KR20060012004A - Ｐｄｅ4 억제제 및 ｐｄｅ5 억제제를 포함하는 조성물 - Google Patents
Ｐｄｅ4 억제제 및 ｐｄｅ5 억제제를 포함하는 조성물 Download PDFInfo
- Publication number
- KR20060012004A KR20060012004A KR1020057021796A KR20057021796A KR20060012004A KR 20060012004 A KR20060012004 A KR 20060012004A KR 1020057021796 A KR1020057021796 A KR 1020057021796A KR 20057021796 A KR20057021796 A KR 20057021796A KR 20060012004 A KR20060012004 A KR 20060012004A
- Authority
- KR
- South Korea
- Prior art keywords
- tetrahydro
- piperidin
- phthalazin
- oxo
- dimethoxyphenyl
- 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.)
- Ceased
Links
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title claims abstract description 100
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 title claims abstract description 100
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 100
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 title claims abstract description 99
- 239000000203 mixture Substances 0.000 title description 4
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 67
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 67
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims abstract description 66
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 64
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 64
- 201000010099 disease Diseases 0.000 claims abstract description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 64
- 230000000694 effects Effects 0.000 claims abstract description 44
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 230000001627 detrimental effect Effects 0.000 claims abstract description 17
- -1 phospho Chemical class 0.000 claims description 98
- 150000003839 salts Chemical class 0.000 claims description 93
- 150000001875 compounds Chemical class 0.000 claims description 75
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 39
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 208000024891 symptom Diseases 0.000 claims description 24
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 claims description 21
- 150000001204 N-oxides Chemical class 0.000 claims description 19
- 208000006673 asthma Diseases 0.000 claims description 18
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 claims description 17
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 16
- 229960003310 sildenafil Drugs 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 15
- 229960000835 tadalafil Drugs 0.000 claims description 14
- 229960002381 vardenafil Drugs 0.000 claims description 14
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 claims description 12
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 10
- YWHBSFAATHJDAA-VQTJNVASSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-(1-pyrimidin-2-ylpiperidin-4-yl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C=2N=CC=CN=2)CC1 YWHBSFAATHJDAA-VQTJNVASSA-N 0.000 claims description 9
- VUNOKMWSRYYBGQ-XZOQPEGZSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC=2N=CC=CC=2)CC1 VUNOKMWSRYYBGQ-XZOQPEGZSA-N 0.000 claims description 9
- 206010014561 Emphysema Diseases 0.000 claims description 9
- 206010006451 bronchitis Diseases 0.000 claims description 9
- BBMPVQXZSZSEDG-ZWKOTPCHSA-N 2-[4-[(4as,8ar)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]piperidin-1-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC(N)=O)CC1 BBMPVQXZSZSEDG-ZWKOTPCHSA-N 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 8
- 206010052613 Allergic bronchitis Diseases 0.000 claims description 8
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 8
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 8
- 208000007451 chronic bronchitis Diseases 0.000 claims description 8
- 201000008383 nephritis Diseases 0.000 claims description 8
- 229960002586 roflumilast Drugs 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- WWXPHRJCGKFIQK-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-3-(2-methylpropanoyl)-2-propylindole-6-carboxamide Chemical compound CCCC1=C(C(=O)C(C)C)C2=CC=C(C(N)=O)C=C2N1CC1=CC=CC=C1Cl WWXPHRJCGKFIQK-UHFFFAOYSA-N 0.000 claims description 6
- MFKZGAAAKCDLHM-UHFFFAOYSA-N 1-cyclopentyl-6-(3-ethoxypyridin-4-yl)-3-ethyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCOC1=CN=CC=C1C(N1)=NC(=O)C2=C1N(C1CCCC1)N=C2CC MFKZGAAAKCDLHM-UHFFFAOYSA-N 0.000 claims description 6
- WKISNFXGTYNPOO-OAHLLOKOSA-N 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-[(2r)-1-methoxypropan-2-yl]oxypyridin-3-yl]-2-methyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CN=C(O[C@H](C)COC)C(C=2NC(=O)C3=NN(C)C(CC)=C3N=2)=C1 WKISNFXGTYNPOO-OAHLLOKOSA-N 0.000 claims description 6
- 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 6
- ZISFCTXLAXIEMV-GFCCVEGCSA-N n-[(3,4-dimethoxyphenyl)methyl]-2-[[(2r)-1-hydroxypropan-2-yl]amino]-5-nitrobenzamide Chemical compound C1=C(OC)C(OC)=CC=C1CNC(=O)C1=CC([N+]([O-])=O)=CC=C1N[C@H](C)CO ZISFCTXLAXIEMV-GFCCVEGCSA-N 0.000 claims description 6
- IYFNEFQTYQPVOC-UHFFFAOYSA-N udenafil Chemical compound C1=C(C=2NC=3C(CCC)=NN(C)C=3C(=O)N=2)C(OCCC)=CC=C1S(=O)(=O)NCCC1CCCN1C IYFNEFQTYQPVOC-UHFFFAOYSA-N 0.000 claims description 6
- NHVCANZLYPMKSR-LEWJYISDSA-N (4as,8ar)-2-(1-acetylpiperidin-4-yl)-4-(3,4-diethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(C)=O)CC1 NHVCANZLYPMKSR-LEWJYISDSA-N 0.000 claims description 5
- DZUJGZGLPQEEDQ-LEWJYISDSA-N (4as,8ar)-2-[1-[2-(4-amino-3,5-dichlorophenyl)-2-oxoethyl]piperidin-4-yl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC(=O)C=2C=C(Cl)C(N)=C(Cl)C=2)CC1 DZUJGZGLPQEEDQ-LEWJYISDSA-N 0.000 claims description 5
- LSOGXQFCQOSGNV-BJKOFHAPSA-N (4as,8ar)-4-(3,4-diethoxyphenyl)-2-[1-(2-morpholin-4-ylacetyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)CN2CCOCC2)CC1 LSOGXQFCQOSGNV-BJKOFHAPSA-N 0.000 claims description 5
- IRQAORMVIRUVSL-IZZNHLLZSA-N (4as,8ar)-4-(3,4-diethoxyphenyl)-2-[1-(4-methylphenyl)sulfonylpiperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 IRQAORMVIRUVSL-IZZNHLLZSA-N 0.000 claims description 5
- RLBQZJLGPGGCRU-BJKOFHAPSA-N (4as,8ar)-4-(3,4-diethoxyphenyl)-2-[1-(pyridine-4-carbonyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)C=2C=CN=CC=2)CC1 RLBQZJLGPGGCRU-BJKOFHAPSA-N 0.000 claims description 5
- WGTSMCZWJIQJKN-WUFINQPMSA-N (4as,8ar)-4-(3,4-diethoxyphenyl)-2-[1-[2-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]acetyl]piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)CN2CCN(CCN(C)C)CC2)CC1 WGTSMCZWJIQJKN-WUFINQPMSA-N 0.000 claims description 5
- ZLSJEILNOWSWRS-VQTJNVASSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-(1-thieno[2,3-d]pyrimidin-4-ylpiperidin-4-yl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C=2C=3C=CSC=3N=CN=2)CC1 ZLSJEILNOWSWRS-VQTJNVASSA-N 0.000 claims description 5
- YPJUCIMTDOZWSM-FCHUYYIVSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(2-morpholin-4-yl-2-oxoethyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC(=O)N2CCOCC2)CC1 YPJUCIMTDOZWSM-FCHUYYIVSA-N 0.000 claims description 5
- AMRVEJYMDSINDP-XZOQPEGZSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(4-nitrophenyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C=2C=CC(=CC=2)[N+]([O-])=O)CC1 AMRVEJYMDSINDP-XZOQPEGZSA-N 0.000 claims description 5
- JBXODHBHAPVHDX-LEWJYISDSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(morpholine-4-carbonyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)N2CCOCC2)CC1 JBXODHBHAPVHDX-LEWJYISDSA-N 0.000 claims description 5
- HTHOGIQHWPPOOJ-XZOQPEGZSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC=2C=NC=CC=2)CC1 HTHOGIQHWPPOOJ-XZOQPEGZSA-N 0.000 claims description 5
- LWTZEJDQHWUMON-XZOQPEGZSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-(pyridin-4-ylmethyl)piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC=2C=CN=CC=2)CC1 LWTZEJDQHWUMON-XZOQPEGZSA-N 0.000 claims description 5
- RYRAJXPFVSZNKM-LOSJGSFVSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-[(2-oxochromen-7-yl)methyl]piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC=2C=C3OC(=O)C=CC3=CC=2)CC1 RYRAJXPFVSZNKM-LOSJGSFVSA-N 0.000 claims description 5
- IDSNOSDXUZNXFS-RRPNLBNLSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(S(=O)(=O)C=2C3=CC=CC(=C3C=CC=2)N(C)C)CC1 IDSNOSDXUZNXFS-RRPNLBNLSA-N 0.000 claims description 5
- CEDBOSAGZPVJAF-LOSJGSFVSA-N (4as,8ar)-4-(3,4-dimethoxyphenyl)-2-[1-[[4-(thiadiazol-4-yl)phenyl]methyl]piperidin-4-yl]-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC=2C=CC(=CC=2)C=2N=NSC=2)CC1 CEDBOSAGZPVJAF-LOSJGSFVSA-N 0.000 claims description 5
- QUUJQFQTLSFCKW-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-ylmethylamino)-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=NC(NCC=2C=C3OCOC3=CC=2)=C(C=C(Cl)C=C2)C2=N1 QUUJQFQTLSFCKW-UHFFFAOYSA-N 0.000 claims description 5
- DAJWIIRGQKQYAW-UHFFFAOYSA-N 2-(2-propoxyphenyl)-3,7-dihydropurin-6-one;2-(2-propoxyphenyl)-1,2,5,9-tetrahydropurin-6-one Chemical compound CCCOC1=CC=CC=C1C1N=C2N=CNC2C(=O)N1.CCCOC1=CC=CC=C1C(NC1=O)=NC2=C1NC=N2 DAJWIIRGQKQYAW-UHFFFAOYSA-N 0.000 claims description 5
- JEMJAABFSYOLAP-UHFFFAOYSA-N 2-[(2-methyl-4-pyridinyl)methyl]-1-oxo-8-(2-pyrimidinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-2,7-naphthyridine-3-carboxylic acid methyl ester Chemical compound C12=CC=NC(OCC=3N=CC=CN=3)=C2C(=O)N(CC=2C=C(C)N=CC=2)C(C(=O)OC)=C1C1=CC(OC)=C(OC)C(OC)=C1 JEMJAABFSYOLAP-UHFFFAOYSA-N 0.000 claims description 5
- IQNXBPPUIVQJLE-LEWJYISDSA-N 2-[4-[(4as,8ar)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]piperidin-1-yl]-n-propan-2-ylacetamide Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(CC(=O)NC(C)C)CC1 IQNXBPPUIVQJLE-LEWJYISDSA-N 0.000 claims description 5
- LNSWDTFYXQGHQZ-UHFFFAOYSA-N 2-imidazol-1-yl-6-methoxy-n-(2-methoxyethyl)quinazolin-4-amine Chemical compound N=1C2=CC=C(OC)C=C2C(NCCOC)=NC=1N1C=CN=C1 LNSWDTFYXQGHQZ-UHFFFAOYSA-N 0.000 claims description 5
- NMKUPEWPVORTPC-UHFFFAOYSA-N 3-ethyl-8-[[2-[4-(hydroxymethyl)piperidin-1-yl]phenyl]methylamino]-1h-imidazo[4,5-g]quinazoline-2-thione Chemical compound C=12C=C3NC(=S)N(CC)C3=CC2=NC=NC=1NCC1=CC=CC=C1N1CCC(CO)CC1 NMKUPEWPVORTPC-UHFFFAOYSA-N 0.000 claims description 5
- VDXZLVXFVYDBNH-UHFFFAOYSA-N 4-[(3-chloro-4-methoxyphenyl)methylamino]-1-(4-hydroxypiperidin-1-yl)phthalazine-6-carbonitrile Chemical compound C1=C(Cl)C(OC)=CC=C1CNC(C1=CC(=CC=C11)C#N)=NN=C1N1CCC(O)CC1 VDXZLVXFVYDBNH-UHFFFAOYSA-N 0.000 claims description 5
- XHJIETATODEJOS-LOSJGSFVSA-N 4-[(4as,8ar)-4-(3,4-diethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]-n-phenylpiperidine-1-carboxamide Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)NC=2C=CC=CC=2)CC1 XHJIETATODEJOS-LOSJGSFVSA-N 0.000 claims description 5
- LWBCVAKHMSFVIE-FCHUYYIVSA-N 4-[(4as,8ar)-4-(3,4-diethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]-n-tert-butylpiperidine-1-carboxamide Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)NC(C)(C)C)CC1 LWBCVAKHMSFVIE-FCHUYYIVSA-N 0.000 claims description 5
- OBLQGGDVCNLUBG-VQTJNVASSA-N 4-[(4as,8ar)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]-n-tert-butylpiperidine-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)NC(C)(C)C)CC1 OBLQGGDVCNLUBG-VQTJNVASSA-N 0.000 claims description 5
- LNMMZMTWCOIELH-UHFFFAOYSA-N 4-methyl-5-pyridin-4-yl-1,3-thiazole-2-carboxamide Chemical compound N1=C(C(N)=O)SC(C=2C=CN=CC=2)=C1C LNMMZMTWCOIELH-UHFFFAOYSA-N 0.000 claims description 5
- HPAKPHNDMHWESA-FCHUYYIVSA-N 5-[4-[(4as,8ar)-4-(3,4-diethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2-yl]piperidin-1-yl]-5-oxopentanoic acid Chemical compound C1=C(OCC)C(OCC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)CCCC(O)=O)CC1 HPAKPHNDMHWESA-FCHUYYIVSA-N 0.000 claims description 5
- OJQQFXIVAUZCJB-UHFFFAOYSA-N 6-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1,5-dihydroimidazo[4,5-g]quinazolin-8-one Chemical compound C1=C(C=2NC(=O)C3=CC=4NC=NC=4C=C3N=2)C(OCCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 OJQQFXIVAUZCJB-UHFFFAOYSA-N 0.000 claims description 5
- OEFNVAZNTGKKSO-CTNGQTDRSA-N C1=2CC(C)(C)OC=2C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(C(=O)NC(C)(C)C)CC1 Chemical compound C1=2CC(C)(C)OC=2C(OC)=CC=C1C([C@@H]1CC=CC[C@@H]1C1=O)=NN1C1CCN(C(=O)NC(C)(C)C)CC1 OEFNVAZNTGKKSO-CTNGQTDRSA-N 0.000 claims description 5
- CCXIVOGMSQZBSB-UHFFFAOYSA-N [5-(1-benzyl-6-fluoroindazol-3-yl)furan-2-yl]methanol Chemical compound O1C(CO)=CC=C1C(C1=CC=C(F)C=C11)=NN1CC1=CC=CC=C1 CCXIVOGMSQZBSB-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Transplantation (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
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| JP (1) | JP2006528229A (enExample) |
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| CO (1) | CO5660275A2 (enExample) |
| EA (1) | EA012279B1 (enExample) |
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| ZA (1) | ZA200508116B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101427163B1 (ko) * | 2011-09-09 | 2014-08-07 | 에스케이케미칼주식회사 | Ｐｄｅ5 억제제를 함유하는 피부 주름 개선용 조성물 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| MXPA04008070A (es) | 2003-03-10 | 2004-11-26 | Altana Pharma Ag | Novedoso proceso para la preparacion de roflumilasto. |
| WO2005023253A1 (en) | 2003-09-05 | 2005-03-17 | Altana Pharma Ag | Use of pde4 inhibitors for the treatment of diabetes mellitus |
| WO2005107749A1 (en) * | 2004-05-10 | 2005-11-17 | Altana Pharma Ag | Use of roflumilast for the prophylaxis or treatment of emphysema |
| MX2007010560A (es) * | 2005-03-08 | 2008-02-21 | Nycomed Gmbh | Roflumilast para el tratamiento de diabetes mellitus. |
| WO2006094942A1 (en) * | 2005-03-08 | 2006-09-14 | Nycomed Gmbh | Roflumilast for the treatment of diabetes mellitus |
| US8663694B2 (en) | 2005-03-16 | 2014-03-04 | Takeda Gmbh | Taste masked dosage form containing roflumilast |
| DE102005016345A1 (de) * | 2005-04-09 | 2006-10-12 | Bayer Healthcare Ag | Neue Verwendung von 2-Phenyl-substituierten Imidazotriazinon-Derivaten |
| CA2604295C (en) * | 2005-04-19 | 2014-10-07 | Nycomed Gmbh | Roflumilast for the treatment of pulmonary hypertension |
| NL2000291C2 (nl) | 2005-11-10 | 2009-02-17 | Pfizer Prod Inc | 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2-ylamino)-1H- pyrazool(4,3-d)pyrimidine-5-yl)piperidine-4-carbonzuur en zouten daarvan. |
| UA106422C2 (uk) * | 2006-07-05 | 2014-08-26 | Такеда Гмбх | КОМБІНОВАНЕ ЗАСТОСУВАННЯ ІНГІБІТОРА PDE4 ТА ІНГІБІТОРА HMG-CоA-РЕДУКТАЗИ ДЛЯ ПРОФІЛАКТИКИ АБО ЗЦІЛЮВАЛЬНОГО ЛІКУВАННЯ ЗАПАЛЬНОГО ЗАХВОРЮВАННЯ ЛЕГЕНІВ |
| CN101547922B (zh) * | 2006-10-04 | 2012-06-20 | 辉瑞产品公司 | 作为钙受体拮抗剂的吡啶并[4,3-d]嘧啶-4(3H)-酮衍生物 |
| WO2010013925A2 (en) * | 2008-07-31 | 2010-02-04 | Dong-A Pharmaceutical. Co., Ltd. | Pharmacological composition for prevention and treatment of respiratory disease containing pyrazolopyrimidinone compound or pharmaceutically acceptable salts thereof |
| JP6225178B2 (ja) * | 2012-05-31 | 2017-11-01 | フェネックス ファーマシューティカルス アーゲー | オーファン核内受容体ＲＯＲγの調整剤としてのカルボキサミドまたはスルホンアミド置換されたチアゾールおよび関連する誘導体 |
| WO2015089105A1 (en) | 2013-12-09 | 2015-06-18 | Respira Therapeutics, Inc. | Pde5 inhibitor powder formulations and methods relating thereto |
| EP3165224A1 (en) | 2015-11-09 | 2017-05-10 | Albert-Ludwigs-Universität Freiburg | Use of pde4 inhibitors for the prophylaxis and/or therapy of dyslipoproteinaemia and related disorders |
| US10058545B2 (en) * | 2016-08-09 | 2018-08-28 | Cipla Limited | Method of treating pulmonary arterial hypertension |
| CN107648224A (zh) * | 2017-10-31 | 2018-02-02 | 泰州中国医药城中医药研究院 | 一种治疗和预防心力衰竭药物及其在制药中的应用 |
| US20210031012A1 (en) | 2018-01-26 | 2021-02-04 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a pde4 inhibitor |
| CN108976107B (zh) * | 2018-08-23 | 2021-03-23 | 南方医科大学 | 3-芳基-4-烷氧基苄胺衍生物及其制备方法和应用 |
| WO2020106704A2 (en) | 2018-11-19 | 2020-05-28 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
| CN121197633A (zh) | 2019-12-13 | 2025-12-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| US20230124467A1 (en) * | 2020-03-03 | 2023-04-20 | Mios Pharmaceuticals Limited | Compounds and methods for treating diseases and/or conditions caused by coronavirus |
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| GB9013750D0 (en) | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| HU220041B (hu) | 1993-07-02 | 2001-10-28 | Byk Gulden Lomberg Chemische Fabrik Gmbh. | Fluor-alkoxi-helyettesített benzamidszármazékok, eljárás előállításukra és ezeket a vegyületeket tartalmazó gyógyászati készítmények |
| GB9401090D0 (en) | 1994-01-21 | 1994-03-16 | Glaxo Lab Sa | Chemical compounds |
| EP0779292A4 (en) * | 1994-08-29 | 1997-09-24 | Yamanouchi Pharma Co Ltd | NEW NAPHTHYRIDE DERIVATIVES AND MEDICAL COMPOSITIONS CONTAINING THEM |
| US6127363A (en) * | 1997-10-28 | 2000-10-03 | Vivus, Inc. | Local administration of Type IV phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| US6362178B1 (en) | 1997-11-12 | 2002-03-26 | Bayer Aktiengesellschaft | 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors |
| US6417190B1 (en) * | 1998-12-17 | 2002-07-09 | Boehringer Ingelheim Pharma Kg | Tricyclic nitrogen heterocycles as PDE IV inhibitors |
| TWI224966B (en) * | 1999-11-02 | 2004-12-11 | Pfizer | Pharmaceutical composition (I) useful for treating or preventing pulmonary hypertension in a patient |
| EA200300836A1 (ru) * | 2001-02-15 | 2004-02-26 | Алтана Фарма Аг | Производные фталазинон-пиперидина в качестве ингибиторов pde4 |
| AU2002314102A1 (en) * | 2001-05-25 | 2002-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Combination of a pde4 inhibitor and tiotropium or derivate thereof for treating obstructive airways |
| US20030114469A1 (en) * | 2001-09-27 | 2003-06-19 | Cohen David Saul | Combinations |
| GB0202254D0 (en) * | 2002-01-31 | 2002-03-20 | Pfizer Ltd | Prevention of scarring |
| US20030216407A1 (en) * | 2002-01-31 | 2003-11-20 | Pfizer Inc. | Use of PDE5 inhibitors in the treatment of scarring |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
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2005
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101427163B1 (ko) * | 2011-09-09 | 2014-08-07 | 에스케이케미칼주식회사 | Ｐｄｅ5 억제제를 함유하는 피부 주름 개선용 조성물 |
Also Published As
| Publication number | Publication date |
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| EP1628682A2 (en) | 2006-03-01 |
| NO20055941L (no) | 2005-12-14 |
| RS20050858A (sr) | 2007-12-31 |
| AU2004241749A1 (en) | 2004-12-02 |
| RS52730B (sr) | 2013-08-30 |
| MXPA05012302A (es) | 2006-01-30 |
| UA83041C2 (ru) | 2008-06-10 |
| CA2525946C (en) | 2013-01-29 |
| ECSP056173A (es) | 2006-04-19 |
| EP1628682B1 (en) | 2013-09-25 |
| TNSN05265A1 (en) | 2007-07-10 |
| MA27855A1 (fr) | 2006-04-03 |
| US20100234382A1 (en) | 2010-09-16 |
| NZ544040A (en) | 2009-03-31 |
| BRPI0410326A (pt) | 2006-05-23 |
| IL171306A (en) | 2013-08-29 |
| JP2006528229A (ja) | 2006-12-14 |
| CN1791429A (zh) | 2006-06-21 |
| US20120196867A1 (en) | 2012-08-02 |
| AU2004241749B2 (en) | 2010-03-25 |
| WO2004103407A3 (en) | 2005-02-17 |
| CO5660275A2 (es) | 2006-07-31 |
| EA200501690A1 (ru) | 2006-06-30 |
| WO2004103407A2 (en) | 2004-12-02 |
| ZA200508116B (en) | 2007-01-31 |
| CA2525946A1 (en) | 2004-12-02 |
| GEP20084342B (en) | 2008-03-25 |
| EA012279B1 (ru) | 2009-08-28 |
| NO333501B1 (no) | 2013-06-24 |
| US20060094723A1 (en) | 2006-05-04 |
| IS8181A (is) | 2005-12-14 |
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