JP2004523585A - サイクリックグアノシン３’，５’−モノホスフェートホスホジエステラーゼ阻害剤 - Google Patents
サイクリックグアノシン３’，５’−モノホスフェートホスホジエステラーゼ阻害剤 Download PDFInfo
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- JP2004523585A JP2004523585A JP2002573783A JP2002573783A JP2004523585A JP 2004523585 A JP2004523585 A JP 2004523585A JP 2002573783 A JP2002573783 A JP 2002573783A JP 2002573783 A JP2002573783 A JP 2002573783A JP 2004523585 A JP2004523585 A JP 2004523585A
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- alkyl
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- ethyl
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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 abstract description 31
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 title 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 570
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 230000005764 inhibitory process Effects 0.000 claims abstract description 5
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 claims abstract 3
- 101150098694 PDE5A gene Proteins 0.000 claims abstract 3
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 claims abstract 3
- 238000002360 preparation method Methods 0.000 claims description 281
- 125000001424 substituent group Chemical group 0.000 claims description 150
- 238000000034 method Methods 0.000 claims description 120
- 239000000203 mixture Chemical group 0.000 claims description 118
- 125000005843 halogen group Chemical group 0.000 claims description 89
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 78
- 125000003118 aryl group Chemical group 0.000 claims description 75
- -1 are independently H Chemical group 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 14
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 206010057671 Female sexual dysfunction Diseases 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 230000004064 dysfunction Effects 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 230000001568 sexual effect Effects 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 201000001881 impotence Diseases 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- IVBLNBSQGVIIHC-UHFFFAOYSA-N 2-[2-[di(propan-2-yl)amino]ethyl]-3-ethyl-5-(5-methylsulfonyl-2-propoxyphenyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C1=NC2=C(CC)N(CCN(C(C)C)C(C)C)N=C2C(=O)N1 IVBLNBSQGVIIHC-UHFFFAOYSA-N 0.000 claims description 4
- QWJYUFUNAUMBLH-UHFFFAOYSA-N 3-ethyl-1-[(1-methylimidazol-2-yl)methyl]-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C=2C(=CC=C(C=2)S(C)(=O)=O)OCC(C)C)NC(=O)C2=C1C(CC)=NN2CC1=NC=CN1C QWJYUFUNAUMBLH-UHFFFAOYSA-N 0.000 claims description 4
- WNGQRPDJJMNTGZ-INIZCTEOSA-N 3-ethyl-1-[[(2s)-1-methylpiperidin-2-yl]methyl]-5-(5-methylsulfonyl-2-propoxyphenyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC1=O)=NC2=C1N(C[C@H]1N(CCCC1)C)N=C2CC WNGQRPDJJMNTGZ-INIZCTEOSA-N 0.000 claims description 4
- WIKKCYQPPMXKAY-UHFFFAOYSA-N 5-(2-butoxy-5-methylsulfonylphenyl)-3-ethyl-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=CC=C(S(C)(=O)=O)C=C1C1=NC2=C(CC)N(CCOC)N=C2C(=O)N1 WIKKCYQPPMXKAY-UHFFFAOYSA-N 0.000 claims description 4
- JWQFBJQJGITHSY-UHFFFAOYSA-N 5-(2-ethoxy-5-methylsulfonylphenyl)-1-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C1=CC(S(C)(=O)=O)=CC=C1OCC JWQFBJQJGITHSY-UHFFFAOYSA-N 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- PIKPOIQYNGBWCI-UHFFFAOYSA-N 1-[2-[di(propan-2-yl)amino]ethyl]-3-ethyl-5-(5-methylsulfonyl-2-propoxyphenyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC1=O)=NC2=C1N(CCN(C(C)C)C(C)C)N=C2CC PIKPOIQYNGBWCI-UHFFFAOYSA-N 0.000 claims description 3
- YVUSUVMJHKDRDZ-UHFFFAOYSA-N 2-(cyclopropylmethyl)-3-ethyl-5-(5-methylsulfonyl-2-propoxyphenyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2CC1CC1 YVUSUVMJHKDRDZ-UHFFFAOYSA-N 0.000 claims description 3
- WWQWUKGFSVJWGQ-HNNXBMFYSA-N 3-ethyl-1-[[(2s)-1-methylpyrrolidin-2-yl]methyl]-5-(5-methylsulfonyl-2-propoxyphenyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC1=O)=NC2=C1N(C[C@H]1N(CCC1)C)N=C2CC WWQWUKGFSVJWGQ-HNNXBMFYSA-N 0.000 claims description 3
- VWDAVCYECNRGMJ-UHFFFAOYSA-N 3-ethyl-2-(1-methylpiperidin-4-yl)-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCC=1N(C2CCN(C)CC2)N=C(C(N2)=O)C=1N=C2C1=CC(S(C)(=O)=O)=CC=C1OCC(C)C VWDAVCYECNRGMJ-UHFFFAOYSA-N 0.000 claims description 3
- QHDKLOVUZYGQFQ-INIZCTEOSA-N 3-ethyl-5-(5-ethylsulfonyl-2-propoxyphenyl)-1-[[(2s)-1-methylpyrrolidin-2-yl]methyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(=O)(=O)CC)C=C1C(NC1=O)=NC2=C1N(C[C@H]1N(CCC1)C)N=C2CC QHDKLOVUZYGQFQ-INIZCTEOSA-N 0.000 claims description 3
- GGJDBGQWIQPMOD-UHFFFAOYSA-N 3-ethyl-5-(5-methylsulfonyl-2-propoxyphenyl)-1-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC1=O)=NC2=C1N(CC=1N=CC=CC=1)N=C2CC GGJDBGQWIQPMOD-UHFFFAOYSA-N 0.000 claims description 3
- SBVCLWYADDSRFV-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-1-(1-propan-2-ylazetidin-3-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C=2C(=CC=C(C=2)S(C)(=O)=O)OCC(C)C)NC(=O)C2=C1C(CC)=NN2C1CN(C(C)C)C1 SBVCLWYADDSRFV-UHFFFAOYSA-N 0.000 claims description 3
- MCBPCZHOJMXQNQ-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-1-(pyridazin-3-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C=2C(=CC=C(C=2)S(C)(=O)=O)OCC(C)C)NC(=O)C2=C1C(CC)=NN2CC1=CC=CN=N1 MCBPCZHOJMXQNQ-UHFFFAOYSA-N 0.000 claims description 3
- QHCIJIWDKIAJKV-INIZCTEOSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-1-[[(2s)-1-methylpyrrolidin-2-yl]methyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C=2C(=CC=C(C=2)S(C)(=O)=O)OCC(C)C)NC(=O)C2=C1C(CC)=NN2C[C@@H]1CCCN1C QHCIJIWDKIAJKV-INIZCTEOSA-N 0.000 claims description 3
- PDYRLQIFHRDIOM-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-2-(1-propan-2-ylpiperidin-4-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCC=1N(C2CCN(CC2)C(C)C)N=C(C(N2)=O)C=1N=C2C1=CC(S(C)(=O)=O)=CC=C1OCC(C)C PDYRLQIFHRDIOM-UHFFFAOYSA-N 0.000 claims description 3
- MJQTUQXKHJMTSP-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-2-(2-morpholin-4-ylethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=CC=C(C=3)S(C)(=O)=O)OCC(C)C)=O)C2=C(CC)N1CCN1CCOCC1 MJQTUQXKHJMTSP-UHFFFAOYSA-N 0.000 claims description 3
- JVYCVEJUZOOADZ-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-2-(pyridazin-3-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=CC=C(C=3)S(C)(=O)=O)OCC(C)C)=O)C2=C(CC)N1CC1=CC=CN=N1 JVYCVEJUZOOADZ-UHFFFAOYSA-N 0.000 claims description 3
- DYOXXYIEPSTIBL-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-2-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=CC=C(C=3)S(C)(=O)=O)OCC(C)C)=O)C2=C(CC)N1CC1=CC=CC=N1 DYOXXYIEPSTIBL-UHFFFAOYSA-N 0.000 claims description 3
- AIWNYWDOCHMLND-MRXNPFEDSA-N 3-ethyl-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-2-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=CC=C(C=3)S(C)(=O)=O)OCC(C)C)=O)C2=C(CC)N1C[C@H]1CCCN1C AIWNYWDOCHMLND-MRXNPFEDSA-N 0.000 claims description 3
- JHNISIYCOASGJZ-UHFFFAOYSA-N 5-(2-butoxy-5-methylsulfonylphenyl)-3-ethyl-1-(pyridin-2-ylmethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC1=O)=NC2=C1N(CC=1N=CC=CC=1)N=C2CC JHNISIYCOASGJZ-UHFFFAOYSA-N 0.000 claims description 3
- ZKPGDHFFXKOUDE-UHFFFAOYSA-N 5-(2-butoxy-5-methylsulfonylphenyl)-3-ethyl-2-(1-propan-2-ylazetidin-3-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=CC=C(S(C)(=O)=O)C=C1C1=NC2=C(CC)N(C3CN(C3)C(C)C)N=C2C(=O)N1 ZKPGDHFFXKOUDE-UHFFFAOYSA-N 0.000 claims description 3
- FYJHRHOEHOZHEH-UHFFFAOYSA-N 5-(2-butoxy-5-methylsulfonylphenyl)-3-ethyl-2-(2-morpholin-4-ylethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=CC=C(S(C)(=O)=O)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2CCN1CCOCC1 FYJHRHOEHOZHEH-UHFFFAOYSA-N 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 208000021663 Female sexual arousal disease Diseases 0.000 claims description 3
- 206010024419 Libido decreased Diseases 0.000 claims description 3
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims description 3
- 208000017020 hypoactive sexual desire disease Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- SBLQIIKQJKOYSF-UHFFFAOYSA-N 3-ethyl-2-[(1-methylimidazol-2-yl)methyl]-5-[2-(2-methylpropoxy)-5-methylsulfonylphenyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=CC=C(C=3)S(C)(=O)=O)OCC(C)C)=O)C2=C(CC)N1CC1=NC=CN1C SBLQIIKQJKOYSF-UHFFFAOYSA-N 0.000 claims description 2
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- QYCUDRKEQFHGDK-UHFFFAOYSA-N spiro[1,3-oxazolidine-5,9'-fluorene]-2,4-dione Chemical compound O1C(=O)NC(=O)C21C1=CC=CC=C1C1=CC=CC=C12 QYCUDRKEQFHGDK-UHFFFAOYSA-N 0.000 claims 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 abstract description 23
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 19
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 209
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
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- 238000005481 NMR spectroscopy Methods 0.000 description 57
- 239000007787 solid Substances 0.000 description 56
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 27
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- 125000001246 bromo group Chemical group Br* 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
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- 125000002346 iodo group Chemical group I* 0.000 description 7
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0106661.2A GB0106661D0 (en) | 2001-03-16 | 2001-03-16 | Pharmaceutically active compounds |
| PCT/IB2002/000659 WO2002074774A1 (en) | 2001-03-16 | 2002-03-04 | Cyclic guanosine 3',5'-monophosphate phosphodiesterase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004523585A true JP2004523585A (ja) | 2004-08-05 |
| JP2004523585A5 JP2004523585A5 (https=) | 2005-12-22 |
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| JP2002573783A Pending JP2004523585A (ja) | 2001-03-16 | 2002-03-04 | サイクリックグアノシン３’，５’−モノホスフェートホスホジエステラーゼ阻害剤 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1368352B1 (https=) |
| JP (1) | JP2004523585A (https=) |
| AT (1) | ATE283856T1 (https=) |
| BR (1) | BR0208154A (https=) |
| CA (1) | CA2439528A1 (https=) |
| DE (1) | DE60202134T2 (https=) |
| ES (1) | ES2231667T3 (https=) |
| GB (1) | GB0106661D0 (https=) |
| MX (1) | MXPA03005937A (https=) |
| WO (1) | WO2002074774A1 (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005527565A (ja) * | 2002-03-28 | 2005-09-15 | ウスタフ エクスペリメンタルニ ボタニキ エーブイ シーアール （インスティチュート オブ エクスペリメンタル ボタニー アカデミー オブ サイエンシーズ オブ ザ チェコ リパブリック） | 新しいピラゾロ［４，３−ｄ］ピリミジン、その調整方法、及び治療方法 |
| JP2009515924A (ja) * | 2005-11-16 | 2009-04-16 | エフ．ホフマン−ラ ロシュ アーゲー | Ｔｈｏｃの新規製造方法 |
| JP2017500333A (ja) * | 2013-12-20 | 2017-01-05 | バイエル・ファルマ・アクティエンゲゼルシャフト | グルコース輸送阻害剤 |
| JP2018535259A (ja) * | 2015-11-16 | 2018-11-29 | トパドゥール ファーマ アーゲー | ホスホジエステラーゼ阻害剤としての２−フェニル−３，４−ジヒドロピロロ［２，１−ｆ］［１，２，４］トリアジノン誘導体およびその使用 |
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| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| WO2004054560A1 (en) | 2002-12-13 | 2004-07-01 | Warner-Lambert Company Llc | Alpha-2-delta ligand to treat lower urinary tract symptoms |
| CN100374441C (zh) * | 2003-06-06 | 2008-03-12 | 天津倍方科技发展有限公司 | 二氢吡咯[2，3-d]嘧啶-4-酮衍生物，其制备方法及其制药用途 |
| JP2006219374A (ja) | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Ｐｄｅ７阻害作用を有するイミダゾトリアジノン誘導体 |
| PL2256106T3 (pl) | 2003-07-22 | 2015-08-31 | Astex Therapeutics Ltd | Związki 3,4-pochodne 1h-pirazolu i ich zastosowanie jako kinazy zależne od cyklin (cdk) i modulatory kinazy syntazy glikogenu-3 (gsk-3) |
| WO2005028480A2 (en) * | 2003-09-03 | 2005-03-31 | Neurogen Corporation | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
| US7485637B2 (en) | 2005-01-04 | 2009-02-03 | Hoffmann-La Roche Inc. | Benzoyl-tetrahydropiperidine derivatives |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| DE602006010665D1 (en) | 2005-02-07 | 2010-01-07 | Hoffmann La Roche | Heterocyclsche substituierte phenylmethanone als inhibitoren des glycintransporters 1 |
| CA2598271A1 (en) * | 2005-02-18 | 2006-08-24 | Surface Logix, Inc. | Pharmacokinetically improved compounds |
| US8017781B2 (en) | 2005-11-15 | 2011-09-13 | Vertex Pharmaceuticals Incorporated | Azaindazoles useful as inhibitors of kinases |
| US8071765B2 (en) * | 2006-12-21 | 2011-12-06 | Topharman Shanghai Co., Ltd. | Process for the preparation of sildenafil and intermediates thereof |
| RU2470635C2 (ru) * | 2007-05-11 | 2012-12-27 | Сантен Фармасьютикал Ко., Лтд. | Профилактическое или терапевтическое средство, применяемое при заболеваниях заднего отдела глаза |
| JP5498392B2 (ja) | 2007-11-30 | 2014-05-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | １，５−ジヒドロ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体及びｃｎｓ障害の治療のためのｐｄｅ９ａモジュレーターとしてのそれらの使用 |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| JP5453431B2 (ja) | 2008-09-08 | 2014-03-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピラゾロピリミジン及びｃｎｓ障害の治療のためのそれらの使用 |
| EP2379076B1 (en) | 2008-12-23 | 2014-11-12 | The Trustees of Columbia University in the City of New York | Phosphodiesterase inhibitors and uses thereof |
| PE20120505A1 (es) | 2009-03-31 | 2012-05-09 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-dihidro-pirazolo[3,4-d]pirimidin-4-ona como moduladores de pde9a |
| TWI393578B (zh) | 2009-07-07 | 2013-04-21 | Shl Group Ab | 注射裝置 |
| AP2012006631A0 (en) | 2010-08-12 | 2012-12-31 | Boehringer Ingelheim Int | 6-Cycloalkyl-1, 5-dihydro-pyrazolo[3,4-D] pyrimidin-4-one derivatives and their use as PDE9A inhibitors |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| EP2699572B1 (en) | 2011-04-21 | 2016-08-10 | Origenis GmbH | Heterocyclic compounds as kinase inhibitors |
| MX363696B (es) | 2011-04-21 | 2019-03-28 | Origenis Gmbh | Pirazolo[4,3-d]pirimidinas utiles como inhibidores de cinasas. |
| KR20140138293A (ko) | 2012-03-16 | 2014-12-03 | 액시킨 파마수티컬스 인코포레이티드 | 3,5-다이아미노피라졸 키나아제 억제제 |
| WO2014060112A1 (en) | 2012-10-19 | 2014-04-24 | Origenis Gmbh | Pyrazolo[4,3-d]pyrimidines as kinase inhibitors |
| US10000482B2 (en) | 2012-10-19 | 2018-06-19 | Origenis Gmbh | Kinase inhibitors |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| US9546163B2 (en) | 2014-12-23 | 2017-01-17 | Axikin Pharmaceuticals, Inc. | 3,5-diaminopyrazole kinase inhibitors |
| CN105669680B (zh) * | 2016-03-24 | 2018-02-23 | 南京药捷安康生物科技有限公司 | 吡咯并[2,1‑f][1,2,4]三嗪‑4(1H)‑酮衍生物类PDE9A抑制剂 |
| UY40234A (es) | 2022-04-22 | 2023-11-15 | Vertex Pharma | Compuestos heteroarilo para el tratamiento del dolor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1493685A (en) * | 1970-12-15 | 1977-11-30 | May & Baker Ltd | 8-azapurinones |
| GB8817651D0 (en) * | 1988-07-25 | 1988-09-01 | Smith Kline French Lab | Chemical compounds |
| US6225315B1 (en) * | 1998-11-30 | 2001-05-01 | Pfizer Inc | Method of treating nitrate-induced tolerance |
| AP2002002455A0 (en) * | 1999-10-11 | 2002-06-30 | Pfizer | 5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dIhydropyrazolo[4,3-D] pyrimidin-7-ones as phosphodiesterase inhibitors. |
-
2001
- 2001-03-16 GB GBGB0106661.2A patent/GB0106661D0/en not_active Ceased
-
2002
- 2002-03-04 EP EP02701497A patent/EP1368352B1/en not_active Expired - Lifetime
- 2002-03-04 BR BR0208154-7A patent/BR0208154A/pt not_active IP Right Cessation
- 2002-03-04 AT AT02701497T patent/ATE283856T1/de not_active IP Right Cessation
- 2002-03-04 MX MXPA03005937A patent/MXPA03005937A/es unknown
- 2002-03-04 JP JP2002573783A patent/JP2004523585A/ja active Pending
- 2002-03-04 ES ES02701497T patent/ES2231667T3/es not_active Expired - Lifetime
- 2002-03-04 DE DE60202134T patent/DE60202134T2/de not_active Expired - Fee Related
- 2002-03-04 WO PCT/IB2002/000659 patent/WO2002074774A1/en not_active Ceased
- 2002-03-04 CA CA002439528A patent/CA2439528A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005527565A (ja) * | 2002-03-28 | 2005-09-15 | ウスタフ エクスペリメンタルニ ボタニキ エーブイ シーアール （インスティチュート オブ エクスペリメンタル ボタニー アカデミー オブ サイエンシーズ オブ ザ チェコ リパブリック） | 新しいピラゾロ［４，３−ｄ］ピリミジン、その調整方法、及び治療方法 |
| JP2009515924A (ja) * | 2005-11-16 | 2009-04-16 | エフ．ホフマン−ラ ロシュ アーゲー | Ｔｈｏｃの新規製造方法 |
| JP2017500333A (ja) * | 2013-12-20 | 2017-01-05 | バイエル・ファルマ・アクティエンゲゼルシャフト | グルコース輸送阻害剤 |
| JP2018535259A (ja) * | 2015-11-16 | 2018-11-29 | トパドゥール ファーマ アーゲー | ホスホジエステラーゼ阻害剤としての２−フェニル−３，４−ジヒドロピロロ［２，１−ｆ］［１，２，４］トリアジノン誘導体およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE60202134T2 (de) | 2005-11-24 |
| ES2231667T3 (es) | 2005-05-16 |
| ATE283856T1 (de) | 2004-12-15 |
| DE60202134D1 (en) | 2005-01-05 |
| GB0106661D0 (en) | 2001-05-09 |
| EP1368352A1 (en) | 2003-12-10 |
| CA2439528A1 (en) | 2002-09-26 |
| BR0208154A (pt) | 2004-03-02 |
| MXPA03005937A (es) | 2003-09-10 |
| EP1368352B1 (en) | 2004-12-01 |
| WO2002074774A1 (en) | 2002-09-26 |
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