JP5934778B2 - Trpv1拮抗薬 - Google Patents
Trpv1拮抗薬 Download PDFInfo
- Publication number
- JP5934778B2 JP5934778B2 JP2014501238A JP2014501238A JP5934778B2 JP 5934778 B2 JP5934778 B2 JP 5934778B2 JP 2014501238 A JP2014501238 A JP 2014501238A JP 2014501238 A JP2014501238 A JP 2014501238A JP 5934778 B2 JP5934778 B2 JP 5934778B2
- Authority
- JP
- Japan
- Prior art keywords
- urea
- indazol
- phenylcyclopentyl
- methyl
- compound
- 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
- PJAAESPGJOSQGZ-DZGBDDFRSA-N Isovelleral Chemical compound O=CC1=C[C@@H]2CC(C)(C)C[C@@H]2[C@@]2(C)C[C@]21C=O PJAAESPGJOSQGZ-DZGBDDFRSA-N 0.000 title description 3
- 229940126422 TRPV1 antagonist Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 558
- 229910052739 hydrogen Inorganic materials 0.000 claims description 251
- 239000001257 hydrogen Substances 0.000 claims description 251
- 125000000217 alkyl group Chemical group 0.000 claims description 193
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 135
- -1 - CN Inorganic materials 0.000 claims description 133
- 238000000034 method Methods 0.000 claims description 88
- 208000002193 Pain Diseases 0.000 claims description 83
- 150000003839 salts Chemical class 0.000 claims description 74
- 230000036407 pain Effects 0.000 claims description 69
- 125000001188 haloalkyl group Chemical group 0.000 claims description 64
- 239000012453 solvate Substances 0.000 claims description 55
- 239000003814 drug Substances 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 125000005466 alkylenyl group Chemical group 0.000 claims description 29
- 239000004202 carbamide Substances 0.000 claims description 28
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 230000004044 response Effects 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000003981 vehicle Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 239000003937 drug carrier Substances 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 230000004913 activation Effects 0.000 claims description 15
- 229940035676 analgesics Drugs 0.000 claims description 13
- 239000000730 antalgic agent Substances 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 230000003040 nociceptive effect Effects 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 230000001473 noxious effect Effects 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 230000000202 analgesic effect Effects 0.000 claims description 10
- JSEHDPNFIUYQLO-CABCVRRESA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 JSEHDPNFIUYQLO-CABCVRRESA-N 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- QBZJKZLZONBSQS-LSDHHAIUSA-N 1-(1h-indazol-4-yl)-3-[(1s,4r)-4-phenylcyclopent-2-en-1-yl]urea Chemical compound C1([C@@H]2C[C@@H](C=C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 QBZJKZLZONBSQS-LSDHHAIUSA-N 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- JSEHDPNFIUYQLO-LSDHHAIUSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 JSEHDPNFIUYQLO-LSDHHAIUSA-N 0.000 claims description 7
- JSEHDPNFIUYQLO-GJZGRUSLSA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 JSEHDPNFIUYQLO-GJZGRUSLSA-N 0.000 claims description 7
- YZQTXNNYKDDAPW-JQHSSLGASA-N 1-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-JQHSSLGASA-N 0.000 claims description 7
- 238000007654 immersion Methods 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- ZUBKNAZCFHWQRU-JKSUJKDBSA-N 1-(1-methylindazol-4-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1 ZUBKNAZCFHWQRU-JKSUJKDBSA-N 0.000 claims description 6
- FPFQYWQWBIOHBB-NVXWUHKLSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxoquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC(F)=C1 FPFQYWQWBIOHBB-NVXWUHKLSA-N 0.000 claims description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 6
- ADHPABPSTJYXKJ-DLBZAZTESA-N 1-(1-methyl-2-oxoquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC=C1 ADHPABPSTJYXKJ-DLBZAZTESA-N 0.000 claims description 5
- 230000003185 calcium uptake Effects 0.000 claims description 5
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- ADHPABPSTJYXKJ-SJORKVTESA-N 1-(1-methyl-2-oxoquinolin-5-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC=C1 ADHPABPSTJYXKJ-SJORKVTESA-N 0.000 claims description 4
- NKALKRMYMAIVGL-UKRRQHHQSA-N 1-(1h-indazol-4-yl)-3-[(1r,3r)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 NKALKRMYMAIVGL-UKRRQHHQSA-N 0.000 claims description 4
- HLGPATMBCZPXJD-FOIQADDNSA-N 1-(1h-indazol-4-yl)-3-[(1r,3r)-3-methyl-3-phenylcyclopentyl]urea Chemical compound C1([C@]2(C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)C)=CC=CC=C1 HLGPATMBCZPXJD-FOIQADDNSA-N 0.000 claims description 4
- JSEHDPNFIUYQLO-HUUCEWRRSA-N 1-(1h-indazol-4-yl)-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 JSEHDPNFIUYQLO-HUUCEWRRSA-N 0.000 claims description 4
- NKALKRMYMAIVGL-DZGCQCFKSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 NKALKRMYMAIVGL-DZGCQCFKSA-N 0.000 claims description 4
- WKQXTHBIRKOSOW-JKSUJKDBSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-phenylcyclohexyl]urea Chemical compound C1([C@H]2CCC[C@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 WKQXTHBIRKOSOW-JKSUJKDBSA-N 0.000 claims description 4
- QBZJKZLZONBSQS-CABCVRRESA-N 1-(1h-indazol-4-yl)-3-[(1r,4s)-4-phenylcyclopent-2-en-1-yl]urea Chemical compound C1([C@H]2C[C@H](C=C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 QBZJKZLZONBSQS-CABCVRRESA-N 0.000 claims description 4
- MNEYZABFWBZKLE-MMMWYMCRSA-N 1-(1h-indazol-4-yl)-3-[(1s,2r,4s,5s)-4-phenyl-2-bicyclo[3.1.0]hexanyl]urea Chemical compound C1([C@H]2C[C@H]([C@H]3C[C@H]32)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 MNEYZABFWBZKLE-MMMWYMCRSA-N 0.000 claims description 4
- HLGPATMBCZPXJD-MGPUTAFESA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-methyl-3-phenylcyclopentyl]urea Chemical compound C1([C@]2(C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)C)=CC=CC=C1 HLGPATMBCZPXJD-MGPUTAFESA-N 0.000 claims description 4
- NYRYHBOJBYCZTL-OLZOCXBDSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-pyridin-2-ylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=N1 NYRYHBOJBYCZTL-OLZOCXBDSA-N 0.000 claims description 4
- NKALKRMYMAIVGL-ZFWWWQNUSA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 NKALKRMYMAIVGL-ZFWWWQNUSA-N 0.000 claims description 4
- WKQXTHBIRKOSOW-HOTGVXAUSA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-phenylcyclohexyl]urea Chemical compound C1([C@H]2CCC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 WKQXTHBIRKOSOW-HOTGVXAUSA-N 0.000 claims description 4
- ZICZWKKYCQOTAD-BTPDRXCOSA-N 1-[(1r,2r,4s,5r)-6,6-difluoro-4-phenyl-2-bicyclo[3.1.0]hexanyl]-3-(1h-indazol-4-yl)urea Chemical compound C1([C@@H]2[C@@H]3[C@H]([C@@H](C2)NC(=O)NC=2C=4C=NNC=4C=CC=2)C3(F)F)=CC=CC=C1 ZICZWKKYCQOTAD-BTPDRXCOSA-N 0.000 claims description 4
- MNXPYZUSFURMKS-CHWSQXEVSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC=C1[C@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 MNXPYZUSFURMKS-CHWSQXEVSA-N 0.000 claims description 4
- ROOFFAWDIFZLQB-UKRRQHHQSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC([C@H]2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 ROOFFAWDIFZLQB-UKRRQHHQSA-N 0.000 claims description 4
- MNXPYZUSFURMKS-QWHCGFSZSA-N 1-[(1r,3s)-3-(2-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC=C1[C@@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 MNXPYZUSFURMKS-QWHCGFSZSA-N 0.000 claims description 4
- NGJOCHXSRSVEDI-CABCVRRESA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxoquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC=C1F NGJOCHXSRSVEDI-CABCVRRESA-N 0.000 claims description 4
- RVOBNXHEQUSXBI-CABCVRRESA-N 1-[(1s,3r)-3-cyclohexylcyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)CCCCC1 RVOBNXHEQUSXBI-CABCVRRESA-N 0.000 claims description 4
- ROOFFAWDIFZLQB-ZFWWWQNUSA-N 1-[(1s,3s)-3-(3-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC([C@@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 ROOFFAWDIFZLQB-ZFWWWQNUSA-N 0.000 claims description 4
- YZQTXNNYKDDAPW-KBAYOESNSA-N 1-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-KBAYOESNSA-N 0.000 claims description 4
- YZQTXNNYKDDAPW-CGTJXYLNSA-N 1-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-CGTJXYLNSA-N 0.000 claims description 4
- SWTVJTQZGUXESH-UHFFFAOYSA-N 1-[3-(4-tert-butylphenyl)cyclohexyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=CC(C(C)(C)C)=CC=C1C1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 SWTVJTQZGUXESH-UHFFFAOYSA-N 0.000 claims description 4
- WVMIJWVJPZITOC-OKILXGFUSA-N C1([C@@H]2C[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 Chemical compound C1([C@@H]2C[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 WVMIJWVJPZITOC-OKILXGFUSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- LROUIROOTPZFRQ-DLBZAZTESA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC=C1 LROUIROOTPZFRQ-DLBZAZTESA-N 0.000 claims description 3
- LROUIROOTPZFRQ-SJORKVTESA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC=C1 LROUIROOTPZFRQ-SJORKVTESA-N 0.000 claims description 3
- CLYGEYINXAEOCM-MSOLQXFVSA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC=C1 CLYGEYINXAEOCM-MSOLQXFVSA-N 0.000 claims description 3
- CLYGEYINXAEOCM-ROUUACIJSA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC=C1 CLYGEYINXAEOCM-ROUUACIJSA-N 0.000 claims description 3
- ADHPABPSTJYXKJ-IRXDYDNUSA-N 1-(1-methyl-2-oxoquinolin-5-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC=C1 ADHPABPSTJYXKJ-IRXDYDNUSA-N 0.000 claims description 3
- ZUBKNAZCFHWQRU-HZPDHXFCSA-N 1-(1-methylindazol-4-yl)-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1 ZUBKNAZCFHWQRU-HZPDHXFCSA-N 0.000 claims description 3
- ZUBKNAZCFHWQRU-CVEARBPZSA-N 1-(1-methylindazol-4-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1 ZUBKNAZCFHWQRU-CVEARBPZSA-N 0.000 claims description 3
- ZUBKNAZCFHWQRU-HOTGVXAUSA-N 1-(1-methylindazol-4-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1 ZUBKNAZCFHWQRU-HOTGVXAUSA-N 0.000 claims description 3
- MZEPFERSLWBFLU-QVDQXJPCSA-N 1-(1h-indazol-4-yl)-3-[(1r)-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclopentyl]urea Chemical compound FC(F)(F)C1=CSC(C2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MZEPFERSLWBFLU-QVDQXJPCSA-N 0.000 claims description 3
- LIRWTZNTTSCOQV-NEPJUHHUSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-(4-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound CC1=COC([C@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 LIRWTZNTTSCOQV-NEPJUHHUSA-N 0.000 claims description 3
- NKALKRMYMAIVGL-HIFRSBDPSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 NKALKRMYMAIVGL-HIFRSBDPSA-N 0.000 claims description 3
- MHISROGAGXEXMG-RYUDHWBXSA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MHISROGAGXEXMG-RYUDHWBXSA-N 0.000 claims description 3
- NYRYHBOJBYCZTL-STQMWFEESA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-pyridin-2-ylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=N1 NYRYHBOJBYCZTL-STQMWFEESA-N 0.000 claims description 3
- WKYAYIGRLGYSBA-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[3-(4-methoxyphenyl)cyclopentyl]urea Chemical compound C1=CC(OC)=CC=C1C1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 WKYAYIGRLGYSBA-UHFFFAOYSA-N 0.000 claims description 3
- UYSOXJBPQRLAAV-JKSUJKDBSA-N 1-(1h-indol-4-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=3C=CNC=3C=CC=2)=CC=CC=C1 UYSOXJBPQRLAAV-JKSUJKDBSA-N 0.000 claims description 3
- KNGIMRWQSYAXPJ-ZWKOTPCHSA-N 1-(2,3-dihydro-1h-inden-4-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=3CCCC=3C=CC=2)=CC=CC=C1 KNGIMRWQSYAXPJ-ZWKOTPCHSA-N 0.000 claims description 3
- KNGIMRWQSYAXPJ-MSOLQXFVSA-N 1-(2,3-dihydro-1h-inden-4-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=3CCCC=3C=CC=2)=CC=CC=C1 KNGIMRWQSYAXPJ-MSOLQXFVSA-N 0.000 claims description 3
- KNGIMRWQSYAXPJ-ROUUACIJSA-N 1-(2,3-dihydro-1h-inden-4-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=3CCCC=3C=CC=2)=CC=CC=C1 KNGIMRWQSYAXPJ-ROUUACIJSA-N 0.000 claims description 3
- FXEKRZUWDWVCFU-IAGOWNOFSA-N 1-(2-oxo-3,4-dihydro-1h-quinolin-7-yl)-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=C3NC(=O)CCC3=CC=2)=CC=CC=C1 FXEKRZUWDWVCFU-IAGOWNOFSA-N 0.000 claims description 3
- FXEKRZUWDWVCFU-DLBZAZTESA-N 1-(2-oxo-3,4-dihydro-1h-quinolin-7-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=C3NC(=O)CCC3=CC=2)=CC=CC=C1 FXEKRZUWDWVCFU-DLBZAZTESA-N 0.000 claims description 3
- FXEKRZUWDWVCFU-SJORKVTESA-N 1-(2-oxo-3,4-dihydro-1h-quinolin-7-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=C3NC(=O)CCC3=CC=2)=CC=CC=C1 FXEKRZUWDWVCFU-SJORKVTESA-N 0.000 claims description 3
- FXEKRZUWDWVCFU-IRXDYDNUSA-N 1-(2-oxo-3,4-dihydro-1h-quinolin-7-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=C3NC(=O)CCC3=CC=2)=CC=CC=C1 FXEKRZUWDWVCFU-IRXDYDNUSA-N 0.000 claims description 3
- HCZOAGMQIGHSPQ-HUUCEWRRSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC=C1F HCZOAGMQIGHSPQ-HUUCEWRRSA-N 0.000 claims description 3
- RTYYAYSQQDQQIF-HZPDHXFCSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC=C1F RTYYAYSQQDQQIF-HZPDHXFCSA-N 0.000 claims description 3
- NGJOCHXSRSVEDI-HUUCEWRRSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxoquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC=C1F NGJOCHXSRSVEDI-HUUCEWRRSA-N 0.000 claims description 3
- CTXFBRJRFVJZDD-ZIAGYGMSSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1F CTXFBRJRFVJZDD-ZIAGYGMSSA-N 0.000 claims description 3
- CWCHZORHHWEPPM-BZUAXINKSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1F CWCHZORHHWEPPM-BZUAXINKSA-N 0.000 claims description 3
- CWCHZORHHWEPPM-OAGGEKHMSA-N 1-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]-3-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1F CWCHZORHHWEPPM-OAGGEKHMSA-N 0.000 claims description 3
- QLRXWFZBURBKFL-NVXWUHKLSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC(F)=C1 QLRXWFZBURBKFL-NVXWUHKLSA-N 0.000 claims description 3
- YSBCSCDCKFNRJN-SJLPKXTDSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC(F)=C1 YSBCSCDCKFNRJN-SJLPKXTDSA-N 0.000 claims description 3
- HQLJSFBVHMPCSV-ZTFGCOKTSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC(F)=C1 HQLJSFBVHMPCSV-ZTFGCOKTSA-N 0.000 claims description 3
- HQLJSFBVHMPCSV-OLMNPRSZSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC(F)=C1 HQLJSFBVHMPCSV-OLMNPRSZSA-N 0.000 claims description 3
- ROOFFAWDIFZLQB-DZGCQCFKSA-N 1-[(1r,3s)-3-(3-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC([C@@H]2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 ROOFFAWDIFZLQB-DZGCQCFKSA-N 0.000 claims description 3
- FCGAPTQXTDOHAX-GYIHYUDTSA-N 1-[(1s,2r,3s,4s)-2,3-dihydroxy-4-phenylcyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1([C@@H]2C[C@@H]([C@H]([C@H]2O)O)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 FCGAPTQXTDOHAX-GYIHYUDTSA-N 0.000 claims description 3
- FCGAPTQXTDOHAX-BIMQEMHKSA-N 1-[(1s,2s,3r,4s)-2,3-dihydroxy-4-phenylcyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1([C@@H]2C[C@@H]([C@@H]([C@@H]2O)O)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 FCGAPTQXTDOHAX-BIMQEMHKSA-N 0.000 claims description 3
- HCZOAGMQIGHSPQ-CABCVRRESA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC=C1F HCZOAGMQIGHSPQ-CABCVRRESA-N 0.000 claims description 3
- RTYYAYSQQDQQIF-CVEARBPZSA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC=C1F RTYYAYSQQDQQIF-CVEARBPZSA-N 0.000 claims description 3
- CTXFBRJRFVJZDD-KGLIPLIRSA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC=C1F CTXFBRJRFVJZDD-KGLIPLIRSA-N 0.000 claims description 3
- MNXPYZUSFURMKS-OLZOCXBDSA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC=C1[C@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 MNXPYZUSFURMKS-OLZOCXBDSA-N 0.000 claims description 3
- CWCHZORHHWEPPM-OWCLPIDISA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1F CWCHZORHHWEPPM-OWCLPIDISA-N 0.000 claims description 3
- CWCHZORHHWEPPM-PMPSAXMXSA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1F CWCHZORHHWEPPM-PMPSAXMXSA-N 0.000 claims description 3
- QLRXWFZBURBKFL-WBVHZDCISA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC(F)=C1 QLRXWFZBURBKFL-WBVHZDCISA-N 0.000 claims description 3
- YSBCSCDCKFNRJN-AEFFLSMTSA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC(F)=C1 YSBCSCDCKFNRJN-AEFFLSMTSA-N 0.000 claims description 3
- FPFQYWQWBIOHBB-WBVHZDCISA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methyl-2-oxoquinolin-5-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3N(C(C=CC3=2)=O)C)=CC=CC(F)=C1 FPFQYWQWBIOHBB-WBVHZDCISA-N 0.000 claims description 3
- VWPBEOFJNRTTPX-ZBFHGGJFSA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC(F)=C1 VWPBEOFJNRTTPX-ZBFHGGJFSA-N 0.000 claims description 3
- ROOFFAWDIFZLQB-HIFRSBDPSA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC([C@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=C1 ROOFFAWDIFZLQB-HIFRSBDPSA-N 0.000 claims description 3
- HQLJSFBVHMPCSV-FHLIZLRMSA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC(F)=C1 HQLJSFBVHMPCSV-FHLIZLRMSA-N 0.000 claims description 3
- HQLJSFBVHMPCSV-JLSDUUJJSA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC(F)=C1 HQLJSFBVHMPCSV-JLSDUUJJSA-N 0.000 claims description 3
- MNXPYZUSFURMKS-STQMWFEESA-N 1-[(1s,3s)-3-(2-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound FC1=CC=CC=C1[C@@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 MNXPYZUSFURMKS-STQMWFEESA-N 0.000 claims description 3
- YZQTXNNYKDDAPW-BPQIPLTHSA-N 1-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-BPQIPLTHSA-N 0.000 claims description 3
- YZQTXNNYKDDAPW-RYQLBKOJSA-N 1-[(2r)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-RYQLBKOJSA-N 0.000 claims description 3
- TWCGLMWGYCDORZ-FVQBIDKESA-N 1-[(2r)-2-methyl-3-oxo-4h-1,4-benzoxazin-8-yl]-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3O[C@@H](C(NC3=CC=C2)=O)C)=CC=CC=C1 TWCGLMWGYCDORZ-FVQBIDKESA-N 0.000 claims description 3
- TWCGLMWGYCDORZ-VNQPRFMTSA-N 1-[(2r)-2-methyl-3-oxo-4h-1,4-benzoxazin-8-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3O[C@@H](C(NC3=CC=C2)=O)C)=CC=CC=C1 TWCGLMWGYCDORZ-VNQPRFMTSA-N 0.000 claims description 3
- YZQTXNNYKDDAPW-NXHRZFHOSA-N 1-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-NXHRZFHOSA-N 0.000 claims description 3
- YZQTXNNYKDDAPW-NJAFHUGGSA-N 1-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-NJAFHUGGSA-N 0.000 claims description 3
- YZQTXNNYKDDAPW-SZMVWBNQSA-N 1-[(2s)-2-hydroxy-2,3-dihydro-1h-inden-4-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@@H](CC3=2)O)=CC=CC=C1 YZQTXNNYKDDAPW-SZMVWBNQSA-N 0.000 claims description 3
- FVKLJXVKEMVGAL-CFMCSPIPSA-N 1-[(3s)-3-(4-fluorophenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=CC(F)=CC=C1[C@@H]1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 FVKLJXVKEMVGAL-CFMCSPIPSA-N 0.000 claims description 3
- FXMUKCRGKDOSMF-AEFFLSMTSA-N 1-[3-(2-hydroxyethyl)-2-oxo-1,4-dihydroquinazolin-7-yl]-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CN(C(NC3=C2)=O)CCO)=CC=CC=C1 FXMUKCRGKDOSMF-AEFFLSMTSA-N 0.000 claims description 3
- FXMUKCRGKDOSMF-WMZOPIPTSA-N 1-[3-(2-hydroxyethyl)-2-oxo-1,4-dihydroquinazolin-7-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CN(C(NC3=C2)=O)CCO)=CC=CC=C1 FXMUKCRGKDOSMF-WMZOPIPTSA-N 0.000 claims description 3
- FKXSIWZCXCHUOB-IXDOHACOSA-N C1([C@@H]2C[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 Chemical compound C1([C@@H]2C[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 FKXSIWZCXCHUOB-IXDOHACOSA-N 0.000 claims description 3
- WVMIJWVJPZITOC-HDJSIYSDSA-N C1([C@H]2C[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 Chemical compound C1([C@H]2C[C@@H](C2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=CC=CC=C1 WVMIJWVJPZITOC-HDJSIYSDSA-N 0.000 claims description 3
- FKXSIWZCXCHUOB-BRWVUGGUSA-N C1([C@H]2C[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 Chemical compound C1([C@H]2C[C@@H](C2)NC(=O)NC=2C=CC=C3C[C@H](CC3=2)O)=CC=CC=C1 FKXSIWZCXCHUOB-BRWVUGGUSA-N 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- 229960001680 ibuprofen Drugs 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- AVTYVUMSPWLWRY-GDBMZVCRSA-N 1-(1h-indazol-4-yl)-3-[(1r,3r)-3-[4-(trifluoromethyl)phenyl]cyclohexyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 AVTYVUMSPWLWRY-GDBMZVCRSA-N 0.000 claims description 2
- LIRWTZNTTSCOQV-NWDGAFQWSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-(4-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound CC1=COC([C@@H]2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 LIRWTZNTTSCOQV-NWDGAFQWSA-N 0.000 claims description 2
- MHISROGAGXEXMG-NWDGAFQWSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@@H]2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MHISROGAGXEXMG-NWDGAFQWSA-N 0.000 claims description 2
- YTNNETGBDWRGMM-NWDGAFQWSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-(5-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound O1C(C)=CN=C1[C@@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 YTNNETGBDWRGMM-NWDGAFQWSA-N 0.000 claims description 2
- AVTYVUMSPWLWRY-GOEBONIOSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-[4-(trifluoromethyl)phenyl]cyclohexyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@@H]1C[C@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 AVTYVUMSPWLWRY-GOEBONIOSA-N 0.000 claims description 2
- MHISROGAGXEXMG-NEPJUHHUSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MHISROGAGXEXMG-NEPJUHHUSA-N 0.000 claims description 2
- YTNNETGBDWRGMM-NEPJUHHUSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-(5-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound O1C(C)=CN=C1[C@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 YTNNETGBDWRGMM-NEPJUHHUSA-N 0.000 claims description 2
- AVTYVUMSPWLWRY-ZBFHGGJFSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-[4-(trifluoromethyl)phenyl]cyclohexyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 AVTYVUMSPWLWRY-ZBFHGGJFSA-N 0.000 claims description 2
- AVTYVUMSPWLWRY-HOCLYGCPSA-N 1-(1h-indazol-4-yl)-3-[(1s,3s)-3-[4-(trifluoromethyl)phenyl]cyclohexyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1[C@@H]1C[C@@H](NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 AVTYVUMSPWLWRY-HOCLYGCPSA-N 0.000 claims description 2
- BMPPXPJQMXLRFH-MLCCFXAWSA-N 1-(1h-indazol-4-yl)-3-[(3s)-3-(4-methylsulfanylphenyl)cyclopentyl]urea Chemical compound C1=CC(SC)=CC=C1[C@@H]1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 BMPPXPJQMXLRFH-MLCCFXAWSA-N 0.000 claims description 2
- AVTYVUMSPWLWRY-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[3-[4-(trifluoromethyl)phenyl]cyclohexyl]urea Chemical compound C1=CC(C(F)(F)F)=CC=C1C1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CCC1 AVTYVUMSPWLWRY-UHFFFAOYSA-N 0.000 claims description 2
- ONAHFNVLVGMRIM-CDOORCJHSA-N 1-(3-morpholin-4-yl-2-oxo-3,4-dihydro-1h-quinolin-7-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=C3NC(=O)C(N4CCOCC4)CC3=CC=2)=CC=CC=C1 ONAHFNVLVGMRIM-CDOORCJHSA-N 0.000 claims description 2
- VWPBEOFJNRTTPX-GDBMZVCRSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-(1-methylindazol-4-yl)urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C)=CC=CC(F)=C1 VWPBEOFJNRTTPX-GDBMZVCRSA-N 0.000 claims description 2
- GAEXNZNJBBGMQI-CRAIPNDOSA-N 1-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[3-(2-hydroxyethyl)-2-oxo-1,4-dihydroquinazolin-7-yl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=CC=C3CN(C(NC3=C2)=O)CCO)=CC=CC(F)=C1 GAEXNZNJBBGMQI-CRAIPNDOSA-N 0.000 claims description 2
- HCJRRLHGQPTXJV-ZBFHGGJFSA-N 1-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]-3-[3-(2-hydroxyethyl)-2-oxo-1,4-dihydroquinazolin-7-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CN(C(NC3=C2)=O)CCO)=CC=CC=C1F HCJRRLHGQPTXJV-ZBFHGGJFSA-N 0.000 claims description 2
- GAEXNZNJBBGMQI-QAPCUYQASA-N 1-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]-3-[3-(2-hydroxyethyl)-2-oxo-1,4-dihydroquinazolin-7-yl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=CC=C3CN(C(NC3=C2)=O)CCO)=CC=CC(F)=C1 GAEXNZNJBBGMQI-QAPCUYQASA-N 0.000 claims description 2
- TWCGLMWGYCDORZ-BMFZPTHFSA-N 1-[(2r)-2-methyl-3-oxo-4h-1,4-benzoxazin-8-yl]-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3O[C@@H](C(NC3=CC=C2)=O)C)=CC=CC=C1 TWCGLMWGYCDORZ-BMFZPTHFSA-N 0.000 claims description 2
- TWCGLMWGYCDORZ-KBMXLJTQSA-N 1-[(2r)-2-methyl-3-oxo-4h-1,4-benzoxazin-8-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3O[C@@H](C(NC3=CC=C2)=O)C)=CC=CC=C1 TWCGLMWGYCDORZ-KBMXLJTQSA-N 0.000 claims description 2
- BXLKMTBOOTUIDN-WXFOFVMLSA-N 1-[3-(1,4-oxazepan-4-yl)-2-oxo-3,4-dihydro-1h-quinolin-7-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=C3NC(=O)C(N4CCOCCC4)CC3=CC=2)=CC=CC=C1 BXLKMTBOOTUIDN-WXFOFVMLSA-N 0.000 claims description 2
- GEXGOLTUHBAKRJ-UHFFFAOYSA-N 1-[3-(4-tert-butylphenyl)cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=CC(C(C)(C)C)=CC=C1C1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 GEXGOLTUHBAKRJ-UHFFFAOYSA-N 0.000 claims description 2
- OLPKNPZTKHTEEO-CDOORCJHSA-N 1-[3-[2-methoxyethyl(methyl)amino]-2-oxo-3,4-dihydro-1h-quinolin-7-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=CC=C3CC(C(NC3=C2)=O)N(C)CCOC)=CC=CC=C1 OLPKNPZTKHTEEO-CDOORCJHSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 230000010989 thermoception Effects 0.000 claims 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 160
- 238000005481 NMR spectroscopy Methods 0.000 description 160
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 158
- 239000000203 mixture Substances 0.000 description 136
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 128
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 122
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 121
- 239000000243 solution Substances 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 235000019439 ethyl acetate Nutrition 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 239000011734 sodium Substances 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 30
- 239000002002 slurry Substances 0.000 description 29
- 229960002504 capsaicin Drugs 0.000 description 28
- 235000017663 capsaicin Nutrition 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000012267 brine Substances 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 235000013877 carbamide Nutrition 0.000 description 26
- 241000700159 Rattus Species 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 229910052760 oxygen Inorganic materials 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- 238000010828 elution Methods 0.000 description 21
- 238000002347 injection Methods 0.000 description 21
- 239000007924 injection Substances 0.000 description 21
- 238000000926 separation method Methods 0.000 description 21
- 208000004454 Hyperalgesia Diseases 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 18
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 125000002950 monocyclic group Chemical group 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 208000004296 neuralgia Diseases 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 15
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
- 229910052700 potassium Inorganic materials 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 108010025083 TRPV1 receptor Proteins 0.000 description 13
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- 208000021722 neuropathic pain Diseases 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 230000001154 acute effect Effects 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 12
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 125000004429 atom Chemical group 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 125000005842 heteroatom Chemical group 0.000 description 11
- 125000002971 oxazolyl group Chemical group 0.000 description 11
- 125000004076 pyridyl group Chemical group 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 125000000335 thiazolyl group Chemical group 0.000 description 11
- 108091006146 Channels Proteins 0.000 description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 10
- 229910004298 SiO 2 Inorganic materials 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000011575 calcium Substances 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 208000014674 injury Diseases 0.000 description 10
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 9
- 208000008035 Back Pain Diseases 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 208000006011 Stroke Diseases 0.000 description 9
- 208000027418 Wounds and injury Diseases 0.000 description 9
- 230000006399 behavior Effects 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 210000000929 nociceptor Anatomy 0.000 description 9
- 108091008700 nociceptors Proteins 0.000 description 9
- 229960005489 paracetamol Drugs 0.000 description 9
- 208000009935 visceral pain Diseases 0.000 description 9
- ZNMXRCDHEJJIIK-MNOVXSKESA-N (1s,3r)-3-phenylcyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@H]1C1=CC=CC=C1 ZNMXRCDHEJJIIK-MNOVXSKESA-N 0.000 description 8
- 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 8
- 206010058019 Cancer Pain Diseases 0.000 description 8
- 229910000564 Raney nickel Inorganic materials 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 150000002537 isoquinolines Chemical class 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 229940005483 opioid analgesics Drugs 0.000 description 8
- 201000008482 osteoarthritis Diseases 0.000 description 8
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000001953 sensory effect Effects 0.000 description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 8
- ZNMXRCDHEJJIIK-QWRGUYRKSA-N (1s,3s)-3-phenylcyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@@H]1C1=CC=CC=C1 ZNMXRCDHEJJIIK-QWRGUYRKSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 208000000094 Chronic Pain Diseases 0.000 description 7
- 206010011224 Cough Diseases 0.000 description 7
- 206010065390 Inflammatory pain Diseases 0.000 description 7
- 208000004550 Postoperative Pain Diseases 0.000 description 7
- 208000026935 allergic disease Diseases 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 210000002683 foot Anatomy 0.000 description 7
- 231100000869 headache Toxicity 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- NYGYORXJYHUSOR-UHFFFAOYSA-N methyl 4-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1NC(=O)ON1C(=O)CCC1=O NYGYORXJYHUSOR-UHFFFAOYSA-N 0.000 description 7
- 208000033808 peripheral neuropathy Diseases 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 description 6
- SOKTXJGBXRRDGK-UHFFFAOYSA-N 7-amino-1-methyl-3,4-dihydroquinolin-2-one Chemical compound C1=C(N)C=C2N(C)C(=O)CCC2=C1 SOKTXJGBXRRDGK-UHFFFAOYSA-N 0.000 description 6
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 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 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 206010019233 Headaches Diseases 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 208000001294 Nociceptive Pain Diseases 0.000 description 6
- 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 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 239000000835 fiber Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 description 6
- 208000028867 ischemia Diseases 0.000 description 6
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 201000001119 neuropathy Diseases 0.000 description 6
- 230000007823 neuropathy Effects 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- VJZSRIHPRAZHIW-ZETCQYMHSA-N (2s)-4-amino-2,3-dihydro-1h-inden-2-ol Chemical compound NC1=CC=CC2=C1C[C@@H](O)C2 VJZSRIHPRAZHIW-ZETCQYMHSA-N 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 206010015958 Eye pain Diseases 0.000 description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 5
- 208000035154 Hyperesthesia Diseases 0.000 description 5
- 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 5
- 208000008930 Low Back Pain Diseases 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 239000004677 Nylon Substances 0.000 description 5
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 208000005298 acute pain Diseases 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
- DRCMAZOSEIMCHM-UHFFFAOYSA-N capsazepine Chemical compound C1C=2C=C(O)C(O)=CC=2CCCN1C(=S)NCCC1=CC=C(Cl)C=C1 DRCMAZOSEIMCHM-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000004296 chiral HPLC Methods 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 210000000548 hind-foot Anatomy 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 5
- 210000004126 nerve fiber Anatomy 0.000 description 5
- 229920001778 nylon Polymers 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 150000003672 ureas Chemical class 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- AJKPXKHWCHZLSF-VIFPVBQESA-N (3s)-3-(4-bromophenyl)cyclopentan-1-one Chemical compound C1=CC(Br)=CC=C1[C@@H]1CC(=O)CC1 AJKPXKHWCHZLSF-VIFPVBQESA-N 0.000 description 4
- QDFKKJYEIFBEFC-UHFFFAOYSA-N 1-bromo-3-fluorobenzene Chemical compound FC1=CC=CC(Br)=C1 QDFKKJYEIFBEFC-UHFFFAOYSA-N 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
- YZYJYCPYUXPNPE-UHFFFAOYSA-N 3-amino-1-methyl-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(C)C(=O)C(N)CC2=C1 YZYJYCPYUXPNPE-UHFFFAOYSA-N 0.000 description 4
- HTKXRTUKPXEALT-UHFFFAOYSA-N 3-bromo-2h-indazole Chemical class C1=CC=CC2=C(Br)NN=C21 HTKXRTUKPXEALT-UHFFFAOYSA-N 0.000 description 4
- ZNMXRCDHEJJIIK-UHFFFAOYSA-N 3-phenylcyclopentan-1-amine Chemical class C1C(N)CCC1C1=CC=CC=C1 ZNMXRCDHEJJIIK-UHFFFAOYSA-N 0.000 description 4
- JQWIVBCJVMEXMT-UHFFFAOYSA-N 5-amino-1-methyl-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2N(C)C(=O)CCC2=C1N JQWIVBCJVMEXMT-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000633069 Homo sapiens Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 206010021113 Hypothermia Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 208000019695 Migraine disease Diseases 0.000 description 4
- 208000028389 Nerve injury Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 4
- 238000010240 RT-PCR analysis Methods 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 206010053552 allodynia Diseases 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 238000005452 bending Methods 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 4
- 229910052805 deuterium Inorganic materials 0.000 description 4
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 4
- 102000045756 human TRPV1 Human genes 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- 230000002631 hypothermal effect Effects 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 206010027599 migraine Diseases 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 230000008764 nerve damage Effects 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000007665 sagging Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- AGDSCTQQXMDDCV-UHFFFAOYSA-M sodium;2-iodoacetate Chemical compound [Na+].[O-]C(=O)CI AGDSCTQQXMDDCV-UHFFFAOYSA-M 0.000 description 4
- 210000001032 spinal nerve Anatomy 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
- QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 3
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 3
- KJNMEDAWCQXQQL-UKRRQHHQSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3r)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@H]2C[C@@H](CC2)NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)=N1 KJNMEDAWCQXQQL-UKRRQHHQSA-N 0.000 description 3
- PAFRMBKESKKSIA-MAUKXSAKSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3s)-3-(3-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC(F)=C1 PAFRMBKESKKSIA-MAUKXSAKSA-N 0.000 description 3
- KJNMEDAWCQXQQL-DZGCQCFKSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@@H]2C[C@@H](CC2)NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)=N1 KJNMEDAWCQXQQL-DZGCQCFKSA-N 0.000 description 3
- BLFYIBROKHRKEJ-FUHWJXTLSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1 BLFYIBROKHRKEJ-FUHWJXTLSA-N 0.000 description 3
- KJNMEDAWCQXQQL-HIFRSBDPSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3r)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@H]2C[C@H](CC2)NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)=N1 KJNMEDAWCQXQQL-HIFRSBDPSA-N 0.000 description 3
- KJNMEDAWCQXQQL-ZFWWWQNUSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]urea Chemical compound CC1=CSC([C@@H]2C[C@H](CC2)NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)=N1 KJNMEDAWCQXQQL-ZFWWWQNUSA-N 0.000 description 3
- ASPDTLYCFOPVFV-AZUAARDMSA-N 1-[6-fluoro-3-(2-methylpropyl)isoquinolin-5-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)CC(C)C)=CC=CC=C1 ASPDTLYCFOPVFV-AZUAARDMSA-N 0.000 description 3
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 3
- RNJQBGXOSAQQDG-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1CCC(C(O)=O)C1 RNJQBGXOSAQQDG-UHFFFAOYSA-N 0.000 description 3
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 3
- VJZSRIHPRAZHIW-UHFFFAOYSA-N 4-amino-2,3-dihydro-1h-inden-2-ol Chemical compound NC1=CC=CC2=C1CC(O)C2 VJZSRIHPRAZHIW-UHFFFAOYSA-N 0.000 description 3
- NFTZRYJWHUBKIU-UHFFFAOYSA-N 7-amino-3-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-1,4-dihydroquinazolin-2-one Chemical compound C1=C(N)C=C2NC(=O)N(CCO[Si](C)(C)C(C)(C)C)CC2=C1 NFTZRYJWHUBKIU-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 3
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 3
- 206010013774 Dry eye Diseases 0.000 description 3
- 208000005171 Dysmenorrhea Diseases 0.000 description 3
- 208000001640 Fibromyalgia Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 206010021639 Incontinence Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 208000000450 Pelvic Pain Diseases 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 206010038419 Renal colic Diseases 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 3
- 206010046543 Urinary incontinence Diseases 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 239000000440 bentonite Substances 0.000 description 3
- 229910000278 bentonite Inorganic materials 0.000 description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000007885 bronchoconstriction Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 3
- 238000013375 chromatographic separation Methods 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
- 238000000576 coating method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000036757 core body temperature Effects 0.000 description 3
- 150000001941 cyclopentenes Chemical class 0.000 description 3
- 201000003146 cystitis Diseases 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 125000004438 haloalkoxy group Chemical group 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 210000000629 knee joint Anatomy 0.000 description 3
- 210000002414 leg Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000028161 membrane depolarization Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000003349 osteoarthritic effect Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- 238000004808 supercritical fluid chromatography Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 208000004371 toothache Diseases 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 239000002023 wood Substances 0.000 description 3
- SPJRIONCBFWLJI-KZYPOYLOSA-N (1r,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.CC1=CSC([C@@H]2C[C@H](N)CC2)=N1 SPJRIONCBFWLJI-KZYPOYLOSA-N 0.000 description 2
- SPJRIONCBFWLJI-WLYNEOFISA-N (1s,3r)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.CC1=CSC([C@H]2C[C@@H](N)CC2)=N1 SPJRIONCBFWLJI-WLYNEOFISA-N 0.000 description 2
- MEFKFJOEVLUFAY-UHFFFAOYSA-N (2,2,2-trichloroacetyl) 2,2,2-trichloroacetate Chemical compound ClC(Cl)(Cl)C(=O)OC(=O)C(Cl)(Cl)Cl MEFKFJOEVLUFAY-UHFFFAOYSA-N 0.000 description 2
- UHRVKUQPJJFREE-RXMQYKEDSA-N (2r)-8-amino-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)[C@@H](C)OC2=C1N UHRVKUQPJJFREE-RXMQYKEDSA-N 0.000 description 2
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical group OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LROUIROOTPZFRQ-IRXDYDNUSA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-5-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3CCC(=O)N(C3=CC=C2)C)=CC=CC=C1 LROUIROOTPZFRQ-IRXDYDNUSA-N 0.000 description 2
- CLYGEYINXAEOCM-ZWKOTPCHSA-N 1-(1-methyl-2-oxo-3,4-dihydroquinolin-7-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=CC=C3CCC(=O)N(C3=C2)C)=CC=CC=C1 CLYGEYINXAEOCM-ZWKOTPCHSA-N 0.000 description 2
- GFPVJLWOJXJCEL-DLBZAZTESA-N 1-(3-amino-1-methylisoquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N)N=C(C3=CC=C2)C)=CC=CC=C1 GFPVJLWOJXJCEL-DLBZAZTESA-N 0.000 description 2
- BJZNLILSDYLCPF-QFBILLFUSA-N 1-(3-ethyl-6-fluoroisoquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)CC)=CC=CC=C1 BJZNLILSDYLCPF-QFBILLFUSA-N 0.000 description 2
- PJVXUKARZNCIRA-GDBMZVCRSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3r)-3-(2-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1F PJVXUKARZNCIRA-GDBMZVCRSA-N 0.000 description 2
- PAFRMBKESKKSIA-CRAIPNDOSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3r)-3-(3-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC(F)=C1 PAFRMBKESKKSIA-CRAIPNDOSA-N 0.000 description 2
- FJFRQBMBDFUPSL-WZONZLPQSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3r)-3-methyl-3-phenylcyclopentyl]urea Chemical compound C1([C@]2(C)CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1 FJFRQBMBDFUPSL-WZONZLPQSA-N 0.000 description 2
- BLFYIBROKHRKEJ-SJLPKXTDSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1 BLFYIBROKHRKEJ-SJLPKXTDSA-N 0.000 description 2
- PJVXUKARZNCIRA-GOEBONIOSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3s)-3-(2-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1F PJVXUKARZNCIRA-GOEBONIOSA-N 0.000 description 2
- PJVXUKARZNCIRA-ZBFHGGJFSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3r)-3-(2-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1F PJVXUKARZNCIRA-ZBFHGGJFSA-N 0.000 description 2
- PAFRMBKESKKSIA-QAPCUYQASA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3r)-3-(3-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC(F)=C1 PAFRMBKESKKSIA-QAPCUYQASA-N 0.000 description 2
- BLFYIBROKHRKEJ-AEFFLSMTSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1 BLFYIBROKHRKEJ-AEFFLSMTSA-N 0.000 description 2
- PJVXUKARZNCIRA-HOCLYGCPSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3s)-3-(2-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1F PJVXUKARZNCIRA-HOCLYGCPSA-N 0.000 description 2
- PAFRMBKESKKSIA-YJBOKZPZSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3s)-3-(3-fluorophenyl)cyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC(F)=C1 PAFRMBKESKKSIA-YJBOKZPZSA-N 0.000 description 2
- BLFYIBROKHRKEJ-WMZOPIPTSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3C=C(N=CC3=CC=C2F)C)=CC=CC=C1 BLFYIBROKHRKEJ-WMZOPIPTSA-N 0.000 description 2
- GAGNRHVYADVXOE-RBUKOAKNSA-N 1-[(1r,3s)-3-phenylcyclopentyl]-3-(5,6,7,8-tetrahydronaphthalen-1-yl)urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=3CCCCC=3C=CC=2)=CC=CC=C1 GAGNRHVYADVXOE-RBUKOAKNSA-N 0.000 description 2
- WENISBCJPGSITQ-UHFFFAOYSA-N 1-azatricyclo[3.3.1.13,7]decane Chemical compound C1C(C2)CC3CC1CN2C3 WENISBCJPGSITQ-UHFFFAOYSA-N 0.000 description 2
- DDELEGMETMZLAF-UHFFFAOYSA-N 1-chloroisoquinolin-5-amine Chemical compound N1=CC=C2C(N)=CC=CC2=C1Cl DDELEGMETMZLAF-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical class OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 206010003497 Asphyxia Diseases 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- XITAKRDLJLSRRC-UHFFFAOYSA-N CC(C)(C)[Si](C)(C)OCCN(CC1=CC=CC=C1N1)C1=O Chemical compound CC(C)(C)[Si](C)(C)OCCN(CC1=CC=CC=C1N1)C1=O XITAKRDLJLSRRC-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 208000006561 Cluster Headache Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000034656 Contusions Diseases 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 206010016059 Facial pain Diseases 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 208000010496 Heart Arrest Diseases 0.000 description 2
- 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 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000008765 Sciatica Diseases 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 208000010040 Sprains and Strains Diseases 0.000 description 2
- 108010062740 TRPV Cation Channels Proteins 0.000 description 2
- 102000011040 TRPV Cation Channels Human genes 0.000 description 2
- 108050004388 Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical group OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 208000018912 cluster headache syndrome Diseases 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 230000009519 contusion Effects 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000003885 eye ointment Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical class C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 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
- 239000003701 inert diluent Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- OELZFJUWWFRWLC-UHFFFAOYSA-N oxazine-1 Chemical compound C1=CC(N(CC)CC)=CC2=[O+]C3=CC(N(CC)CC)=CC=C3N=C21 OELZFJUWWFRWLC-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 2
- 208000000689 peptic esophagitis Diseases 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 210000003131 sacroiliac joint Anatomy 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 239000003206 sterilizing agent Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- JSJVQUQGLOHDKC-SFYZADRCSA-N tert-butyl N-[(1S,3R)-3-carbamothioylcyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C(N)=S)C1 JSJVQUQGLOHDKC-SFYZADRCSA-N 0.000 description 2
- JAZMUABLLOLBIG-SFYZADRCSA-N tert-butyl n-[(1s,3r)-3-carbamoylcyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C(N)=O)C1 JAZMUABLLOLBIG-SFYZADRCSA-N 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- KRDKASNSRBGEFG-DBIOUOCHSA-N (1r,2r,4s,5r)-6,6-difluoro-4-phenylbicyclo[3.1.0]hexan-2-amine Chemical compound C1([C@H]2C[C@H]([C@H]3[C@@H]2C3(F)F)N)=CC=CC=C1 KRDKASNSRBGEFG-DBIOUOCHSA-N 0.000 description 1
- CQMMRSCAQIXNTN-RKDXNWHRSA-N (1r,3r)-3-(2-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@H](N)CC[C@H]1C1=CC=CC=C1F CQMMRSCAQIXNTN-RKDXNWHRSA-N 0.000 description 1
- SXEOLQMEORRYNB-MWLCHTKSSA-N (1r,3r)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@H](N)CC[C@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-MWLCHTKSSA-N 0.000 description 1
- SPJRIONCBFWLJI-SCLLHFNJSA-N (1r,3r)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.CC1=CSC([C@H]2C[C@H](N)CC2)=N1 SPJRIONCBFWLJI-SCLLHFNJSA-N 0.000 description 1
- ZNMXRCDHEJJIIK-GHMZBOCLSA-N (1r,3r)-3-phenylcyclopentan-1-amine Chemical compound C1[C@H](N)CC[C@H]1C1=CC=CC=C1 ZNMXRCDHEJJIIK-GHMZBOCLSA-N 0.000 description 1
- SXEOLQMEORRYNB-GXSJLCMTSA-N (1r,3s)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@H](N)CC[C@@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-GXSJLCMTSA-N 0.000 description 1
- ZNMXRCDHEJJIIK-WDEREUQCSA-N (1r,3s)-3-phenylcyclopentan-1-amine Chemical compound C1[C@H](N)CC[C@@H]1C1=CC=CC=C1 ZNMXRCDHEJJIIK-WDEREUQCSA-N 0.000 description 1
- HZWNINMYOODHIV-MNOVXSKESA-N (1r,4s)-4-phenylcyclopent-2-en-1-amine Chemical compound C1=C[C@H](N)C[C@@H]1C1=CC=CC=C1 HZWNINMYOODHIV-MNOVXSKESA-N 0.000 description 1
- VATVDRUWKSYADK-NOOOWODRSA-N (1s,2r,4s,5s)-4-phenylbicyclo[3.1.0]hexan-2-amine Chemical compound C1([C@H]2C[C@H]([C@H]3C[C@H]32)N)=CC=CC=C1 VATVDRUWKSYADK-NOOOWODRSA-N 0.000 description 1
- CQMMRSCAQIXNTN-BDAKNGLRSA-N (1s,3r)-3-(2-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@H]1C1=CC=CC=C1F CQMMRSCAQIXNTN-BDAKNGLRSA-N 0.000 description 1
- SXEOLQMEORRYNB-KOLCDFICSA-N (1s,3r)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-KOLCDFICSA-N 0.000 description 1
- UBGCPHGJOCSXGB-WLYNEOFISA-N (1s,3r)-3-(4-methyl-1,3-oxazol-2-yl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.CC1=COC([C@H]2C[C@@H](N)CC2)=N1 UBGCPHGJOCSXGB-WLYNEOFISA-N 0.000 description 1
- BGAHBXALLIIJSU-MNOVXSKESA-N (1s,3r)-3-cyclohexylcyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@H]1C1CCCCC1 BGAHBXALLIIJSU-MNOVXSKESA-N 0.000 description 1
- SXEOLQMEORRYNB-ONGXEEELSA-N (1s,3s)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1[C@@H](N)CC[C@@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-ONGXEEELSA-N 0.000 description 1
- SPJRIONCBFWLJI-WSZWBAFRSA-N (1s,3s)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.CC1=CSC([C@@H]2C[C@@H](N)CC2)=N1 SPJRIONCBFWLJI-WSZWBAFRSA-N 0.000 description 1
- HZWNINMYOODHIV-WDEREUQCSA-N (1s,4r)-4-phenylcyclopent-2-en-1-amine Chemical compound C1=C[C@@H](N)C[C@H]1C1=CC=CC=C1 HZWNINMYOODHIV-WDEREUQCSA-N 0.000 description 1
- CFJUXEAYSIGXTF-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy-phenylborinic acid Chemical compound CC(C)(C)OB(O)C1=CC=CC=C1 CFJUXEAYSIGXTF-UHFFFAOYSA-N 0.000 description 1
- UHEPSJJJMTWUCP-DHDYTCSHSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-[(1r)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N UHEPSJJJMTWUCP-DHDYTCSHSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- CQMMRSCAQIXNTN-VEDVMXKPSA-N (3r)-3-(2-fluorophenyl)cyclopentan-1-amine Chemical compound C1C(N)CC[C@H]1C1=CC=CC=C1F CQMMRSCAQIXNTN-VEDVMXKPSA-N 0.000 description 1
- SXEOLQMEORRYNB-BFHBGLAWSA-N (3r)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1C(N)CC[C@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-BFHBGLAWSA-N 0.000 description 1
- PTVZUCNAEPFXRE-SECBINFHSA-N (3r)-3-(3-fluorophenyl)cyclopentan-1-one Chemical compound FC1=CC=CC([C@H]2CC(=O)CC2)=C1 PTVZUCNAEPFXRE-SECBINFHSA-N 0.000 description 1
- AJKPXKHWCHZLSF-SECBINFHSA-N (3r)-3-(4-bromophenyl)cyclopentan-1-one Chemical group C1=CC(Br)=CC=C1[C@H]1CC(=O)CC1 AJKPXKHWCHZLSF-SECBINFHSA-N 0.000 description 1
- CQMMRSCAQIXNTN-IENPIDJESA-N (3s)-3-(2-fluorophenyl)cyclopentan-1-amine Chemical compound C1C(N)CC[C@@H]1C1=CC=CC=C1F CQMMRSCAQIXNTN-IENPIDJESA-N 0.000 description 1
- NAMVLGXNAYXYMG-QMMMGPOBSA-N (3s)-3-(2-fluorophenyl)cyclopentan-1-one Chemical compound FC1=CC=CC=C1[C@@H]1CC(=O)CC1 NAMVLGXNAYXYMG-QMMMGPOBSA-N 0.000 description 1
- SXEOLQMEORRYNB-FTNKSUMCSA-N (3s)-3-(3-fluorophenyl)cyclopentan-1-amine Chemical compound C1C(N)CC[C@@H]1C1=CC=CC(F)=C1 SXEOLQMEORRYNB-FTNKSUMCSA-N 0.000 description 1
- PTVZUCNAEPFXRE-VIFPVBQESA-N (3s)-3-(3-fluorophenyl)cyclopentan-1-one Chemical compound FC1=CC=CC([C@@H]2CC(=O)CC2)=C1 PTVZUCNAEPFXRE-VIFPVBQESA-N 0.000 description 1
- CJRUDCMOPMVAIB-PXYINDEMSA-N (3s)-3-phenylcyclohexan-1-amine Chemical compound C1C(N)CCC[C@@H]1C1=CC=CC=C1 CJRUDCMOPMVAIB-PXYINDEMSA-N 0.000 description 1
- ZNMXRCDHEJJIIK-VUWPPUDQSA-N (3s)-3-phenylcyclopentan-1-amine Chemical compound C1C(N)CC[C@@H]1C1=CC=CC=C1 ZNMXRCDHEJJIIK-VUWPPUDQSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
- FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
- YJEVAUSLDPCMNO-UHFFFAOYSA-N 1,6-dihydropentalene Chemical compound C1C=CC2=C1CC=C2 YJEVAUSLDPCMNO-UHFFFAOYSA-N 0.000 description 1
- WXNWCQLDJQBJGZ-JKSUJKDBSA-N 1-(1-chloroisoquinolin-5-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=CN=C(C3=CC=C2)Cl)=CC=CC=C1 WXNWCQLDJQBJGZ-JKSUJKDBSA-N 0.000 description 1
- WVMIJWVJPZITOC-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(3-phenylcyclobutyl)urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1)CC1C1=CC=CC=C1 WVMIJWVJPZITOC-UHFFFAOYSA-N 0.000 description 1
- MZEPFERSLWBFLU-VHSXEESVSA-N 1-(1h-indazol-4-yl)-3-[(1r,3s)-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclopentyl]urea Chemical compound FC(F)(F)C1=CSC([C@@H]2C[C@@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MZEPFERSLWBFLU-VHSXEESVSA-N 0.000 description 1
- MZEPFERSLWBFLU-ZJUUUORDSA-N 1-(1h-indazol-4-yl)-3-[(1s,3r)-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclopentyl]urea Chemical compound FC(F)(F)C1=CSC([C@H]2C[C@H](CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MZEPFERSLWBFLU-ZJUUUORDSA-N 0.000 description 1
- MZEPFERSLWBFLU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclopentyl]urea Chemical compound FC(F)(F)C1=CSC(C2CC(CC2)NC(=O)NC=2C=3C=NNC=3C=CC=2)=N1 MZEPFERSLWBFLU-UHFFFAOYSA-N 0.000 description 1
- QEYGJVPTKOJYMI-JKSUJKDBSA-N 1-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=C3NCCOC3=CC=2)=CC=CC=C1 QEYGJVPTKOJYMI-JKSUJKDBSA-N 0.000 description 1
- WNPQNHYRUWERGH-DLBZAZTESA-N 1-(4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=CC=C3OCCN(C3=C2)C)=CC=CC=C1 WNPQNHYRUWERGH-DLBZAZTESA-N 0.000 description 1
- RLIYUKZFFNLZSO-DZGCQCFKSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1r,3s)-3-(5-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound O1C(C)=CN=C1[C@@H]1C[C@H](NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)CC1 RLIYUKZFFNLZSO-DZGCQCFKSA-N 0.000 description 1
- RLIYUKZFFNLZSO-HIFRSBDPSA-N 1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1s,3r)-3-(5-methyl-1,3-oxazol-2-yl)cyclopentyl]urea Chemical compound O1C(C)=CN=C1[C@H]1C[C@@H](NC(=O)NC=2C3=CC(C)=NC=C3C=CC=2F)CC1 RLIYUKZFFNLZSO-HIFRSBDPSA-N 0.000 description 1
- UAIXVDDRIGKSCV-VYRBHSGPSA-N 1-[(3s)-3-[4-(dimethylamino)phenyl]cyclopentyl]-3-(1h-indazol-4-yl)urea Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1CC(NC(=O)NC=2C=3C=NNC=3C=CC=2)CC1 UAIXVDDRIGKSCV-VYRBHSGPSA-N 0.000 description 1
- VDZTXFMUUMHYNW-GUDVDZBRSA-N 1-[(7r)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3CC[C@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-GUDVDZBRSA-N 0.000 description 1
- VDZTXFMUUMHYNW-IPMKNSEASA-N 1-[(7r)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3CC[C@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-IPMKNSEASA-N 0.000 description 1
- VDZTXFMUUMHYNW-GBESFXJTSA-N 1-[(7r)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3CC[C@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-GBESFXJTSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- VDZTXFMUUMHYNW-QRVBRYPASA-N 1-[(7s)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1r,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3CC[C@@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-QRVBRYPASA-N 0.000 description 1
- VDZTXFMUUMHYNW-OTWHNJEPSA-N 1-[(7s)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1r,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC=2C=CC=C3CC[C@@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-OTWHNJEPSA-N 0.000 description 1
- VDZTXFMUUMHYNW-QYZOEREBSA-N 1-[(7s)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1s,3r)-3-phenylcyclopentyl]urea Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3CC[C@@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-QYZOEREBSA-N 0.000 description 1
- VDZTXFMUUMHYNW-FHWLQOOXSA-N 1-[(7s)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]-3-[(1s,3s)-3-phenylcyclopentyl]urea Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC=2C=CC=C3CC[C@@H](CC3=2)O)=CC=CC=C1 VDZTXFMUUMHYNW-FHWLQOOXSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- FNEPMMJDCROXSK-UHFFFAOYSA-N 1-methyl-5-nitroquinolin-2-one Chemical compound C1=CC([N+]([O-])=O)=C2C=CC(=O)N(C)C2=C1 FNEPMMJDCROXSK-UHFFFAOYSA-N 0.000 description 1
- NYLGITXFVVEBLZ-UHFFFAOYSA-N 1-methylindazol-3-amine Chemical compound C1=CC=C2N(C)N=C(N)C2=C1 NYLGITXFVVEBLZ-UHFFFAOYSA-N 0.000 description 1
- LXCFBXJAERRYNS-UHFFFAOYSA-N 1-methylisoquinolin-3-amine Chemical compound C1=CC=C2C(C)=NC(N)=CC2=C1 LXCFBXJAERRYNS-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YXAQCAOJLDGGDZ-UHFFFAOYSA-N 1-phenylcyclopentan-1-amine Chemical compound C=1C=CC=CC=1C1(N)CCCC1 YXAQCAOJLDGGDZ-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- MECQPIPDPNGZPF-UHFFFAOYSA-N 2,2,2-trichloro-n-(6-fluoro-3-methylisoquinolin-5-yl)acetamide Chemical compound FC1=CC=C2C=NC(C)=CC2=C1NC(=O)C(Cl)(Cl)Cl MECQPIPDPNGZPF-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- RXTJLDXSGNEJIT-UHFFFAOYSA-N 2,3-dihydro-1h-inden-4-amine Chemical compound NC1=CC=CC2=C1CCC2 RXTJLDXSGNEJIT-UHFFFAOYSA-N 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- XCYIQQPKTCUEHD-UHFFFAOYSA-N 2-(3-hydroxy-3-phenylcyclopentyl)isoindole-1,3-dione Chemical compound C1CC(N2C(C3=CC=CC=C3C2=O)=O)CC1(O)C1=CC=CC=C1 XCYIQQPKTCUEHD-UHFFFAOYSA-N 0.000 description 1
- GKHSEDFDYXZGCG-UHFFFAOYSA-N 2-(cyanomethyl)benzonitrile Chemical compound N#CCC1=CC=CC=C1C#N GKHSEDFDYXZGCG-UHFFFAOYSA-N 0.000 description 1
- DHVOCARMULYCQY-VQHPVUNQSA-N 2-[(1r,2r,4s,5r)-6,6-difluoro-4-phenyl-2-bicyclo[3.1.0]hexanyl]isoindole-1,3-dione Chemical compound C1([C@@H]2[C@@H]3[C@H]([C@@H](C2)N2C(C4=CC=CC=C4C2=O)=O)C3(F)F)=CC=CC=C1 DHVOCARMULYCQY-VQHPVUNQSA-N 0.000 description 1
- RUZVFTBCQBWUIA-CABCVRRESA-N 2-[(1r,4s)-4-phenylcyclopent-2-en-1-yl]isoindole-1,3-dione Chemical compound C1([C@H]2C[C@H](C=C2)N2C(C3=CC=CC=C3C2=O)=O)=CC=CC=C1 RUZVFTBCQBWUIA-CABCVRRESA-N 0.000 description 1
- XKSAJZSJKURQRX-UHFFFAOYSA-N 2-acetyloxy-5-(4-fluorophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC(=O)C)=CC=C1C1=CC=C(F)C=C1 XKSAJZSJKURQRX-UHFFFAOYSA-N 0.000 description 1
- OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 1
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical class BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- CESUXLKAADQNTB-ZETCQYMHSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](N)=O CESUXLKAADQNTB-ZETCQYMHSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- NJMHBZGSRCYQNK-UHFFFAOYSA-N 2-oxatricyclo[3.3.1.03,7]nonane Chemical compound C1C(O2)C3CC2CC1C3 NJMHBZGSRCYQNK-UHFFFAOYSA-N 0.000 description 1
- CDRMKXVSBHJXJF-UHFFFAOYSA-N 2-oxatricyclo[3.3.1.13,7]decane Chemical compound C1C(O2)CC3CC1CC2C3.C1C(O2)CC3CC1CC2C3 CDRMKXVSBHJXJF-UHFFFAOYSA-N 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- UVBBHZOXIJAPAW-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-n-methoxycyclohexan-1-imine Chemical compound C1C(=NOC)CCCC1C1=CC=C(C(C)(C)C)C=C1 UVBBHZOXIJAPAW-UHFFFAOYSA-N 0.000 description 1
- GVRIBRNAJQADDA-UHFFFAOYSA-N 3-(4-tert-butylphenyl)cyclohexan-1-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1C1CC(N)CCC1 GVRIBRNAJQADDA-UHFFFAOYSA-N 0.000 description 1
- UAZCHOPIHWUWIP-UHFFFAOYSA-N 3-(4-tert-butylphenyl)cyclohexan-1-one Chemical compound C1=CC(C(C)(C)C)=CC=C1C1CC(=O)CCC1 UAZCHOPIHWUWIP-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- XJXHBNKHPBWPEW-UHFFFAOYSA-N 3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclopentan-1-amine;hydrochloride Chemical compound Cl.C1C(N)CCC1C1=NC(C(F)(F)F)=CS1 XJXHBNKHPBWPEW-UHFFFAOYSA-N 0.000 description 1
- CZIUGYRNEFEWJZ-UHFFFAOYSA-N 3-amino-1-phenylcyclopentan-1-ol Chemical compound C1C(N)CCC1(O)C1=CC=CC=C1 CZIUGYRNEFEWJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OONJVQFMOZAXOI-UHFFFAOYSA-N 3-chloro-1,1,1-trifluoropropan-2-one Chemical group FC(F)(F)C(=O)CCl OONJVQFMOZAXOI-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VJXKVDLXKYYYBX-UHFFFAOYSA-N 3-phenylcyclobutan-1-amine Chemical compound C1C(N)CC1C1=CC=CC=C1 VJXKVDLXKYYYBX-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- JRBAQAMOIBHJRP-UHFFFAOYSA-N 4,5,6,7-tetrahydro-3ah-indene Chemical group C1CCCC2=CC=CC21 JRBAQAMOIBHJRP-UHFFFAOYSA-N 0.000 description 1
- LUNUNJFSHKSXGQ-UHFFFAOYSA-N 4-Aminoindole Chemical group NC1=CC=CC2=C1C=CN2 LUNUNJFSHKSXGQ-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- AQUSISHVASVOBL-UHFFFAOYSA-N 4-bromo-1-methylindazole Chemical compound C1=CC=C2N(C)N=CC2=C1Br AQUSISHVASVOBL-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- OXRWICUICBZVAE-UHFFFAOYSA-N 4-methylpent-1-yne Chemical group CC(C)CC#C OXRWICUICBZVAE-UHFFFAOYSA-N 0.000 description 1
- UAJMAXODMCNQIY-UHFFFAOYSA-N 4-oxa-tricyclo[4.3.0.03,7]nonane Chemical compound C1C2CCC3C2COC31 UAJMAXODMCNQIY-UHFFFAOYSA-N 0.000 description 1
- XUNJKWXYQMKWHJ-UHFFFAOYSA-N 5-amino-1-methylquinolin-2-one Chemical compound C1=CC(N)=C2C=CC(=O)N(C)C2=C1 XUNJKWXYQMKWHJ-UHFFFAOYSA-N 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- NDDZXHOCOKCNBM-UHFFFAOYSA-N 5-nitroquinoline Chemical compound C1=CC=C2C([N+](=O)[O-])=CC=CC2=N1 NDDZXHOCOKCNBM-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- APJPLUGLHKSNPR-UHFFFAOYSA-N 6-fluoro-3-(2-methylpropyl)-5-nitroisoquinoline Chemical compound FC1=CC=C2C=NC(CC(C)C)=CC2=C1[N+]([O-])=O APJPLUGLHKSNPR-UHFFFAOYSA-N 0.000 description 1
- KHDQUCCUPBJMJG-UHFFFAOYSA-N 6-fluoro-3-(2-methylpropyl)isoquinolin-5-amine Chemical compound FC1=CC=C2C=NC(CC(C)C)=CC2=C1N KHDQUCCUPBJMJG-UHFFFAOYSA-N 0.000 description 1
- NFCCHFLMWLSIAR-UHFFFAOYSA-N 6-fluoro-3-(2-methylpropyl)isoquinoline Chemical compound FC1=CC=C2C=NC(CC(C)C)=CC2=C1 NFCCHFLMWLSIAR-UHFFFAOYSA-N 0.000 description 1
- KTSBVWXWGVUSNR-UHFFFAOYSA-N 6-fluoro-3-methyl-5-nitroisoquinoline Chemical compound FC1=CC=C2C=NC(C)=CC2=C1[N+]([O-])=O KTSBVWXWGVUSNR-UHFFFAOYSA-N 0.000 description 1
- JJQKJVZURBXDCF-UHFFFAOYSA-N 6-fluoro-3-methylisoquinolin-5-amine Chemical compound FC1=CC=C2C=NC(C)=CC2=C1N JJQKJVZURBXDCF-UHFFFAOYSA-N 0.000 description 1
- VOPGKTCXFTUWMT-UHFFFAOYSA-N 6-fluoro-3-methylisoquinoline Chemical compound FC1=CC=C2C=NC(C)=CC2=C1 VOPGKTCXFTUWMT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 108010078311 Calcitonin Gene-Related Peptide Receptors Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000023373 Crohn ileitis Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 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
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-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
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014020 Ear pain Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-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
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229910003803 Gold(III) chloride Inorganic materials 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000027109 Headache disease Diseases 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000652482 Homo sapiens TBC1 domain family member 8 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010024453 Ligament sprain Diseases 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000000060 Migraine with aura Diseases 0.000 description 1
- 208000020128 Mitral stenosis Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 206010065016 Post-traumatic pain Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 241000277284 Salvelinus fontinalis Species 0.000 description 1
- 102100032491 Serine protease 1 Human genes 0.000 description 1
- 101710151387 Serine protease 1 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 235000009233 Stachytarpheta cayennensis Nutrition 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102100030302 TBC1 domain family member 8 Human genes 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 101710119665 Trypsin-1 Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000028938 Urination disease Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- HQOXRJRHIYUUDE-MNMPKAIFSA-N [(1r,3r)-3-methyl-3-phenylcyclopentyl]azanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[C@]1(C)CC[C@@H]([NH3+])C1 HQOXRJRHIYUUDE-MNMPKAIFSA-N 0.000 description 1
- IJDYOKVVRXZCFD-NKWVEPMBSA-N [(1s,4r)-4-hydroxycyclopent-2-en-1-yl] acetate Chemical compound CC(=O)O[C@H]1C[C@@H](O)C=C1 IJDYOKVVRXZCFD-NKWVEPMBSA-N 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- JNSBEPKGFVENFS-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC=C1C(F)(F)F JNSBEPKGFVENFS-UHFFFAOYSA-N 0.000 description 1
- RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical group CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
- COHLMUXFVGVBKX-UHFFFAOYSA-N [Li]C1=CC=CC=N1 Chemical compound [Li]C1=CC=CC=N1 COHLMUXFVGVBKX-UHFFFAOYSA-N 0.000 description 1
- DUJJMUHAXLQJBX-UHFFFAOYSA-N [Rh+].C=C Chemical compound [Rh+].C=C DUJJMUHAXLQJBX-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 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
- LWQAIIRKVXOQTL-UHFFFAOYSA-N acetyl acetate N-(1-methylisoquinolin-3-yl)acetamide Chemical compound C(C)(=O)OC(C)=O.CC1=NC(=CC2=CC=CC=C12)NC(C)=O LWQAIIRKVXOQTL-UHFFFAOYSA-N 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical compound C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
- GNTFBMAGLFYMMZ-UHFFFAOYSA-N bicyclo[3.2.2]nonane Chemical compound C1CC2CCC1CCC2 GNTFBMAGLFYMMZ-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 208000029162 bladder disease Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 102000008323 calcitonin gene-related peptide receptor activity proteins Human genes 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 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
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 125000005959 diazepanyl group Chemical group 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000004980 dosimetry Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 206010013990 dysuria Diseases 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 208000007176 earache Diseases 0.000 description 1
- 230000004406 elevated intraocular pressure Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 208000038004 exacerbated respiratory disease Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000010222 extracellular calcium influx Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229950007979 flufenisal Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000004116 glycogenolysis Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- RJHLTVSLYWWTEF-UHFFFAOYSA-K gold trichloride Chemical compound Cl[Au](Cl)Cl RJHLTVSLYWWTEF-UHFFFAOYSA-K 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000003707 hexyloxy 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
- 208000021760 high fever Diseases 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000009220 hypothermia therapy Methods 0.000 description 1
- 208000009326 ileitis Diseases 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000002473 indoazoles Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005969 isothiazolinyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004446 longitudinal ligament Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- VRZIFZJBHKMWPL-UVDYRLMLSA-N methanol;[(1s,3r)-3-methyl-3-phenylcyclopentyl]azanium;chloride Chemical compound [Cl-].OC.C=1C=CC=CC=1[C@]1(C)CC[C@H]([NH3+])C1 VRZIFZJBHKMWPL-UVDYRLMLSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- YGQRELOIBFZEJW-GDBMZVCRSA-N methyl 4-[[(1r,3r)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=C(C(F)(F)F)C=C1 YGQRELOIBFZEJW-GDBMZVCRSA-N 0.000 description 1
- YGQRELOIBFZEJW-GOEBONIOSA-N methyl 4-[[(1r,3s)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@H]2CC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=C(C(F)(F)F)C=C1 YGQRELOIBFZEJW-GOEBONIOSA-N 0.000 description 1
- XPYUYAPWTBEUDN-DLBZAZTESA-N methyl 4-[[(1r,3s)-3-phenylcyclohexyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@H]2CCC[C@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=CC=C1 XPYUYAPWTBEUDN-DLBZAZTESA-N 0.000 description 1
- YGQRELOIBFZEJW-ZBFHGGJFSA-N methyl 4-[[(1s,3r)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=C(C(F)(F)F)C=C1 YGQRELOIBFZEJW-ZBFHGGJFSA-N 0.000 description 1
- YGQRELOIBFZEJW-HOCLYGCPSA-N methyl 4-[[(1s,3s)-3-[4-(trifluoromethyl)phenyl]cyclopentyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@H]2CC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=C(C(F)(F)F)C=C1 YGQRELOIBFZEJW-HOCLYGCPSA-N 0.000 description 1
- XPYUYAPWTBEUDN-IRXDYDNUSA-N methyl 4-[[(1s,3s)-3-phenylcyclohexyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1([C@H]2CCC[C@@H](C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=CC=C1 XPYUYAPWTBEUDN-IRXDYDNUSA-N 0.000 description 1
- XPYUYAPWTBEUDN-BHWOMJMDSA-N methyl 4-[[(3s)-3-phenylcyclohexyl]carbamoylamino]indazole-1-carboxylate Chemical group C1([C@H]2CCCC(C2)NC(=O)NC2=C3C=NN(C3=CC=C2)C(=O)OC)=CC=CC=C1 XPYUYAPWTBEUDN-BHWOMJMDSA-N 0.000 description 1
- RTYWTPNXQNNZRM-UHFFFAOYSA-N methyl 4-[[3-(4-tert-butylphenyl)cyclohexyl]carbamoylamino]indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC)N=CC2=C1NC(=O)NC(C1)CCCC1C1=CC=C(C(C)(C)C)C=C1 RTYWTPNXQNNZRM-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 206010052787 migraine without aura Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000006887 mitral valve stenosis Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000006082 mold release agent Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JWRDFGPGTJKAKV-OLZOCXBDSA-N n-[(1r,4s)-4-phenylcyclopent-2-en-1-yl]acetamide Chemical compound C1=C[C@H](NC(=O)C)C[C@@H]1C1=CC=CC=C1 JWRDFGPGTJKAKV-OLZOCXBDSA-N 0.000 description 1
- VOVFLRUFTIVPRM-ZOBORPQBSA-N n-[(1s,2r,4s,5s)-4-phenyl-2-bicyclo[3.1.0]hexanyl]acetamide Chemical compound C1([C@H]2C[C@H]([C@H]3C[C@H]32)NC(=O)C)=CC=CC=C1 VOVFLRUFTIVPRM-ZOBORPQBSA-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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 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
- 229960004270 nabumetone Drugs 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- DLWSRGHNJVLJAH-UHFFFAOYSA-N nitroflurbiprofen Chemical compound FC1=CC(C(C(=O)OCCCCO[N+]([O-])=O)C)=CC=C1C1=CC=CC=C1 DLWSRGHNJVLJAH-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
- 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000003544 oxime group Chemical group 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000003863 physical function Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 210000002248 primary sensory neuron Anatomy 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical group NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 230000005180 public health Effects 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
- 125000003072 pyrazolidinyl 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
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000008439 repair process Effects 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
- 230000003938 response to stress Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- 210000001738 temporomandibular joint Anatomy 0.000 description 1
- JSJVQUQGLOHDKC-JGVFFNPUSA-N tert-butyl N-[(1R,3S)-3-carbamothioylcyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CC[C@H](C(N)=S)C1 JSJVQUQGLOHDKC-JGVFFNPUSA-N 0.000 description 1
- BIDMCNYWJMNXOO-MNOVXSKESA-N tert-butyl N-[(1S,3R)-3-(4-methyl-1,3-thiazol-2-yl)cyclopentyl]carbamate Chemical compound CC1=CSC([C@H]2C[C@H](CC2)NC(=O)OC(C)(C)C)=N1 BIDMCNYWJMNXOO-MNOVXSKESA-N 0.000 description 1
- CPXLOCFDEIRGOV-MNOVXSKESA-N tert-butyl N-[(1S,3R)-3-(5-methyl-1,3-oxazol-2-yl)cyclopentyl]carbamate Chemical compound O1C(C)=CN=C1[C@H]1C[C@@H](NC(=O)OC(C)(C)C)CC1 CPXLOCFDEIRGOV-MNOVXSKESA-N 0.000 description 1
- GHHNHLZDQRPWDM-MNOVXSKESA-N tert-butyl N-[(1S,3R)-3-(prop-2-ynylcarbamoyl)cyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](C(=O)NCC#C)C1 GHHNHLZDQRPWDM-MNOVXSKESA-N 0.000 description 1
- JAZMUABLLOLBIG-JGVFFNPUSA-N tert-butyl n-[(1r,3s)-3-carbamoylcyclopentyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CC[C@H](C(N)=O)C1 JAZMUABLLOLBIG-JGVFFNPUSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000001331 thermoregulatory effect Effects 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 230000009092 tissue dysfunction Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- XHVSCKNABCCCAC-UHFFFAOYSA-N trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound C[Si](C)(C)OC(=O)C(F)(F)S(F)(=O)=O XHVSCKNABCCCAC-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 231100000691 up-and-down procedure Toxicity 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 208000026533 urinary bladder disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
- 210000002517 zygapophyseal joint Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/48—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Amplifiers (AREA)
- Peptides Or Proteins (AREA)
- Two-Way Televisions, Distribution Of Moving Picture Or The Like (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161467533P | 2011-03-25 | 2011-03-25 | |
| US61/467,533 | 2011-03-25 | ||
| PCT/US2012/030096 WO2012134943A1 (en) | 2011-03-25 | 2012-03-22 | Trpv1 antagonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014514286A JP2014514286A (ja) | 2014-06-19 |
| JP2014514286A5 JP2014514286A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-05-07 |
| JP5934778B2 true JP5934778B2 (ja) | 2016-06-15 |
Family
ID=45894702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014501238A Expired - Fee Related JP5934778B2 (ja) | 2011-03-25 | 2012-03-22 | Trpv1拮抗薬 |
Country Status (10)
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| US8969325B2 (en) | 2011-12-19 | 2015-03-03 | Abbvie Inc. | TRPV1 antagonists |
| WO2013096223A1 (en) | 2011-12-19 | 2013-06-27 | Abbvie Inc. | Trpv1 antagonists |
| ES2984771T3 (es) | 2012-06-13 | 2024-10-31 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| US8796328B2 (en) | 2012-06-20 | 2014-08-05 | Abbvie Inc. | TRPV1 antagonists |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| ES2657451T3 (es) | 2013-04-19 | 2018-03-05 | Incyte Holdings Corporation | Heterocíclicos bicíclicos como inhibidores del FGFR |
| HUE045511T2 (hu) | 2014-02-03 | 2020-01-28 | Vitae Pharmaceuticals Llc | A ror-gamma dihidro-pirrolopiridin inhibitorai |
| ES2715458T7 (es) | 2014-10-14 | 2020-05-28 | Vitae Pharmaceuticals Llc | Inhibidores de dihidropirrolopiridina de ROR-gamma |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| US9663515B2 (en) | 2014-11-05 | 2017-05-30 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| CN107438607B (zh) | 2015-02-20 | 2021-02-05 | 因赛特公司 | 作为fgfr抑制剂的双环杂环 |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| EP3331876B1 (en) | 2015-08-05 | 2020-10-07 | Vitae Pharmaceuticals, LLC | Modulators of ror-gamma |
| MA53943A (fr) | 2015-11-20 | 2021-08-25 | Vitae Pharmaceuticals Llc | Modulateurs de ror-gamma |
| TWI757266B (zh) | 2016-01-29 | 2022-03-11 | 美商維它藥物有限責任公司 | ROR-γ調節劑 |
| US9481674B1 (en) | 2016-06-10 | 2016-11-01 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| CN107674029A (zh) * | 2016-08-02 | 2018-02-09 | 上海迪诺医药科技有限公司 | 多环化合物、其药物组合物及应用 |
| CN109689652B (zh) * | 2016-08-23 | 2022-04-26 | 北京诺诚健华医药科技有限公司 | 稠杂环类衍生物、其制备方法及其在医学上的应用 |
| EP3534961A4 (en) | 2016-11-02 | 2020-05-27 | Centrexion Therapeutics Corporation | STABLE AQUEOUS INJECTABLE CAPSAICIN FORMULATIONS AND MEDICAL USES THEREOF |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| WO2019023207A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | Inhibitors of rorϒ |
| WO2019018975A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF ROR GAMMA |
| FI3788047T3 (fi) | 2018-05-04 | 2024-11-02 | Incyte Corp | Fgft-estäjän kiinteitä muotoja ja menetelmiä niiden valmistamiseksi |
| JP7568512B2 (ja) | 2018-05-04 | 2024-10-16 | インサイト・コーポレイション | Fgfr阻害剤の塩 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021030537A1 (en) | 2019-08-14 | 2021-02-18 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| MX2022004390A (es) | 2019-10-11 | 2022-08-08 | Incyte Corp | Aminas biciclicas como inhibidores de la cinasa dependiente de ciclina 2 (cdk2). |
| WO2021076602A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| CA3163875A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021183970A1 (en) * | 2020-03-13 | 2021-09-16 | University Of Maryland, Baltimore | Non-atp/catalytic site p38 mitogen activated protein kinase inhibitors |
| UY39681A (es) | 2021-03-26 | 2022-10-31 | Novartis Ag | Derivados de ciclobutilo 1,3–sustituidos y sus usos |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含fgfr抑制劑及nectin-4靶向劑之組合療法 |
| TW202313611A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為fgfr抑制劑之三環雜環 |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| DE69631347T2 (de) | 1995-09-15 | 2004-10-07 | Upjohn Co | Aminoaryl oxazolidinone n-oxide |
| US20030220234A1 (en) | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
| US6204288B1 (en) | 1999-03-08 | 2001-03-20 | The University Of Mississippi | 1,2-dithiolane derivatives |
| GB9918037D0 (en) | 1999-07-30 | 1999-09-29 | Biochemie Gmbh | Organic compounds |
| ES2240420T3 (es) | 2000-01-18 | 2005-10-16 | Novartis Ag | Carboxamidas utiles como inhibidores de la proteina de transferencia de trigliceridos microsomicos y de la secrecion de apolipoproteina b. |
| US6993311B2 (en) | 2002-02-20 | 2006-01-31 | Freescale Semiconductor, Inc. | Radio receiver having an adaptive equalizer and method therefor |
| GB0206876D0 (en) * | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
| AU2003241453A1 (en) | 2002-05-17 | 2003-12-02 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid vr1 receptor |
| GB0226724D0 (en) | 2002-11-15 | 2002-12-24 | Merck Sharp & Dohme | Therapeutic agents |
| US6933311B2 (en) * | 2003-02-11 | 2005-08-23 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| JP2006519806A (ja) * | 2003-03-07 | 2006-08-31 | グラクソ グループ リミテッド | 尿素誘導体および疼痛治療におけるバニロイド受容体拮抗剤としてのそれらの使用。 |
| US7015233B2 (en) | 2003-06-12 | 2006-03-21 | Abbott Laboratories | Fused compounds that inhibit vanilloid subtype 1 (VR1) receptor |
| US7375126B2 (en) | 2003-06-12 | 2008-05-20 | Abbott Laboratories | Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| GB0319150D0 (en) | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Novel compounds |
| JP2007509846A (ja) * | 2003-10-15 | 2007-04-19 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | テトラヒドロ−ナフタレンおよび尿素誘導体 |
| US7307163B2 (en) | 2004-04-19 | 2007-12-11 | Symed Labs Limited | Process for the preparation of linezolid and related compounds |
| US7429661B2 (en) | 2004-07-20 | 2008-09-30 | Symed Labs Limited | Intermediates for linezolid and related compounds |
| EP1804823A4 (en) | 2004-09-29 | 2010-06-09 | Amr Technology Inc | NEW CYCLOSPORIN ANALOGUE AND ITS PHARMACEUTICAL APPLICATIONS |
| US7812019B2 (en) | 2004-11-24 | 2010-10-12 | Abbott Laboratories | Chromanylurea compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor and uses thereof |
| US7875627B2 (en) | 2004-12-07 | 2011-01-25 | Abbott Laboratories | Thienopyridyl compounds that inhibit vanilloid receptor subtype 1 (VR1) and uses thereof |
| EP1885704B1 (en) | 2005-05-11 | 2011-09-28 | Abbott Laboratories | Antagonists of the vanilloid receptor subtype 1 (vr1) and uses thereof |
| TW200716636A (en) | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| US7910751B2 (en) | 2005-07-22 | 2011-03-22 | Mochida Pharmaceutical Co., Ltd. | Heterocyclidene acetamide derivative |
| US7514068B2 (en) | 2005-09-14 | 2009-04-07 | Concert Pharmaceuticals Inc. | Biphenyl-pyrazolecarboxamide compounds |
| EA200801013A1 (ru) | 2005-10-07 | 2008-10-30 | Гленмарк Фармасеутикалс С.А. | Производные замещённых соединений, содержащих конденсированные бензольные кольца, и их применение в качестве лигандов ванилоидных рецепторов |
| CA2626593A1 (en) | 2005-10-28 | 2007-05-03 | Abbott Laboratories | Indazole derivatives that inhibit trpv1 receptor |
| CN101426498A (zh) | 2006-04-18 | 2009-05-06 | 艾博特公司 | 香草素受体亚型1(vr1)的拮抗剂及其用途 |
| WO2008040360A2 (en) | 2006-10-04 | 2008-04-10 | Neurokey A/S | Use of hypothermia inducing drugs to treat ischemia |
| US20100029739A1 (en) | 2006-10-04 | 2010-02-04 | Uno Jakob Weber | Use of a combination of hypothermia inducing drugs |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| WO2008059339A2 (en) | 2006-11-13 | 2008-05-22 | Glenmark Pharmaceuticals S.A. | Isoquinoline derivatives as vanilloid receptor modulators |
| JP2010513263A (ja) * | 2006-12-15 | 2010-04-30 | ファイザー・プロダクツ・インク | ベンズイミダゾール誘導体 |
| MX2009006730A (es) * | 2006-12-20 | 2009-06-30 | Abbott Lab | Derivados de n-(5, 6, 7, 8-tetrahidronaftalen-1-il) urea y compuestos relacionados como antagonistas de receptor vaniloide trpv1 par el tratamiento de dolor. |
| US20100016285A1 (en) | 2007-01-24 | 2010-01-21 | Mochida Pharmaceutical Co., Ltd. | Heterocyclidene-n-(aryl) acetamide derivative |
| PE20081692A1 (es) | 2007-01-24 | 2008-12-18 | Mochida Pharm Co Ltd | Nuevo derivado de heterocicliden acetamida |
| RU2460725C2 (ru) | 2007-02-15 | 2012-09-10 | Ф. Хоффманн-Ля Рош Аг | Новые 2-аминооксазолины в качестве лигандов taar1 |
| WO2008110863A1 (en) | 2007-03-15 | 2008-09-18 | Glenmark Pharmaceuticals S.A. | Indazole derivatives and their use as vanilloid receptor ligands |
| BRPI0810362A2 (pt) | 2007-04-19 | 2014-10-29 | Concert Pharmaceuticals Inc | Compostos de morfolinila deuterados |
| US7531685B2 (en) | 2007-06-01 | 2009-05-12 | Protia, Llc | Deuterium-enriched oxybutynin |
| CN101801953A (zh) | 2007-08-09 | 2010-08-11 | 雅培制药有限公司 | 作为trpv1拮抗剂的四氢吡啶甲酰胺衍生物 |
| US20090131485A1 (en) | 2007-09-10 | 2009-05-21 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
| US20090118238A1 (en) | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090082471A1 (en) | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| US20090088416A1 (en) | 2007-09-26 | 2009-04-02 | Protia, Llc | Deuterium-enriched lapaquistat |
| JP2010540635A (ja) | 2007-10-02 | 2010-12-24 | コンサート ファーマシューティカルズ インコーポレイテッド | ピリミジンジオン誘導体 |
| US20090105338A1 (en) | 2007-10-18 | 2009-04-23 | Protia, Llc | Deuterium-enriched gabexate mesylate |
| US8410124B2 (en) | 2007-10-18 | 2013-04-02 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| US8084616B2 (en) | 2007-10-24 | 2011-12-27 | Abbott Laboratories | TRPV1 antagonists |
| CA2703591C (en) | 2007-10-26 | 2013-05-07 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| TW200927192A (en) | 2007-11-19 | 2009-07-01 | Alcon Res Ltd | Use of TRPV1 receptor antagonists for treating dry eye and ocular pain |
| JP2011201777A (ja) | 2008-07-23 | 2011-10-13 | Mochida Pharmaceut Co Ltd | 光学活性なヘテロシクリデン−n−アリールアセトアミド誘導体 |
| AR073631A1 (es) | 2008-10-17 | 2010-11-17 | Abbott Lab | Antagonistas del receptor transitorio potencial de vanilloides 1 ( trpv1) utiles para tratar inflamacion y dolor |
| WO2010045402A1 (en) | 2008-10-17 | 2010-04-22 | Abbott Laboratories | Trpv1 antagonists |
| KR101361858B1 (ko) * | 2008-12-05 | 2014-02-12 | 에프. 호프만-라 로슈 아게 | 피롤로피라지닐 우레아 키나아제 저해제 |
| US8969325B2 (en) | 2011-12-19 | 2015-03-03 | Abbvie Inc. | TRPV1 antagonists |
| WO2013096223A1 (en) | 2011-12-19 | 2013-06-27 | Abbvie Inc. | Trpv1 antagonists |
| US8796328B2 (en) | 2012-06-20 | 2014-08-05 | Abbvie Inc. | TRPV1 antagonists |
-
2012
- 2012-03-22 AR ARP120100956A patent/AR085530A1/es not_active Application Discontinuation
- 2012-03-22 US US13/426,732 patent/US8802711B2/en not_active Expired - Fee Related
- 2012-03-22 UY UY0001033966A patent/UY33966A/es not_active Application Discontinuation
- 2012-03-22 CA CA2831146A patent/CA2831146C/en not_active Expired - Fee Related
- 2012-03-22 TW TW101109947A patent/TW201302681A/zh unknown
- 2012-03-22 CN CN201280024628.4A patent/CN103635458B/zh not_active Expired - Fee Related
- 2012-03-22 JP JP2014501238A patent/JP5934778B2/ja not_active Expired - Fee Related
- 2012-03-22 WO PCT/US2012/030096 patent/WO2012134943A1/en active Application Filing
- 2012-03-22 MX MX2013011054A patent/MX351165B/es active IP Right Grant
- 2012-03-22 EP EP12711103.7A patent/EP2688866A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| TW201302681A (zh) | 2013-01-16 |
| US8802711B2 (en) | 2014-08-12 |
| WO2012134943A1 (en) | 2012-10-04 |
| CN103635458B (zh) | 2016-10-19 |
| UY33966A (es) | 2012-10-31 |
| MX351165B (es) | 2017-10-04 |
| EP2688866A1 (en) | 2014-01-29 |
| JP2014514286A (ja) | 2014-06-19 |
| AR085530A1 (es) | 2013-10-09 |
| MX2013011054A (es) | 2014-04-16 |
| CA2831146A1 (en) | 2012-10-04 |
| CN103635458A (zh) | 2014-03-12 |
| US20120245163A1 (en) | 2012-09-27 |
| CA2831146C (en) | 2019-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5934778B2 (ja) | Trpv1拮抗薬 | |
| AU2016226340B2 (en) | Bicyclic ketone sulfonamide compounds | |
| JP6014154B2 (ja) | ベンゼンスルホンアミド化合物および治療剤としてのそれらの使用 | |
| AU2016223072B2 (en) | Selective BACE1 inhibitors | |
| US7998982B2 (en) | Amide derivatives as TRPV1 antagonists | |
| JP7450606B2 (ja) | ヘテロアリール置換スルホンアミド化合物および治療剤としてのそれらの使用 | |
| TW201329050A (zh) | Trpv1拮抗劑 | |
| CA3023465A1 (en) | Benzenesulfonamide compounds and their use as therapeutic agents | |
| JP2012505907A (ja) | Trpv1拮抗薬 | |
| US20130045948A1 (en) | Azocyclic inhibitors of fatty acid amide hydrolase | |
| EP3253737A1 (en) | Autotaxin inhibitory compounds | |
| JP2019536810A (ja) | ベンゼンスルホンアミド化合物および治療剤としてのそれらの使用 | |
| JP6322275B2 (ja) | ヤヌスキナーゼ阻害剤としてのn−(2−シアノヘテロシクリル)ピラゾロピリドン | |
| JP6754828B2 (ja) | ピリジン及びピリミジン誘導体 | |
| JP2011500839A (ja) | シクロヘキセンアミド誘導体およびtrpv1拮抗剤としてのその使用 | |
| CA3106354A1 (en) | Amino-pyridinyl-azetidinyl-carboxamide derivatives and pharmaceutical compositions thereof useful as inhibitors of histone deacetylase | |
| WO2020117877A1 (en) | Compounds, compositions and methods of use | |
| TW201323408A (zh) | 新穎trpv3調節劑 | |
| JP2006503094A (ja) | 化合物 | |
| CA3102903A1 (en) | Oga inhibitor compounds | |
| WO2023023670A1 (en) | Compositions and methods of using the same for treatment of neurodegenerative and mitochondrial disease | |
| US8796328B2 (en) | TRPV1 antagonists | |
| US9388181B2 (en) | Substituted 1,2,3,4-tetrahydropyrido[3,4-E] pyrrolo[1,2-A]pyrimidines as kinase | |
| CA3025129A1 (en) | N-[3-[2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]oxazin-7a-yl]-4-fluoro-phenyl]-5-(trifluoromethyl)pyridine-2-carboxamide and its (4ar,5s,7as) isomer as a selective bace1 inhibitor for treating e.g. alzheimer's disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150320 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150320 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150910 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150915 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151209 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160314 |
|
| 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: 20160412 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160509 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5934778 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |