AU2002342735B2 - Quinoline derivatives as neuropeptide Y antagonists - Google Patents
Quinoline derivatives as neuropeptide Y antagonists Download PDFInfo
- Publication number
- AU2002342735B2 AU2002342735B2 AU2002342735A AU2002342735A AU2002342735B2 AU 2002342735 B2 AU2002342735 B2 AU 2002342735B2 AU 2002342735 A AU2002342735 A AU 2002342735A AU 2002342735 A AU2002342735 A AU 2002342735A AU 2002342735 B2 AU2002342735 B2 AU 2002342735B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- quinolin
- pyrrolidin
- benzonitrile
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 101710151321 Melanostatin Proteins 0.000 title claims description 14
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 11
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 6
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 title description 6
- 239000005557 antagonist Substances 0.000 title description 4
- 102400000064 Neuropeptide Y Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 312
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 149
- -1 amino, acetylamino Chemical group 0.000 claims description 128
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 208000008589 Obesity Diseases 0.000 claims description 25
- 235000020824 obesity Nutrition 0.000 claims description 25
- 238000011321 prophylaxis Methods 0.000 claims description 25
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 150000002148 esters Chemical class 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- OFCMJTXCXQZZHQ-UHFFFAOYSA-N (2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CCCC1 OFCMJTXCXQZZHQ-UHFFFAOYSA-N 0.000 claims description 18
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 17
- 208000030814 Eating disease Diseases 0.000 claims description 17
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 17
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 17
- 206010003246 arthritis Diseases 0.000 claims description 17
- 206010012601 diabetes mellitus Diseases 0.000 claims description 17
- 235000014632 disordered eating Nutrition 0.000 claims description 17
- 201000006370 kidney failure Diseases 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group 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 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 229960001243 orlistat Drugs 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 14
- 102100028427 Pro-neuropeptide Y Human genes 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Chemical group 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Chemical group 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 238000002560 therapeutic procedure Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 150000004678 hydrides Chemical class 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- BHJULLBAVAZKLV-UHFFFAOYSA-N n-butyl-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=1C(C)=NC2=CC(C(=O)NCCCC)=CC=C2C=1N1CCCC1 BHJULLBAVAZKLV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 4
- XATCREPNDSEOGK-UHFFFAOYSA-N 2-chloro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(Cl)C(C#N)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 XATCREPNDSEOGK-UHFFFAOYSA-N 0.000 claims description 4
- OSHRLFZAABJWIA-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=C(C)C(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 OSHRLFZAABJWIA-UHFFFAOYSA-N 0.000 claims description 4
- RVEDDNXDVZBQNM-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 RVEDDNXDVZBQNM-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- VORUYQGEUJBGHH-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzene-1,2-dicarbonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 VORUYQGEUJBGHH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 3
- CHRSSSYOZYZOFK-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 CHRSSSYOZYZOFK-UHFFFAOYSA-N 0.000 claims description 2
- SNRXFJAQZXURJY-UHFFFAOYSA-N 2-methyl-7-(pyridin-4-yloxymethyl)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCC1 SNRXFJAQZXURJY-UHFFFAOYSA-N 0.000 claims description 2
- FQMBNIOZTFMQEB-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 FQMBNIOZTFMQEB-UHFFFAOYSA-N 0.000 claims description 2
- 239000007787 solid Substances 0.000 description 145
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- 238000007429 general method Methods 0.000 description 108
- 239000000243 solution Substances 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 83
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- KALINDFRXWSFSG-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=CC(CO)=CC2=NC(C)=CC=1N1CCCC1 KALINDFRXWSFSG-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- 239000000203 mixture Substances 0.000 description 42
- 239000002904 solvent Substances 0.000 description 39
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- 239000012044 organic layer Substances 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- XJALNDJLTTXUGN-UHFFFAOYSA-N (4-chloro-2-methylquinolin-7-yl)methanol Chemical compound C1=CC(CO)=CC2=NC(C)=CC(Cl)=C21 XJALNDJLTTXUGN-UHFFFAOYSA-N 0.000 description 28
- 229910004298 SiO 2 Inorganic materials 0.000 description 26
- 238000001816 cooling Methods 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 25
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 239000006260 foam Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 235000019270 ammonium chloride Nutrition 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- HNLMDHLGHYLXHV-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1COC1=CC=C(C#N)C=C1 HNLMDHLGHYLXHV-UHFFFAOYSA-N 0.000 description 11
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 11
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- SELLRXHGEKIKKL-UHFFFAOYSA-N [4-(azepan-1-yl)-2-methylquinolin-7-yl]methanol Chemical compound C=12C=CC(CO)=CC2=NC(C)=CC=1N1CCCCCC1 SELLRXHGEKIKKL-UHFFFAOYSA-N 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 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 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000006880 cross-coupling reaction Methods 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 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 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000007903 gelatin capsule Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 239000000454 talc Substances 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- HOSOQDOSOGQBPQ-UHFFFAOYSA-N 4-chloro-2-methylquinoline-7-carbaldehyde Chemical compound C1=CC(C=O)=CC2=NC(C)=CC(Cl)=C21 HOSOQDOSOGQBPQ-UHFFFAOYSA-N 0.000 description 5
- LCCPQUYXMFXCAC-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(C#N)C(C(F)(F)F)=C1 LCCPQUYXMFXCAC-UHFFFAOYSA-N 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 5
- XXDMNRLCGQNDEH-UHFFFAOYSA-N [4-(azepan-1-yl)-2-(dimethylamino)-6-methylquinolin-7-yl]methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(N(C)C)=CC=1N1CCCCCC1 XXDMNRLCGQNDEH-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- XDFORSMZCYHNBG-UHFFFAOYSA-N benzonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=CC=C1 XDFORSMZCYHNBG-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 239000002198 insoluble material Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 5
- 229920005862 polyol Polymers 0.000 description 5
- 150000003077 polyols Chemical class 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 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 4
- MMHRIZCFQKJFNA-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinoline-7-carbonitrile Chemical compound C=12C=CC(C#N)=CC2=NC(C)=CC=1N1CCCC1 MMHRIZCFQKJFNA-UHFFFAOYSA-N 0.000 description 4
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 101100460785 Mus musculus Npy5r gene Proteins 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 4
- FIZCOXUNHFSRKU-UHFFFAOYSA-N [4-(azepan-1-yl)-2-chloro-6-methylquinolin-7-yl]methanol Chemical compound C1=C(Cl)N=C2C=C(CO)C(C)=CC2=C1N1CCCCCC1 FIZCOXUNHFSRKU-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 4
- IVRIROLGUQIHPU-UHFFFAOYSA-N ethyl 2,4-dichloro-6-methylquinoline-7-carboxylate Chemical compound ClC1=CC(Cl)=C2C=C(C)C(C(=O)OCC)=CC2=N1 IVRIROLGUQIHPU-UHFFFAOYSA-N 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 235000012631 food intake Nutrition 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- DDCLCVPHNUWYRZ-UHFFFAOYSA-N methyl 6-bromo-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxylate Chemical compound C=12C=C(Br)C(C(=O)OC)=CC2=NC(C)=CC=1N1CCCC1 DDCLCVPHNUWYRZ-UHFFFAOYSA-N 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920006391 phthalonitrile polymer Polymers 0.000 description 4
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 4
- 150000003248 quinolines Chemical class 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- LESWSBYGMHSGBZ-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)-pyrrolidin-1-ylmethanone Chemical compound C=12C=CC(C(=O)N3CCCC3)=CC2=NC(C)=CC=1N1CCCC1 LESWSBYGMHSGBZ-UHFFFAOYSA-N 0.000 description 3
- HLBSRKYIJKITOM-UHFFFAOYSA-N (4-chloro-2,6-dimethylquinolin-7-yl)methanol Chemical compound C1=C(C)C(CO)=CC2=NC(C)=CC(Cl)=C21 HLBSRKYIJKITOM-UHFFFAOYSA-N 0.000 description 3
- NGJYGEXDJJZESQ-UHFFFAOYSA-N (4-chloro-6-methoxy-2-methylquinolin-7-yl)methanol Chemical compound C1=C(C)N=C2C=C(CO)C(OC)=CC2=C1Cl NGJYGEXDJJZESQ-UHFFFAOYSA-N 0.000 description 3
- GWGFKYZNIPPKSE-UHFFFAOYSA-N (4-chloro-6-methylquinolin-7-yl)methanol Chemical compound C1=CN=C2C=C(CO)C(C)=CC2=C1Cl GWGFKYZNIPPKSE-UHFFFAOYSA-N 0.000 description 3
- FRONIFQNPCAWAG-UHFFFAOYSA-N (4-chloroquinolin-7-yl)methanol Chemical class ClC1=CC=NC2=CC(CO)=CC=C21 FRONIFQNPCAWAG-UHFFFAOYSA-N 0.000 description 3
- NRLVGANXPRQTJN-UHFFFAOYSA-N (6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl) trifluoromethanesulfonate Chemical compound C=12C=C(Br)C(OS(=O)(=O)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 NRLVGANXPRQTJN-UHFFFAOYSA-N 0.000 description 3
- WRMFAZWGPTWSCG-UHFFFAOYSA-N 2,4-dichloro-7-iodo-6-methylquinoline Chemical compound C1=C(Cl)N=C2C=C(I)C(C)=CC2=C1Cl WRMFAZWGPTWSCG-UHFFFAOYSA-N 0.000 description 3
- WZPFMRQQQRSMNO-UHFFFAOYSA-N 2,6-dimethyl-4-pyrrolidin-1-ylquinoline-7-carbaldehyde Chemical compound C=12C=C(C)C(C=O)=CC2=NC(C)=CC=1N1CCCC1 WZPFMRQQQRSMNO-UHFFFAOYSA-N 0.000 description 3
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 3
- XWOKDQGJISYYDI-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=12C=CC(C(N)=O)=CC2=NC(C)=CC=1N1CCCC1 XWOKDQGJISYYDI-UHFFFAOYSA-N 0.000 description 3
- RRUDMHNAMZFNEK-UHFFFAOYSA-N 3-iodo-4-methylaniline Chemical compound CC1=CC=C(N)C=C1I RRUDMHNAMZFNEK-UHFFFAOYSA-N 0.000 description 3
- IGPFOKFDBICQMC-UHFFFAOYSA-N 3-phenylmethoxyaniline Chemical class NC1=CC=CC(OCC=2C=CC=CC=2)=C1 IGPFOKFDBICQMC-UHFFFAOYSA-N 0.000 description 3
- QDHXKYCADNGVSF-UHFFFAOYSA-N 4-chloro-2-methylquinoline-7-carbonitrile Chemical compound C1=CC(C#N)=CC2=NC(C)=CC(Cl)=C21 QDHXKYCADNGVSF-UHFFFAOYSA-N 0.000 description 3
- NZEYYJJUYIBPBY-UHFFFAOYSA-N 4-chloro-7-iodo-2,6-dimethylquinoline Chemical compound C1=C(C)C(I)=CC2=NC(C)=CC(Cl)=C21 NZEYYJJUYIBPBY-UHFFFAOYSA-N 0.000 description 3
- LLBYZZCOVUGZSS-UHFFFAOYSA-N 4-chloro-7-iodo-2-methylquinoline Chemical compound C1=CC(I)=CC2=NC(C)=CC(Cl)=C21 LLBYZZCOVUGZSS-UHFFFAOYSA-N 0.000 description 3
- CQZQCORFYSSCFY-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(C#N)C=C1C(F)(F)F CQZQCORFYSSCFY-UHFFFAOYSA-N 0.000 description 3
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](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](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](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](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010020710 Hyperphagia Diseases 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- 239000004367 Lipase Substances 0.000 description 3
- SIKWOTFNWURSAY-UHFFFAOYSA-N Lipstatin Natural products CCCCCCC1C(CC(CC=CCC=CCCCCC)C(=O)OC(CC(C)C)NC=O)OC1=O SIKWOTFNWURSAY-UHFFFAOYSA-N 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 description 3
- 101710198055 Neuropeptide Y receptor type 5 Proteins 0.000 description 3
- 102100029909 Peptide YY Human genes 0.000 description 3
- 108010088847 Peptide YY Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- YBGJZYCWGNYUMA-UHFFFAOYSA-M [Cl-].[P+]=O Chemical compound [Cl-].[P+]=O YBGJZYCWGNYUMA-UHFFFAOYSA-M 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229910052681 coesite Inorganic materials 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229910052906 cristobalite Inorganic materials 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- RFGCNIVWFPZAMH-UHFFFAOYSA-N ethyl 4-chloro-2-methylquinoline-7-carboxylate Chemical compound ClC1=CC(C)=NC2=CC(C(=O)OCC)=CC=C21 RFGCNIVWFPZAMH-UHFFFAOYSA-N 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- OQMAKWGYQLJJIA-CUOOPAIESA-N lipstatin Chemical compound CCCCCC[C@H]1[C@H](C[C@H](C\C=C/C\C=C/CCCCC)OC(=O)[C@H](CC(C)C)NC=O)OC1=O OQMAKWGYQLJJIA-CUOOPAIESA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- BPGXUIVWLQTVLZ-OFGSCBOVSA-N neuropeptide y(npy) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 BPGXUIVWLQTVLZ-OFGSCBOVSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
- XQZYPMVTSDWCCE-UHFFFAOYSA-N phthalonitrile Chemical compound N#CC1=CC=CC=C1C#N XQZYPMVTSDWCCE-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 3
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 3
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
- 229910052682 stishovite Inorganic materials 0.000 description 3
- 229910052905 tridymite Inorganic materials 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- HZFRNCVZSHOIGY-UHFFFAOYSA-N (6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=C(Br)C(CO)=CC2=NC(C)=CC=1N1CCCC1 HZFRNCVZSHOIGY-UHFFFAOYSA-N 0.000 description 2
- KLGIOJHTZBSJTC-UHFFFAOYSA-N (6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=CN=C2C=C(CO)C(C)=CC2=C1N1CCCC1 KLGIOJHTZBSJTC-UHFFFAOYSA-N 0.000 description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- VXUVGSRJTGCPBO-UHFFFAOYSA-N 1-ethoxypyrrolidine Chemical compound CCON1CCCC1 VXUVGSRJTGCPBO-UHFFFAOYSA-N 0.000 description 2
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 2
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical group CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 2
- QNBJYUUUYZVIJP-UHFFFAOYSA-N 2,4-dichloroquinoline Chemical class C1=CC=CC2=NC(Cl)=CC(Cl)=C21 QNBJYUUUYZVIJP-UHFFFAOYSA-N 0.000 description 2
- KORMWSBLSJUAKF-UHFFFAOYSA-N 2-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=C(C)C(COC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 KORMWSBLSJUAKF-UHFFFAOYSA-N 0.000 description 2
- DVNYSCUIDIGYPN-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-6-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=C(C=CC=3)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 DVNYSCUIDIGYPN-UHFFFAOYSA-N 0.000 description 2
- ZLGYFHNGOIEULT-UHFFFAOYSA-N 2-chloro-6-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=C(Cl)C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ZLGYFHNGOIEULT-UHFFFAOYSA-N 0.000 description 2
- YCRWUXYRSACDBI-UHFFFAOYSA-N 2-iodo-6-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=C(I)C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YCRWUXYRSACDBI-UHFFFAOYSA-N 0.000 description 2
- WWSYBBDZQRYWJF-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-(pyrrolidin-1-ylmethyl)quinoline Chemical compound C=12C=CC(CN3CCCC3)=CC2=NC(C)=CC=1N1CCCC1 WWSYBBDZQRYWJF-UHFFFAOYSA-N 0.000 description 2
- KYBIBARYJXLJSU-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 KYBIBARYJXLJSU-UHFFFAOYSA-N 0.000 description 2
- DVCLTMIFEHEKLU-UHFFFAOYSA-N 2-methyl-7-(phenoxymethyl)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 DVCLTMIFEHEKLU-UHFFFAOYSA-N 0.000 description 2
- AGUZXFZMKJPLSX-UHFFFAOYSA-N 3,5-difluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(F)=CC=3F)C#N)=CC2=NC(C)=CC=1N1CCCC1 AGUZXFZMKJPLSX-UHFFFAOYSA-N 0.000 description 2
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 2
- TZFWMBWZEOVYGC-UHFFFAOYSA-N 3-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 TZFWMBWZEOVYGC-UHFFFAOYSA-N 0.000 description 2
- WROYXEJEURABQE-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 WROYXEJEURABQE-UHFFFAOYSA-N 0.000 description 2
- XMBLFMQJNDATJQ-UHFFFAOYSA-N 3-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=CC=3F)C#N)=CC2=NC(C)=CC=1N1CCCC1 XMBLFMQJNDATJQ-UHFFFAOYSA-N 0.000 description 2
- SGHBRHKBCLLVCI-UHFFFAOYSA-N 3-hydroxybenzonitrile Chemical compound OC1=CC=CC(C#N)=C1 SGHBRHKBCLLVCI-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- UNRZSWGCDDVUDS-UHFFFAOYSA-N 4-(azepan-1-yl)-7-(2-methoxyethoxymethyl)-2-methylquinoline Chemical compound C=1C(C)=NC2=CC(COCCOC)=CC=C2C=1N1CCCCCC1 UNRZSWGCDDVUDS-UHFFFAOYSA-N 0.000 description 2
- ABDJRZPMOKRWTJ-UHFFFAOYSA-N 4-(azepan-1-yl)-7-(methoxymethyl)-2-methylquinoline Chemical compound C=1C(C)=NC2=CC(COC)=CC=C2C=1N1CCCCCC1 ABDJRZPMOKRWTJ-UHFFFAOYSA-N 0.000 description 2
- PFWRJJVQJOIMCZ-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-3-(trifluoromethyl)benzonitrile Chemical compound C=12C=C(C)C(COC=3C(=CC(=CC=3)C#N)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 PFWRJJVQJOIMCZ-UHFFFAOYSA-N 0.000 description 2
- PORCTTYQFJTLCB-UHFFFAOYSA-N 4-[(2-methyl-4-piperidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCC1 PORCTTYQFJTLCB-UHFFFAOYSA-N 0.000 description 2
- MBDBJBMKQYJGAQ-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-2-nitrobenzonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)[N+]([O-])=O)=CC2=NC(C)=CC=1N1CCCC1 MBDBJBMKQYJGAQ-UHFFFAOYSA-N 0.000 description 2
- PGDWOHFKILYROS-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-3-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C#N)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 PGDWOHFKILYROS-UHFFFAOYSA-N 0.000 description 2
- YRGQRXMURUGZDN-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YRGQRXMURUGZDN-UHFFFAOYSA-N 0.000 description 2
- KGXYHSCGEGKMTI-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)methoxy]benzene-1,2-dicarbonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1COC1=CC=C(C#N)C(C#N)=C1 KGXYHSCGEGKMTI-UHFFFAOYSA-N 0.000 description 2
- VOROVDVRLLHAAV-UHFFFAOYSA-N 4-[(6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound CC1=CC2=C(N3CCCC3)C=CN=C2C=C1COC1=CC=C(C#N)C=C1 VOROVDVRLLHAAV-UHFFFAOYSA-N 0.000 description 2
- FJSZFDSFTZKCGA-UHFFFAOYSA-N 4-[[2-methyl-4-(4-methylpiperazin-1-yl)quinolin-7-yl]methoxy]benzonitrile Chemical compound C1CN(C)CCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=CC=C12 FJSZFDSFTZKCGA-UHFFFAOYSA-N 0.000 description 2
- PMDYLCUKSLBUHO-UHFFFAOYSA-N 4-amino-2-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C#N)C(C(F)(F)F)=C1 PMDYLCUKSLBUHO-UHFFFAOYSA-N 0.000 description 2
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 2
- RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 2
- KOOBQQIFZSZSGN-UHFFFAOYSA-N 4-bromo-3-phenylmethoxyaniline Chemical compound NC1=CC=C(Br)C(OCC=2C=CC=CC=2)=C1 KOOBQQIFZSZSGN-UHFFFAOYSA-N 0.000 description 2
- RMRFMLNNNPIKIV-UHFFFAOYSA-N 4-chloro-7-iodo-6-methylquinoline Chemical compound C1=CN=C2C=C(I)C(C)=CC2=C1Cl RMRFMLNNNPIKIV-UHFFFAOYSA-N 0.000 description 2
- XGAFCCUNHIMIRV-UHFFFAOYSA-N 4-chloropyridine;hydron;chloride Chemical compound Cl.ClC1=CC=NC=C1 XGAFCCUNHIMIRV-UHFFFAOYSA-N 0.000 description 2
- 150000005653 4-chloroquinolines Chemical class 0.000 description 2
- QQEKYCCJLSRLEC-UHFFFAOYSA-N 4-fluorobenzene-1,2-dicarbonitrile Chemical compound FC1=CC=C(C#N)C(C#N)=C1 QQEKYCCJLSRLEC-UHFFFAOYSA-N 0.000 description 2
- QJRWLNLUIAJTAD-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1O QJRWLNLUIAJTAD-UHFFFAOYSA-N 0.000 description 2
- UTWKTHGCIITRAB-UHFFFAOYSA-N 5-amino-2-bromophenol Chemical compound NC1=CC=C(Br)C(O)=C1 UTWKTHGCIITRAB-UHFFFAOYSA-N 0.000 description 2
- ZDMJKIPIHILMCC-UHFFFAOYSA-N 5-chloro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(Cl)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ZDMJKIPIHILMCC-UHFFFAOYSA-N 0.000 description 2
- NKKFQEBSLZDISC-UHFFFAOYSA-N 5-methyl-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound N#CC1=CC(C)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 NKKFQEBSLZDISC-UHFFFAOYSA-N 0.000 description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
- RKCBBZIIIDKJKF-UHFFFAOYSA-N 6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=C(Br)C(O)=CC2=NC(C)=CC=1N1CCCC1 RKCBBZIIIDKJKF-UHFFFAOYSA-N 0.000 description 2
- FMNPFGKVFPGMOC-UHFFFAOYSA-N 6-bromo-2-methyl-7-phenylmethoxy-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(Br)C(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 FMNPFGKVFPGMOC-UHFFFAOYSA-N 0.000 description 2
- ZFKBHOWKQKZKGX-UHFFFAOYSA-N 6-bromo-4-chloro-2-methyl-7-phenylmethoxyquinoline Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=C(Br)C=1OCC1=CC=CC=C1 ZFKBHOWKQKZKGX-UHFFFAOYSA-N 0.000 description 2
- NKQXWXCDYBQSQZ-UHFFFAOYSA-N 7-[(2-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C(=CC=CC=3)F)=CC2=NC(C)=CC=1N1CCCC1 NKQXWXCDYBQSQZ-UHFFFAOYSA-N 0.000 description 2
- LQMTXSODFQPYKS-UHFFFAOYSA-N 7-[(3-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(OCC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 LQMTXSODFQPYKS-UHFFFAOYSA-N 0.000 description 2
- WUKXTJQCEGKRDX-UHFFFAOYSA-N 7-iodo-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(I)=CC2=NC(C)=CC=1N1CCCC1 WUKXTJQCEGKRDX-UHFFFAOYSA-N 0.000 description 2
- BDEZSSRBHHIWPU-UHFFFAOYSA-N 7-iodo-6-methyl-1h-quinolin-4-one Chemical compound N1C=CC(=O)C2=C1C=C(I)C(C)=C2 BDEZSSRBHHIWPU-UHFFFAOYSA-N 0.000 description 2
- FIJKYFYZRANBBG-UHFFFAOYSA-N 7-iodo-6-methyl-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound N1C=C(C(O)=O)C(=O)C2=C1C=C(I)C(C)=C2 FIJKYFYZRANBBG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
- 229940127470 Lipase Inhibitors Drugs 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000021407 appetite control Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000005604 azodicarboxylate group Chemical group 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 2
- 239000012888 bovine serum Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- NYFAEDDOYZXWIW-UHFFFAOYSA-N ethyl 3-(4-bromo-3-phenylmethoxyanilino)but-2-enoate Chemical compound CCOC(=O)C=C(C)NC1=CC=C(Br)C(OCC=2C=CC=CC=2)=C1 NYFAEDDOYZXWIW-UHFFFAOYSA-N 0.000 description 2
- RUIJNYJNQQTNJD-UHFFFAOYSA-N ethyl 4-chloro-2,6-dimethylquinoline-7-carboxylate Chemical compound CC1=CC(Cl)=C2C=C(C)C(C(=O)OCC)=CC2=N1 RUIJNYJNQQTNJD-UHFFFAOYSA-N 0.000 description 2
- GJMAVLVRTPWHJI-UHFFFAOYSA-N ethyl 4-chloro-6-methylquinoline-7-carboxylate Chemical compound C1=CC(Cl)=C2C=C(C)C(C(=O)OCC)=CC2=N1 GJMAVLVRTPWHJI-UHFFFAOYSA-N 0.000 description 2
- AKCVBQLQCUMRNE-UHFFFAOYSA-N ethyl 7-iodo-6-methyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound IC1=C(C)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 AKCVBQLQCUMRNE-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 150000004675 formic acid derivatives Chemical class 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 229940074439 potassium sodium tartrate Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- XCRPPAPDRUBKRJ-UHFFFAOYSA-N quinolin-7-ol Chemical compound C1=CC=NC2=CC(O)=CC=C21 XCRPPAPDRUBKRJ-UHFFFAOYSA-N 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 125000001302 tertiary amino group Chemical group 0.000 description 2
- 238000001214 thermospray mass spectrometry Methods 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- VWPVQNTUNNNHGZ-UHFFFAOYSA-N (2,4-dichloro-6-methylquinolin-7-yl)methanol Chemical compound C1=C(Cl)N=C2C=C(CO)C(C)=CC2=C1Cl VWPVQNTUNNNHGZ-UHFFFAOYSA-N 0.000 description 1
- HOTUXSIVLXHYAG-UHFFFAOYSA-N (2-chloro-6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=C(Cl)N=C2C=C(CO)C(C)=CC2=C1N1CCCC1 HOTUXSIVLXHYAG-UHFFFAOYSA-N 0.000 description 1
- BSDVWBISVNDMEB-ZDUSSCGKSA-N (3s)-1-[7-(hydroxymethyl)-2,6-dimethylquinolin-4-yl]pyrrolidin-3-ol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 BSDVWBISVNDMEB-ZDUSSCGKSA-N 0.000 description 1
- UELXROMSFBLNMV-UHFFFAOYSA-N (4-chloroquinolin-7-yl)methanamine Chemical compound ClC1=CC=NC2=CC(CN)=CC=C21 UELXROMSFBLNMV-UHFFFAOYSA-N 0.000 description 1
- GATMSTWMFBCCGA-UHFFFAOYSA-N (6-methoxy-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=C(C)N=C2C=C(CO)C(OC)=CC2=C1N1CCCC1 GATMSTWMFBCCGA-UHFFFAOYSA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- GZPMMQGPHXEMSZ-UHFFFAOYSA-N 1-(methoxymethyl)pyrrolidine Chemical compound COCN1CCCC1 GZPMMQGPHXEMSZ-UHFFFAOYSA-N 0.000 description 1
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 description 1
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- MMPKVFQMDMBXSG-UHFFFAOYSA-N 2,3,5-trifluorobenzonitrile Chemical compound FC1=CC(F)=C(F)C(C#N)=C1 MMPKVFQMDMBXSG-UHFFFAOYSA-N 0.000 description 1
- FBNHHKLZBCDJQU-UHFFFAOYSA-N 2,3-difluoro-4-(trifluoromethyl)benzonitrile Chemical compound FC1=C(F)C(C(F)(F)F)=CC=C1C#N FBNHHKLZBCDJQU-UHFFFAOYSA-N 0.000 description 1
- GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 1
- LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
- SOZGHDCEWOLLHV-UHFFFAOYSA-N 2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=CC=C1C#N SOZGHDCEWOLLHV-UHFFFAOYSA-N 0.000 description 1
- MBQLPSQCPXDOCG-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-4-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(C=3)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 MBQLPSQCPXDOCG-UHFFFAOYSA-N 0.000 description 1
- YDBKEULJXYUDHI-UHFFFAOYSA-N 2-[(4-chloro-2-methylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1COC1=CC=CC=C1C#N YDBKEULJXYUDHI-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
- 150000005013 2-aminoquinolines Chemical class 0.000 description 1
- PGKPNNMOFHNZJX-UHFFFAOYSA-N 2-chloro-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(Cl)=C1 PGKPNNMOFHNZJX-UHFFFAOYSA-N 0.000 description 1
- 150000005642 2-chloroquinolines Chemical class 0.000 description 1
- DERAACKMMNJAFU-UHFFFAOYSA-N 2-ethoxy-1,3-dioxane-4,6-dione Chemical compound CCOC1OC(=O)CC(=O)O1 DERAACKMMNJAFU-UHFFFAOYSA-N 0.000 description 1
- JLTYVTXTSOYXMX-UHFFFAOYSA-N 2-fluoro-4-(trifluoromethyl)benzonitrile Chemical compound FC1=CC(C(F)(F)F)=CC=C1C#N JLTYVTXTSOYXMX-UHFFFAOYSA-N 0.000 description 1
- GREJUAIIYPUSGP-UHFFFAOYSA-N 2-fluoro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(F)C(C#N)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 GREJUAIIYPUSGP-UHFFFAOYSA-N 0.000 description 1
- OGQYJDHTHFAPRN-UHFFFAOYSA-N 2-fluoro-6-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=CC(C(F)(F)F)=C1C#N OGQYJDHTHFAPRN-UHFFFAOYSA-N 0.000 description 1
- FAACTMVXBNSPJA-UHFFFAOYSA-N 2-fluoro-6-iodobenzonitrile Chemical compound FC1=CC=CC(I)=C1C#N FAACTMVXBNSPJA-UHFFFAOYSA-N 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- TYXJCGQGRUXPPD-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[4-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 TYXJCGQGRUXPPD-UHFFFAOYSA-N 0.000 description 1
- GNVKPJJTMMKXCV-UHFFFAOYSA-N 2-methyl-7-[(2-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C(=CC=CC=3)C)=CC2=NC(C)=CC=1N1CCCC1 GNVKPJJTMMKXCV-UHFFFAOYSA-N 0.000 description 1
- QVYCJMJBMKODFM-UHFFFAOYSA-N 2-methyl-7-[(3-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound CC1=CC=CC(OCC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 QVYCJMJBMKODFM-UHFFFAOYSA-N 0.000 description 1
- FZJQNXJRMQBCQA-UHFFFAOYSA-N 2-methyl-7-[(4-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound C1=CC(C)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 FZJQNXJRMQBCQA-UHFFFAOYSA-N 0.000 description 1
- HDQQMKIESYYHRJ-UHFFFAOYSA-N 2-methyl-7-[(4-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(C)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 HDQQMKIESYYHRJ-UHFFFAOYSA-N 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-M 2-methylbutyrate Chemical compound CCC(C)C([O-])=O WLAMNBDJUVNPJU-UHFFFAOYSA-M 0.000 description 1
- BTBFCBQZFMQBNT-UHFFFAOYSA-N 3,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1F BTBFCBQZFMQBNT-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BYWDCMQRVTUUPY-UHFFFAOYSA-N 3-chloro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C#N)Cl)=CC2=NC(C)=CC=1N1CCCC1 BYWDCMQRVTUUPY-UHFFFAOYSA-N 0.000 description 1
- VAHXXQJJZKBZDX-UHFFFAOYSA-N 3-chloro-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1Cl VAHXXQJJZKBZDX-UHFFFAOYSA-N 0.000 description 1
- XMTFHHGBBFFOHD-UHFFFAOYSA-N 3-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-4-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(C=3F)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 XMTFHHGBBFFOHD-UHFFFAOYSA-N 0.000 description 1
- SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 1
- UHPNLGCUIGEZRB-UHFFFAOYSA-N 3-iodo-4-methoxyaniline Chemical compound COC1=CC=C(N)C=C1I UHPNLGCUIGEZRB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HRXSZSYQFGVUCL-YSYXNDDBSA-N 4-(3-methoxypyrrolidin-1-yl)-2,6-dimethyl-7-[[(2s)-oxan-2-yl]oxymethyl]quinoline Chemical compound C1C(OC)CCN1C1=CC(C)=NC2=CC(CO[C@@H]3OCCCC3)=C(C)C=C12 HRXSZSYQFGVUCL-YSYXNDDBSA-N 0.000 description 1
- CSCCGZCPGBQTMN-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCCCC1 CSCCGZCPGBQTMN-UHFFFAOYSA-N 0.000 description 1
- PLAWARAAQGAMFW-UHFFFAOYSA-N 4-(azepan-1-yl)-n,6-dimethyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinolin-2-amine Chemical compound C=12C=C(C)C(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(NC)=CC=1N1CCCCCC1 PLAWARAAQGAMFW-UHFFFAOYSA-N 0.000 description 1
- NCQACUCGBCKKCV-UHFFFAOYSA-N 4-(azepan-1-yl)-n,n,6-trimethyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinolin-2-amine Chemical compound C=12C=C(C)C(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(N(C)C)=CC=1N1CCCCCC1 NCQACUCGBCKKCV-UHFFFAOYSA-N 0.000 description 1
- DCIWEDMHNOWCTK-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=C(C)C(COC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 DCIWEDMHNOWCTK-UHFFFAOYSA-N 0.000 description 1
- UUJRPJPWYOIWTP-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl-methylamino]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1N(C)CC(C(=CC1=2)C)=CC1=NC(C)=CC=2N1CCCC1 UUJRPJPWYOIWTP-UHFFFAOYSA-N 0.000 description 1
- FBJUQLXTVWMSMQ-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]benzonitrile Chemical compound C=12C=C(C)C(CNC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 FBJUQLXTVWMSMQ-UHFFFAOYSA-N 0.000 description 1
- ZHYGCONYRFDRIP-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)methoxy]-2-(trifluoromethyl)benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1COC1=CC=C(C#N)C(C(F)(F)F)=C1 ZHYGCONYRFDRIP-UHFFFAOYSA-N 0.000 description 1
- ULOMPSGOQQSFAN-UHFFFAOYSA-N 4-aminoquinoline-7-carbonitrile Chemical class N#CC1=CC=C2C(N)=CC=NC2=C1 ULOMPSGOQQSFAN-UHFFFAOYSA-N 0.000 description 1
- DRNOUAUANPKLON-UHFFFAOYSA-N 4-aminoquinoline-7-carboxamide Chemical class NC1=CC=NC2=CC(C(=O)N)=CC=C21 DRNOUAUANPKLON-UHFFFAOYSA-N 0.000 description 1
- CHTDXTLZBDJJFV-UHFFFAOYSA-N 4-bromo-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(Br)C=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 CHTDXTLZBDJJFV-UHFFFAOYSA-N 0.000 description 1
- HGXWRDPQFZKOLZ-UHFFFAOYSA-N 4-bromo-2-fluorobenzonitrile Chemical compound FC1=CC(Br)=CC=C1C#N HGXWRDPQFZKOLZ-UHFFFAOYSA-N 0.000 description 1
- AVMRBHDHNUEGNT-UHFFFAOYSA-N 4-chloro-2,6-dimethyl-7-(oxan-2-yloxymethyl)quinoline Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=C(C)C=1COC1CCCCO1 AVMRBHDHNUEGNT-UHFFFAOYSA-N 0.000 description 1
- KQJOGVOOJHJKAN-UHFFFAOYSA-N 4-chloro-2,6-dimethylquinoline-7-carbaldehyde Chemical compound C1=C(C)C(C=O)=CC2=NC(C)=CC(Cl)=C21 KQJOGVOOJHJKAN-UHFFFAOYSA-N 0.000 description 1
- YPRJEPFAKUXNBU-UHFFFAOYSA-N 4-chloro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(Cl)C=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YPRJEPFAKUXNBU-UHFFFAOYSA-N 0.000 description 1
- JRDMGVGCATYZPW-UHFFFAOYSA-N 4-chloro-2-fluorobenzonitrile Chemical compound FC1=CC(Cl)=CC=C1C#N JRDMGVGCATYZPW-UHFFFAOYSA-N 0.000 description 1
- UBGQOSUHXMHCCV-UHFFFAOYSA-N 4-chloro-5-iodo-6-methoxy-2-methylquinoline Chemical compound N1=C(C)C=C(Cl)C2=C(I)C(OC)=CC=C21 UBGQOSUHXMHCCV-UHFFFAOYSA-N 0.000 description 1
- UKTYNFPTZDSBLR-UHFFFAOYSA-N 4-chloro-7-methoxyquinoline Chemical compound ClC1=CC=NC2=CC(OC)=CC=C21 UKTYNFPTZDSBLR-UHFFFAOYSA-N 0.000 description 1
- KNDOFJFSHZCKGT-UHFFFAOYSA-N 4-chloroquinoline Chemical compound C1=CC=C2C(Cl)=CC=NC2=C1 KNDOFJFSHZCKGT-UHFFFAOYSA-N 0.000 description 1
- NTLCAGGRCRJARZ-UHFFFAOYSA-N 4-chloroquinoline-7-carbaldehyde Chemical compound O=CC1=CC=C2C(Cl)=CC=NC2=C1 NTLCAGGRCRJARZ-UHFFFAOYSA-N 0.000 description 1
- NFCSRTCOMSRFOC-UHFFFAOYSA-N 4-chloroquinoline-7-carbonitrile Chemical compound N#CC1=CC=C2C(Cl)=CC=NC2=C1 NFCSRTCOMSRFOC-UHFFFAOYSA-N 0.000 description 1
- VMGVGPMZWPOPJP-UHFFFAOYSA-N 4-chloroquinoline-7-carboxylic acid Chemical compound ClC1=CC=NC2=CC(C(=O)O)=CC=C21 VMGVGPMZWPOPJP-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- MNEAKKQYFSYZEU-UHFFFAOYSA-N 4-fluoro-2-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1C#N MNEAKKQYFSYZEU-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 1
- FYFLUWOGTOSAGD-UHFFFAOYSA-N 4-hydroxy-7-iodo-6-methyl-1h-quinolin-2-one Chemical compound OC1=CC(=O)NC2=C1C=C(C)C(I)=C2 FYFLUWOGTOSAGD-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- YCAZALSUJDPQPP-UHFFFAOYSA-N 4-oxo-3h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(=O)O)C=NC2=C1 YCAZALSUJDPQPP-UHFFFAOYSA-N 0.000 description 1
- ADQOOTSUKUZXTL-UHFFFAOYSA-N 5-bromo-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(Br)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ADQOOTSUKUZXTL-UHFFFAOYSA-N 0.000 description 1
- GYCNHFWRPJXTSB-UHFFFAOYSA-N 5-bromo-2-fluorobenzonitrile Chemical compound FC1=CC=C(Br)C=C1C#N GYCNHFWRPJXTSB-UHFFFAOYSA-N 0.000 description 1
- GJNJDELEHIGPKJ-UHFFFAOYSA-N 5-chloro-2-fluorobenzonitrile Chemical compound FC1=CC=C(Cl)C=C1C#N GJNJDELEHIGPKJ-UHFFFAOYSA-N 0.000 description 1
- AFNOQYAETCRRLG-UHFFFAOYSA-N 5-iodo-2,6-dimethyl-1h-quinolin-4-one Chemical compound CC1=CC=C2NC(C)=CC(=O)C2=C1I AFNOQYAETCRRLG-UHFFFAOYSA-N 0.000 description 1
- QIDYUMIHIVJJHQ-UHFFFAOYSA-N 6-bromo-2-methyl-7-phenylmethoxy-1h-quinolin-4-one Chemical compound C=1C2=NC(C)=CC(O)=C2C=C(Br)C=1OCC1=CC=CC=C1 QIDYUMIHIVJJHQ-UHFFFAOYSA-N 0.000 description 1
- VFQKWDQLORBSTC-UHFFFAOYSA-N 6-bromo-4-chloro-2-methyl-7-phenylmethoxyquinoline;6-bromo-2-methyl-7-phenylmethoxy-1h-quinolin-4-one Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=C(Br)C=1OCC1=CC=CC=C1.C1=C2NC(C)=CC(=O)C2=CC(Br)=C1OCC1=CC=CC=C1 VFQKWDQLORBSTC-UHFFFAOYSA-N 0.000 description 1
- 150000005639 6-haloquinolines Chemical class 0.000 description 1
- AYNKSWTVVXGZOH-UHFFFAOYSA-N 7-(aminomethyl)quinolin-4-amine Chemical class NC1=CC=NC2=CC(CN)=CC=C21 AYNKSWTVVXGZOH-UHFFFAOYSA-N 0.000 description 1
- BXDKEBOAEQYWLL-UHFFFAOYSA-N 7-(quinolin-7-ylmethoxymethyl)quinoline Chemical compound C1=CC=NC2=CC(COCC=3C=C4N=CC=CC4=CC=3)=CC=C21 BXDKEBOAEQYWLL-UHFFFAOYSA-N 0.000 description 1
- RHSJUIIVCCKPLQ-UHFFFAOYSA-N 7-[(2-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 RHSJUIIVCCKPLQ-UHFFFAOYSA-N 0.000 description 1
- KROQRBVJERZNHY-UHFFFAOYSA-N 7-[(2-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline;oxalic acid Chemical compound OC(=O)C(O)=O.COC1=CC=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 KROQRBVJERZNHY-UHFFFAOYSA-N 0.000 description 1
- UDXITQOJMCZFES-UHFFFAOYSA-N 7-[(3-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=C(F)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 UDXITQOJMCZFES-UHFFFAOYSA-N 0.000 description 1
- FERSBDNXERXWTP-UHFFFAOYSA-N 7-[(3-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline;oxalic acid Chemical compound OC(=O)C(O)=O.C=12C=CC(COC=3C=C(F)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 FERSBDNXERXWTP-UHFFFAOYSA-N 0.000 description 1
- ZKAIWVFOSMRDEE-UHFFFAOYSA-N 7-[(4-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CC(F)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 ZKAIWVFOSMRDEE-UHFFFAOYSA-N 0.000 description 1
- SEIKATQWLFCPFW-UHFFFAOYSA-N 7-[(4-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C1=CC(OC)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 SEIKATQWLFCPFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OVGWXTLNYZTFRU-UHFFFAOYSA-N C(C(C)C)[AlH]CC(C)C.N1(CCCCCC1)C1=CC(=NC2=CC(=C(C=C12)C)CO)Cl Chemical compound C(C(C)C)[AlH]CC(C)C.N1(CCCCCC1)C1=CC(=NC2=CC(=C(C=C12)C)CO)Cl OVGWXTLNYZTFRU-UHFFFAOYSA-N 0.000 description 1
- VROLQUMSYOHSNY-GWUAMTPNSA-N C(C1=CC=CC=C1)OC(=O)N1[C@@H](CCC1)COC1OCCCC1.O1C(CCCC1)OC[C@H]1NCCC1 Chemical compound C(C1=CC=CC=C1)OC(=O)N1[C@@H](CCC1)COC1OCCCC1.O1C(CCCC1)OC[C@H]1NCCC1 VROLQUMSYOHSNY-GWUAMTPNSA-N 0.000 description 1
- QYOVMAREBTZLBT-KTKRTIGZSA-N CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO QYOVMAREBTZLBT-KTKRTIGZSA-N 0.000 description 1
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- NBYYFRQALXEYDP-UHFFFAOYSA-N Cc1cc(Cl)c2ccc(CO)cc2n1.Cc1cc(N2CCCC2)c2ccc(CO)cc2n1 Chemical compound Cc1cc(Cl)c2ccc(CO)cc2n1.Cc1cc(N2CCCC2)c2ccc(CO)cc2n1 NBYYFRQALXEYDP-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- 102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 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
- 241000282412 Homo Species 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 1
- 102000028582 Neuropeptide Y5 receptor Human genes 0.000 description 1
- 229940116685 Neuropeptide receptor antagonist Drugs 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- UEZAQHNVTWKJPD-PBVYKCSPSA-N [2-methyl-4-[(2s)-2-(oxan-2-yloxymethyl)pyrrolidin-1-yl]quinolin-7-yl]methanol Chemical compound C([C@@H]1CCCN1C=1C=C(N=C2C=C(CO)C=CC2=1)C)OC1CCCCO1 UEZAQHNVTWKJPD-PBVYKCSPSA-N 0.000 description 1
- OGXFNYOKBJDFGZ-UHFFFAOYSA-N [3-methoxy-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]phenyl]-pyrrolidin-1-ylmethanone Chemical compound COC1=CC(C(=O)N2CCCC2)=CC=C1OCC(C=C1N=C(C)C=2)=CC=C1C=2N1CCCC1 OGXFNYOKBJDFGZ-UHFFFAOYSA-N 0.000 description 1
- MXAWUMMTIJTJRY-UHFFFAOYSA-N [4-(azepan-1-yl)-2,6-dimethylquinolin-7-yl]methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CCCCCC1 MXAWUMMTIJTJRY-UHFFFAOYSA-N 0.000 description 1
- WCJMGMURINVYNK-UHFFFAOYSA-N [Na].CC1=NC2=CC(=CC=C2C(=C1)N1CCCC1)CNC1=CC=C(C#N)C=C1 Chemical compound [Na].CC1=NC2=CC(=CC=C2C(=C1)N1CCCC1)CNC1=CC=C(C#N)C=C1 WCJMGMURINVYNK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- AEBLIUSQFUXCJS-BHWOMJMDSA-N benzyl (2s)-2-(oxan-2-yloxymethyl)pyrrolidine-1-carboxylate Chemical compound N1([C@@H](CCC1)COC1OCCCC1)C(=O)OCC1=CC=CC=C1 AEBLIUSQFUXCJS-BHWOMJMDSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940125890 compound Ia Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical group C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical group C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229960001867 guaiacol Drugs 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
- 125000006517 heterocyclyl carbonyl group Chemical group 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
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000011551 log transformation method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- OMEWIJDNHNOVGC-UHFFFAOYSA-N n,n'-bis(3-iodo-4-methylphenyl)propanediamide Chemical compound C1=C(I)C(C)=CC=C1NC(=O)CC(=O)NC1=CC=C(C)C(I)=C1 OMEWIJDNHNOVGC-UHFFFAOYSA-N 0.000 description 1
- FQOCWGYTLIBKNP-UHFFFAOYSA-N n,n'-bis(3-iodo-4-methylphenyl)propanediamide;4-hydroxy-7-iodo-6-methyl-1h-quinolin-2-one Chemical compound OC1=CC(=O)NC2=C1C=C(C)C(I)=C2.C1=C(I)C(C)=CC=C1NC(=O)CC(=O)NC1=CC=C(C)C(I)=C1 FQOCWGYTLIBKNP-UHFFFAOYSA-N 0.000 description 1
- DTKKDUXAKODAIE-UHFFFAOYSA-N n,n-dimethylpyrrolidin-1-amine Chemical compound CN(C)N1CCCC1 DTKKDUXAKODAIE-UHFFFAOYSA-N 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- RNBRGFBBPVFNQJ-UHFFFAOYSA-N n-(4-cyanophenyl)-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=12C=CC(C(=O)NC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 RNBRGFBBPVFNQJ-UHFFFAOYSA-N 0.000 description 1
- DXHPEXGXMQTFLJ-UHFFFAOYSA-N n-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C=12C=CC(CNC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 DXHPEXGXMQTFLJ-UHFFFAOYSA-N 0.000 description 1
- IBQQZUFOYSTLFX-UHFFFAOYSA-N n-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl]butan-1-amine Chemical compound C=1C(C)=NC2=CC(CNCCCC)=CC=C2C=1N1CCCC1 IBQQZUFOYSTLFX-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 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
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- VLCMRTMCMQJSKM-UHFFFAOYSA-N phenyl-[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CN=C2C(C(F)(F)F)=CC=CC2=C1C1=CC=CC=C1 VLCMRTMCMQJSKM-UHFFFAOYSA-N 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- FPSAXXSFDJDIRR-UHFFFAOYSA-N quinolin-7-yl trifluoromethanesulfonate Chemical class C1=CC=NC2=CC(OS(=O)(=O)C(F)(F)F)=CC=C21 FPSAXXSFDJDIRR-UHFFFAOYSA-N 0.000 description 1
- WINWAFCAQPFBQA-UHFFFAOYSA-N quinoline-7-carbaldehyde Chemical class C1=CC=NC2=CC(C=O)=CC=C21 WINWAFCAQPFBQA-UHFFFAOYSA-N 0.000 description 1
- MMCIXNVRVDTQSG-UHFFFAOYSA-N quinoline-7-carboxamide Chemical class C1=CC=NC2=CC(C(=O)N)=CC=C21 MMCIXNVRVDTQSG-UHFFFAOYSA-N 0.000 description 1
- WXXVQWSDMOAHHV-UHFFFAOYSA-N quinoline-7-carboxylic acid Chemical compound C1=CC=NC2=CC(C(=O)O)=CC=C21 WXXVQWSDMOAHHV-UHFFFAOYSA-N 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 125000004360 trifluorophenyl group Chemical group 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Nutrition Science (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Quinoline Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01123496 | 2001-09-28 | ||
| EP01123496.0 | 2001-09-28 | ||
| PCT/EP2002/010618 WO2003028726A1 (en) | 2001-09-28 | 2002-09-20 | Quinoline derivatives as neuropeptide y antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002342735A1 AU2002342735A1 (en) | 2003-06-26 |
| AU2002342735B2 true AU2002342735B2 (en) | 2005-09-22 |
Family
ID=8178804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002342735A Ceased AU2002342735B2 (en) | 2001-09-28 | 2002-09-20 | Quinoline derivatives as neuropeptide Y antagonists |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US6787558B2 (enExample) |
| EP (1) | EP1432421A1 (enExample) |
| JP (1) | JP4187652B2 (enExample) |
| KR (1) | KR100605765B1 (enExample) |
| CN (1) | CN1289087C (enExample) |
| AR (1) | AR040626A1 (enExample) |
| AU (1) | AU2002342735B2 (enExample) |
| BR (1) | BR0212929A (enExample) |
| CA (1) | CA2460865C (enExample) |
| GT (1) | GT200200197A (enExample) |
| HR (1) | HRP20040272A2 (enExample) |
| HU (1) | HUP0401481A2 (enExample) |
| IL (1) | IL160750A0 (enExample) |
| MX (1) | MXPA04002825A (enExample) |
| NO (1) | NO20041235L (enExample) |
| NZ (1) | NZ531517A (enExample) |
| PA (1) | PA8555401A1 (enExample) |
| PE (1) | PE20030603A1 (enExample) |
| PL (1) | PL370414A1 (enExample) |
| RU (1) | RU2300531C2 (enExample) |
| UY (1) | UY27462A1 (enExample) |
| WO (1) | WO2003028726A1 (enExample) |
| ZA (1) | ZA200402359B (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| AU2008252636B2 (en) * | 2007-05-17 | 2013-10-31 | Helperby Therapeutics Limited | Use of 4-(pyrrolidin-1-yl)quinoline compounds to kill clinically latent microorganisms |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| JP5546451B2 (ja) | 2007-06-04 | 2014-07-09 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸の障害、炎症、癌および他の障害の処置に有用なグアニル酸シクラーゼのアゴニスト |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| CA2713998A1 (en) * | 2008-01-28 | 2009-08-06 | Janssen Pharmaceutica N.V. | 6-substituted-thio-2-amino-quinoline derivatives useful as inhibitors of.beta.-secretase (bace) |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| EP2348857B1 (en) | 2008-10-22 | 2016-02-24 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| AU2009309037A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| MY159058A (en) | 2011-02-25 | 2016-12-15 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agent |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| JP2016516004A (ja) | 2013-02-22 | 2016-06-02 | 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． | 抗糖尿病二環式化合物 |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| HK1220696A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 鸟苷酸环化酶激动剂及其用途 |
| AU2014235209B2 (en) | 2013-03-15 | 2018-06-14 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonists combined with other drugs |
| EP4424697A3 (en) | 2013-06-05 | 2024-12-25 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| US9212144B2 (en) * | 2014-01-10 | 2015-12-15 | Northwestern University | 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition |
| US9663468B2 (en) | 2014-01-10 | 2017-05-30 | Northwestern University | 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition |
| US10577362B2 (en) * | 2016-05-04 | 2020-03-03 | Genoscience Pharma | Substituted 2, 4-diamino-quinoline derivatives for use in the treatment of proliferative diseases |
| US11072602B2 (en) | 2016-12-06 | 2021-07-27 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| US10968232B2 (en) | 2016-12-20 | 2021-04-06 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| WO2020160151A1 (en) * | 2019-01-31 | 2020-08-06 | Kyorin Pharmaceutical Co., Ltd. | 15-pgdh inhibitors |
| US12312337B2 (en) | 2019-05-10 | 2025-05-27 | Antidote Ip Holdings, Llc | Compounds and methods for treating cancer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001023389A2 (en) * | 1999-09-30 | 2001-04-05 | Neurogen Corporation | Certain alkylene diamine-substituted heterocycles |
| WO2002020488A2 (en) * | 2000-09-06 | 2002-03-14 | F. Hoffmann-La Roche Ag | Quinoline and quinazoline derivatives as ligands for the neuropeptide y receptor |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3272824A (en) * | 1962-12-06 | 1966-09-13 | Norwich Pharma Co | 4-amino-6, 7-di(lower) alkoxyquinolines |
| US4035367A (en) * | 1974-09-09 | 1977-07-12 | Sandoz, Inc. | Hydroxyalkyl-substituted-amino-quinolines |
| CA1247547A (en) | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
| CA1270837A (en) | 1984-12-21 | 1990-06-26 | Hoffmann-La Roche Limited | Oxetanones |
| CA1328881C (en) | 1984-12-21 | 1994-04-26 | Pierre Barbier | Process for the manufacture of oxetanones |
| JPH068292B2 (ja) * | 1985-05-07 | 1994-02-02 | アルカロイダ ベギエスゼティ ギャル | トリアゾリルキノリン誘導体 |
| CA2035972C (en) | 1990-02-23 | 2006-07-11 | Martin Karpf | Process for the preparation of oxetanones |
| US5274143A (en) | 1991-07-23 | 1993-12-28 | Hoffmann-La Roche Inc. | Process for the preparation of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-pyran-2-one and (R)-5,6-dihydro-6-undecyl-2H-pyran-2,4(3H)-dione |
| WO1998014431A1 (en) | 1996-10-01 | 1998-04-09 | Kyowa Hakko Kogyo Co., Ltd. | Nitrogenous heterocyclic compounds |
| US6004996A (en) | 1997-02-05 | 1999-12-21 | Hoffman-La Roche Inc. | Tetrahydrolipstatin containing compositions |
| US6267952B1 (en) | 1998-01-09 | 2001-07-31 | Geltex Pharmaceuticals, Inc. | Lipase inhibiting polymers |
| US6199042B1 (en) * | 1998-06-19 | 2001-03-06 | L&H Applications Usa, Inc. | Reading system |
| AU759388B2 (en) | 1998-08-14 | 2003-04-10 | Cheplapharm Arzneimittel Gmbh | Pharmaceutical compositions containing lipase inhibitors and chitosan |
| TR200100471T2 (tr) | 1998-08-14 | 2001-07-23 | F.Hoffmann-La Roche Ag | Lipaz inhibitörleri içeren farmasötik bileşimler |
| FR2795726A1 (fr) * | 1999-06-30 | 2001-01-05 | Aventis Cropscience Sa | Nouveaux pyrazoles fongicides |
-
2002
- 2002-09-19 US US10/247,009 patent/US6787558B2/en not_active Expired - Fee Related
- 2002-09-20 HR HR20040272A patent/HRP20040272A2/hr not_active Application Discontinuation
- 2002-09-20 EP EP02779399A patent/EP1432421A1/en not_active Withdrawn
- 2002-09-20 WO PCT/EP2002/010618 patent/WO2003028726A1/en not_active Ceased
- 2002-09-20 AU AU2002342735A patent/AU2002342735B2/en not_active Ceased
- 2002-09-20 RU RU2004113207/04A patent/RU2300531C2/ru not_active IP Right Cessation
- 2002-09-20 KR KR1020047004591A patent/KR100605765B1/ko not_active Expired - Fee Related
- 2002-09-20 MX MXPA04002825A patent/MXPA04002825A/es active IP Right Grant
- 2002-09-20 HU HU0401481A patent/HUP0401481A2/hu unknown
- 2002-09-20 CN CNB028191919A patent/CN1289087C/zh not_active Expired - Fee Related
- 2002-09-20 JP JP2003532058A patent/JP4187652B2/ja not_active Expired - Fee Related
- 2002-09-20 IL IL16075002A patent/IL160750A0/xx unknown
- 2002-09-20 NZ NZ531517A patent/NZ531517A/en unknown
- 2002-09-20 BR BR0212929-9A patent/BR0212929A/pt not_active IP Right Cessation
- 2002-09-20 CA CA002460865A patent/CA2460865C/en not_active Expired - Fee Related
- 2002-09-20 PL PL02370414A patent/PL370414A1/xx not_active Application Discontinuation
- 2002-09-25 PA PA20028555401A patent/PA8555401A1/es unknown
- 2002-09-26 PE PE2002000952A patent/PE20030603A1/es not_active Application Discontinuation
- 2002-09-27 GT GT200200197A patent/GT200200197A/es unknown
- 2002-09-27 AR AR20020103663A patent/AR040626A1/es not_active Application Discontinuation
- 2002-09-27 UY UY27462A patent/UY27462A1/es not_active Application Discontinuation
-
2004
- 2004-03-24 NO NO20041235A patent/NO20041235L/no not_active Application Discontinuation
- 2004-03-25 ZA ZA200402359A patent/ZA200402359B/en unknown
- 2004-07-22 US US10/896,445 patent/US7012073B2/en not_active Expired - Fee Related
-
2005
- 2005-11-10 US US11/272,207 patent/US7064134B2/en not_active Expired - Fee Related
-
2006
- 2006-03-16 US US11/376,976 patent/US7166589B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001023389A2 (en) * | 1999-09-30 | 2001-04-05 | Neurogen Corporation | Certain alkylene diamine-substituted heterocycles |
| WO2002020488A2 (en) * | 2000-09-06 | 2002-03-14 | F. Hoffmann-La Roche Ag | Quinoline and quinazoline derivatives as ligands for the neuropeptide y receptor |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002342735B2 (en) | Quinoline derivatives as neuropeptide Y antagonists | |
| AU2002342735A1 (en) | Quinoline derivatives as neuropeptide Y antagonists | |
| AU2002338896B2 (en) | Quinoline derivatives as ligands for the neuropeptide Y receptor | |
| AU2003205679B2 (en) | Quinoline derivatives as NPY antagonists | |
| AU2002210474A1 (en) | Quinoline and quinazoline derivatives as ligands for the neuropetide Y receptor | |
| AU2003281346B2 (en) | Quinazoline derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |