
| CN1145627C (zh) | 吡唑并[4,3-d]嘧啶类 | |
| CN1134695A (zh) | 具有血小板凝聚抑制作用的新颖化合物 | |
| CN1144788C (zh) | 双环血管加压素激动剂 | |
| CN1333755A (zh) | 为玻连蛋白受体拮抗剂的苯并咪唑化合物 | |
| CN1221538C (zh) | 1,5－苯并二氮杂䓬衍生物的钙盐、该盐的制备方法及含有该盐的药物 | |
| CN1092074A (zh) | 二氮杂䓬衍生物 | |
| CN1126738C (zh) | 苯甲酰胺衍生物及含有它们的药物 | |
| CN1257482A (zh) | 喹啉－2－羧酸衍生物及其作为兴奋性氨基酸拮抗剂的用途 | |
| CN1158257C (zh) | 新型氨基吡咯啉化合物、其制备方法以及含有它们的药物组合物 | |
| CN1104898C (zh) | 眼压降低剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090116 Address after: British Southampton Patentee after: Vantia Ltd. Address before: Holland Hoofddorp Patentee before: Ferring BV |
|
| ASS | Succession or assignment of patent right |
Owner name: WANTIYA CO., LTD. Free format text: FORMER OWNER: FEHLING STOCK CO., LTD. Effective date: 20090116 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050105 Termination date: 20200104 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |