HRP20040823A2 - Substituted amides active at the cannabinoid-1 receptor - Google Patents
Substituted amides active at the cannabinoid-1 receptor Download PDFInfo
- Publication number
- HRP20040823A2 HRP20040823A2 HR20040823A HRP20040823A HRP20040823A2 HR P20040823 A2 HRP20040823 A2 HR P20040823A2 HR 20040823 A HR20040823 A HR 20040823A HR P20040823 A HRP20040823 A HR P20040823A HR P20040823 A2 HRP20040823 A2 HR P20040823A2
- Authority
- HR
- Croatia
- Prior art keywords
- methylpropanamide
- trifluoromethyl
- chlorophenyl
- pyridyloxy
- methylpropyl
- Prior art date
Links
- 150000001408 amides Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 223
- 238000011282 treatment Methods 0.000 claims description 63
- -1 7-aza-indolyl Chemical group 0.000 claims description 56
- 208000008589 Obesity Diseases 0.000 claims description 42
- 235000020824 obesity Nutrition 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 20
- 230000002265 prevention Effects 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 208000030814 Eating disease Diseases 0.000 claims description 8
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 235000012631 food intake Nutrition 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 5
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- GBNVKEMIYIPZCN-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-4-(4-fluorophenyl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(F)C=CC=1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 GBNVKEMIYIPZCN-UHFFFAOYSA-N 0.000 claims description 4
- GZDIFABQZOFECI-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(5-cyanopyridin-3-yl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(C=NC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 GZDIFABQZOFECI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- UTXYKJJGFQXXRK-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-4-(4-methoxyphenyl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C1=CC(OC)=CC=C1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 UTXYKJJGFQXXRK-UHFFFAOYSA-N 0.000 claims description 3
- NJSONKDWRVNYCL-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-4-cyclobutylbutan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C1CCC1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 NJSONKDWRVNYCL-UHFFFAOYSA-N 0.000 claims description 3
- WDRZQEUNPQWHSG-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-4-cyclohexylbutan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C1CCCCC1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 WDRZQEUNPQWHSG-UHFFFAOYSA-N 0.000 claims description 3
- TZYRPDAFSAFZSQ-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-4-cyclopentylbutan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C1CCCC1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 TZYRPDAFSAFZSQ-UHFFFAOYSA-N 0.000 claims description 3
- SPSJRZBNCFXKKY-UHFFFAOYSA-N n-[3-(3-cyanophenyl)-5-methylhexan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=CC(C#N)=CC=1C(CC(C)C)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 SPSJRZBNCFXKKY-UHFFFAOYSA-N 0.000 claims description 3
- XKRNJPBSBDVDNO-UHFFFAOYSA-N n-[3-(3-cyanophenyl)octan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=CC(C#N)=CC=1C(CCCCC)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 XKRNJPBSBDVDNO-UHFFFAOYSA-N 0.000 claims description 3
- ZDCFNYJKARMUMR-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(2,3-dihydroindol-1-yl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(N1C2=CC=CC=C2CC1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 ZDCFNYJKARMUMR-UHFFFAOYSA-N 0.000 claims description 3
- QLYKJCMUNUWAGO-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 QLYKJCMUNUWAGO-UHFFFAOYSA-N 0.000 claims description 3
- BINCMSJEDLRTJN-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(3-methylphenyl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(C)C=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 BINCMSJEDLRTJN-UHFFFAOYSA-N 0.000 claims description 3
- UYTUXABSUBMTPQ-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(5-chloropyridin-3-yl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(Cl)C=NC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 UYTUXABSUBMTPQ-UHFFFAOYSA-N 0.000 claims description 3
- VOQBJQSZKDQBAI-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(5-methylpyridin-3-yl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(C)C=NC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 VOQBJQSZKDQBAI-UHFFFAOYSA-N 0.000 claims description 3
- TZEDJGFVXNFQOF-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(n-methylanilino)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(N(C)C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 TZEDJGFVXNFQOF-UHFFFAOYSA-N 0.000 claims description 3
- MJDFMECYCIGIDO-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-pyridin-3-ylbutan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=NC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 MJDFMECYCIGIDO-UHFFFAOYSA-N 0.000 claims description 3
- BBWVLURTUBPRIY-UHFFFAOYSA-N n-[4-(5-chloropyridin-2-yl)-3-phenylbutan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=NC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 BBWVLURTUBPRIY-UHFFFAOYSA-N 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- WADFFGDAIJGNFH-UHFFFAOYSA-N 2-(3-chlorophenoxy)-n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=CC(Cl)=C1 WADFFGDAIJGNFH-UHFFFAOYSA-N 0.000 claims description 2
- SZTZUGGWPZIINA-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 SZTZUGGWPZIINA-UHFFFAOYSA-N 0.000 claims description 2
- JQWPFJSGBASENO-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-[4-(4-chlorophenyl)-3-pyridin-3-ylbutan-2-yl]-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=NC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 JQWPFJSGBASENO-UHFFFAOYSA-N 0.000 claims description 2
- IKYKULSSMUZFBR-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylphenyl)-3-phenylbutan-2-yl]-2-[4-(trifluoromethyl)phenoxy]propanamide Chemical compound C=1C=C(C)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=C1 IKYKULSSMUZFBR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000005002 aryl methyl group Chemical group 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- KTKLSBXRQVNEOR-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(3,5-difluorophenyl)butan-2-yl]-2-methyl-2-pyridin-2-yloxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(F)C=C(F)C=1)C(C)NC(=O)C(C)(C)OC1=CC=CC=N1 KTKLSBXRQVNEOR-UHFFFAOYSA-N 0.000 claims description 2
- IJFIWFQLUGPOIX-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[6-(trifluoromethyl)pyrimidin-4-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=C(C=CC=1)C#N)C(C)NC(=O)C(C)(C)OC1=CC(C(F)(F)F)=NC=N1 IJFIWFQLUGPOIX-UHFFFAOYSA-N 0.000 claims description 2
- XLZDVTNCFPUPNX-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-(3,5-dichlorophenoxy)-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC(Cl)=CC(Cl)=C1 XLZDVTNCFPUPNX-UHFFFAOYSA-N 0.000 claims description 2
- MRECCTXLXCELBU-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-(3,5-difluorophenoxy)-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC(F)=CC(F)=C1 MRECCTXLXCELBU-UHFFFAOYSA-N 0.000 claims description 2
- VQOOAQMFUGGWKX-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-(5-chloropyridin-2-yl)oxy-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=N1 VQOOAQMFUGGWKX-UHFFFAOYSA-N 0.000 claims description 2
- UAFYQYJLBSEILF-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methyl-2-(6-methylpyridin-2-yl)oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=CC(C)=N1 UAFYQYJLBSEILF-UHFFFAOYSA-N 0.000 claims description 2
- PVAFUYMWCZKQQA-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methyl-2-[4-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC(C(F)(F)F)=CC=N1 PVAFUYMWCZKQQA-UHFFFAOYSA-N 0.000 claims description 2
- VGXVGVLUSMHCIK-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methyl-2-[4-(trifluoromethyl)pyrimidin-2-yl]oxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=NC=CC(C(F)(F)F)=N1 VGXVGVLUSMHCIK-UHFFFAOYSA-N 0.000 claims description 2
- IROBMYGWVLTDFP-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methyl-2-phenoxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=CC=C1 IROBMYGWVLTDFP-UHFFFAOYSA-N 0.000 claims description 2
- KSKXQOGPSBZBSW-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-phenylbutan-2-yl]-2-methyl-2-pyridin-2-yloxypropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=CC=N1 KSKXQOGPSBZBSW-UHFFFAOYSA-N 0.000 claims description 2
- RCVDIOBRLUTXHY-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-3-thiophen-3-ylbutan-2-yl]-2-(5-chloropyridin-2-yl)oxy-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C1=CSC=C1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=N1 RCVDIOBRLUTXHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 134
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 90
- 238000000034 method Methods 0.000 description 73
- 239000000203 mixture Substances 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 63
- 238000005160 1H NMR spectroscopy Methods 0.000 description 61
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- 239000000243 solution Substances 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 26
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 239000000284 extract Substances 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 208000035475 disorder Diseases 0.000 description 20
- 230000014759 maintenance of location Effects 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- 239000004480 active ingredient Substances 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 230000037396 body weight Effects 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- KHKARPYRYIPKRD-UHFFFAOYSA-N 3,4-bis(4-chlorophenyl)butan-2-amine;hydrochloride Chemical compound Cl.C=1C=C(Cl)C=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 KHKARPYRYIPKRD-UHFFFAOYSA-N 0.000 description 11
- 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 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 229940075993 receptor modulator Drugs 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000000556 agonist Substances 0.000 description 10
- 239000000164 antipsychotic agent Substances 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000001273 butane Substances 0.000 description 10
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 239000000825 pharmaceutical preparation Substances 0.000 description 9
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 8
- 108050007331 Cannabinoid receptor Proteins 0.000 description 8
- 244000025254 Cannabis sativa Species 0.000 description 8
- 150000001263 acyl chlorides Chemical class 0.000 description 8
- 208000006673 asthma Diseases 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 7
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- 208000016261 weight loss Diseases 0.000 description 7
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 6
- SZFUWUOHDRMCKD-UHFFFAOYSA-N 5-chloro-1h-pyridin-2-one Chemical compound OC1=CC=C(Cl)C=N1 SZFUWUOHDRMCKD-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 6
- 108090001061 Insulin Proteins 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 208000019425 cirrhosis of liver Diseases 0.000 description 6
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 6
- 229940125396 insulin Drugs 0.000 description 6
- 229960002715 nicotine Drugs 0.000 description 6
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 6
- 229940127240 opiate Drugs 0.000 description 6
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 6
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- YFIZFZIGRLVARQ-BLLLJJGKSA-N (2s,3s)-4-(4-chlorophenyl)-3-phenylbutan-2-amine Chemical compound C([C@H]([C@@H](N)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=C1 YFIZFZIGRLVARQ-BLLLJJGKSA-N 0.000 description 5
- YNZFFALZMRAPHQ-SYYKKAFVSA-N 2-[(1r,2r,5r)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol Chemical compound OC1=CC(C(C)(C)CCCCCC)=CC=C1[C@H]1[C@H](CCCO)CC[C@@H](O)C1 YNZFFALZMRAPHQ-SYYKKAFVSA-N 0.000 description 5
- 239000005909 Kieselgur Substances 0.000 description 5
- 206010026749 Mania Diseases 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000009739 binding Methods 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 208000014797 chronic intestinal pseudoobstruction Diseases 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 208000011117 substance-related disease Diseases 0.000 description 5
- 239000013585 weight reducing agent Substances 0.000 description 5
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 4
- ATWPCKIRUOPVOI-UHFFFAOYSA-N 3-[3-amino-1-(4-fluorophenyl)butan-2-yl]benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C(C(N)C)CC1=CC=C(F)C=C1 ATWPCKIRUOPVOI-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- 206010010774 Constipation Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 208000028017 Psychotic disease Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000000924 antiasthmatic agent Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 235000017168 chlorine Nutrition 0.000 description 4
- 201000001883 cholelithiasis Diseases 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 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
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000006186 oral dosage form Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 150000005334 phenylbutanes Chemical class 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 201000009032 substance abuse Diseases 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- FQIZFAJMBXZVOL-UHFFFAOYSA-N 1-(3-bromophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=CC(Br)=C1 FQIZFAJMBXZVOL-UHFFFAOYSA-N 0.000 description 3
- YLNLWCJYVBTPBF-UHFFFAOYSA-N 1-(5-bromopyridin-3-yl)propan-2-one Chemical compound CC(=O)CC1=CN=CC(Br)=C1 YLNLWCJYVBTPBF-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 3
- WGUXTQDCAZNJIF-UHFFFAOYSA-N 1-methyl-3,5-bis(trifluoromethyl)benzene Chemical compound CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WGUXTQDCAZNJIF-UHFFFAOYSA-N 0.000 description 3
- XRXRADIPZRXCQJ-UHFFFAOYSA-N 2-(bromomethyl)-5-chloropyridine Chemical compound ClC1=CC=C(CBr)N=C1 XRXRADIPZRXCQJ-UHFFFAOYSA-N 0.000 description 3
- ZUTDVFRJNNKHND-UHFFFAOYSA-N 2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 ZUTDVFRJNNKHND-UHFFFAOYSA-N 0.000 description 3
- SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 3
- XECXKMQLEFHQHM-UHFFFAOYSA-N 3-(2-oxopropyl)benzonitrile Chemical compound CC(=O)CC1=CC=CC(C#N)=C1 XECXKMQLEFHQHM-UHFFFAOYSA-N 0.000 description 3
- FRMQIGNMWCKPMD-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-phenylbutan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 FRMQIGNMWCKPMD-UHFFFAOYSA-N 0.000 description 3
- ZNDASIJAOCVBPR-UHFFFAOYSA-N 4-(4-methylphenyl)-3-phenylbutan-2-amine Chemical compound C=1C=CC=CC=1C(C(N)C)CC1=CC=C(C)C=C1 ZNDASIJAOCVBPR-UHFFFAOYSA-N 0.000 description 3
- DEMKNLXJQNYAFY-UHFFFAOYSA-N 5-chloro-2-methylpyridine Chemical compound CC1=CC=C(Cl)C=N1 DEMKNLXJQNYAFY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 3
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 206010013654 Drug abuse Diseases 0.000 description 3
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- 206010014612 Encephalitis viral Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 3
- 206010019196 Head injury Diseases 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 3
- 208000016285 Movement disease Diseases 0.000 description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229940125709 anorectic agent Drugs 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 239000002830 appetite depressant Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229930003827 cannabinoid Natural products 0.000 description 3
- 239000003557 cannabinoid Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 229940125425 inverse agonist Drugs 0.000 description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- 230000037323 metabolic rate Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- HAMLZAXSMZZNHH-UHFFFAOYSA-N n-[3,4-bis(4-chlorophenyl)butan-2-yl]-2-(4-chlorophenoxy)-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC(Cl)=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 HAMLZAXSMZZNHH-UHFFFAOYSA-N 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 201000002498 viral encephalitis Diseases 0.000 description 3
- YVCOJTATJWDGEU-APPZFPTMSA-N (2r,3r)-2-methyl-3-phenyloxirane Chemical compound C[C@H]1O[C@@H]1C1=CC=CC=C1 YVCOJTATJWDGEU-APPZFPTMSA-N 0.000 description 2
- MXSNMCYQLIMLBS-MLGOLLRUSA-N (2r,3s)-4-(4-chlorophenyl)-3-phenylbutan-2-ol Chemical compound C([C@H]([C@H](O)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=C1 MXSNMCYQLIMLBS-MLGOLLRUSA-N 0.000 description 2
- FRMQIGNMWCKPMD-CVHDTDHSSA-N (2s,3s)-4-(4-chlorophenyl)-3-phenylbutan-2-amine;hydrochloride Chemical compound Cl.C([C@H]([C@@H](N)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=C1 FRMQIGNMWCKPMD-CVHDTDHSSA-N 0.000 description 2
- WBGTZKFPBKRBGA-XHDPSFHLSA-N (2s,3s)-4-(5-chloropyridin-2-yl)-3-phenylbutan-2-amine Chemical compound C([C@H]([C@@H](N)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=N1 WBGTZKFPBKRBGA-XHDPSFHLSA-N 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- VQQMTJFLYKJSEY-UHFFFAOYSA-N 1-(3-azido-2-phenylbutyl)-4-chlorobenzene Chemical compound C=1C=CC=CC=1C(C(N=[N+]=[N-])C)CC1=CC=C(Cl)C=C1 VQQMTJFLYKJSEY-UHFFFAOYSA-N 0.000 description 2
- MUCZEKUJOCBOOL-UHFFFAOYSA-N 1-(5-chloropyridin-3-yl)propan-2-one Chemical compound CC(=O)CC1=CN=CC(Cl)=C1 MUCZEKUJOCBOOL-UHFFFAOYSA-N 0.000 description 2
- MMSMNBHQVKSTRE-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)pyridin-3-yl]butan-2-one Chemical compound CCC(=O)CC1=CN=CC=C1C1=CC=C(Cl)C=C1 MMSMNBHQVKSTRE-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- JGFXUYLYPITYGR-UHFFFAOYSA-N 2-(2-diphenylphosphanylphenyl)-n,n-dimethylaniline Chemical group CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JGFXUYLYPITYGR-UHFFFAOYSA-N 0.000 description 2
- QZKDJMZKAILCIA-UHFFFAOYSA-N 2-(2-fluorophenoxy)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC=C1F QZKDJMZKAILCIA-UHFFFAOYSA-N 0.000 description 2
- DORYZHTVUAFKQK-UHFFFAOYSA-N 2-(5-chloropyridin-2-yl)oxy-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=N1 DORYZHTVUAFKQK-UHFFFAOYSA-N 0.000 description 2
- HDAKEDWUESRKDA-UHFFFAOYSA-N 2-(benzotriazol-1-yl)-3-(4-chlorophenyl)-n-methoxy-n-methylpropanamide Chemical compound N1=NC2=CC=CC=C2N1C(C(=O)N(C)OC)CC1=CC=C(Cl)C=C1 HDAKEDWUESRKDA-UHFFFAOYSA-N 0.000 description 2
- OQGJGMOFCDBHFN-UHFFFAOYSA-N 2-(benzotriazol-1-yl)-n-methoxy-n-methylacetamide Chemical compound C1=CC=C2N(CC(=O)N(C)OC)N=NC2=C1 OQGJGMOFCDBHFN-UHFFFAOYSA-N 0.000 description 2
- QOXXZTPKJWPIDK-UHFFFAOYSA-N 2-(benzotriazol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)N=NC2=C1 QOXXZTPKJWPIDK-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RCRCTBLIHCHWDZ-UHFFFAOYSA-N 2-Arachidonoyl Glycerol Chemical compound CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO RCRCTBLIHCHWDZ-UHFFFAOYSA-N 0.000 description 2
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 2
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 2
- IJVZMSVDEPSDHH-UHFFFAOYSA-N 2-methyl-2-pyridin-2-yloxybutanoic acid Chemical compound CCC(C)(C(O)=O)OC1=CC=CC=N1 IJVZMSVDEPSDHH-UHFFFAOYSA-N 0.000 description 2
- VOYQXIGXEUQCBP-UHFFFAOYSA-N 3-(3-amino-1-cyclobutylbutan-2-yl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C(C(N)C)CC1CCC1 VOYQXIGXEUQCBP-UHFFFAOYSA-N 0.000 description 2
- SWSXUIFHQYDLHO-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-phenylpropanoic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)CC1=CC=C(Cl)C=C1 SWSXUIFHQYDLHO-UHFFFAOYSA-N 0.000 description 2
- NUQFOCZJHBDDCY-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-methoxy-n-methyl-2-phenylpropanamide Chemical compound C=1C=CC=CC=1C(C(=O)N(C)OC)CC1=CC=C(Cl)C=C1 NUQFOCZJHBDDCY-UHFFFAOYSA-N 0.000 description 2
- MCIJMQJTTHRCQC-UHFFFAOYSA-N 3-(benzotriazol-1-yl)-4-(4-chlorophenyl)butan-2-amine Chemical compound N1=NC2=CC=CC=C2N1C(C(N)C)CC1=CC=C(Cl)C=C1 MCIJMQJTTHRCQC-UHFFFAOYSA-N 0.000 description 2
- YPCMLZCPZCPGCT-UHFFFAOYSA-N 3-[3-amino-1-(4-chlorophenyl)butan-2-yl]benzonitrile;hydrochloride Chemical compound Cl.C=1C=CC(C#N)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 YPCMLZCPZCPGCT-UHFFFAOYSA-N 0.000 description 2
- UAPGJPYBLNMWRA-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-(3-methylphenyl)butan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC(C)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 UAPGJPYBLNMWRA-UHFFFAOYSA-N 0.000 description 2
- GOLSTSUNSCUYOO-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-(5-chloropyridin-3-yl)butan-2-amine;hydrochloride Chemical compound Cl.C=1N=CC(Cl)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 GOLSTSUNSCUYOO-UHFFFAOYSA-N 0.000 description 2
- MXSNMCYQLIMLBS-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-phenylbutan-2-ol Chemical compound C=1C=CC=CC=1C(C(O)C)CC1=CC=C(Cl)C=C1 MXSNMCYQLIMLBS-UHFFFAOYSA-N 0.000 description 2
- BRPUMIYBQYEVHM-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-phenylbutan-2-one Chemical compound C=1C=CC=CC=1C(C(=O)C)CC1=CC=C(Cl)C=C1 BRPUMIYBQYEVHM-UHFFFAOYSA-N 0.000 description 2
- PRCDFCBCHLBJAE-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-pyridin-3-ylbutan-2-amine Chemical compound C=1C=CN=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 PRCDFCBCHLBJAE-UHFFFAOYSA-N 0.000 description 2
- MXZIUDIOUUOXTG-UHFFFAOYSA-N 4-(4-methylphenyl)-3-phenylbutan-2-one Chemical compound C=1C=CC=CC=1C(C(=O)C)CC1=CC=C(C)C=C1 MXZIUDIOUUOXTG-UHFFFAOYSA-N 0.000 description 2
- ARPDFGKPVADMIR-UHFFFAOYSA-N 5-(2-oxopropyl)pyridine-3-carbonitrile Chemical compound CC(=O)CC1=CN=CC(C#N)=C1 ARPDFGKPVADMIR-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 208000032841 Bulimia Diseases 0.000 description 2
- 206010006550 Bulimia nervosa Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 2
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 101000710899 Homo sapiens Cannabinoid receptor 1 Proteins 0.000 description 2
- 101000875075 Homo sapiens Cannabinoid receptor 2 Proteins 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010020710 Hyperphagia Diseases 0.000 description 2
- 206010021113 Hypothermia Diseases 0.000 description 2
- 206010021403 Illusion Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 206010035004 Pickwickian syndrome Diseases 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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- ZVIVRNPNVMJAKA-UHFFFAOYSA-N [4-(4-chlorophenyl)-3-phenylbutan-2-yl] methanesulfonate Chemical compound C=1C=CC=CC=1C(C(OS(C)(=O)=O)C)CC1=CC=C(Cl)C=C1 ZVIVRNPNVMJAKA-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000029650 alcohol withdrawal Diseases 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000000561 anti-psychotic effect Effects 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- KJZZFHGKLQOGOF-UHFFFAOYSA-N benzyl 2-methyl-2-pyridin-2-yloxybutanoate Chemical compound C=1C=CC=CC=1COC(=O)C(C)(CC)OC1=CC=CC=N1 KJZZFHGKLQOGOF-UHFFFAOYSA-N 0.000 description 2
- ZVKCIDZFHPKTAH-UHFFFAOYSA-N benzyl 2-pyridin-2-yloxypropanoate Chemical compound C=1C=CC=CC=1COC(=O)C(C)OC1=CC=CC=N1 ZVKCIDZFHPKTAH-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 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 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 230000010083 bronchial hyperresponsiveness Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- TXCGAZHTZHNUAI-UHFFFAOYSA-N clofibric acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 TXCGAZHTZHNUAI-UHFFFAOYSA-N 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- COOWRSNQEDDDBI-UHFFFAOYSA-N ethyl 2-(5-chloropyridin-2-yl)oxy-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=N1 COOWRSNQEDDDBI-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 238000009207 exercise therapy Methods 0.000 description 2
- 230000003631 expected effect Effects 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 102000056693 human CNR2 Human genes 0.000 description 2
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000000147 hypnotic effect Effects 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- IQVJEYTWJIORDB-UHFFFAOYSA-N methyl 3-(4-chlorophenyl)-2-phenylpropanoate Chemical compound C=1C=CC=CC=1C(C(=O)OC)CC1=CC=C(Cl)C=C1 IQVJEYTWJIORDB-UHFFFAOYSA-N 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 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 2
- 230000037023 motor activity Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- OYVXVLSZQHSNDK-UHFFFAOYSA-N n-methoxy-n-methylacetamide Chemical compound CON(C)C(C)=O OYVXVLSZQHSNDK-UHFFFAOYSA-N 0.000 description 2
- 230000007171 neuropathology Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 235000020830 overeating Nutrition 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 230000005586 smoking cessation Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 208000011580 syndromic disease Diseases 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
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- GOHUMGNZYNZEFF-IAQYHMDHSA-N (2r,3s)-4-(5-chloropyridin-2-yl)-3-phenylbutan-2-ol Chemical compound C([C@H]([C@H](O)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=N1 GOHUMGNZYNZEFF-IAQYHMDHSA-N 0.000 description 1
- UXUUXQCLFKPVET-OTKFKWBMSA-N (2s,3s)-4-(5-chloropyridin-2-yl)-3-phenylbutan-2-amine;hydrochloride Chemical compound Cl.C([C@H]([C@@H](N)C)C=1C=CC=CC=1)C1=CC=C(Cl)C=N1 UXUUXQCLFKPVET-OTKFKWBMSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
- DMHZDOTYAVHSEH-UHFFFAOYSA-N 1-(chloromethyl)-4-methylbenzene Chemical compound CC1=CC=C(CCl)C=C1 DMHZDOTYAVHSEH-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 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
- XFCBHJHQYPNYHS-UHFFFAOYSA-N 1-pyridin-1-ium-3-ylpropan-2-one;chloride Chemical compound Cl.CC(=O)CC1=CC=CN=C1 XFCBHJHQYPNYHS-UHFFFAOYSA-N 0.000 description 1
- WPDJRDYNRNXPBX-UHFFFAOYSA-N 1-pyridin-3-ylpropan-2-one Chemical compound CC(=O)CC1=CC=CN=C1 WPDJRDYNRNXPBX-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- GCTFDMFLLBCLPF-UHFFFAOYSA-N 2,5-dichloropyridine Chemical compound ClC1=CC=C(Cl)N=C1 GCTFDMFLLBCLPF-UHFFFAOYSA-N 0.000 description 1
- DUEGMWKLBXXFOA-UHFFFAOYSA-N 2-(3,5-dichlorophenoxy)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC(Cl)=CC(Cl)=C1 DUEGMWKLBXXFOA-UHFFFAOYSA-N 0.000 description 1
- IGGNSAVLXJKCNH-UHFFFAOYSA-N 2-(3,5-difluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(F)=CC(F)=C1 IGGNSAVLXJKCNH-UHFFFAOYSA-N 0.000 description 1
- PZBIVIXQLIVFHJ-UHFFFAOYSA-N 2-(3-chlorophenoxy)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC(Cl)=C1 PZBIVIXQLIVFHJ-UHFFFAOYSA-N 0.000 description 1
- OIWFXFNZHAOBJP-UHFFFAOYSA-N 2-(4-chloroanilino)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)NC1=CC=C(Cl)C=C1 OIWFXFNZHAOBJP-UHFFFAOYSA-N 0.000 description 1
- UNIXCKUMWRLUBV-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-(3,4-diphenylbutan-2-yl)-2-methylpropanamide Chemical compound C=1C=CC=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 UNIXCKUMWRLUBV-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- WAKFRZBXTKUFIW-UHFFFAOYSA-M 2-bromo-2-phenylacetate Chemical compound [O-]C(=O)C(Br)C1=CC=CC=C1 WAKFRZBXTKUFIW-UHFFFAOYSA-M 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- GXSHULAGEKSWOX-UHFFFAOYSA-N 2-ethoxy-5-(trifluoromethyl)pyridine Chemical compound CCOC1=CC=C(C(F)(F)F)C=N1 GXSHULAGEKSWOX-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- UUOFEUNPCWIZKP-UHFFFAOYSA-N 2-methyl-2-(6-methylpyridin-2-yl)oxypropanoic acid Chemical compound CC1=CC=CC(OC(C)(C)C(O)=O)=N1 UUOFEUNPCWIZKP-UHFFFAOYSA-N 0.000 description 1
- NARGBGXBGLUPLB-UHFFFAOYSA-N 2-methyl-2-[4-(trifluoromethyl)pyridin-2-yl]oxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC(C(F)(F)F)=CC=N1 NARGBGXBGLUPLB-UHFFFAOYSA-N 0.000 description 1
- WNLKFFVWZDIHOZ-UHFFFAOYSA-N 2-methyl-2-[6-(trifluoromethyl)pyrimidin-4-yl]oxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC(C(F)(F)F)=NC=N1 WNLKFFVWZDIHOZ-UHFFFAOYSA-N 0.000 description 1
- UBNLQBJKNBWIEO-UHFFFAOYSA-N 2-methyl-2-pyridin-2-yloxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC=N1 UBNLQBJKNBWIEO-UHFFFAOYSA-N 0.000 description 1
- FVMKLZZXTKWIAE-UHFFFAOYSA-N 2-methyl-2-pyrimidin-2-yloxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=NC=CC=N1 FVMKLZZXTKWIAE-UHFFFAOYSA-N 0.000 description 1
- BOZLAQWSKVCYCR-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylphenyl)-3-phenylbutan-2-yl]-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide Chemical compound C=1C=C(C)C=CC=1CC(C=1C=CC=CC=1)C(C)NC(=O)C(C)(C)OC1=CC=C(C(F)(F)F)C=N1 BOZLAQWSKVCYCR-UHFFFAOYSA-N 0.000 description 1
- RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- WPGHPGAUFIJVJF-UHFFFAOYSA-N 3,5-dichloropyridine Chemical compound ClC1=CN=CC(Cl)=C1 WPGHPGAUFIJVJF-UHFFFAOYSA-N 0.000 description 1
- UTISNEMDHDJLOW-UHFFFAOYSA-N 3-(1-cyclobutyl-3-oxobutan-2-yl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C(C(=O)C)CC1CCC1 UTISNEMDHDJLOW-UHFFFAOYSA-N 0.000 description 1
- QLTPOGPPHVVNAW-UHFFFAOYSA-N 3-(3-amino-1-cyclohexylbutan-2-yl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C(C(N)C)CC1CCCCC1 QLTPOGPPHVVNAW-UHFFFAOYSA-N 0.000 description 1
- ZVQABPJMESIHOM-UHFFFAOYSA-N 3-(3-amino-1-cyclopentylbutan-2-yl)benzonitrile Chemical compound C=1C=CC(C#N)=CC=1C(C(N)C)CC1CCCC1 ZVQABPJMESIHOM-UHFFFAOYSA-N 0.000 description 1
- SKIPPBDLPDBCJZ-UHFFFAOYSA-N 3-(3-bromophenyl)-4-(5-chloropyridin-2-yl)butan-2-amine Chemical compound C=1C=CC(Br)=CC=1C(C(N)C)CC1=CC=C(Cl)C=N1 SKIPPBDLPDBCJZ-UHFFFAOYSA-N 0.000 description 1
- BCXLQSVRUJFDSN-UHFFFAOYSA-N 3-(3-bromophenyl)-4-(5-chloropyridin-2-yl)butan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC(Br)=CC=1C(C(N)C)CC1=CC=C(Cl)C=N1 BCXLQSVRUJFDSN-UHFFFAOYSA-N 0.000 description 1
- DLFUGLXZWASHHT-UHFFFAOYSA-N 3-(3-bromophenyl)-4-(5-chloropyridin-2-yl)butan-2-ol Chemical compound C=1C=CC(Br)=CC=1C(C(O)C)CC1=CC=C(Cl)C=N1 DLFUGLXZWASHHT-UHFFFAOYSA-N 0.000 description 1
- WINKREGAKISAPP-UHFFFAOYSA-N 3-(3-bromophenyl)-4-(5-chloropyridin-2-yl)butan-2-one Chemical compound C=1C=CC(Br)=CC=1C(C(=O)C)CC1=CC=C(Cl)C=N1 WINKREGAKISAPP-UHFFFAOYSA-N 0.000 description 1
- ZKYQBMSRDAGSIV-UHFFFAOYSA-N 3-(5-bromopyridin-2-yl)-4-(4-chlorophenyl)butan-2-amine;hydrochloride Chemical compound Cl.C=1C=C(Br)C=NC=1C(C(N)C)CC1=CC=C(Cl)C=C1 ZKYQBMSRDAGSIV-UHFFFAOYSA-N 0.000 description 1
- ICHLEROHEXSILU-UHFFFAOYSA-N 3-(5-bromopyridin-3-yl)-4-(4-chlorophenyl)butan-2-amine;hydrochloride Chemical compound Cl.C=1N=CC(Br)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 ICHLEROHEXSILU-UHFFFAOYSA-N 0.000 description 1
- XWPVWEMNQSNKHH-UHFFFAOYSA-N 3-(5-bromopyridin-3-yl)-4-(4-chlorophenyl)butan-2-ol Chemical compound C=1N=CC(Br)=CC=1C(C(O)C)CC1=CC=C(Cl)C=C1 XWPVWEMNQSNKHH-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
- STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- CXZQJLGWVBSKMQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-(3,5-difluorophenyl)butan-2-amine;hydrochloride Chemical compound Cl.C=1C(F)=CC(F)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 CXZQJLGWVBSKMQ-UHFFFAOYSA-N 0.000 description 1
- JFFVJCZMNLBCPE-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-(5-methylpyridin-3-yl)butan-2-amine;hydrochloride Chemical compound Cl.C=1N=CC(C)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 JFFVJCZMNLBCPE-UHFFFAOYSA-N 0.000 description 1
- MRVSELHQNPDXSA-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-thiophen-3-ylbutan-2-amine Chemical compound C1=CSC=C1C(C(N)C)CC1=CC=C(Cl)C=C1 MRVSELHQNPDXSA-UHFFFAOYSA-N 0.000 description 1
- GOHUMGNZYNZEFF-UHFFFAOYSA-N 4-(5-chloropyridin-2-yl)-3-phenylbutan-2-ol Chemical compound C=1C=CC=CC=1C(C(O)C)CC1=CC=C(Cl)C=N1 GOHUMGNZYNZEFF-UHFFFAOYSA-N 0.000 description 1
- IKHLLNMSMFVTLP-UHFFFAOYSA-N 4-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=CC(C(F)(F)F)=CC=N1 IKHLLNMSMFVTLP-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- BYRJSCNPUHYZQE-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=CC=C(C(F)(F)F)C=N1 BYRJSCNPUHYZQE-UHFFFAOYSA-N 0.000 description 1
- XBWTWDHLEXBQRR-UHFFFAOYSA-N 5-[3-amino-1-(4-chlorophenyl)butan-2-yl]pyridine-3-carbonitrile;hydrochloride Chemical compound Cl.C=1N=CC(C#N)=CC=1C(C(N)C)CC1=CC=C(Cl)C=C1 XBWTWDHLEXBQRR-UHFFFAOYSA-N 0.000 description 1
- VFMPNFQQXHJUEV-UHFFFAOYSA-N 5-bromopyridine-3-carbonitrile Chemical compound BrC1=CN=CC(C#N)=C1.BrC1=CN=CC(C#N)=C1 VFMPNFQQXHJUEV-UHFFFAOYSA-N 0.000 description 1
- LVOYSBZJJWPUBD-UHFFFAOYSA-N 6-(trifluoromethyl)-1h-pyrimidin-4-one Chemical compound OC1=CC(C(F)(F)F)=NC=N1 LVOYSBZJJWPUBD-UHFFFAOYSA-N 0.000 description 1
- GABORTSSBWZBLC-UHFFFAOYSA-N 6-[3-amino-1-(4-chlorophenyl)butan-2-yl]pyridine-3-carbonitrile;hydrochloride Chemical compound Cl.C=1C=C(C#N)C=NC=1C(C(N)C)CC1=CC=C(Cl)C=C1 GABORTSSBWZBLC-UHFFFAOYSA-N 0.000 description 1
- JEAVIRYCMBDJIU-UHFFFAOYSA-N 6-methyl-1h-pyridin-2-one Chemical compound CC1=CC=CC(O)=N1 JEAVIRYCMBDJIU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical class [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000031873 Animal Disease Models Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010004716 Binge eating Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 1
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 1
- 235000008697 Cannabis sativa Nutrition 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XXGMIHXASFDFSM-UHFFFAOYSA-N Delta9-tetrahydrocannabinol Natural products CCCCCc1cc2OC(C)(C)C3CCC(=CC3c2c(O)c1O)C XXGMIHXASFDFSM-UHFFFAOYSA-N 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 208000010235 Food Addiction Diseases 0.000 description 1
- 201000001498 Froelich syndrome Diseases 0.000 description 1
- 208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
- 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 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000004866 Hashish Substances 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010056997 Impaired fasting glucose Diseases 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 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 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- FHCJOVFTRJALCF-UHFFFAOYSA-N N-[4-(4-chlorophenyl)-3-(5-cyanopyridin-3-yl)butan-2-yl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide 1-oxidopyridin-1-ium Chemical compound ClC1=CC=C(C=C1)CC(C(C)NC(C(C)(C)OC1=NC=C(C=C1)C(F)(F)F)=O)C=1C=NC=C(C1)C#N.[N+]1(=CC=CC=C1)[O-] FHCJOVFTRJALCF-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 208000004166 Obesity Hypoventilation Syndrome Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010036049 Polycystic ovaries Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 208000020221 Short stature Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000011962 Substance-induced mood disease Diseases 0.000 description 1
- 231100000395 Substance-induced mood disorder Toxicity 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001062 anti-nausea Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002282 antimigraine agent Substances 0.000 description 1
- 229940125684 antimigraine agent Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
- 150000001539 azetidines Chemical class 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 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
- 229940049706 benzodiazepine 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
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- KZNCFIIFMFCSHL-UHFFFAOYSA-N benzyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)NC(C)C(=O)OCC1=CC=CC=C1 KZNCFIIFMFCSHL-UHFFFAOYSA-N 0.000 description 1
- ZYTLPUIDJRKAAM-UHFFFAOYSA-N benzyl 2-hydroxypropanoate Chemical compound CC(O)C(=O)OCC1=CC=CC=C1 ZYTLPUIDJRKAAM-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 208000014679 binge eating disease Diseases 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical class Br* 0.000 description 1
- KXVUSQIDCZRUKF-UHFFFAOYSA-N bromocyclobutane Chemical compound BrC1CCC1 KXVUSQIDCZRUKF-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
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 235000019577 caloric intake 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
- 239000003520 cannabinoid receptor affecting agent Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- ABSOMGPQFXJESQ-UHFFFAOYSA-M cesium;hydroxide;hydrate Chemical compound O.[OH-].[Cs+] ABSOMGPQFXJESQ-UHFFFAOYSA-M 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical class Cl* 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000037410 cognitive enhancement Effects 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 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 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229940048820 edetates Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002085 enols Chemical group 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
- GFUIDHWFLMPAGY-UHFFFAOYSA-N ethyl 2-hydroxy-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)O GFUIDHWFLMPAGY-UHFFFAOYSA-N 0.000 description 1
- HUVCUPRXUAMHRB-UHFFFAOYSA-N ethyl 3-(4-chlorophenyl)-2-(2,3-dihydroindol-1-yl)propanoate Chemical compound C1CC2=CC=CC=C2N1C(C(=O)OCC)CC1=CC=C(Cl)C=C1 HUVCUPRXUAMHRB-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019000 fluorine Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 208000019622 heart disease Diseases 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
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000036032 hypoalgesia Effects 0.000 description 1
- 208000021731 hypoalgesia Diseases 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- DIQDUFVJZPNLJQ-UHFFFAOYSA-N indol-1-yl(phenyl)methanone Chemical class C1=CC2=CC=CC=C2N1C(=O)C1=CC=CC=C1 DIQDUFVJZPNLJQ-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 235000013675 iodine Nutrition 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 150000003903 lactic acid esters Chemical class 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YBJMEHGTPXJXHZ-UHFFFAOYSA-N methyl 2-(3,5-difluorophenyl)acetate Chemical compound COC(=O)CC1=CC(F)=CC(F)=C1 YBJMEHGTPXJXHZ-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- WVFKSOOBEAEOLB-UHFFFAOYSA-N n-[3,4-bis(4-chlorophenyl)butan-2-yl]-2-(4-chloroanilino)-2-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1CC(C=1C=CC(Cl)=CC=1)C(C)NC(=O)C(C)(C)NC1=CC=C(Cl)C=C1 WVFKSOOBEAEOLB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 230000008518 non respiratory effect Effects 0.000 description 1
- 125000001400 nonyl 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])[H] 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000007943 positive regulation of appetite Effects 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000003373 pyrazinyl 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
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229960003015 rimonabant Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 201000006152 substance dependence Diseases 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000021147 sweet food Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- 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
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/08—Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- 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
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Structural Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US42841502P | 2002-11-22 | 2002-11-22 | |
PCT/US2003/007039 WO2004048317A1 (en) | 2002-11-22 | 2003-03-07 | Substituted amides active at the cannabinoid-1 receptor |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20040823A2 true HRP20040823A2 (en) | 2005-06-30 |
Family
ID=32393400
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20040823A HRP20040823A2 (en) | 2002-11-22 | 2004-09-10 | Substituted amides active at the cannabinoid-1 receptor |
Country Status (25)
Country | Link |
---|---|
KR (1) | KR100748380B1 (es) |
CN (1) | CN1639112A (es) |
AR (1) | AR038948A1 (es) |
AU (1) | AU2003218005A1 (es) |
BR (1) | BR0308349A (es) |
CR (1) | CR7432A (es) |
DO (1) | DOP2003000609A (es) |
EA (1) | EA007747B1 (es) |
EC (1) | ECSP045289A (es) |
GE (1) | GEP20074208B (es) |
HR (1) | HRP20040823A2 (es) |
IL (1) | IL163824A0 (es) |
IS (1) | IS7411A (es) |
JO (1) | JO2482B1 (es) |
MA (1) | MA27185A1 (es) |
MX (1) | MXPA04008748A (es) |
MY (1) | MY134457A (es) |
NO (1) | NO20043803L (es) |
PE (1) | PE20040599A1 (es) |
PL (1) | PL200328B1 (es) |
RS (1) | RS79104A (es) |
TN (1) | TNSN04176A1 (es) |
TW (1) | TW200408620A (es) |
UA (1) | UA76590C2 (es) |
WO (1) | WO2004048317A1 (es) |
Families Citing this family (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2478183C (en) | 2002-03-12 | 2010-02-16 | Merck & Co. Inc. | Substituted amides |
AU2003257145B2 (en) | 2002-08-02 | 2008-11-13 | Merck Sharp & Dohme Corp. | Substituted furo (2,3-b) pyridine derivatives |
EP1575901B1 (en) | 2002-12-19 | 2012-10-10 | Merck Sharp & Dohme Corp. | Substituted amides |
WO2005009479A1 (en) * | 2003-06-30 | 2005-02-03 | Merck & Co., Inc. | Radiolabeled cannabinoid-1 receptor modulators |
JP2007510647A (ja) * | 2003-10-30 | 2007-04-26 | メルク エンド カムパニー インコーポレーテッド | カンナビノイド受容体調節剤としてのアラルキルアミン類 |
US7649002B2 (en) | 2004-02-04 | 2010-01-19 | Pfizer Inc | (3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists |
US7629470B2 (en) | 2004-07-08 | 2009-12-08 | Merck & Co., Inc. | Formation of tetra-substituted enamides and stereoselective reduction thereof |
US20060025448A1 (en) | 2004-07-22 | 2006-02-02 | Cadila Healthcare Limited | Hair growth stimulators |
WO2006035759A1 (ja) * | 2004-09-27 | 2006-04-06 | Santen Pharmaceutical Co., Ltd. | 呼吸器疾患治療剤 |
WO2006035760A1 (ja) * | 2004-09-27 | 2006-04-06 | Santen Pharmaceutical Co., Ltd. | 皮膚疾患治療剤 |
WO2006043518A1 (ja) * | 2004-10-18 | 2006-04-27 | Santen Pharmaceutical Co., Ltd. | 神経疾患治療剤 |
PA8660701A1 (es) | 2005-02-04 | 2006-09-22 | Pfizer Prod Inc | Agonistas de pyy y sus usos |
CN101426500A (zh) * | 2005-05-02 | 2009-05-06 | 默克公司 | 治疗糖尿病和肥胖症的二肽基肽酶iv抑制剂和cb1受体拮抗剂的药物组合物 |
CN101277960A (zh) | 2005-09-29 | 2008-10-01 | 默克公司 | 作为黑皮质素-4受体调节剂的酰化螺哌啶衍生物 |
US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
ES2402581T3 (es) | 2006-02-23 | 2013-05-06 | Pfizer Limited | Piperidinoilpirrolidinas como agonistas del receptor de melanocortina tipo 4 |
WO2008017381A1 (de) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituierte imidazolidin-2,4-dione, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und ihre verwendung |
US8173629B2 (en) | 2006-09-22 | 2012-05-08 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
JP2010509392A (ja) | 2006-11-13 | 2010-03-25 | ファイザー・プロダクツ・インク | ジアリール、ジピリジニルおよびアリール−ピリジニル誘導体ならびにその使用 |
CN101663262B (zh) | 2006-12-01 | 2014-03-26 | 百时美施贵宝公司 | 用于治疗动脉粥样硬化和心血管疾病的作为cetp抑制剂的n-(3-苄基)-2,2-(二苯基)-丙-1胺衍生物 |
EP2145884B1 (en) | 2007-04-02 | 2014-08-06 | Msd K.K. | Indoledione derivative |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
TW201014822A (en) | 2008-07-09 | 2010-04-16 | Sanofi Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
WO2010015972A1 (en) | 2008-08-06 | 2010-02-11 | Pfizer Limited | Diazepine and diazocane compounds as mc4 agonists |
JP5635991B2 (ja) | 2008-10-30 | 2014-12-03 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | イソニコチンアミドオレキシン受容体アンタゴニスト |
US8759539B2 (en) | 2008-11-17 | 2014-06-24 | Merck Sharp & Dohme Corp. | Substituted bicyclic amines for the treatment of diabetes |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
CA2768577A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
SG178880A1 (en) | 2009-08-26 | 2012-04-27 | Sanofi Sa | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
US8785634B2 (en) | 2010-04-26 | 2014-07-22 | Merck Sharp & Dohme Corp | Spiropiperidine prolylcarboxypeptidase inhibitors |
WO2011143057A1 (en) | 2010-05-11 | 2011-11-17 | Merck Sharp & Dohme Corp. | Novel prolylcarboxypeptidase inhibitors |
EP2579873A4 (en) | 2010-06-11 | 2013-11-27 | Merck Sharp & Dohme | NOVEL PROLYLCARBOXYPEPTIDASE HEMMER |
US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8846666B2 (en) | 2011-03-08 | 2014-09-30 | Sanofi | Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
US8809325B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof |
WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
US8895547B2 (en) | 2011-03-08 | 2014-11-25 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
WO2020167706A1 (en) | 2019-02-13 | 2020-08-20 | Merck Sharp & Dohme Corp. | 5-alkyl pyrrolidine orexin receptor agonists |
US20230018413A1 (en) | 2019-08-08 | 2023-01-19 | Merck Sharp & Dohme Corp. | Heteroaryl pyrrolidine and piperidine orexin receptor agonists |
EP4200295A1 (en) | 2020-08-18 | 2023-06-28 | Merck Sharp & Dohme LLC | Bicycloheptane pyrrolidine orexin receptor agonists |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001516361A (ja) * | 1997-03-18 | 2001-09-25 | スミスクライン・ビーチャム・コーポレイション | 新規カンナビノイド受容体作動薬 |
GEP20053710B (en) * | 2001-02-28 | 2005-12-26 | Merck & Co Inc | Acylated Piperidine Derivatives as Melanocortin-4 Receptor Agonists |
-
2003
- 2003-02-11 MY MYPI20030464A patent/MY134457A/en unknown
- 2003-02-18 TW TW092103282A patent/TW200408620A/zh unknown
- 2003-03-03 JO JO200320A patent/JO2482B1/en active
- 2003-03-07 EA EA200401066A patent/EA007747B1/ru not_active IP Right Cessation
- 2003-03-07 WO PCT/US2003/007039 patent/WO2004048317A1/en not_active Application Discontinuation
- 2003-03-07 MX MXPA04008748A patent/MXPA04008748A/es active IP Right Grant
- 2003-03-07 GE GEAP8404A patent/GEP20074208B/en unknown
- 2003-03-07 KR KR1020047014299A patent/KR100748380B1/ko not_active IP Right Cessation
- 2003-03-07 PL PL373656A patent/PL200328B1/pl not_active IP Right Cessation
- 2003-03-07 BR BR0308349-7A patent/BR0308349A/pt not_active IP Right Cessation
- 2003-03-07 PE PE2003000230A patent/PE20040599A1/es not_active Application Discontinuation
- 2003-03-07 AU AU2003218005A patent/AU2003218005A1/en not_active Abandoned
- 2003-03-07 IL IL16382403A patent/IL163824A0/xx unknown
- 2003-03-07 CN CNA03805678XA patent/CN1639112A/zh active Pending
- 2003-03-07 RS YUP-791/04A patent/RS79104A/sr unknown
- 2003-03-12 AR ARP030100857A patent/AR038948A1/es unknown
- 2003-03-12 DO DO2003000609A patent/DOP2003000609A/es unknown
- 2003-07-03 UA UA20040907424A patent/UA76590C2/uk unknown
-
2004
- 2004-08-19 IS IS7411A patent/IS7411A/is unknown
- 2004-08-24 CR CR7432A patent/CR7432A/es unknown
- 2004-09-10 TN TNP2004000176A patent/TNSN04176A1/en unknown
- 2004-09-10 EC EC2004005289A patent/ECSP045289A/es unknown
- 2004-09-10 MA MA27851A patent/MA27185A1/fr unknown
- 2004-09-10 HR HR20040823A patent/HRP20040823A2/hr not_active Application Discontinuation
- 2004-09-10 NO NO20043803A patent/NO20043803L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
AU2003218005A1 (en) | 2004-06-18 |
EA200401066A1 (ru) | 2005-04-28 |
WO2004048317A1 (en) | 2004-06-10 |
BR0308349A (pt) | 2005-01-25 |
NO20043803L (no) | 2005-05-24 |
GEP20074208B (en) | 2007-10-10 |
RS79104A (en) | 2007-02-05 |
EA007747B1 (ru) | 2006-12-29 |
MY134457A (en) | 2007-12-31 |
KR100748380B1 (ko) | 2007-08-10 |
TW200408620A (en) | 2004-06-01 |
PE20040599A1 (es) | 2004-09-08 |
PL373656A1 (en) | 2005-09-05 |
CN1639112A (zh) | 2005-07-13 |
AR038948A1 (es) | 2005-02-02 |
DOP2003000609A (es) | 2004-06-15 |
MA27185A1 (fr) | 2005-01-03 |
PL200328B1 (pl) | 2008-12-31 |
ECSP045289A (es) | 2004-10-26 |
IL163824A0 (en) | 2005-12-18 |
KR20050083563A (ko) | 2005-08-26 |
TNSN04176A1 (en) | 2007-03-12 |
MXPA04008748A (es) | 2004-12-06 |
UA76590C2 (en) | 2006-08-15 |
CR7432A (es) | 2005-10-05 |
JO2482B1 (en) | 2009-01-20 |
IS7411A (is) | 2004-08-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20040823A2 (en) | Substituted amides active at the cannabinoid-1 receptor | |
JP4719469B2 (ja) | 置換アミド類 | |
JP4459629B2 (ja) | 二環式アミド | |
JP3813152B2 (ja) | 置換アミド類 | |
CN104968647B (zh) | 作为钠通道调节剂的酰胺 | |
AU2003226149A1 (en) | Substituted aryl amides | |
JP2005528366A (ja) | カンナビノイド受容体モジュレータとしてのスピロ環式アミド | |
US7135472B2 (en) | 3-Heterocyclic benzylamide derivatives as potassium channel openers | |
JP5057982B2 (ja) | ヒスタミンh3受容体阻害剤、製造及び治療的使用 | |
SK113199A3 (en) | Atropisomers of 3-heteroaryl-4(3h)-quinazolinones for the treatment of neurodegenerative and cns-trauma related conditions | |
JP3110049B2 (ja) | 新規イミダゾールリポキシゲナーゼ阻害剤 | |
KR20180135448A (ko) | Kcnq2∼5 채널 활성화제의 결정다형 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20090305 Year of fee payment: 7 |
|
OBST | Application withdrawn |