JP2005529180A - ２−ナフトアミド誘導体 - Google Patents
２−ナフトアミド誘導体 Download PDFInfo
- Publication number
- JP2005529180A JP2005529180A JP2004513236A JP2004513236A JP2005529180A JP 2005529180 A JP2005529180 A JP 2005529180A JP 2004513236 A JP2004513236 A JP 2004513236A JP 2004513236 A JP2004513236 A JP 2004513236A JP 2005529180 A JP2005529180 A JP 2005529180A
- Authority
- JP
- Japan
- Prior art keywords
- naphthoyl
- phenylalanine
- aryl
- benzyloxy
- alkyl
- 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.)
- Pending
Links
- JVXXKQIRGQDWOJ-UHFFFAOYSA-N naphthalene-2-carboxamide Chemical class C1=CC=CC2=CC(C(=O)N)=CC=C21 JVXXKQIRGQDWOJ-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 92
- 108091006335 Prostaglandin I receptors Proteins 0.000 claims abstract description 34
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 21
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 21
- 230000002265 prevention Effects 0.000 claims abstract description 15
- 208000002193 Pain Diseases 0.000 claims abstract description 14
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 208000014001 urinary system disease Diseases 0.000 claims abstract description 11
- 208000001953 Hypotension Diseases 0.000 claims abstract description 9
- 230000036543 hypotension Effects 0.000 claims abstract description 9
- 206010061218 Inflammation Diseases 0.000 claims abstract description 8
- 230000004054 inflammatory process Effects 0.000 claims abstract description 8
- 208000031220 Hemophilia Diseases 0.000 claims abstract description 6
- 208000009292 Hemophilia A Diseases 0.000 claims abstract description 6
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 6
- 208000034158 bleeding Diseases 0.000 claims abstract description 6
- 230000000740 bleeding effect Effects 0.000 claims abstract description 6
- -1 hydroxy, amino Chemical group 0.000 claims description 63
- 125000003118 aryl group Chemical group 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- ZXHMHVLLLYJHCA-VWLOTQADSA-N (2s)-3-phenyl-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 ZXHMHVLLLYJHCA-VWLOTQADSA-N 0.000 claims description 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- BUHUSYHVRVAOGE-SANMLTNESA-N (2S)-3-(4-hydroxyphenyl)-2-[methyl-(6-phenylmethoxynaphthalene-2-carbonyl)oxyamino]propanoic acid Chemical compound C(C1=CC=CC=C1)OC=1C=C2C=CC(=CC2=CC=1)C(=O)ON([C@@H](CC1=CC=C(C=C1)O)C(=O)O)C BUHUSYHVRVAOGE-SANMLTNESA-N 0.000 claims description 2
- YTORALQOHQBKLD-VWLOTQADSA-N (2s)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]-3-[3-(trifluoromethyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC(C(F)(F)F)=C1 YTORALQOHQBKLD-VWLOTQADSA-N 0.000 claims description 2
- FEEQKVHOBXISEA-VWLOTQADSA-N (2s)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]-3-[4-(trifluoromethyl)phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=C(C(F)(F)F)C=C1 FEEQKVHOBXISEA-VWLOTQADSA-N 0.000 claims description 2
- JUZSLGLIOKYLRR-DEOSSOPVSA-N (2s)-2-[[6-[(2,3-dichlorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C(=C(Cl)C=CC=3)Cl)=CC2=CC=1)C1=CC=CC=C1 JUZSLGLIOKYLRR-DEOSSOPVSA-N 0.000 claims description 2
- YRJJGRFTKMSZFX-VWLOTQADSA-N (2s)-2-[[6-[(2-bromophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C(=CC=CC=3)Br)=CC2=CC=1)C1=CC=CC=C1 YRJJGRFTKMSZFX-VWLOTQADSA-N 0.000 claims description 2
- CQNXPOBQDKDAPX-VWLOTQADSA-N (2s)-2-[[6-[(2-chlorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C(=CC=CC=3)Cl)=CC2=CC=1)C1=CC=CC=C1 CQNXPOBQDKDAPX-VWLOTQADSA-N 0.000 claims description 2
- FIIPDONVDRHDOP-VWLOTQADSA-N (2s)-2-[[6-[(2-fluorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C(=CC=CC=3)F)=CC2=CC=1)C1=CC=CC=C1 FIIPDONVDRHDOP-VWLOTQADSA-N 0.000 claims description 2
- NDMWOLQBUGJNOJ-VWLOTQADSA-N (2s)-2-[[6-[(2-methoxyphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound COC1=CC=CC=C1COC1=CC=C(C=C(C=C2)C(=O)N[C@@H](CC=3C=CC=CC=3)C(O)=O)C2=C1 NDMWOLQBUGJNOJ-VWLOTQADSA-N 0.000 claims description 2
- HZPCJFLXEZXILW-SANMLTNESA-N (2s)-2-[[6-[(2-methylphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound CC1=CC=CC=C1COC1=CC=C(C=C(C=C2)C(=O)N[C@@H](CC=3C=CC=CC=3)C(O)=O)C2=C1 HZPCJFLXEZXILW-SANMLTNESA-N 0.000 claims description 2
- GSZVZJQVUZHDMQ-VWLOTQADSA-N (2s)-2-[[6-[(3,4-difluorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(F)C(F)=CC=3)=CC2=CC=1)C1=CC=CC=C1 GSZVZJQVUZHDMQ-VWLOTQADSA-N 0.000 claims description 2
- PIJJEXAHJYGQEH-VWLOTQADSA-N (2s)-2-[[6-[(3,5-dichlorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(Cl)C=C(Cl)C=3)=CC2=CC=1)C1=CC=CC=C1 PIJJEXAHJYGQEH-VWLOTQADSA-N 0.000 claims description 2
- LYESCKDBXYIXTA-MHZLTWQESA-N (2s)-2-[[6-[(3,5-dimethoxyphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound COC1=CC(OC)=CC(COC=2C=C3C=CC(=CC3=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)=C1 LYESCKDBXYIXTA-MHZLTWQESA-N 0.000 claims description 2
- IMACPGAIZDCBAX-VWLOTQADSA-N (2s)-2-[[6-[(3-bromophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(Br)C=CC=3)=CC2=CC=1)C1=CC=CC=C1 IMACPGAIZDCBAX-VWLOTQADSA-N 0.000 claims description 2
- TUUOKJHZBYYXCA-VWLOTQADSA-N (2s)-2-[[6-[(3-chlorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=CC=1)C1=CC=CC=C1 TUUOKJHZBYYXCA-VWLOTQADSA-N 0.000 claims description 2
- IKKLSGXYXFHLRY-MHZLTWQESA-N (2s)-2-[[6-[(3-ethoxyphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound CCOC1=CC=CC(COC=2C=C3C=CC(=CC3=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)=C1 IKKLSGXYXFHLRY-MHZLTWQESA-N 0.000 claims description 2
- VWNCUHBPKPFXLU-VWLOTQADSA-N (2s)-2-[[6-[(3-fluorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(F)C=CC=3)=CC2=CC=1)C1=CC=CC=C1 VWNCUHBPKPFXLU-VWLOTQADSA-N 0.000 claims description 2
- CCDBMEARNCXPRZ-SANMLTNESA-N (2s)-2-[[6-[(3-methoxyphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound COC1=CC=CC(COC=2C=C3C=CC(=CC3=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)=C1 CCDBMEARNCXPRZ-SANMLTNESA-N 0.000 claims description 2
- CGOZGVCTZMCIJM-SANMLTNESA-N (2s)-2-[[6-[(3-methylphenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound CC1=CC=CC(COC=2C=C3C=CC(=CC3=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)=C1 CGOZGVCTZMCIJM-SANMLTNESA-N 0.000 claims description 2
- MECDMTZYFIVTIY-VWLOTQADSA-N (2s)-2-[[6-[(3-nitrophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=C(C=CC=3)[N+]([O-])=O)=CC2=CC=1)C1=CC=CC=C1 MECDMTZYFIVTIY-VWLOTQADSA-N 0.000 claims description 2
- CFMKLTVMOUBFCX-VWLOTQADSA-N (2s)-2-[[6-[(4-fluorophenyl)methoxy]naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC(F)=CC=3)=CC2=CC=1)C1=CC=CC=C1 CFMKLTVMOUBFCX-VWLOTQADSA-N 0.000 claims description 2
- SQVFFVMPPQLWJC-VWLOTQADSA-N (2s)-3-(2-fluorophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1F SQVFFVMPPQLWJC-VWLOTQADSA-N 0.000 claims description 2
- MLRHCNKXXXZKQK-VWLOTQADSA-N (2s)-3-(3-fluorophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC(F)=C1 MLRHCNKXXXZKQK-VWLOTQADSA-N 0.000 claims description 2
- TWTCEUGQFPSLEC-VWLOTQADSA-N (2s)-3-(3-hydroxyphenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC(O)=C1 TWTCEUGQFPSLEC-VWLOTQADSA-N 0.000 claims description 2
- PQWGNXROACCQPF-VWLOTQADSA-N (2s)-3-(4-bromophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=C(Br)C=C1 PQWGNXROACCQPF-VWLOTQADSA-N 0.000 claims description 2
- FAGVBFPPQBUBSB-VWLOTQADSA-N (2s)-3-(4-chlorophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=C(Cl)C=C1 FAGVBFPPQBUBSB-VWLOTQADSA-N 0.000 claims description 2
- IVOVPEZNMIAURR-DEOSSOPVSA-N (2s)-3-(4-hydroxy-3-methoxyphenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C1=C(O)C(OC)=CC(C[C@H](NC(=O)C=2C=C3C=CC(OCC=4C=CC=CC=4)=CC3=CC=2)C(O)=O)=C1 IVOVPEZNMIAURR-DEOSSOPVSA-N 0.000 claims description 2
- LPQLBDJBZRPRMM-VWLOTQADSA-N (2s)-3-(4-iodophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=C(I)C=C1 LPQLBDJBZRPRMM-VWLOTQADSA-N 0.000 claims description 2
- MVYCNGPCMKBZPB-VWLOTQADSA-N (2s)-3-(4-nitrophenyl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=C([N+]([O-])=O)C=C1 MVYCNGPCMKBZPB-VWLOTQADSA-N 0.000 claims description 2
- XGOIIFMCHYBVEG-MHZLTWQESA-N (2s)-3-(5-fluoro-1h-indol-3-yl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound N([C@@H](CC=1C2=CC(F)=CC=C2NC=1)C(=O)O)C(=O)C(C=C1C=C2)=CC=C1C=C2OCC1=CC=CC=C1 XGOIIFMCHYBVEG-MHZLTWQESA-N 0.000 claims description 2
- YCQQEIMVQKRBCA-MHZLTWQESA-N (2s)-3-(5-hydroxy-1h-indol-3-yl)-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound N([C@@H](CC=1C2=CC(O)=CC=C2NC=1)C(=O)O)C(=O)C(C=C1C=C2)=CC=C1C=C2OCC1=CC=CC=C1 YCQQEIMVQKRBCA-MHZLTWQESA-N 0.000 claims description 2
- FMKUOTFTXJGBLH-SKCDSABHSA-N (2s)-3-hydroxy-3-phenyl-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound N([C@@H](C(O)C=1C=CC=CC=1)C(O)=O)C(=O)C(C=C1C=C2)=CC=C1C=C2OCC1=CC=CC=C1 FMKUOTFTXJGBLH-SKCDSABHSA-N 0.000 claims description 2
- ZLGXZBDNOOKPFE-SANMLTNESA-N (2s)-3-phenyl-2-[[6-(2-phenylethoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 ZLGXZBDNOOKPFE-SANMLTNESA-N 0.000 claims description 2
- HJAFLBHHGUZWRV-OHMHCFLMSA-N (2s)-3-phenyl-2-[[6-(2-phenylpropoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@H](NC(=O)C1=CC2=CC=C(C=C2C=C1)OCC(C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 HJAFLBHHGUZWRV-OHMHCFLMSA-N 0.000 claims description 2
- AOSJDEUJANOATM-VWLOTQADSA-N (2s)-3-phenyl-2-[[6-(2-pyridin-4-ylethoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCCC=3C=CN=CC=3)=CC2=CC=1)C1=CC=CC=C1 AOSJDEUJANOATM-VWLOTQADSA-N 0.000 claims description 2
- ZLKIGNWQBDCHJL-DEOSSOPVSA-N (2s)-3-phenyl-2-[[6-(2-pyrrol-1-ylethoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCCN3C=CC=C3)=CC2=CC=1)C1=CC=CC=C1 ZLKIGNWQBDCHJL-DEOSSOPVSA-N 0.000 claims description 2
- RBADCINDQXFTRB-DEOSSOPVSA-N (2s)-3-phenyl-2-[[6-(pyridin-3-ylmethoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=NC=CC=3)=CC2=CC=1)C1=CC=CC=C1 RBADCINDQXFTRB-DEOSSOPVSA-N 0.000 claims description 2
- VOJXBFUXBWLQQV-DEOSSOPVSA-N (2s)-3-phenyl-2-[[6-(pyridin-4-ylmethoxy)naphthalene-2-carbonyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CN=CC=3)=CC2=CC=1)C1=CC=CC=C1 VOJXBFUXBWLQQV-DEOSSOPVSA-N 0.000 claims description 2
- VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 claims description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- ZTXWIKHKNGFJAX-UHFFFAOYSA-N 1-hydroxynaphthalene-2-carboxamide Chemical class C1=CC=CC2=C(O)C(C(=O)N)=CC=C21 ZTXWIKHKNGFJAX-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 21
- 210000003932 urinary bladder Anatomy 0.000 abstract description 21
- 206010020853 Hypertonic bladder Diseases 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000009722 Overactive Urinary Bladder Diseases 0.000 abstract description 7
- 208000020629 overactive bladder Diseases 0.000 abstract description 7
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 6
- 208000026935 allergic disease Diseases 0.000 abstract description 6
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 abstract description 4
- 230000009610 hypersensitivity Effects 0.000 abstract description 4
- 206010046543 Urinary incontinence Diseases 0.000 abstract description 3
- 208000012931 Urologic disease Diseases 0.000 abstract description 3
- 201000003146 cystitis Diseases 0.000 abstract description 3
- 210000002307 prostate Anatomy 0.000 abstract description 3
- 208000000094 Chronic Pain Diseases 0.000 abstract description 2
- 206010019233 Headaches Diseases 0.000 abstract description 2
- 206010065390 Inflammatory pain Diseases 0.000 abstract description 2
- 206010061876 Obstruction Diseases 0.000 abstract description 2
- 208000000450 Pelvic Pain Diseases 0.000 abstract description 2
- 206010065347 Premenstrual pain Diseases 0.000 abstract description 2
- 206010066218 Stress Urinary Incontinence Diseases 0.000 abstract description 2
- 208000005298 acute pain Diseases 0.000 abstract description 2
- 230000003247 decreasing effect Effects 0.000 abstract description 2
- 231100000869 headache Toxicity 0.000 abstract description 2
- 230000004047 hyperresponsiveness Effects 0.000 abstract description 2
- 208000004296 neuralgia Diseases 0.000 abstract description 2
- 208000021722 neuropathic pain Diseases 0.000 abstract description 2
- 201000007094 prostatitis Diseases 0.000 abstract description 2
- 208000011580 syndromic disease Diseases 0.000 abstract description 2
- 208000004371 toothache Diseases 0.000 abstract description 2
- 208000000143 urethritis Diseases 0.000 abstract description 2
- 208000009935 visceral pain Diseases 0.000 abstract description 2
- 230000027939 micturition Effects 0.000 abstract 1
- 206010029446 nocturia Diseases 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 201000004240 prostatic hypertrophy Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000203 mixture Substances 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 230000001953 sensory effect Effects 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 8
- 210000005036 nerve Anatomy 0.000 description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
- 230000008602 contraction Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 6
- 238000004949 mass spectrometry Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 5
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 150000003462 sulfoxides Chemical class 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 206010071445 Bladder outlet obstruction Diseases 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 4
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- 229960002240 iloprost Drugs 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000000737 periodic effect Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000003923 Protein Kinase C Human genes 0.000 description 3
- 108090000315 Protein Kinase C Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- ADGRCXHYBSGXSQ-UHFFFAOYSA-N benzyl 6-(benzylamino)naphthalene-2-carboxylate Chemical compound C=1C=C2C=C(NCC=3C=CC=CC=3)C=CC2=CC=1C(=O)OCC1=CC=CC=C1 ADGRCXHYBSGXSQ-UHFFFAOYSA-N 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 3
- HYWKEJFAGUKOME-SANMLTNESA-N methyl (2s)-2-[[6-(benzylamino)naphthalene-2-carbonyl]amino]-3-phenylpropanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C=1C=C2C=CC(NCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 HYWKEJFAGUKOME-SANMLTNESA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
- 230000008447 perception Effects 0.000 description 3
- 229960005190 phenylalanine Drugs 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 3
- ZXHMHVLLLYJHCA-RUZDIDTESA-N (2r)-3-phenyl-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoic acid Chemical compound C([C@H](C(=O)O)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 ZXHMHVLLLYJHCA-RUZDIDTESA-N 0.000 description 2
- WKVWASPJYFMHJH-VWLOTQADSA-N (2s)-2-[[6-(benzylamino)naphthalene-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(NCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 WKVWASPJYFMHJH-VWLOTQADSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- DUKCNAZJKJRMHA-UHFFFAOYSA-N 6-(benzylamino)naphthalene-2-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2C=C1NCC1=CC=CC=C1 DUKCNAZJKJRMHA-UHFFFAOYSA-N 0.000 description 2
- ZAMRNNPFCAMROT-UHFFFAOYSA-N 6-phenylmethoxynaphthalene-2-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2C=C1OCC1=CC=CC=C1 ZAMRNNPFCAMROT-UHFFFAOYSA-N 0.000 description 2
- 206010005033 Bladder dilatation Diseases 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010036018 Pollakiuria Diseases 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000014384 Type C Phospholipases Human genes 0.000 description 2
- 108010079194 Type C Phospholipases Proteins 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- HKVFISRIUUGTIB-UHFFFAOYSA-O azanium;cerium;nitrate Chemical compound [NH4+].[Ce].[O-][N+]([O-])=O HKVFISRIUUGTIB-UHFFFAOYSA-O 0.000 description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- NVHUHPGVZPNWRK-UHFFFAOYSA-N benzyl 6-phenylmethoxynaphthalene-2-carboxylate Chemical compound C=1C=C2C=C(OCC=3C=CC=CC=3)C=CC2=CC=1C(=O)OCC1=CC=CC=C1 NVHUHPGVZPNWRK-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 230000003491 cAMP production Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- NXPKUYBSGTYTSX-IBGZPJMESA-N methyl (2s)-2-[(6-hydroxynaphthalene-2-carbonyl)amino]-3-phenylpropanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C=1C=C2C=CC(O)=CC2=CC=1)C1=CC=CC=C1 NXPKUYBSGTYTSX-IBGZPJMESA-N 0.000 description 2
- YYFDWNZKBPCGMR-SANMLTNESA-N methyl (2s)-3-phenyl-2-[(6-phenylmethoxynaphthalene-2-carbonyl)amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C=1C=C2C=CC(OCC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 YYFDWNZKBPCGMR-SANMLTNESA-N 0.000 description 2
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 150000003174 prostaglandin I2 derivatives Chemical class 0.000 description 2
- 229940127293 prostanoid Drugs 0.000 description 2
- 150000003814 prostanoids Chemical class 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- ZAIZDXVMSSDZFA-UHFFFAOYSA-N (1-carboxy-2-phenylethyl)azanium;chloride Chemical compound Cl.OC(=O)C(N)CC1=CC=CC=C1 ZAIZDXVMSSDZFA-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BVWQKNHZPCLOHS-DEOSSOPVSA-N (2s)-2-[(6-phenoxynaphthalene-2-carbonyl)amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=C2C=CC(OC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 BVWQKNHZPCLOHS-DEOSSOPVSA-N 0.000 description 1
- 0 **C(C(O)=O)NC(c(cc1)cc2c1cc(*)cc2)=O Chemical compound **C(C(O)=O)NC(c(cc1)cc2c1cc(*)cc2)=O 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- RVDLHGSZWAELAU-UHFFFAOYSA-N 5-tert-butylthiophene-2-carbonyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)S1 RVDLHGSZWAELAU-UHFFFAOYSA-N 0.000 description 1
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 1
- NZTPZUIIYNYZKT-UHFFFAOYSA-N 6-aminonaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(N)=CC=C21 NZTPZUIIYNYZKT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108010073099 Epoprostenol Receptors Proteins 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- IKYCZSUNGFRBJS-UHFFFAOYSA-N Euphorbia factor RL9 = U(1) = Resiniferatoxin Natural products COC1=CC(O)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 IKYCZSUNGFRBJS-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 206010071289 Lower urinary tract symptoms Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027566 Micturition urgency Diseases 0.000 description 1
- WLHBRQYVZLNQFE-UHFFFAOYSA-N O[S+]1C2=CC=CC=C2N=C1 Chemical compound O[S+]1C2=CC=CC=C2N=C1 WLHBRQYVZLNQFE-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100040460 P2X purinoceptor 3 Human genes 0.000 description 1
- 101710189970 P2X purinoceptor 3 Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100026476 Prostacyclin receptor Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000005236 alkanoylamino group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000028004 allergic respiratory disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000013262 cAMP assay Methods 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000012937 correction Methods 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
- 230000002939 deleterious effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 125000000597 dioxinyl group Chemical group 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000036724 intravesical pressure Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UFUXUSKWFPRABN-VWLOTQADSA-N methyl (2s)-2-[(6-phenoxynaphthalene-2-carbonyl)amino]-3-phenylpropanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C=1C=C2C=CC(OC=3C=CC=CC=3)=CC2=CC=1)C1=CC=CC=C1 UFUXUSKWFPRABN-VWLOTQADSA-N 0.000 description 1
- VSDUZFOSJDMAFZ-UHFFFAOYSA-N methyl 2-amino-3-phenylpropanoate Chemical compound COC(=O)C(N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
- 230000003957 neurotransmitter release Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 description 1
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 description 1
- 229940073454 resiniferatoxin Drugs 0.000 description 1
- 201000004335 respiratory allergy Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000008275 solid aerosol Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- FDMCEXDXULPJPG-RFVHGSKJSA-N tert-butyl (2r)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@H](N)CC1=CC=CC=C1 FDMCEXDXULPJPG-RFVHGSKJSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 208000022934 urinary frequency Diseases 0.000 description 1
- 230000036318 urination frequency Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/66—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems and singly-bound oxygen atoms, bound to the same carbon skeleton
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0213488A GB2389580A (en) | 2002-06-12 | 2002-06-12 | 2-Naphthamide PGI2 antagonists |
| PCT/EP2003/005705 WO2003106402A1 (en) | 2002-06-12 | 2003-05-30 | 2-naphtamide derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005529180A true JP2005529180A (ja) | 2005-09-29 |
| JP2005529180A5 JP2005529180A5 (enExample) | 2006-07-13 |
Family
ID=9938442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004513236A Pending JP2005529180A (ja) | 2002-06-12 | 2003-05-30 | ２−ナフトアミド誘導体 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20060166989A1 (enExample) |
| EP (1) | EP1515941A1 (enExample) |
| JP (1) | JP2005529180A (enExample) |
| AU (1) | AU2003238180A1 (enExample) |
| CA (1) | CA2489286A1 (enExample) |
| GB (1) | GB2389580A (enExample) |
| WO (1) | WO2003106402A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1676834A1 (en) * | 2004-12-30 | 2006-07-05 | Sanofi-Aventis Deutschland GmbH | Fused bicyclic carboxamide derivates for use as CXCR2 inhibitors in the treatment of inflammation |
| JP2008530450A (ja) | 2006-05-19 | 2008-08-07 | ビ−エイイ− システムズ パブリック リミテッド カンパニ− | ミリメートルスケールのパルスジェットエンジン |
| WO2008059370A2 (en) | 2006-11-17 | 2008-05-22 | Pfizer Japan Inc. | Substituted bicyclocarboxyamide compounds |
| WO2014086701A1 (en) * | 2012-12-06 | 2014-06-12 | F. Hoffmann-La Roche Ag | Substituted thiazole compounds |
| WO2014114603A1 (en) * | 2013-01-24 | 2014-07-31 | F. Hoffmann-La Roche Ag | Substituted thiazole compounds |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753700A (en) * | 1994-12-28 | 1998-05-19 | Ono Pharmaceutical Co., Ltd. | Naphthyloxyacetic acid derivatives |
| AU4058399A (en) * | 1998-11-20 | 2000-06-13 | Torii Pharmaceutical Co., Ltd. | Naphthalene derivatives |
| WO2001010383A2 (en) * | 1999-08-06 | 2001-02-15 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
| YU68102A (sh) * | 2000-03-16 | 2006-01-16 | F. Hoffmann-La Roche Ag. | Derivati karboksilne kiseline kao ip antagonisti |
| CA2446593A1 (en) * | 2001-05-10 | 2002-11-21 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid derivatives and pharmaceutical compositions comprising the same as an active ingredient |
| US6673791B2 (en) * | 2001-07-30 | 2004-01-06 | Boehringer Ingelheim (Canada) Ltd. | Non-nucleoside reverse transcriptase inhibitors |
-
2002
- 2002-06-12 GB GB0213488A patent/GB2389580A/en not_active Withdrawn
-
2003
- 2003-05-30 US US10/517,677 patent/US20060166989A1/en not_active Abandoned
- 2003-05-30 AU AU2003238180A patent/AU2003238180A1/en not_active Abandoned
- 2003-05-30 CA CA002489286A patent/CA2489286A1/en not_active Abandoned
- 2003-05-30 JP JP2004513236A patent/JP2005529180A/ja active Pending
- 2003-05-30 WO PCT/EP2003/005705 patent/WO2003106402A1/en not_active Ceased
- 2003-05-30 EP EP03735507A patent/EP1515941A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| CA2489286A1 (en) | 2003-12-24 |
| AU2003238180A1 (en) | 2003-12-31 |
| WO2003106402A1 (en) | 2003-12-24 |
| EP1515941A1 (en) | 2005-03-23 |
| US20060166989A1 (en) | 2006-07-27 |
| GB0213488D0 (en) | 2002-07-24 |
| GB2389580A (en) | 2003-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4191825B2 (ja) | ５−アミノイソキサゾール誘導体 | |
| JP2006514110A (ja) | Ｉｐ受容体アンタゴニストとしてのフェニルまたはヘテロアリールアミノアルカン誘導体 | |
| JP5408434B2 (ja) | アミド化合物 | |
| KR102241111B1 (ko) | Ｍｅｋ 억제제로서 헤테로사이클릴 화합물 | |
| KR20080102181A (ko) | 스핑고신-1-포스페이트 (에스1피) 수용체 길항제 생물학적 활성을 갖는 아릴 또는 헤테로아릴기를 포함하는 인돌-3-카르보실산 아미드, 에스테르, 티오아미드 및 티올 에스테르 화합물 | |
| EP3210969B1 (en) | Kcnq2-5 channel activator | |
| JP2002515919A (ja) | 抗炎症化合物 | |
| CZ20011866A3 (cs) | Nesteroidní antiflogistika | |
| JPWO2008149965A1 (ja) | ピリドン化合物 | |
| RU2765718C1 (ru) | Замещенное производное дигидропирролопиразола | |
| JP2020515583A (ja) | アリールシクロプロピル−アミノ−イソキノリニルアミド化合物 | |
| TW201625620A (zh) | 作為蛋白去乙醯酶抑制劑及雙蛋白去乙醯酶蛋白激酶抑制劑之雜環氧肟酸及其使用方法 | |
| JPWO2008123207A1 (ja) | オルニチン誘導体 | |
| JP2011088826A (ja) | 芳香族カルボン酸化合物 | |
| JP2021515787A (ja) | アミノ−ベンゾイソチアゾール及びアミノ−ベンゾイソチアジアゾールのアミド化合物 | |
| CA2659967C (en) | Quinazoline derivatives | |
| JP2005529180A (ja) | ２−ナフトアミド誘導体 | |
| JP2005527518A (ja) | 新規なカルコン（ｃｈａｌｃｏｎｅ）誘導体とその使用 | |
| JP2006517211A (ja) | Ｐｇｉ２アンタゴニストとして使用するためのビス（ヘテロ）アリールカルボキサミド誘導体 | |
| JP2005529181A (ja) | カルボキサミド誘導体 | |
| JP2001525398A (ja) | 選択的β３アドレナリン作動性アゴニスト | |
| CN107459491A (zh) | 含1,2,3‑三氮唑结构的苯甲酰胺类化合物及其用途 | |
| JP2003523994A (ja) | 新規ｃｄ２３インヒビター | |
| JP2010530367A (ja) | カンナビノイドｃｂ１受容体モジュレーターとしての４，５−ジヒドロ−（１ｈ）−ピラゾール誘導体 | |
| JPWO2002012189A1 (ja) | 縮合二環性アミド化合物およびその医薬用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060529 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060529 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20090812 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090818 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100202 |