JP4571863B2 - 抗痛覚過敏剤として有用なキナゾリノン誘導体 - Google Patents
抗痛覚過敏剤として有用なキナゾリノン誘導体 Download PDFInfo
- Publication number
- JP4571863B2 JP4571863B2 JP2004542493A JP2004542493A JP4571863B2 JP 4571863 B2 JP4571863 B2 JP 4571863B2 JP 2004542493 A JP2004542493 A JP 2004542493A JP 2004542493 A JP2004542493 A JP 2004542493A JP 4571863 B2 JP4571863 B2 JP 4571863B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- isopropyl
- quinazolin
- phenyl
- alkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 6
- 230000003070 anti-hyperalgesia Effects 0.000 title description 2
- -1 6- (3,5-dichloro-phenyl) -7-isopropyl-2-methyl-3H-quinazolin-4-one Chemical compound 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
- JERXWDBVRYWKDD-UHFFFAOYSA-N 6-[4-chloro-3-(cyclopropylmethoxy)phenyl]-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC=2N=C(C)NC(=O)C=2C=C1C(C=1)=CC=C(Cl)C=1OCC1CC1 JERXWDBVRYWKDD-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- ICAKHSWCSZCVGZ-UHFFFAOYSA-N 6-(4-chloro-3-propoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OCCC)=CC(C=2C(=CC3=C(C(NC(C)=N3)=O)C=2)C(C)C)=C1 ICAKHSWCSZCVGZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- IWRPKTFHMYNBLG-UHFFFAOYSA-N 6-(4-chloro-3-fluorophenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC=2N=C(C)NC(=O)C=2C=C1C1=CC=C(Cl)C(F)=C1 IWRPKTFHMYNBLG-UHFFFAOYSA-N 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 claims description 3
- DWZSRSHWSPALHK-UHFFFAOYSA-N 2-amino-6-(4-chlorophenyl)-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC=2N=C(N)NC(=O)C=2C=C1C1=CC=C(Cl)C=C1 DWZSRSHWSPALHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000002346 iodo group Chemical group I* 0.000 claims 2
- IYEAGCFZPPMXAJ-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C2OCOC2=CC(C2=CC3=C(O)N=C(C)N=C3C=C2C(C)C)=C1 IYEAGCFZPPMXAJ-UHFFFAOYSA-N 0.000 claims 1
- RDXYILULMATWRW-UHFFFAOYSA-N 6-(2,4-dichloro-5-ethoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OCC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1Cl RDXYILULMATWRW-UHFFFAOYSA-N 0.000 claims 1
- BWRSQHUDQIKDHM-UHFFFAOYSA-N 6-(3-butoxy-4-chlorophenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OCCCC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 BWRSQHUDQIKDHM-UHFFFAOYSA-N 0.000 claims 1
- CSSXBRYDHQMZRU-UHFFFAOYSA-N 6-(3-chloro-4-methylphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC2=NC(C)=NC(O)=C2C=C1C1=CC=C(C)C(Cl)=C1 CSSXBRYDHQMZRU-UHFFFAOYSA-N 0.000 claims 1
- WNBCBESKJBXZIN-UHFFFAOYSA-N 6-(3-chloro-5-methoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound COC1=CC(Cl)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 WNBCBESKJBXZIN-UHFFFAOYSA-N 0.000 claims 1
- SMRGWACWHWFFKL-UHFFFAOYSA-N 6-(3-ethoxy-4-methoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(OC)C(OCC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 SMRGWACWHWFFKL-UHFFFAOYSA-N 0.000 claims 1
- YTZUAMKAMKGUOC-UHFFFAOYSA-N 6-(4-chloro-3-ethoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OCC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 YTZUAMKAMKGUOC-UHFFFAOYSA-N 0.000 claims 1
- URNSHXGYROWQHW-UHFFFAOYSA-N 6-(4-chloro-3-methoxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 URNSHXGYROWQHW-UHFFFAOYSA-N 0.000 claims 1
- RVJKMGDFPIJABO-UHFFFAOYSA-N 6-(4-chloro-3-propan-2-yloxyphenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OC(C)C)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 RVJKMGDFPIJABO-UHFFFAOYSA-N 0.000 claims 1
- WZEZOMLPFYFWSQ-UHFFFAOYSA-N 6-(4-chlorophenyl)-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC2=NC(C)=NC(O)=C2C=C1C1=CC=C(Cl)C=C1 WZEZOMLPFYFWSQ-UHFFFAOYSA-N 0.000 claims 1
- SFLUCHRLEIGXBQ-UHFFFAOYSA-N 6-[4-chloro-3-(2-hydroxyethoxy)phenyl]-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC2=NC(C)=NC(O)=C2C=C1C1=CC=C(Cl)C(OCCO)=C1 SFLUCHRLEIGXBQ-UHFFFAOYSA-N 0.000 claims 1
- VNQPMWHOGFTRSA-UHFFFAOYSA-N 6-[4-chloro-3-(2-methoxyethoxy)phenyl]-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound C1=C(Cl)C(OCCOC)=CC(C=2C(=CC3=NC(C)=NC(O)=C3C=2)C(C)C)=C1 VNQPMWHOGFTRSA-UHFFFAOYSA-N 0.000 claims 1
- KHBJMEWQCJILRV-UHFFFAOYSA-N 6-[4-chloro-3-(cyclobutylmethoxy)phenyl]-2-methyl-7-propan-2-yl-1h-quinazolin-4-one Chemical compound CC(C)C1=CC2=NC(C)=NC(O)=C2C=C1C(C=1)=CC=C(Cl)C=1OCC1CCC1 KHBJMEWQCJILRV-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 210000002683 foot Anatomy 0.000 description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 208000004454 Hyperalgesia Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 208000004296 neuralgia Diseases 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CMJQIHGBUKZEHP-UHFFFAOYSA-N (4-chloro-3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C(F)=C1 CMJQIHGBUKZEHP-UHFFFAOYSA-N 0.000 description 3
- SKFGRQLMEUDMLM-UHFFFAOYSA-N (4-chloro-3-propoxyphenyl)boronic acid Chemical compound CCCOC1=CC(B(O)O)=CC=C1Cl SKFGRQLMEUDMLM-UHFFFAOYSA-N 0.000 description 3
- LMEMHNYHGJJMEK-UHFFFAOYSA-N 2-nitro-4-propan-2-ylbenzoic acid Chemical compound CC(C)C1=CC=C(C(O)=O)C([N+]([O-])=O)=C1 LMEMHNYHGJJMEK-UHFFFAOYSA-N 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- CIFBIIKFGFJMBD-UHFFFAOYSA-N methyl 2-amino-4-propan-2-ylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)C)C=C1N CIFBIIKFGFJMBD-UHFFFAOYSA-N 0.000 description 3
- JBXCAIRQKAPCJW-UHFFFAOYSA-N methyl 2-amino-5-(4-chloro-3-fluorophenyl)-4-propan-2-ylbenzoate Chemical compound C1=C(N)C(C(=O)OC)=CC(C=2C=C(F)C(Cl)=CC=2)=C1C(C)C JBXCAIRQKAPCJW-UHFFFAOYSA-N 0.000 description 3
- AISFIYCZBJZEGE-UHFFFAOYSA-N methyl 2-amino-5-iodo-4-propan-2-ylbenzoate Chemical compound COC(=O)C1=CC(I)=C(C(C)C)C=C1N AISFIYCZBJZEGE-UHFFFAOYSA-N 0.000 description 3
- MVPARYJCWZYFLK-UHFFFAOYSA-N methyl 2-nitro-4-propan-2-ylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)C)C=C1[N+]([O-])=O MVPARYJCWZYFLK-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- AGYWDGVTLKNTBS-UHFFFAOYSA-N 4-bromo-1-chloro-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1Cl AGYWDGVTLKNTBS-UHFFFAOYSA-N 0.000 description 2
- HUHDUJBASHFLIN-UHFFFAOYSA-N 4-bromo-1-chloro-2-propoxybenzene Chemical compound CCCOC1=CC(Br)=CC=C1Cl HUHDUJBASHFLIN-UHFFFAOYSA-N 0.000 description 2
- ZCJKUXIWCLVCCZ-UHFFFAOYSA-N 6-(4-chlorophenyl)-7-propan-2-yl-1h-3,1-benzoxazine-2,4-dione Chemical compound CC(C)C1=CC=2NC(=O)OC(=O)C=2C=C1C1=CC=C(Cl)C=C1 ZCJKUXIWCLVCCZ-UHFFFAOYSA-N 0.000 description 2
- 208000033116 Asbestos intoxication Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 0 COC(c1ccc(*)cc1N)=O Chemical compound COC(c1ccc(*)cc1N)=O 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical group C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 102000011040 TRPV Cation Channels Human genes 0.000 description 2
- 108010062740 TRPV Cation Channels Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003441 asbestosis Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 229960002504 capsaicin Drugs 0.000 description 2
- 235000017663 capsaicin Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- OKNVKMBANCTYFU-UHFFFAOYSA-N methyl 2-amino-5-(4-chloro-3-propoxyphenyl)-4-propan-2-ylbenzoate Chemical compound C1=C(Cl)C(OCCC)=CC(C=2C(=CC(N)=C(C(=O)OC)C=2)C(C)C)=C1 OKNVKMBANCTYFU-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010517 secondary reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DRKFWQDBPGTSOO-UHFFFAOYSA-N 1-methyl-2-nitro-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(C)C([N+]([O-])=O)=C1 DRKFWQDBPGTSOO-UHFFFAOYSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GNEJSWDBXLWMQW-UHFFFAOYSA-N 2-amino-5-(4-chlorophenyl)-4-propan-2-ylbenzoic acid Chemical compound CC(C)C1=CC(N)=C(C(O)=O)C=C1C1=CC=C(Cl)C=C1 GNEJSWDBXLWMQW-UHFFFAOYSA-N 0.000 description 1
- 239000003185 4 aminobutyric acid B receptor stimulating agent Substances 0.000 description 1
- JJGQFOSYETWZLC-UHFFFAOYSA-N 4-bromo-1-chloro-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC(Br)=CC=C1Cl JJGQFOSYETWZLC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000633069 Homo sapiens Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- OOWLNNDVJJNMDI-UHFFFAOYSA-N NC1=CC=C(C(=C1)C(C)C)C1=CC=C(C=C1)Cl Chemical group NC1=CC=C(C(=C1)C(C)C)C1=CC=C(C=C1)Cl OOWLNNDVJJNMDI-UHFFFAOYSA-N 0.000 description 1
- 206010057178 Osteoarthropathies Diseases 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 241000272534 Struthio camelus Species 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 206010046823 Uterine spasm Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- LLRANSBEYQZKFY-UHFFFAOYSA-N dodecanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCCCCCC(O)=O LLRANSBEYQZKFY-UHFFFAOYSA-N 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940011681 elavil Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000002682 general surgery Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 102000045756 human TRPV1 Human genes 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VJNRIRBOHTXECH-UHFFFAOYSA-N methyl 2-amino-5-(4-chlorophenyl)-4-propan-2-ylbenzoate Chemical compound C1=C(N)C(C(=O)OC)=CC(C=2C=CC(Cl)=CC=2)=C1C(C)C VJNRIRBOHTXECH-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- HXRAMSFGUAOAJR-UHFFFAOYSA-N n,n,n',n'-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine Chemical compound CN(C)C(N(C)C)OC(C)(C)C HXRAMSFGUAOAJR-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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940087480 norpramin Drugs 0.000 description 1
- DBSMLQTUDJVICQ-CJODITQLSA-N onametostat Chemical compound NC1=C2C=CN([C@@H]3C[C@H](CCC4=CC=C5C=C(Br)C(N)=NC5=C4)[C@@H](O)[C@H]3O)C2=NC=N1 DBSMLQTUDJVICQ-CJODITQLSA-N 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940055692 pamelor Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- OGQDIIKRQRZXJH-UHFFFAOYSA-N protriptyline hydrochloride Chemical compound [Cl-].C1=CC2=CC=CC=C2C(CCC[NH2+]C)C2=CC=CC=C21 OGQDIIKRQRZXJH-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000003497 sciatic nerve Anatomy 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
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
- 229940041597 tofranil Drugs 0.000 description 1
- 229940035276 tofranil-pm Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229940045977 vivactil Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0223730.3A GB0223730D0 (en) | 2002-10-11 | 2002-10-11 | Organic compounds |
| PCT/EP2003/011276 WO2004033435A1 (en) | 2002-10-11 | 2003-10-10 | Quinazolinone derivatives useful as anti-hyperalgesic agents |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006503875A JP2006503875A (ja) | 2006-02-02 |
| JP2006503875A5 JP2006503875A5 (enExample) | 2006-11-24 |
| JP4571863B2 true JP4571863B2 (ja) | 2010-10-27 |
Family
ID=9945785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004542493A Expired - Fee Related JP4571863B2 (ja) | 2002-10-11 | 2003-10-10 | 抗痛覚過敏剤として有用なキナゾリノン誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20060154942A1 (enExample) |
| EP (1) | EP1554257A1 (enExample) |
| JP (1) | JP4571863B2 (enExample) |
| CN (1) | CN100432059C (enExample) |
| AR (1) | AR041563A1 (enExample) |
| AU (1) | AU2003273989A1 (enExample) |
| BR (1) | BR0314557A (enExample) |
| CA (1) | CA2501529A1 (enExample) |
| GB (1) | GB0223730D0 (enExample) |
| PE (1) | PE20040736A1 (enExample) |
| TW (1) | TW200410695A (enExample) |
| WO (1) | WO2004033435A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0412769D0 (en) * | 2004-06-08 | 2004-07-07 | Novartis Ag | Organic compounds |
| US20070054916A1 (en) * | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| KR20060087386A (ko) | 2005-01-28 | 2006-08-02 | 주식회사 대웅제약 | 신규 벤조이미다졸 유도체 및 이를 함유하는 약제학적조성물 |
| GB0507298D0 (en) | 2005-04-11 | 2005-05-18 | Novartis Ag | Organic compounds |
| GB0525068D0 (en) * | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| GB0525069D0 (en) * | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| CA2660957C (en) | 2006-08-23 | 2016-10-11 | Neurogen Corporation | 2-phenoxy pyrimidinone analogues |
| EP2079739A2 (en) * | 2006-10-04 | 2009-07-22 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| JP5372138B2 (ja) | 2008-04-18 | 2013-12-18 | テウン ファーマシューティカル カンパニー,リミテッド | 新規ベンゾオキサジンベンズイミダゾール誘導体、これを含む薬学組成物およびこの用途 |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| JP2013518085A (ja) | 2010-02-01 | 2013-05-20 | ノバルティス アーゲー | CRF−1受容体アンタゴニストとしてのピラゾロ[5,1b]オキサゾール誘導体 |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| JP5748777B2 (ja) | 2010-02-02 | 2015-07-15 | ノバルティス アーゲー | Crf受容体アンタゴニストとしてのシクロヘキシルアミド誘導体 |
| EP2588197B1 (en) * | 2010-07-02 | 2014-11-05 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| KR101293384B1 (ko) | 2010-10-13 | 2013-08-05 | 주식회사 대웅제약 | 신규 피리딜 벤조옥사진 유도체, 이를 포함하는 약학 조성물 및 이의 용도 |
| KR20140033377A (ko) | 2011-05-10 | 2014-03-18 | 길리애드 사이언시즈, 인코포레이티드 | 나트륨 채널 조절제로서의 융합된 헤테로시클릭 화합물 |
| UY34094A (es) | 2011-05-27 | 2013-01-03 | Novartis Ag | Derivados de la piperidina 3-espirocíclica como agonistas de receptores de la ghrelina |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| UY34171A (es) | 2011-07-01 | 2013-01-31 | Gilead Sciences Inc | Compuestos heterocíclicos fusionados como moduladores del canal iónico |
| CA2867043A1 (en) | 2012-05-03 | 2013-11-07 | Novartis Ag | L-malate salt of 2,7-diaza-spiro[4.5]dec-7-yle derivatives and crystalline forms thereof as ghrelin receptor agonists |
| US9884841B2 (en) | 2015-04-20 | 2018-02-06 | The Regents Of The University Of Michigan | Small molecule inhibitors of Mcl-1 and uses thereof |
| DE102022104759A1 (de) | 2022-02-28 | 2023-08-31 | SCi Kontor GmbH | Co-Kristall-Screening Verfahren, insbesondere zur Herstellung von Co-Kristallen |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE793737A (fr) * | 1972-01-06 | 1973-07-05 | Alkaline Batteries Ltd | Fermeture de trou de remplissage pour elements d'accumulateurs electriques |
| DE3041678A1 (de) * | 1979-11-15 | 1981-05-27 | Sandoz-Patent-GmbH, 7850 Lörrach | Ein 1-isopropyl-4-phenyl-2(1h)-chinazolinonderivat, dessen herstellung und verwendung |
| JPS56113769A (en) * | 1980-02-13 | 1981-09-07 | Sumitomo Chem Co Ltd | Novel 2 1h -quinazolinone derivative and its preparation |
| JPS5711970A (en) * | 1980-06-24 | 1982-01-21 | Tanabe Seiyaku Co Ltd | Quinazolinone compound and its preparation |
| JPS5714588A (en) * | 1980-07-02 | 1982-01-25 | Kanto Ishi Pharma Co Ltd | 1- tetrahydro-4-pyridyl -2-substituted-quinazolin-4-one derivative and its preparation |
| JPS57149277A (en) * | 1981-03-10 | 1982-09-14 | Taiho Yakuhin Kogyo Kk | Heterocyclic compound |
| DD206995A1 (de) * | 1982-01-20 | 1984-02-15 | Akad Wissenschaften Ddr | Verfahren zur herstellung von 9h-tetrazolo(5,1-b)chinazolin-9-onen |
| CS247557B1 (en) * | 1984-04-06 | 1987-01-15 | Ludmila Fisnerova | Esters of 3-(2-hydroxyethyl)-4(3h)-quinazolinone |
| US5290780A (en) * | 1991-01-30 | 1994-03-01 | American Cyanamid Co. | Angiotensin II receptor blocking 2,3,6 substituted quinazolinones |
| US5284853A (en) * | 1993-04-23 | 1994-02-08 | American Cyanamid Company | Angiotensin II receptor blocking 2,3,6 substituted quinazolinones |
| US5294617A (en) * | 1993-04-23 | 1994-03-15 | American Cyanamid Company | Angiotensin II receptor blocking 2,3,6 substituted quinazolinones |
| EP0635263A3 (en) * | 1993-06-28 | 1995-09-27 | American Cyanamid Co | Angiotensin II antagonists (AII) as inhibitors of the growth of adipose tissue. |
| EP0760819B1 (en) * | 1994-05-24 | 2000-07-19 | F. Hoffmann-La Roche Ag | Tricyclic dicarbonyl derivatives |
| US5783577A (en) * | 1995-09-15 | 1998-07-21 | Trega Biosciences, Inc. | Synthesis of quinazolinone libraries and derivatives thereof |
| US5739330A (en) * | 1996-02-05 | 1998-04-14 | Hoechst Celanese Corporation | Process for preparing quinazolones |
| WO1997044041A1 (en) * | 1996-05-20 | 1997-11-27 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| WO1998018781A2 (en) * | 1996-10-28 | 1998-05-07 | Versicor, Inc. | Fused 2,4-pyrimidinedione combinatorial libraries, their preparation and the use of fused 2,4-pyrimidinediones derivatives as antimicrobial agents |
| AU4742101A (en) * | 2000-03-17 | 2001-10-03 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
-
2002
- 2002-10-11 GB GBGB0223730.3A patent/GB0223730D0/en not_active Ceased
-
2003
- 2003-10-06 TW TW092127685A patent/TW200410695A/zh unknown
- 2003-10-09 PE PE2003001026A patent/PE20040736A1/es not_active Application Discontinuation
- 2003-10-09 AR ARP030103674A patent/AR041563A1/es unknown
- 2003-10-10 EP EP03757959A patent/EP1554257A1/en not_active Withdrawn
- 2003-10-10 WO PCT/EP2003/011276 patent/WO2004033435A1/en not_active Ceased
- 2003-10-10 CA CA002501529A patent/CA2501529A1/en not_active Abandoned
- 2003-10-10 BR BR0314557-3A patent/BR0314557A/pt not_active IP Right Cessation
- 2003-10-10 JP JP2004542493A patent/JP4571863B2/ja not_active Expired - Fee Related
- 2003-10-10 AU AU2003273989A patent/AU2003273989A1/en not_active Abandoned
- 2003-10-10 US US10/530,897 patent/US20060154942A1/en not_active Abandoned
- 2003-10-10 CN CNB2003801029327A patent/CN100432059C/zh not_active Expired - Fee Related
-
2007
- 2007-12-04 US US11/950,079 patent/US20080293939A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003273989A1 (en) | 2004-05-04 |
| JP2006503875A (ja) | 2006-02-02 |
| CN100432059C (zh) | 2008-11-12 |
| TW200410695A (en) | 2004-07-01 |
| PE20040736A1 (es) | 2004-12-08 |
| US20080293939A1 (en) | 2008-11-27 |
| CN1711249A (zh) | 2005-12-21 |
| CA2501529A1 (en) | 2004-04-22 |
| US20060154942A1 (en) | 2006-07-13 |
| WO2004033435A1 (en) | 2004-04-22 |
| EP1554257A1 (en) | 2005-07-20 |
| GB0223730D0 (en) | 2002-11-20 |
| AR041563A1 (es) | 2005-05-18 |
| BR0314557A (pt) | 2005-08-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4571863B2 (ja) | 抗痛覚過敏剤として有用なキナゾリノン誘導体 | |
| JP4054368B2 (ja) | 置換メチルアリール又はヘテロアリールアミド化合物 | |
| JP5400812B2 (ja) | バニロイドアンタゴニストとして有用なキナゾリノン誘導体 | |
| JP4116058B2 (ja) | プロスタグランジンe2拮抗薬としてのフェニルまたはピリジルアミド化合物 | |
| EA011087B1 (ru) | Соединения и фармацевтические композиции для лечения воспалительных заболеваний | |
| TW201302753A (zh) | 9-取代-8-氧基腺嘌呤化合物 | |
| JPH09510191A (ja) | ホスホジエステラーゼ阻害薬としての置換ビフェニル誘導体 | |
| IE913477A1 (en) | Indole derivatives as antiallergy and antiinflammatory agents | |
| CZ178092A3 (en) | Amidine compounds and process for preparing thereof | |
| CA2566053A1 (en) | Phenyl carboxamide compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease | |
| JP2008501762A (ja) | バニロイドアンタゴニストとして有用なクロモン誘導体 | |
| CN117362231A (zh) | 一种取代脒类化合物的合成方法及其用途 | |
| JPH08143525A (ja) | ヒドロキシ安息香酸アミド誘導体を有効成分とする骨疾患の予防・治療剤 | |
| JPS62267250A (ja) | 抗不整脈剤 | |
| CN116082259B (zh) | 氨基甲酸酯基或氨甲酰基取代的5-ht2b拮抗剂 | |
| JPH0629264B2 (ja) | 2‐アミノ‐5‐ヒドロキシ‐4‐ピリミドン | |
| KR102514860B1 (ko) | 5-ht7 세로토닌 수용체 활성 저해용 바이페닐 피롤리딘 및 바이페닐 다이하이드로이미다졸 유도체 및 이를 유효성분으로 포함하는 약학 조성물 | |
| CN114436945B (zh) | 一种苯磺酰胺类化合物、制备方法及应用 | |
| JP2003529532A (ja) | 4−3−置換−アミノ−シクロブト−3−エン−1,2−ジオン及び平滑筋収縮に影響を及ぼすための使用 | |
| WO2010060277A1 (zh) | 取代乙酰肼类衍生物及其制备方法和用途 | |
| JPH0971570A (ja) | ピリミジン誘導体及びこれを含有する医薬 | |
| JPH05262736A (ja) | フェノキシ酢酸誘導体 | |
| CN107304180A (zh) | 苯甲酰胺类衍生物、其制备方法及其在医药上的用途 | |
| IL114388A (en) | Use of 2-amino-n-(1,2-diphenyl-1-methylethyl) acetamide and salts thereof in the manufacture of neuroprotective pharmaceutical compositions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061005 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061005 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100302 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100602 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100629 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100709 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100810 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100813 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130820 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |