NO314585B1 - Pyrazolpyrimidinoner som hemmer cyklisk guanosin-3',5'- monofosfatfosfodiesterase type 5 (cGMP PDE5), for behandling av seksuell dysfunksjon - Google Patents
Pyrazolpyrimidinoner som hemmer cyklisk guanosin-3',5'- monofosfatfosfodiesterase type 5 (cGMP PDE5), for behandling av seksuell dysfunksjon Download PDFInfo
- Publication number
- NO314585B1 NO314585B1 NO19995211A NO995211A NO314585B1 NO 314585 B1 NO314585 B1 NO 314585B1 NO 19995211 A NO19995211 A NO 19995211A NO 995211 A NO995211 A NO 995211A NO 314585 B1 NO314585 B1 NO 314585B1
- Authority
- NO
- Norway
- Prior art keywords
- preparation
- pyrimidin
- title compound
- pyrazolo
- dihydro
- Prior art date
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- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 title claims description 20
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 title description 14
- 238000011282 treatment Methods 0.000 title description 6
- 230000002401 inhibitory effect Effects 0.000 title description 3
- RGTMHUKTLKJHNW-UHFFFAOYSA-N 1H-pyrazole 1H-pyrimidin-2-one Chemical class N1C(N=CC=C1)=O.N1N=CC=C1 RGTMHUKTLKJHNW-UHFFFAOYSA-N 0.000 title 1
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 title 1
- 101150098694 PDE5A gene Proteins 0.000 title 1
- 201000001880 Sexual dysfunction Diseases 0.000 title 1
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 title 1
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 title 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 title 1
- 231100000872 sexual dysfunction Toxicity 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims description 486
- 150000001875 compounds Chemical class 0.000 claims description 430
- 238000000034 method Methods 0.000 claims description 239
- -1 1-oxidopyridinyl Chemical group 0.000 claims description 100
- 230000002829 reductive effect Effects 0.000 claims description 83
- 239000000203 mixture Substances 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000012453 solvate Substances 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 12
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 201000001068 Prinzmetal angina Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- 206010057671 Female sexual dysfunction Diseases 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 201000001881 impotence Diseases 0.000 claims description 7
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 206010071445 Bladder outlet obstruction Diseases 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 206010021639 Incontinence Diseases 0.000 claims description 6
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 6
- 206010036600 Premature labour Diseases 0.000 claims description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 claims description 6
- 201000009961 allergic asthma Diseases 0.000 claims description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 206010006451 bronchitis Diseases 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 208000023819 chronic asthma Diseases 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 230000008991 intestinal motility Effects 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 206010002388 Angina unstable Diseases 0.000 claims description 5
- 208000007718 Stable Angina Diseases 0.000 claims description 5
- 208000007814 Unstable Angina Diseases 0.000 claims description 5
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 238000009109 curative therapy Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 230000017531 blood circulation Effects 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 208000026440 premature labor Diseases 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims description 2
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 2
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 2
- DRIPPBPKPZJMRK-UHFFFAOYSA-N 1-[(1-methylimidazol-2-yl)methyl]-5-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(C)CC2)C=C1C(NC(=O)C=12)=NC=1C(CCC)=NN2CC1=NC=CN1C DRIPPBPKPZJMRK-UHFFFAOYSA-N 0.000 claims description 2
- NIBCDDKWFDEBEP-UHFFFAOYSA-N 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-2-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC1=C2CC)=NC(=O)C1=NN2CC1=CC=CC=N1 NIBCDDKWFDEBEP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- UYAYUQTWQGZTRW-UHFFFAOYSA-N 5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-propyl-2-(pyrazin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CCC)N2CC1=CN=CC=N1 UYAYUQTWQGZTRW-UHFFFAOYSA-N 0.000 claims description 2
- OQYWVCNPOTZBOU-UHFFFAOYSA-N 5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-propyl-2-(pyridazin-3-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CCC)N2CC1=CC=CN=N1 OQYWVCNPOTZBOU-UHFFFAOYSA-N 0.000 claims description 2
- AFXWHZNUUIIFFR-UHFFFAOYSA-N 5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-propyl-2-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CCC)N2CC1=CC=CC=N1 AFXWHZNUUIIFFR-UHFFFAOYSA-N 0.000 claims description 2
- ORWIHWJJQPOUJI-UHFFFAOYSA-N 5-[5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-3-propyl-1-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(CCO)CC2)C=C1C(NC=1C(CCC)=N2)=NC(=O)C=1N2CC1=CC=CC=N1 ORWIHWJJQPOUJI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
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- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000007787 solid Substances 0.000 description 169
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
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- 239000000243 solution Substances 0.000 description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
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- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 55
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000004440 column chromatography Methods 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
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- 238000010992 reflux Methods 0.000 description 25
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- 238000006243 chemical reaction Methods 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
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- 239000003480 eluent Substances 0.000 description 18
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- 239000011734 sodium Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
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- 239000012458 free base Substances 0.000 description 16
- 239000000284 extract Substances 0.000 description 15
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- 239000008346 aqueous phase Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
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- 210000005226 corpus cavernosum Anatomy 0.000 description 5
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- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
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- 229910052791 calcium Inorganic materials 0.000 description 1
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- 239000007810 chemical reaction solvent Substances 0.000 description 1
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- CHWGMNUJUFPVJA-UHFFFAOYSA-N n-[4-[5-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-7-oxo-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-2-yl]phenyl]methanesulfonamide Chemical compound CCCOC1=CC=C(S(=O)(=O)N2CCN(C)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CCC)N2C1=CC=C(NS(C)(=O)=O)C=C1 CHWGMNUJUFPVJA-UHFFFAOYSA-N 0.000 description 1
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- STIKETVNLGXQCS-UHFFFAOYSA-N pyridazin-3-ylmethanol Chemical compound OCC1=CC=CN=N1 STIKETVNLGXQCS-UHFFFAOYSA-N 0.000 description 1
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- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
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- 239000005049 silicon tetrachloride Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical group [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical class [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- 229940001593 sodium carbonate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- UVMAXIWRKVCCRS-UHFFFAOYSA-N sodium;cyclohexylazanide Chemical class [Na+].[NH-]C1CCCCC1 UVMAXIWRKVCCRS-UHFFFAOYSA-N 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
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- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- 229950009390 symclosene Drugs 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- GNMJFQWRASXXMS-UHFFFAOYSA-M trimethyl(phenyl)azanium;bromide Chemical compound [Br-].C[N+](C)(C)C1=CC=CC=C1 GNMJFQWRASXXMS-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9708406.5A GB9708406D0 (en) | 1997-04-25 | 1997-04-25 | Therapeutic agents |
GB9715380A GB9715380D0 (en) | 1997-07-22 | 1997-07-22 | Therapeutic agents |
GBGB9722954.6A GB9722954D0 (en) | 1997-10-30 | 1997-10-30 | Therapeutic agents |
PCT/EP1998/002257 WO1998049166A1 (en) | 1997-04-25 | 1998-04-10 | PYRAZOLOPYRIMIDINONES WHICH INHIBIT TYPE 5 CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE PHOSPHODIESTERASE (cGMP PDE5) FOR THE TREATMENT OF SEXUAL DYSFUNCTION |
Publications (3)
Publication Number | Publication Date |
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NO995211L NO995211L (no) | 1999-10-25 |
NO995211D0 NO995211D0 (no) | 1999-10-25 |
NO314585B1 true NO314585B1 (no) | 2003-04-14 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19995211A NO314585B1 (no) | 1997-04-25 | 1999-10-25 | Pyrazolpyrimidinoner som hemmer cyklisk guanosin-3',5'- monofosfatfosfodiesterase type 5 (cGMP PDE5), for behandling av seksuell dysfunksjon |
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US (2) | US6723719B1 (id) |
EP (1) | EP0977756A1 (id) |
JP (2) | JP3563078B2 (id) |
KR (2) | KR100390612B1 (id) |
CN (2) | CN1188415C (id) |
AP (1) | AP1002A (id) |
AR (1) | AR015595A1 (id) |
AU (1) | AU730670B2 (id) |
BG (1) | BG103828A (id) |
BR (1) | BR9810233A (id) |
CA (1) | CA2288910C (id) |
CO (1) | CO4940472A1 (id) |
CZ (1) | CZ299633B6 (id) |
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EA (2) | EA002057B1 (id) |
HK (1) | HK1027808A1 (id) |
HR (1) | HRP980222B1 (id) |
ID (1) | ID22834A (id) |
IL (5) | IL132276A0 (id) |
IS (1) | IS5200A (id) |
MA (1) | MA24529A1 (id) |
NO (1) | NO314585B1 (id) |
NZ (1) | NZ338075A (id) |
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PA (1) | PA8450401A1 (id) |
PE (1) | PE68699A1 (id) |
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SK (1) | SK285991B6 (id) |
TN (1) | TNSN98053A1 (id) |
TR (1) | TR199902646T2 (id) |
WO (1) | WO1998049166A1 (id) |
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