CA2619228A1 - Pyrazole derivatives as therapeutic agents - Google Patents

Info

Publication number

CA2619228A1

CA2619228A1 CA002619228A CA2619228A CA2619228A1 CA 2619228 A1 CA2619228 A1 CA 2619228A1 CA 002619228 A CA002619228 A CA 002619228A CA 2619228 A CA2619228 A CA 2619228A CA 2619228 A1 CA2619228 A1 CA 2619228A1

Authority

CA

Canada

Prior art keywords

methyl

dichlorophenyl

pyrazol

piperidin

ylcarbamoyl

Prior art date

2005-08-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000003814 drug Substances 0.000 title claims description 47
• 229940124597 therapeutic agent Drugs 0.000 title description 7
• 150000003217 pyrazoles Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 165
• 150000003839 salts Chemical class 0.000 claims abstract description 73
• 238000011282 treatment Methods 0.000 claims abstract description 57
• 238000000034 method Methods 0.000 claims abstract description 28
• 208000008589 Obesity Diseases 0.000 claims abstract description 26
• 235000020824 obesity Nutrition 0.000 claims abstract description 26
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 17
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 17
• 208000020016 psychiatric disease Diseases 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• -1 propane-1-sulfonic acid 4-[2-(2,4-dichlorophenyl)-4-methyl-5-(morpholin-4-ylcarbamoyl)-2H-pyrazol-3-yl]phenyl ester mesylate Chemical compound 0.000 claims description 55
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 208000035475 disorder Diseases 0.000 claims description 26
• 125000001153 fluoro group Chemical group F* 0.000 claims description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 208000032841 Bulimia Diseases 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 12
• 238000011321 prophylaxis Methods 0.000 claims description 12
• 208000024827 Alzheimer disease Diseases 0.000 claims description 11
• 208000019901 Anxiety disease Diseases 0.000 claims description 11
• 208000028017 Psychotic disease Diseases 0.000 claims description 11
• 230000036506 anxiety Effects 0.000 claims description 11
• 239000003085 diluting agent Substances 0.000 claims description 11
• 230000001850 reproductive effect Effects 0.000 claims description 11
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 9
• 208000022531 anorexia Diseases 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 206010061428 decreased appetite Diseases 0.000 claims description 9
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
• 208000020925 Bipolar disease Diseases 0.000 claims description 8
• 208000020401 Depressive disease Diseases 0.000 claims description 8
• 208000017701 Endocrine disease Diseases 0.000 claims description 8
• 208000023105 Huntington disease Diseases 0.000 claims description 8
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 8
• 208000018737 Parkinson disease Diseases 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 210000005095 gastrointestinal system Anatomy 0.000 claims description 8
• 230000000241 respiratory effect Effects 0.000 claims description 8
• 201000000980 schizophrenia Diseases 0.000 claims description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
• 208000010877 cognitive disease Diseases 0.000 claims description 7
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical class OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 claims description 7
• 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 239000005864 Sulphur Substances 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 229920006395 saturated elastomer Polymers 0.000 claims description 6
• 206010012335 Dependence Diseases 0.000 claims description 5
• 208000026139 Memory disease Diseases 0.000 claims description 5
• 206010040070 Septic Shock Diseases 0.000 claims description 5
• AUAVZPQYSXVTLQ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(F)(F)F)C=C1 AUAVZPQYSXVTLQ-UHFFFAOYSA-N 0.000 claims description 5
• YWOALVMKNRNBBO-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3-dimethylbutane-1-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(C)(C)C)C=C1 YWOALVMKNRNBBO-UHFFFAOYSA-N 0.000 claims description 5
• BCCJHTSBSBQLHY-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3-methylbutane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC(C)C)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl BCCJHTSBSBQLHY-UHFFFAOYSA-N 0.000 claims description 5
• LVVUMIYPGFVAJN-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] butane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl LVVUMIYPGFVAJN-UHFFFAOYSA-N 0.000 claims description 5
• VXWQPNOJNRIMBE-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl VXWQPNOJNRIMBE-UHFFFAOYSA-N 0.000 claims description 5
• AHSRHSWEKIGVOH-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propyl carbonate Chemical compound C1=CC(OC(=O)OCCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl AHSRHSWEKIGVOH-UHFFFAOYSA-N 0.000 claims description 5
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 5
• 206010015037 epilepsy Diseases 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 210000002345 respiratory system Anatomy 0.000 claims description 5
• 230000036303 septic shock Effects 0.000 claims description 5
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 4
• QICBNRXJOSZLBJ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(morpholin-4-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NN2CCOCC2)=NN1C1=CC=C(Cl)C=C1Cl QICBNRXJOSZLBJ-UHFFFAOYSA-N 0.000 claims description 4
• 239000002671 adjuvant Substances 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
• IFGQJBDJNDIPDS-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(morpholin-4-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate;hydrochloride Chemical compound Cl.C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NN2CCOCC2)=NN1C1=CC=C(Cl)C=C1Cl IFGQJBDJNDIPDS-UHFFFAOYSA-N 0.000 claims description 3
• DJGFAQDDAOGIPL-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]-2,6-difluorophenyl] propane-1-sulfonate Chemical compound C1=C(F)C(OS(=O)(=O)CCC)=C(F)C=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl DJGFAQDDAOGIPL-UHFFFAOYSA-N 0.000 claims description 3
• VZZOFYHOFUIWOS-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]-2,6-difluorophenyl] propane-1-sulfonate;hydrochloride Chemical compound Cl.C1=C(F)C(OS(=O)(=O)CCC)=C(F)C=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl VZZOFYHOFUIWOS-UHFFFAOYSA-N 0.000 claims description 3
• JGZSYATUMNDYQA-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate;hydrochloride Chemical compound Cl.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(F)(F)F)C=C1 JGZSYATUMNDYQA-UHFFFAOYSA-N 0.000 claims description 3
• NKFZWEKGHHSMAJ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3-methylbutane-1-sulfonate;hydrochloride Chemical compound Cl.C1=CC(OS(=O)(=O)CCC(C)C)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl NKFZWEKGHHSMAJ-UHFFFAOYSA-N 0.000 claims description 3
• MVECALZRTCMCJA-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 4,4,4-trifluorobutane-1-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCCC(F)(F)F)C=C1 MVECALZRTCMCJA-UHFFFAOYSA-N 0.000 claims description 3
• MGIKTAUVCSOXJZ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] butane-1-sulfonate;hydrochloride Chemical compound Cl.C1=CC(OS(=O)(=O)CCCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MGIKTAUVCSOXJZ-UHFFFAOYSA-N 0.000 claims description 3
• JNJQBBZYSOHTOD-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propyl carbonate;hydrochloride Chemical compound Cl.C1=CC(OC(=O)OCCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl JNJQBBZYSOHTOD-UHFFFAOYSA-N 0.000 claims description 3
• SDOFEWBZMHEXMG-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] pyridine-3-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OS(=O)(=O)C1=CC=CN=C1 SDOFEWBZMHEXMG-UHFFFAOYSA-N 0.000 claims description 3
• AXDDHUXBDOCODH-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] pyridine-3-sulfonate;hydrochloride Chemical compound Cl.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OS(=O)(=O)C1=CC=CN=C1 AXDDHUXBDOCODH-UHFFFAOYSA-N 0.000 claims description 3
• FQCBXOUPBCGHEL-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] pyridine-3-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OS(=O)(=O)C1=CC=CN=C1 FQCBXOUPBCGHEL-UHFFFAOYSA-N 0.000 claims description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000000217 alkyl group Chemical group 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 125000004432 carbon atom Chemical group C* 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000001072 heteroaryl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
• 125000005968 oxazolinyl group Chemical group 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• RBMLXUPMQXUJAV-UHFFFAOYSA-N tert-butyl n-[2-[4-[5-[ethyl(methyl)carbamoyl]-2-(4-methoxyphenyl)pyrazol-3-yl]phenoxy]ethyl]carbamate Chemical compound C=1C=C(OC)C=CC=1N1N=C(C(=O)N(C)CC)C=C1C1=CC=C(OCCNC(=O)OC(C)(C)C)C=C1 RBMLXUPMQXUJAV-UHFFFAOYSA-N 0.000 claims description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• GIEMMIKVDOSGKF-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-[4-[2-(1,3-dioxolan-2-yl)ethoxy]phenyl]-4-methyl-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OCCC1OCCO1 GIEMMIKVDOSGKF-UHFFFAOYSA-N 0.000 claims description 2
• MJLVTUHSINIYHD-UHFFFAOYSA-N [3-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]-2,6-difluorophenyl] propane-1-sulfonate Chemical compound CCCS(=O)(=O)OC1=C(F)C=CC(C=2N(N=C(C=2C)C(=O)NN2CCCCC2)C=2C(=CC(Cl)=CC=2)Cl)=C1F MJLVTUHSINIYHD-UHFFFAOYSA-N 0.000 claims description 2
• IAWUDAHNFQTTNV-UHFFFAOYSA-N [4-[2-(2,4-dichloro-3-fluorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C(F)=C1Cl IAWUDAHNFQTTNV-UHFFFAOYSA-N 0.000 claims description 2
• KGLIWEPEGUUVDW-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]-2,6-difluorophenyl] propane-1-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=C(F)C(OS(=O)(=O)CCC)=C(F)C=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl KGLIWEPEGUUVDW-UHFFFAOYSA-N 0.000 claims description 2
• XPHPPWLIVCEAIW-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(F)(F)F)C=C1 XPHPPWLIVCEAIW-UHFFFAOYSA-N 0.000 claims description 2
• UDHMCRJUPMNMGJ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate;sulfuric acid Chemical compound OS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(F)(F)F)C=C1 UDHMCRJUPMNMGJ-UHFFFAOYSA-N 0.000 claims description 2
• PODFRUVHMGSUJP-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3-dimethylbutane-1-sulfonate;hydrochloride Chemical compound Cl.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(C)(C)C)C=C1 PODFRUVHMGSUJP-UHFFFAOYSA-N 0.000 claims description 2
• FLQIERRYPUKNNW-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3,3-dimethylbutane-1-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCC(C)(C)C)C=C1 FLQIERRYPUKNNW-UHFFFAOYSA-N 0.000 claims description 2
• BFGXETDUHATQFL-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 3-methylbutane-1-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(OS(=O)(=O)CCC(C)C)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl BFGXETDUHATQFL-UHFFFAOYSA-N 0.000 claims description 2
• MPBITROOUANOOJ-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 4,4,4-trifluorobutane-1-sulfonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCCC(F)(F)F)C=C1 MPBITROOUANOOJ-UHFFFAOYSA-N 0.000 claims description 2
• GPQUPYHCKACUJO-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 4,4,4-trifluorobutane-1-sulfonate;sulfuric acid Chemical compound OS(O)(=O)=O.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCCC(F)(F)F)C=C1 GPQUPYHCKACUJO-UHFFFAOYSA-N 0.000 claims description 2
• GYYSXUMBLAVNOE-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 5-chlorothiophene-2-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OS(=O)(=O)C1=CC=C(Cl)S1 GYYSXUMBLAVNOE-UHFFFAOYSA-N 0.000 claims description 2
• ZQZLNZPNURMCCV-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate;hydrochloride Chemical compound Cl.C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl ZQZLNZPNURMCCV-UHFFFAOYSA-N 0.000 claims description 2
• RBBZHRDNDVTXDE-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] thiophene-2-sulfonate Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OS(=O)(=O)C1=CC=CS1 RBBZHRDNDVTXDE-UHFFFAOYSA-N 0.000 claims description 2
• ZOYJIPVURNXTRC-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=CC(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl ZOYJIPVURNXTRC-UHFFFAOYSA-N 0.000 claims description 2
• ZBHKGROPMVIULG-UHFFFAOYSA-N [4-[4-bromo-2-(2,4-dichlorophenyl)-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propane-1-sulfonate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(Br)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl ZBHKGROPMVIULG-UHFFFAOYSA-N 0.000 claims description 2
• OIKPHKKMAWAJPO-UHFFFAOYSA-N tert-butyl n-[2-[4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenoxy]ethyl]-n-ethylcarbamate Chemical compound C1=CC(OCCN(CC)C(=O)OC(C)(C)C)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl OIKPHKKMAWAJPO-UHFFFAOYSA-N 0.000 claims description 2
• SZEJCQNZIXNDFX-UHFFFAOYSA-N tert-butyl n-[2-[4-[2-(4-methoxyphenyl)-5-(piperidine-1-carbonyl)pyrazol-3-yl]phenoxy]ethyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(OCCNC(=O)OC(C)(C)C)=CC=2)=CC(C(=O)N2CCCCC2)=N1 SZEJCQNZIXNDFX-UHFFFAOYSA-N 0.000 claims description 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 5
• 125000006647 (C3-C15) cycloalkyl group Chemical group 0.000 claims 1
• YSRNZNXHDBHJAT-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-4-methyl-n-piperidin-1-yl-5-[4-(4,4,4-trifluorobutoxy)phenyl]pyrazole-3-carboxamide Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OCCCC(F)(F)F)C=C1 YSRNZNXHDBHJAT-UHFFFAOYSA-N 0.000 claims 1
• JPVLARRIKHGJJM-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] propyl carbonate;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(OC(=O)OCCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl JPVLARRIKHGJJM-UHFFFAOYSA-N 0.000 claims 1
• ASBHFJFHFVFLJC-UHFFFAOYSA-N methyl 1-[[1-(2,4-dichlorophenyl)-4-methyl-5-(4-propylsulfonyloxyphenyl)pyrazole-3-carbonyl]amino]cyclopentane-1-carboxylate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(C)C(C(=O)NC2(CCCC2)C(=O)OC)=NN1C1=CC=C(Cl)C=C1Cl ASBHFJFHFVFLJC-UHFFFAOYSA-N 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 abstract description 5
• 230000008569 process Effects 0.000 abstract description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 110
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 77
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
• 235000019439 ethyl acetate Nutrition 0.000 description 51
• 239000000047 product Substances 0.000 description 49
• 239000007787 solid Substances 0.000 description 41
• 239000011541 reaction mixture Substances 0.000 description 39
• 239000000203 mixture Substances 0.000 description 38
• 239000000243 solution Substances 0.000 description 38
• 238000002844 melting Methods 0.000 description 35
• 230000008018 melting Effects 0.000 description 35
• 229940079593 drug Drugs 0.000 description 28
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• 239000007832 Na2SO4 Substances 0.000 description 24
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
• 229910052938 sodium sulfate Inorganic materials 0.000 description 24
• 235000011152 sodium sulphate Nutrition 0.000 description 24
• 239000012453 solvate Substances 0.000 description 24
• 238000003818 flash chromatography Methods 0.000 description 23
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 150000002148 esters Chemical class 0.000 description 20
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 19
• 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 18
• 101150041968 CDC13 gene Proteins 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• 238000005160 1H NMR spectroscopy Methods 0.000 description 16
• 238000004128 high performance liquid chromatography Methods 0.000 description 16
• 206010012289 Dementia Diseases 0.000 description 15
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
• 238000006243 chemical reaction Methods 0.000 description 15
• 238000001816 cooling Methods 0.000 description 15
• 230000002829 reductive effect Effects 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 239000000651 prodrug Substances 0.000 description 13
• 229940002612 prodrug Drugs 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 229940086542 triethylamine Drugs 0.000 description 12
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 239000000284 extract Substances 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 239000012267 brine Substances 0.000 description 10
• LMAWZMCTVCMTPC-UHFFFAOYSA-N chembl157201 Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(O)C=C1 LMAWZMCTVCMTPC-UHFFFAOYSA-N 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 229940093499 ethyl acetate Drugs 0.000 description 10
• 230000002265 prevention Effects 0.000 description 10
• KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 230000008901 benefit Effects 0.000 description 9
• 229960003920 cocaine Drugs 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 229960002715 nicotine Drugs 0.000 description 9
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 8
• 239000005695 Ammonium acetate Substances 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 235000019257 ammonium acetate Nutrition 0.000 description 8
• 229940043376 ammonium acetate Drugs 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 239000012044 organic layer Substances 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
• 230000004580 weight loss Effects 0.000 description 8
• 238000002425 crystallisation Methods 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 201000002859 sleep apnea Diseases 0.000 description 7
• 230000004584 weight gain Effects 0.000 description 7
• 235000019786 weight gain Nutrition 0.000 description 7
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 6
• 206010012735 Diarrhoea Diseases 0.000 description 6
• 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 6
• 206010021403 Illusion Diseases 0.000 description 6
• 206010061218 Inflammation Diseases 0.000 description 6
• 208000019022 Mood disease Diseases 0.000 description 6
• 206010035004 Pickwickian syndrome Diseases 0.000 description 6
• 208000006011 Stroke Diseases 0.000 description 6
• 230000032683 aging Effects 0.000 description 6
• 239000002249 anxiolytic agent Substances 0.000 description 6
• 230000000949 anxiolytic effect Effects 0.000 description 6
• 235000019789 appetite Nutrition 0.000 description 6
• 230000036528 appetite Effects 0.000 description 6
• 230000002490 cerebral effect Effects 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 238000001035 drying Methods 0.000 description 6
• 230000004064 dysfunction Effects 0.000 description 6
• 229960004756 ethanol Drugs 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• 230000000147 hypnotic effect Effects 0.000 description 6
• 230000004054 inflammatory process Effects 0.000 description 6
• 201000006417 multiple sclerosis Diseases 0.000 description 6
• XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 6
• 229940127240 opiate Drugs 0.000 description 6
• KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 6
• 239000000932 sedative agent Substances 0.000 description 6
• 230000001624 sedative effect Effects 0.000 description 6
• 208000019116 sleep disease Diseases 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
• 238000003860 storage Methods 0.000 description 6
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 5
• 208000032928 Dyslipidaemia Diseases 0.000 description 5
• 208000004930 Fatty Liver Diseases 0.000 description 5
• 206010020772 Hypertension Diseases 0.000 description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 description 5
• 206010028980 Neoplasm Diseases 0.000 description 5
• 206010033307 Overweight Diseases 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 235000019788 craving Nutrition 0.000 description 5
• 206010012601 diabetes mellitus Diseases 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 238000012423 maintenance Methods 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 229940075993 receptor modulator Drugs 0.000 description 5
• 238000001953 recrystallisation Methods 0.000 description 5
• 230000036186 satiety Effects 0.000 description 5
• 235000019627 satiety Nutrition 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 230000000391 smoking effect Effects 0.000 description 5
• 239000001117 sulphuric acid Substances 0.000 description 5
• 235000011149 sulphuric acid Nutrition 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• 206010004716 Binge eating Diseases 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• 208000030814 Eating disease Diseases 0.000 description 4
• 208000019454 Feeding and Eating disease Diseases 0.000 description 4
• 208000002705 Glucose Intolerance Diseases 0.000 description 4
• 208000031226 Hyperlipidaemia Diseases 0.000 description 4
• 108010028554 LDL Cholesterol Proteins 0.000 description 4
• 238000008214 LDL Cholesterol Methods 0.000 description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 description 4
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
• 241000208125 Nicotiana Species 0.000 description 4
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 4
• 208000003782 Raynaud disease Diseases 0.000 description 4
• 208000012322 Raynaud phenomenon Diseases 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 208000014679 binge eating disease Diseases 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 208000029078 coronary artery disease Diseases 0.000 description 4
• 239000013058 crude material Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 235000014632 disordered eating Nutrition 0.000 description 4
• 235000013305 food Nutrition 0.000 description 4
• 208000020694 gallbladder disease Diseases 0.000 description 4
• 208000019622 heart disease Diseases 0.000 description 4
• 230000002757 inflammatory effect Effects 0.000 description 4
• 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 4
• 235000021073 macronutrients Nutrition 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 230000000926 neurological effect Effects 0.000 description 4
• 201000008482 osteoarthritis Diseases 0.000 description 4
• 238000000634 powder X-ray diffraction Methods 0.000 description 4
• 201000009104 prediabetes syndrome Diseases 0.000 description 4
• 235000010288 sodium nitrite Nutrition 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
• 102000011690 Adiponectin Human genes 0.000 description 3
• 108010076365 Adiponectin Proteins 0.000 description 3
• 206010001540 Akathisia Diseases 0.000 description 3
• 208000000044 Amnesia Diseases 0.000 description 3
• 208000031091 Amnestic disease Diseases 0.000 description 3
• 206010002383 Angina Pectoris Diseases 0.000 description 3
• 206010003210 Arteriosclerosis Diseases 0.000 description 3
• 229940124802 CB1 antagonist Drugs 0.000 description 3
• 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• 206010008088 Cerebral artery embolism Diseases 0.000 description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 description 3
• 206010008132 Cerebral thrombosis Diseases 0.000 description 3
• 206010008190 Cerebrovascular accident Diseases 0.000 description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
• 208000035473 Communicable disease Diseases 0.000 description 3
• 208000009798 Craniopharyngioma Diseases 0.000 description 3
• 206010012218 Delirium Diseases 0.000 description 3
• 206010012225 Delirium tremens Diseases 0.000 description 3
• 206010013654 Drug abuse Diseases 0.000 description 3
• 208000012661 Dyskinesia Diseases 0.000 description 3
• 206010014612 Encephalitis viral Diseases 0.000 description 3
• 208000010228 Erectile Dysfunction Diseases 0.000 description 3
• 201000001498 Froelich syndrome Diseases 0.000 description 3
• 208000001613 Gambling Diseases 0.000 description 3
• 208000010412 Glaucoma Diseases 0.000 description 3
• 201000005569 Gout Diseases 0.000 description 3
• 208000035895 Guillain-Barré syndrome Diseases 0.000 description 3
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
• 206010019280 Heart failures Diseases 0.000 description 3
• 206010019708 Hepatic steatosis Diseases 0.000 description 3
• 206010020112 Hirsutism Diseases 0.000 description 3
• 208000035150 Hypercholesterolemia Diseases 0.000 description 3
• 206010058359 Hypogonadism Diseases 0.000 description 3
• 206010056997 Impaired fasting glucose Diseases 0.000 description 3
• 208000030990 Impulse-control disease Diseases 0.000 description 3
• 206010022489 Insulin Resistance Diseases 0.000 description 3
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 3
• 201000001429 Intracranial Thrombosis Diseases 0.000 description 3
• 206010026749 Mania Diseases 0.000 description 3
• 208000019695 Migraine disease Diseases 0.000 description 3
• 206010049567 Miller Fisher syndrome Diseases 0.000 description 3
• 208000008238 Muscle Spasticity Diseases 0.000 description 3
• 208000023178 Musculoskeletal disease Diseases 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 208000036110 Neuroinflammatory disease Diseases 0.000 description 3
• 208000004166 Obesity Hypoventilation Syndrome Diseases 0.000 description 3
• 206010034158 Pathological gambling Diseases 0.000 description 3
• 208000018262 Peripheral vascular disease Diseases 0.000 description 3
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
• 201000010769 Prader-Willi syndrome Diseases 0.000 description 3
• QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 3
• 208000001431 Psychomotor Agitation Diseases 0.000 description 3
• 208000020221 Short stature Diseases 0.000 description 3
• 208000027520 Somatoform disease Diseases 0.000 description 3
• 208000013200 Stress disease Diseases 0.000 description 3
• 208000000323 Tourette Syndrome Diseases 0.000 description 3
• 208000032109 Transient ischaemic attack Diseases 0.000 description 3
• 206010044565 Tremor Diseases 0.000 description 3
• 208000026928 Turner syndrome Diseases 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• 208000025865 Ulcer Diseases 0.000 description 3
• 208000026723 Urinary tract disease Diseases 0.000 description 3
• 201000004810 Vascular dementia Diseases 0.000 description 3
• 206010047700 Vomiting Diseases 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000007000 age related cognitive decline Effects 0.000 description 3
• 208000029650 alcohol withdrawal Diseases 0.000 description 3
• 208000006246 alcohol withdrawal delirium Diseases 0.000 description 3
• 230000006986 amnesia Effects 0.000 description 3
• 229940025084 amphetamine Drugs 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000003529 anticholesteremic agent Substances 0.000 description 3
• 229940127226 anticholesterol agent Drugs 0.000 description 3
• 206010003119 arrhythmia Diseases 0.000 description 3
• 230000006793 arrhythmia Effects 0.000 description 3
• 208000011775 arteriosclerosis disease Diseases 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 210000000013 bile duct Anatomy 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• 210000000481 breast Anatomy 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 206010008118 cerebral infarction Diseases 0.000 description 3
• 208000026106 cerebrovascular disease Diseases 0.000 description 3
• 210000003679 cervix uteri Anatomy 0.000 description 3
• 201000001883 cholelithiasis Diseases 0.000 description 3
• 230000003920 cognitive function Effects 0.000 description 3
• 210000001072 colon Anatomy 0.000 description 3
• 238000011284 combination treatment Methods 0.000 description 3
• 239000003433 contraceptive agent Substances 0.000 description 3
• 230000002254 contraceptive effect Effects 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
• 208000010118 dystonia Diseases 0.000 description 3
• 210000004696 endometrium Anatomy 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 235000013861 fat-free Nutrition 0.000 description 3
• 235000019197 fats Nutrition 0.000 description 3
• 208000010706 fatty liver disease Diseases 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 210000000232 gallbladder Anatomy 0.000 description 3
• 208000021302 gastroesophageal reflux disease Diseases 0.000 description 3
• 230000005176 gastrointestinal motility Effects 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 3
• 208000006575 hypertriglyceridemia Diseases 0.000 description 3
• 201000001881 impotence Diseases 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 208000000509 infertility Diseases 0.000 description 3
• 231100000535 infertility Toxicity 0.000 description 3
• 230000036512 infertility Effects 0.000 description 3
• 230000000968 intestinal effect Effects 0.000 description 3
• 201000010849 intracranial embolism Diseases 0.000 description 3
• 206010023461 kleptomania Diseases 0.000 description 3
• 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 3
• 230000007074 memory dysfunction Effects 0.000 description 3
• 208000030159 metabolic disease Diseases 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 206010027599 migraine Diseases 0.000 description 3
• 230000036651 mood Effects 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 230000009251 neurologic dysfunction Effects 0.000 description 3
• 208000015015 neurological dysfunction Diseases 0.000 description 3
• 201000001119 neuropathy Diseases 0.000 description 3
• 230000007823 neuropathy Effects 0.000 description 3
• 238000010899 nucleation Methods 0.000 description 3
• 208000001797 obstructive sleep apnea Diseases 0.000 description 3
• 210000001672 ovary Anatomy 0.000 description 3
• 208000027753 pain disease Diseases 0.000 description 3
• 208000033808 peripheral neuropathy Diseases 0.000 description 3
• 201000010065 polycystic ovary syndrome Diseases 0.000 description 3
• 210000002307 prostate Anatomy 0.000 description 3
• 230000000284 resting effect Effects 0.000 description 3
• 230000033764 rhythmic process Effects 0.000 description 3
• 208000022610 schizoaffective disease Diseases 0.000 description 3
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
• 230000001568 sexual effect Effects 0.000 description 3
• 208000020685 sleep-wake disease Diseases 0.000 description 3
• 208000018198 spasticity Diseases 0.000 description 3
• 208000020431 spinal cord injury Diseases 0.000 description 3
• 231100000240 steatosis hepatitis Toxicity 0.000 description 3
• 230000035882 stress Effects 0.000 description 3
• 201000009032 substance abuse Diseases 0.000 description 3
• 208000011117 substance-related disease Diseases 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 208000011580 syndromic disease Diseases 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 231100000397 ulcer Toxicity 0.000 description 3
• 208000014001 urinary system disease Diseases 0.000 description 3
• 210000005166 vasculature Anatomy 0.000 description 3
• 201000002498 viral encephalitis Diseases 0.000 description 3
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
• ZTPAUBJZUBGGEY-UHFFFAOYSA-N (2,4-dichlorophenyl)hydrazine Chemical compound NNC1=CC=C(Cl)C=C1Cl ZTPAUBJZUBGGEY-UHFFFAOYSA-N 0.000 description 2
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 2
• KQCMTOWTPBNWDB-UHFFFAOYSA-N 2,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C=C1Cl KQCMTOWTPBNWDB-UHFFFAOYSA-N 0.000 description 2
• KGSWETKVKNOADH-UHFFFAOYSA-M 2,4-dichlorobenzenediazonium;chloride Chemical compound [Cl-].ClC1=CC=C([N+]#N)C(Cl)=C1 KGSWETKVKNOADH-UHFFFAOYSA-M 0.000 description 2
• 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 2
• FCBIRUMSQYSMOL-UHFFFAOYSA-N 4,4,4-trifluorobutane-1-sulfonyl chloride Chemical compound FC(F)(F)CCCS(Cl)(=O)=O FCBIRUMSQYSMOL-UHFFFAOYSA-N 0.000 description 2
• 208000007848 Alcoholism Diseases 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 2
• 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 2
• 102400001132 Melanin-concentrating hormone Human genes 0.000 description 2
• 101800002739 Melanin-concentrating hormone Proteins 0.000 description 2
• 208000019255 Menstrual disease Diseases 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 102000023984 PPAR alpha Human genes 0.000 description 2
• 108010028924 PPAR alpha Proteins 0.000 description 2
• 102000000536 PPAR gamma Human genes 0.000 description 2
• 108010016731 PPAR gamma Proteins 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
• 239000012317 TBTU Substances 0.000 description 2
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 239000000674 adrenergic antagonist Substances 0.000 description 2
• 206010001584 alcohol abuse Diseases 0.000 description 2
• 208000025746 alcohol use disease Diseases 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 239000002876 beta blocker Substances 0.000 description 2
• 239000003613 bile acid Substances 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 238000002144 chemical decomposition reaction Methods 0.000 description 2
• 235000019219 chocolate Nutrition 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 229940088679 drug related substance Drugs 0.000 description 2
• CYNAUUOBXGYIAE-UHFFFAOYSA-N ethyl 1-(2,4-dichlorophenyl)-5-(4-propylsulfonyloxyphenyl)pyrazole-3-carboxylate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=CC(C(=O)OCC)=NN1C1=CC=C(Cl)C=C1Cl CYNAUUOBXGYIAE-UHFFFAOYSA-N 0.000 description 2
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• ZTNLXZOJUZAGRP-UHFFFAOYSA-N hydron;piperidin-1-amine;chloride Chemical compound Cl.NN1CCCCC1 ZTNLXZOJUZAGRP-UHFFFAOYSA-N 0.000 description 2
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 229940125425 inverse agonist Drugs 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 235000020845 low-calorie diet Nutrition 0.000 description 2
• ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 2
• 231100000551 menstrual abnormality Toxicity 0.000 description 2
• 208000027061 mild cognitive impairment Diseases 0.000 description 2
• 239000002899 monoamine oxidase inhibitor Substances 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 2
• 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 description 2
• 239000006186 oral dosage form Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• 210000002381 plasma Anatomy 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 238000010561 standard procedure Methods 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
• 230000008733 trauma Effects 0.000 description 2
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 235000020852 very low calorie diet Nutrition 0.000 description 2
• 238000010626 work up procedure Methods 0.000 description 2
• 101150084750 1 gene Proteins 0.000 description 1
• LNDGACQEAYKNOI-UHFFFAOYSA-N 1,1,1-trifluoro-4-iodobutane Chemical compound FC(F)(F)CCCI LNDGACQEAYKNOI-UHFFFAOYSA-N 0.000 description 1
• HJUKIOXAFWKFLP-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-4-methyl-5-(4-phenylmethoxyphenyl)pyrazole-3-carboxylic acid Chemical group CC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1)=CC=C1OCC1=CC=CC=C1 HJUKIOXAFWKFLP-UHFFFAOYSA-N 0.000 description 1
• RTUCERKGPJKHHJ-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-(3,5-difluoro-4-hydroxyphenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC(F)=C(O)C(F)=C1 RTUCERKGPJKHHJ-UHFFFAOYSA-N 0.000 description 1
• KASCMVYWQHBKIK-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-(3,5-difluoro-4-phenylmethoxyphenyl)-4-methyl-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C(C=C1F)=CC(F)=C1OCC1=CC=CC=C1 KASCMVYWQHBKIK-UHFFFAOYSA-N 0.000 description 1
• OMYNYPNQTOGQOW-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-(4-hydroxyphenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide Chemical compound CC=1C(C(=O)NN2CCOCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(O)C=C1 OMYNYPNQTOGQOW-UHFFFAOYSA-N 0.000 description 1
• YIXLKHCHEWGFLK-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-(4-phenylmethoxyphenyl)pyrazole-3-carboxylic acid Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)C1=CC(=NN1C1=C(C=C(C=C1)Cl)Cl)C(=O)O YIXLKHCHEWGFLK-UHFFFAOYSA-N 0.000 description 1
• CUQVXRLMTQLKIX-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-5-[4-[2-(ethylamino)ethoxy]phenyl]-4-methyl-n-piperidin-1-ylpyrazole-3-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCCNCC)=CC=C1C1=C(C)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl CUQVXRLMTQLKIX-UHFFFAOYSA-N 0.000 description 1
• PJIDRPUAOWTRGM-UHFFFAOYSA-N 1-(3,5-difluoro-4-hydroxyphenyl)propan-1-one Chemical compound CCC(=O)C1=CC(F)=C(O)C(F)=C1 PJIDRPUAOWTRGM-UHFFFAOYSA-N 0.000 description 1
• JYNOHNWYJCISKJ-UHFFFAOYSA-N 1-(3,5-difluoro-4-phenylmethoxyphenyl)propan-1-one Chemical compound FC1=CC(C(=O)CC)=CC(F)=C1OCC1=CC=CC=C1 JYNOHNWYJCISKJ-UHFFFAOYSA-N 0.000 description 1
• MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 1
• IKFGSOJYHVTNDV-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCC1=CC=CC=C1 IKFGSOJYHVTNDV-UHFFFAOYSA-N 0.000 description 1
• NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 description 1
• QDWAYVZXKAWFPX-UHFFFAOYSA-N 1-piperidin-1-ylpyrazole-3-carboxamide Chemical compound N1=C(C(=O)N)C=CN1N1CCCCC1 QDWAYVZXKAWFPX-UHFFFAOYSA-N 0.000 description 1
• VEBWZLHNQCQDSY-UHFFFAOYSA-N 2,4-dichloro-3-fluoroaniline Chemical compound NC1=CC=C(Cl)C(F)=C1Cl VEBWZLHNQCQDSY-UHFFFAOYSA-N 0.000 description 1
• GGZQLTVZPOGLCC-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-dioxolane Chemical compound BrCCC1OCCO1 GGZQLTVZPOGLCC-UHFFFAOYSA-N 0.000 description 1
• MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
• OZMLUMPWPFZWTP-UHFFFAOYSA-N 2-(tributyl-$l^{5}-phosphanylidene)acetonitrile Chemical compound CCCCP(CCCC)(CCCC)=CC#N OZMLUMPWPFZWTP-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
• SMOXNAJQTZDRPO-UHFFFAOYSA-N 2-bromo-1-(3,5-difluoro-4-phenylmethoxyphenyl)propan-1-one Chemical compound FC1=CC(C(=O)C(Br)C)=CC(F)=C1OCC1=CC=CC=C1 SMOXNAJQTZDRPO-UHFFFAOYSA-N 0.000 description 1
• LSQLSCUJBXFBRB-UHFFFAOYSA-N 2-bromo-1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C1=CC(C(=O)C(Br)C)=CC=C1OCC1=CC=CC=C1 LSQLSCUJBXFBRB-UHFFFAOYSA-N 0.000 description 1
• XKPFLKWPESVZJF-UHFFFAOYSA-N 3,3,3-trifluoropropane-1-sulfonic acid Chemical compound OS(=O)(=O)CCC(F)(F)F XKPFLKWPESVZJF-UHFFFAOYSA-N 0.000 description 1
• OXKHPRFGCFJUSK-UHFFFAOYSA-N 3,3,3-trifluoropropane-1-sulfonyl chloride Chemical compound FC(F)(F)CCS(Cl)(=O)=O OXKHPRFGCFJUSK-UHFFFAOYSA-N 0.000 description 1
• WXFKSAMQYRGPCU-UHFFFAOYSA-N 3,3-dimethylbutane-1-sulfonyl chloride Chemical compound CC(C)(C)CCS(Cl)(=O)=O WXFKSAMQYRGPCU-UHFFFAOYSA-N 0.000 description 1
• 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
• CHJYKNDQMVDBKS-UHFFFAOYSA-N 4,4,4-trifluorobutane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCC(F)(F)F CHJYKNDQMVDBKS-UHFFFAOYSA-N 0.000 description 1
• AIZPEHDXQVEVRI-UHFFFAOYSA-N 5-[4-(2-aminoethoxy)phenyl]-n-ethyl-1-(4-methoxyphenyl)-n-methylpyrazole-3-carboxamide Chemical compound C=1C=C(OC)C=CC=1N1N=C(C(=O)N(C)CC)C=C1C1=CC=C(OCCN)C=C1 AIZPEHDXQVEVRI-UHFFFAOYSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• BLKOSTJSUMJMSR-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)S1 BLKOSTJSUMJMSR-UHFFFAOYSA-N 0.000 description 1
• SORSTNOXGOXWAO-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)S1 SORSTNOXGOXWAO-UHFFFAOYSA-N 0.000 description 1
• 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
• 229910015845 BBr3 Inorganic materials 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• 206010065687 Bone loss Diseases 0.000 description 1
• FHAHXTQJCQHHHF-UHFFFAOYSA-N CC1=C(C(C=C2)=CC=C2OC)N(C(C=CC(Cl)=C2F)=C2Cl)N=C1C(O)=O.NN1CCCCC1 Chemical compound CC1=C(C(C=C2)=CC=C2OC)N(C(C=CC(Cl)=C2F)=C2Cl)N=C1C(O)=O.NN1CCCCC1 FHAHXTQJCQHHHF-UHFFFAOYSA-N 0.000 description 1
• PCFHOUZYFUOXIJ-UHFFFAOYSA-N CC1=C(C(C=C2)=CC=C2OCC2=CC=CC=C2)N(C(C=CC(Cl)=C2)=C2Cl)N=C1C(NN1CCCCC1)=O.NN1CCCCC1 Chemical compound CC1=C(C(C=C2)=CC=C2OCC2=CC=CC=C2)N(C(C=CC(Cl)=C2)=C2Cl)N=C1C(NN1CCCCC1)=O.NN1CCCCC1 PCFHOUZYFUOXIJ-UHFFFAOYSA-N 0.000 description 1
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• 102000018208 Cannabinoid Receptor Human genes 0.000 description 1
• 108050007331 Cannabinoid receptor Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 229920002905 Colesevelam Polymers 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 208000000289 Esophageal Achalasia Diseases 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
• 101800001586 Ghrelin Proteins 0.000 description 1
• 108010016122 Ghrelin Receptors Proteins 0.000 description 1
• 102400000442 Ghrelin-28 Human genes 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
• 102100039256 Growth hormone secretagogue receptor type 1 Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 101000851700 Homo sapiens Steroid hormone receptor ERR1 Proteins 0.000 description 1
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
• 229940125922 IBAT inhibitor Drugs 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
• 208000012659 Joint disease Diseases 0.000 description 1
• 108010007622 LDL Lipoproteins Proteins 0.000 description 1
• 102000016267 Leptin Human genes 0.000 description 1
• 108010092277 Leptin Proteins 0.000 description 1
• 102000018658 Myotonin-Protein Kinase Human genes 0.000 description 1
• 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 1
• 229910004879 Na2S2O5 Inorganic materials 0.000 description 1
• 102400000064 Neuropeptide Y Human genes 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
• 206010030136 Oesophageal achalasia Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 108050000742 Orexin Receptor Proteins 0.000 description 1
• 102000008834 Orexin receptor Human genes 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 101150014691 PPARA gene Proteins 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 108091008731 RAR-related orphan receptors α Proteins 0.000 description 1
• 238000001069 Raman spectroscopy Methods 0.000 description 1
• 102100036832 Steroid hormone receptor ERR1 Human genes 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• QFLFGPYVVPZLIL-UHFFFAOYSA-N [4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl] 4,4,4-trifluorobutane-1-sulfonate;hydrochloride Chemical compound Cl.CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(OS(=O)(=O)CCCC(F)(F)F)C=C1 QFLFGPYVVPZLIL-UHFFFAOYSA-N 0.000 description 1
• URDIXWDMIYSTHS-UHFFFAOYSA-N [5-[4-(2-aminoethoxy)phenyl]-1-(4-methoxyphenyl)pyrazol-3-yl]-piperidin-1-ylmethanone Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(OCCN)=CC=2)=CC(C(=O)N2CCCCC2)=N1 URDIXWDMIYSTHS-UHFFFAOYSA-N 0.000 description 1
• NYYSLJGCNZSJKL-UHFFFAOYSA-N [Li+].C[Si]([N-][Si](C)(C)C)(C)C.C[Si](N[Si](C)(C)C)(C)C Chemical compound [Li+].C[Si]([N-][Si](C)(C)C)(C)C.C[Si](N[Si](C)(C)C)(C)C NYYSLJGCNZSJKL-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 201000000621 achalasia Diseases 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 230000001800 adrenalinergic effect Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000001270 agonistic effect Effects 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000003579 anti-obesity Effects 0.000 description 1
• 230000000561 anti-psychotic effect Effects 0.000 description 1
• 239000012296 anti-solvent Substances 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 239000000164 antipsychotic agent Substances 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 229920000080 bile acid sequestrant Polymers 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 238000010241 blood sampling Methods 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
• 229960001058 bupropion Drugs 0.000 description 1
• QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 description 1
• WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-UHFFFAOYSA-N 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000000480 calcium channel blocker Substances 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 230000009084 cardiovascular function Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 235000013351 cheese Nutrition 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 229960004170 clozapine Drugs 0.000 description 1
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 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 1
• 230000001419 dependent effect Effects 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 238000013229 diet-induced obese mouse Methods 0.000 description 1
• WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 230000001882 diuretic effect Effects 0.000 description 1
• 238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 1
• 229960002179 ephedrine Drugs 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• GGSNDEZDGOPFPL-UHFFFAOYSA-N ethyl 1-(2,4-dichlorophenyl)-5-(4-hydroxyphenyl)pyrazole-3-carboxylate Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1N=C(C(=O)OCC)C=C1C1=CC=C(O)C=C1 GGSNDEZDGOPFPL-UHFFFAOYSA-N 0.000 description 1
• BTUJZIGPAGODTR-UHFFFAOYSA-N ethyl 2,4-dioxo-4-(4-phenylmethoxyphenyl)butanoate Chemical compound C1=CC(C(=O)CC(=O)C(=O)OCC)=CC=C1OCC1=CC=CC=C1 BTUJZIGPAGODTR-UHFFFAOYSA-N 0.000 description 1
• WQHSCDRSCDLWAD-UHFFFAOYSA-N ethyl 2-acetyl-4-(3,5-difluoro-4-phenylmethoxyphenyl)-3-methyl-4-oxobutanoate Chemical compound FC1=CC(C(=O)C(C)C(C(=O)OCC)C(C)=O)=CC(F)=C1OCC1=CC=CC=C1 WQHSCDRSCDLWAD-UHFFFAOYSA-N 0.000 description 1
• MQMUSRCUXHVOIA-UHFFFAOYSA-N ethyl 2-acetyl-4-(4-methoxyphenyl)-3-methyl-4-oxobutanoate Chemical compound CCOC(=O)C(C(C)=O)C(C)C(=O)C1=CC=C(OC)C=C1 MQMUSRCUXHVOIA-UHFFFAOYSA-N 0.000 description 1
• LYFNSCAREYZKEW-UHFFFAOYSA-N ethyl 2-acetyl-4-oxo-4-(4-phenylmethoxyphenyl)butanoate Chemical compound C1=CC(C(=O)CC(C(=O)OCC)C(C)=O)=CC=C1OCC1=CC=CC=C1 LYFNSCAREYZKEW-UHFFFAOYSA-N 0.000 description 1
• ZERNMSVUJUHUHK-UHFFFAOYSA-N ethyl 4-bromo-1-(2,4-dichlorophenyl)-5-(4-propylsulfonyloxyphenyl)pyrazole-3-carboxylate Chemical compound C1=CC(OS(=O)(=O)CCC)=CC=C1C1=C(Br)C(C(=O)OCC)=NN1C1=CC=C(Cl)C=C1Cl ZERNMSVUJUHUHK-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 230000007661 gastrointestinal function Effects 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 0.000 description 1
• 230000004110 gluconeogenesis Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000034659 glycolysis Effects 0.000 description 1
• 235000003642 hunger Nutrition 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 230000003516 hyperlipidaemic effect Effects 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
• 229940039781 leptin Drugs 0.000 description 1
• 102000005861 leptin receptors Human genes 0.000 description 1
• 108010019813 leptin receptors Proteins 0.000 description 1
• 231100001231 less toxic Toxicity 0.000 description 1
• 230000004132 lipogenesis Effects 0.000 description 1
• 230000004130 lipolysis Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 159000000003 magnesium salts Chemical class 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
• 239000011976 maleic acid Substances 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• QVDYHEDPTBKPFQ-UHFFFAOYSA-N methyl 1-[[1-(2,4-dichlorophenyl)-5-(4-hydroxyphenyl)-4-methylpyrazole-3-carbonyl]amino]cyclopentane-1-carboxylate Chemical compound N=1N(C=2C(=CC(Cl)=CC=2)Cl)C(C=2C=CC(O)=CC=2)=C(C)C=1C(=O)NC1(C(=O)OC)CCCC1 QVDYHEDPTBKPFQ-UHFFFAOYSA-N 0.000 description 1
• OPUJUITUYWGUEP-UHFFFAOYSA-N methyl 1-aminocyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(N)CCCC1 OPUJUITUYWGUEP-UHFFFAOYSA-N 0.000 description 1
• 206010062198 microangiopathy Diseases 0.000 description 1
• 230000003228 microsomal effect Effects 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 230000008450 motivation Effects 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 239000003176 neuroleptic agent Substances 0.000 description 1
• 230000000701 neuroleptic effect Effects 0.000 description 1
• VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
• 230000002474 noradrenergic effect Effects 0.000 description 1
• 235000015145 nougat Nutrition 0.000 description 1
• 102000006255 nuclear receptors Human genes 0.000 description 1
• 108020004017 nuclear receptors Proteins 0.000 description 1
• 229960005017 olanzapine Drugs 0.000 description 1
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
• 229940012843 omega-3 fatty acid Drugs 0.000 description 1
• 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 229960001243 orlistat Drugs 0.000 description 1
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
• 229940080358 other antiobesity drug in atc Drugs 0.000 description 1
• RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 235000014594 pastries Nutrition 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
• 229960003912 probucol Drugs 0.000 description 1
• QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
• DVECLMOWYVDJRM-UHFFFAOYSA-M pyridine-3-sulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CN=C1 DVECLMOWYVDJRM-UHFFFAOYSA-M 0.000 description 1
• DVECLMOWYVDJRM-UHFFFAOYSA-N pyridine-3-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CN=C1 DVECLMOWYVDJRM-UHFFFAOYSA-N 0.000 description 1
• CDRNYKLYADJTMN-UHFFFAOYSA-N pyridine-3-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CN=C1 CDRNYKLYADJTMN-UHFFFAOYSA-N 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000000894 saliuretic effect Effects 0.000 description 1
• 238000011894 semi-preparative HPLC Methods 0.000 description 1
• 239000003352 sequestering agent Substances 0.000 description 1
• 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 1
• 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• 230000005586 smoking cessation Effects 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
• 235000010262 sodium metabisulphite Nutrition 0.000 description 1
• 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000000859 sublimation Methods 0.000 description 1
• 230000008022 sublimation Effects 0.000 description 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• OPSQZIGTEBZROY-UHFFFAOYSA-N tert-butyl n-ethyl-n-(2-hydroxyethyl)carbamate Chemical compound OCCN(CC)C(=O)OC(C)(C)C OPSQZIGTEBZROY-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• UBBZKZRMWONRRS-UHFFFAOYSA-N thionyl dichloride hydrochloride Chemical compound Cl.ClS(Cl)=O UBBZKZRMWONRRS-UHFFFAOYSA-N 0.000 description 1
• 229940034208 thyroxine Drugs 0.000 description 1
• XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 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
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 239000013585 weight reducing agent Substances 0.000 description 1