HRP20010057A2 - Phthalazine derivatives phosphodiesterase 4 inhibitors - Google Patents
Phthalazine derivatives phosphodiesterase 4 inhibitors Download PDFInfo
- Publication number
- HRP20010057A2 HRP20010057A2 HR20010057A HRP20010057A HRP20010057A2 HR P20010057 A2 HRP20010057 A2 HR P20010057A2 HR 20010057 A HR20010057 A HR 20010057A HR P20010057 A HRP20010057 A HR P20010057A HR P20010057 A2 HRP20010057 A2 HR P20010057A2
- Authority
- HR
- Croatia
- Prior art keywords
- mmol
- methoxy
- dichloro
- pyridin
- ylmethyl
- Prior art date
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- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 title description 9
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 281
- 239000000203 mixture Substances 0.000 claims description 200
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 33
- -1 nitro, carboxy groups Chemical group 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 230000000172 allergic effect Effects 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- XXWSOEGOQFQTGV-UHFFFAOYSA-N 1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxy-4-(1,2,4-triazol-1-yl)phthalazine Chemical compound N=1N=C(N2N=CN=C2)C2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl XXWSOEGOQFQTGV-UHFFFAOYSA-N 0.000 claims description 4
- HMTGPYRFOCPERJ-UHFFFAOYSA-N 1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxy-4-phenylphthalazine Chemical compound N=1N=C(C=2C=CC=CC=2)C2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl HMTGPYRFOCPERJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- NMRVFWXFMCLBGE-UHFFFAOYSA-N 3-[1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazin-5-yl]prop-2-yn-1-ol Chemical compound N=1N=CC2=C(C#CCO)C(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl NMRVFWXFMCLBGE-UHFFFAOYSA-N 0.000 claims description 3
- NBNCEZNBWYPDFB-UHFFFAOYSA-N 4-[4-[(3,5-dichloropyridin-4-yl)methyl]-7-methoxyphthalazin-1-yl]morpholine Chemical compound N=1N=C(N2CCOCC2)C2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl NBNCEZNBWYPDFB-UHFFFAOYSA-N 0.000 claims description 3
- AOIWKZZBIKUELG-UHFFFAOYSA-N 4-[5-[1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazin-5-yl]pent-4-ynyl]morpholine;dihydrochloride Chemical compound Cl.Cl.N=1N=CC2=C(C#CCCCN3CCOCC3)C(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl AOIWKZZBIKUELG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- PUQBWQLJPRIWLI-UHFFFAOYSA-N methyl 4-[(3,5-dichloropyridin-4-yl)methyl]-7-methoxy-1h-phthalazine-2-carboxylate Chemical compound N=1N(C(=O)OC)CC2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl PUQBWQLJPRIWLI-UHFFFAOYSA-N 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 101100295741 Gallus gallus COR4 gene Chemical group 0.000 claims description 2
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- DOOIJLDJPKOZRB-UHFFFAOYSA-N n-benzyl-3-[1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazin-5-yl]-n-methylprop-2-yn-1-amine Chemical compound N=1N=CC2=C(C#CCN(C)CC=3C=CC=CC=3)C(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl DOOIJLDJPKOZRB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
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- 239000003480 eluent Substances 0.000 description 50
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 46
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- 238000003756 stirring Methods 0.000 description 40
- 239000000725 suspension Substances 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 34
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 26
- 229910000104 sodium hydride Inorganic materials 0.000 description 24
- 239000004264 Petrolatum Substances 0.000 description 22
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- INJOULQGSUBQJR-UHFFFAOYSA-N 4-[(3,5-dichloropyridin-4-yl)methyl]-7-methoxy-1,2-dihydrophthalazine Chemical compound N=1NCC2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl INJOULQGSUBQJR-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
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- 235000011152 sodium sulphate Nutrition 0.000 description 14
- RPQKQQJAHJDVOD-UHFFFAOYSA-N 4-chloro-1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazine Chemical compound N=1N=C(Cl)C2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl RPQKQQJAHJDVOD-UHFFFAOYSA-N 0.000 description 13
- 229910019213 POCl3 Inorganic materials 0.000 description 13
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DLZVZNAPRCRXEG-UHFFFAOYSA-N methyl 4-oxobutanoate Chemical compound COC(=O)CCC=O DLZVZNAPRCRXEG-UHFFFAOYSA-N 0.000 description 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
- VARXMZFLHHHZPT-UHFFFAOYSA-N n-[4-[(3,5-dichloropyridin-4-yl)methyl]-7-methoxyphthalazin-1-yl]-1,3-thiazol-2-amine Chemical compound N=1N=C(NC=2SC=CN=2)C2=CC(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl VARXMZFLHHHZPT-UHFFFAOYSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- TXPBCWVERVBYPG-UHFFFAOYSA-N n-benzyl-3-[1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazin-5-yl]-n-methylprop-2-yn-1-amine;dihydrochloride Chemical compound Cl.Cl.N=1N=CC2=C(C#CCN(C)CC=3C=CC=CC=3)C(OC)=CC=C2C=1CC1=C(Cl)C=NC=C1Cl TXPBCWVERVBYPG-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- OEEYZSKXPQQSBY-UHFFFAOYSA-N n-hydroxy-3-[6-methoxy-4-(1,3-thiazol-2-yl)phthalazin-1-yl]propanamide Chemical compound C12=CC(OC)=CC=C2C(CCC(=O)NO)=NN=C1C1=NC=CS1 OEEYZSKXPQQSBY-UHFFFAOYSA-N 0.000 description 1
- YANGDHSUFHVSFW-UHFFFAOYSA-N n-hydroxy-4-[6-methoxy-4-(1,3-thiazol-2-yl)phthalazin-1-yl]butanamide Chemical compound C12=CC(OC)=CC=C2C(CCCC(=O)NO)=NN=C1C1=NC=CS1 YANGDHSUFHVSFW-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
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- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- GUWZGMWHDAJAOC-UHFFFAOYSA-N oxoplatinum;hydrate Chemical compound O.[Pt]=O GUWZGMWHDAJAOC-UHFFFAOYSA-N 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
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- KOSORCNALVBYBP-UHFFFAOYSA-N pent-4-ynylbenzene Chemical compound C#CCCCC1=CC=CC=C1 KOSORCNALVBYBP-UHFFFAOYSA-N 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- IEVXRRZWEHUEHP-UHFFFAOYSA-M potassium;3-ethoxy-3-oxoprop-1-en-1-olate Chemical compound [K+].CCOC(=O)C=C[O-] IEVXRRZWEHUEHP-UHFFFAOYSA-M 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000036303 septic shock Effects 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
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000006478 transmetalation reaction Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/34—Phthalazines with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/28—Radicals substituted by nitrogen atoms
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT98MI001670A ITMI981670A1 (it) | 1998-07-21 | 1998-07-21 | Derivati ftalazinici inibitori della fosfodiesterasi 4 |
PCT/EP1999/004904 WO2000005218A1 (en) | 1998-07-21 | 1999-07-13 | Phthalazine derivatives phosphodiesterase 4 inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20010057A2 true HRP20010057A2 (en) | 2002-04-30 |
Family
ID=11380474
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20010057A HRP20010057A2 (en) | 1998-07-21 | 2001-01-22 | Phthalazine derivatives phosphodiesterase 4 inhibitors |
Country Status (35)
Country | Link |
---|---|
US (2) | US6329370B1 (hu) |
EP (2) | EP1097142B1 (hu) |
JP (1) | JP2002521370A (hu) |
KR (1) | KR20010087161A (hu) |
CN (1) | CN1127486C (hu) |
AP (1) | AP2000001993A0 (hu) |
AR (1) | AR019409A1 (hu) |
AT (1) | ATE279397T1 (hu) |
AU (1) | AU765457B2 (hu) |
BG (1) | BG105063A (hu) |
BR (1) | BR9911175A (hu) |
CA (1) | CA2338044A1 (hu) |
CO (1) | CO5090842A1 (hu) |
DE (1) | DE69921139T2 (hu) |
EA (1) | EA200100062A1 (hu) |
EE (1) | EE200100039A (hu) |
HK (1) | HK1039124B (hu) |
HR (1) | HRP20010057A2 (hu) |
HU (1) | HUP0102646A3 (hu) |
ID (1) | ID28874A (hu) |
IL (1) | IL139490A0 (hu) |
IS (1) | IS5772A (hu) |
IT (1) | ITMI981670A1 (hu) |
MX (1) | MXPA01000670A (hu) |
NO (1) | NO318988B1 (hu) |
NZ (1) | NZ507926A (hu) |
OA (1) | OA11582A (hu) |
PA (1) | PA8478301A1 (hu) |
PE (1) | PE20000755A1 (hu) |
PL (1) | PL345187A1 (hu) |
SK (1) | SK1002001A3 (hu) |
TW (1) | TW509682B (hu) |
UA (1) | UA68383C2 (hu) |
WO (1) | WO2000005218A1 (hu) |
YU (1) | YU77500A (hu) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
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CO4950519A1 (es) * | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
IT1296984B1 (it) * | 1997-12-19 | 1999-08-03 | Zambon Spa | Derivati ftalazinici inibitori della fosfodiesterasi 4 |
ITMI981671A1 (it) | 1998-07-21 | 2000-01-21 | Zambon Spa | Derivati ftalazinici inibitori della fosfodisterasi 4 |
DE19921567A1 (de) | 1999-05-11 | 2000-11-16 | Basf Ag | Verwendung von Phthalazine-Derivaten |
DE19963607B4 (de) * | 1999-12-23 | 2005-12-15 | Schering Ag | Verfahren zur Herstellung von 4-(Heteroaryl-methyl) halogen-1(2H)-phthalazinonen |
ITMI20000261A1 (it) * | 2000-02-16 | 2001-08-16 | Zambon Group | Processo per la preparazione di piridiniliden-ftalidi |
EP1274689A2 (en) * | 2000-04-13 | 2003-01-15 | Annovis, Inc. | Sulfur containing dihydrophthalazine antagonists of excitatory amino acid receptors |
US6525049B2 (en) * | 2000-07-05 | 2003-02-25 | Pharmacia & Upjohn Company | Pyrroloquinolones as antiviral agents |
AU2002220241A1 (en) * | 2000-12-01 | 2002-06-11 | Iconix Pharmaceuticals, Inc. | Parb inhibitors |
ITMI20022738A1 (it) * | 2002-12-23 | 2004-06-24 | Zambon Spa | Derivati ftalazinici inibitori della fosfodiesterasi 4. |
ITMI20022739A1 (it) * | 2002-12-23 | 2004-06-24 | Zambon Spa | Derivati ftalazinici inibitori della fosfodiesterasi 4. |
US7652036B2 (en) | 2003-02-25 | 2010-01-26 | Topotarget Uk Limited | Carbamic acid compounds comprising a bicyclic heteroaryl group as HDAC inhibitors |
ITMI20031451A1 (it) * | 2003-07-16 | 2005-01-17 | Zambon Spa | Derivati diidro-ftalazinici inibitori della fosfodiesterasi 4 |
EP1745039A4 (en) * | 2004-05-08 | 2009-07-22 | Neurogen Corp | 3-ARYL-5,6-DISUBSTITUTED PYRIDAZINES |
EP1833803A4 (en) * | 2005-01-03 | 2009-08-05 | Myriad Genetics Inc | PHARMACEUTICAL COMPOUNDS COMPRISING CASPASE ACTIVATORS AND INDUCERS OF APOPTOSIS AND THE USE THEREOF |
US20090221664A1 (en) | 2005-10-19 | 2009-09-03 | Abhijit Ray | Pharmaceutical compositions of muscarinic receptor antagonists |
EP2131656A4 (en) | 2006-11-15 | 2011-12-07 | Forest Lab Holdings Ltd | phthalazine |
JP5529131B2 (ja) * | 2008-08-13 | 2014-06-25 | 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 | キマーゼ阻害薬 |
CN102108078B (zh) * | 2009-12-24 | 2013-10-30 | 沈阳药科大学 | 1,4-取代酞嗪类化合物及其制备方法和用途 |
RU2014123352A (ru) * | 2011-11-09 | 2015-12-20 | Эббви Дойчланд Гмбх Унд Ко. Кг | Гетероциклические карбоксамиды, полезные в качестве ингибиторов фосфодиэстеразы типа 10а |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2063249A (en) * | 1979-10-09 | 1981-06-03 | Mitsubishi Yuka Pharma | 4-Phenylphthalazine derivatives |
JPH03106873A (ja) * | 1989-09-20 | 1991-05-07 | Morishita Pharmaceut Co Ltd | 1―ピリジルフタラジン誘導体及びそれらを含有する血小板凝集抑制剤 |
ATE115136T1 (de) * | 1990-03-30 | 1994-12-15 | Mitsubishi Chem Ind | 4-phenylphthalazin-derivate. |
EP0634404A1 (en) * | 1993-07-13 | 1995-01-18 | Rhone Poulenc Agriculture Ltd. | Phtalazin derivatives and their use as pesticides |
NZ290952A (en) * | 1994-08-09 | 1998-05-27 | Eisai Co Ltd | Phthalazine derivatives optionally substituted in position-1 by (generally benzyl) amino groups |
IT1296984B1 (it) * | 1997-12-19 | 1999-08-03 | Zambon Spa | Derivati ftalazinici inibitori della fosfodiesterasi 4 |
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1998
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2001
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