NZ531517A - Quinoline derivatives as neuropeptide Y antagonists - Google Patents

Info

Publication number

NZ531517A

NZ531517A NZ531517A NZ53151702A NZ531517A NZ 531517 A NZ531517 A NZ 531517A NZ 531517 A NZ531517 A NZ 531517A NZ 53151702 A NZ53151702 A NZ 53151702A NZ 531517 A NZ531517 A NZ 531517A

Authority

NZ

New Zealand

Prior art keywords

methyl

quinolin

pyrrolidin

benzonitrile

alkyl

Prior art date

2001-09-28

Links

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• Global Dossier
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• 101710151321 Melanostatin Proteins 0.000 title claims abstract description 10
• 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 abstract description 287
• 238000000034 method Methods 0.000 claims abstract description 32
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 229940086609 Lipase inhibitor Drugs 0.000 claims abstract description 23
• 208000008589 Obesity Diseases 0.000 claims abstract description 21
• 238000004519 manufacturing process Methods 0.000 claims abstract description 21
• 235000020824 obesity Nutrition 0.000 claims abstract description 21
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims abstract description 18
• 239000003814 drug Substances 0.000 claims abstract description 17
• 229960001243 orlistat Drugs 0.000 claims abstract description 17
• 238000011321 prophylaxis Methods 0.000 claims abstract description 17
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 13
• 208000030814 Eating disease Diseases 0.000 claims abstract description 13
• 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 13
• 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 13
• 206010003246 arthritis Diseases 0.000 claims abstract description 13
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
• 235000014632 disordered eating Nutrition 0.000 claims abstract description 13
• 201000006370 kidney failure Diseases 0.000 claims abstract description 13
• 230000008569 process Effects 0.000 claims abstract description 11
• 102100028427 Pro-neuropeptide Y Human genes 0.000 claims abstract description 9
• 238000002360 preparation method Methods 0.000 claims abstract description 7
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 126
• 125000000217 alkyl group Chemical group 0.000 claims description 86
• 239000000243 solution Substances 0.000 claims description 85
• -1 amino, acetylamino Chemical group 0.000 claims description 66
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 61
• 239000000203 mixture Substances 0.000 claims description 44
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 42
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 32
• 150000002367 halogens Chemical group 0.000 claims description 32
• 125000000623 heterocyclic group Chemical group 0.000 claims description 32
• 238000006243 chemical reaction Methods 0.000 claims description 31
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
• 150000002148 esters Chemical class 0.000 claims description 21
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
• 150000001412 amines Chemical class 0.000 claims description 16
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 14
• 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 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
• 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
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000003710 aryl alkyl group Chemical group 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
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• 229920002261 Corn starch Polymers 0.000 claims description 6
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
• QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical group C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 claims description 6
• 150000004678 hydrides Chemical class 0.000 claims description 6
• 239000000454 talc Substances 0.000 claims description 6
• 229910052623 talc Inorganic materials 0.000 claims description 6
• 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 claims description 5
• 239000002775 capsule Substances 0.000 claims description 5
• 239000008101 lactose Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 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
• 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 4
• ZETVYJWZAJSNLN-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(CNC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 ZETVYJWZAJSNLN-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
• 239000013543 active substance Substances 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 239000004615 ingredient Substances 0.000 claims description 4
• 125000002346 iodo group Chemical group I* 0.000 claims description 4
• 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 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• 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 3
• DGEQVTJQZRYCHX-QFIPXVFZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methylamino]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(CNC=3C=CC(=CC=3)C#N)=C(C)C=C12 DGEQVTJQZRYCHX-QFIPXVFZSA-N 0.000 claims description 3
• 235000019759 Maize starch Nutrition 0.000 claims description 3
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
• LGQODQYMJCBWSG-HNNXBMFYSA-N [4-[(3s)-3-ethoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methanol Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(CO)=C(C)C=C12 LGQODQYMJCBWSG-HNNXBMFYSA-N 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• 238000002347 injection Methods 0.000 claims description 3
• 239000007924 injection Substances 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 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
• 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 2
• 229920000159 gelatin Polymers 0.000 claims description 2
• 235000019322 gelatine Nutrition 0.000 claims description 2
• 239000001828 Gelatine Substances 0.000 claims 1
• 239000008215 water for injection Substances 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
• 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
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
• 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 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
• 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 36
• 239000012044 organic layer Substances 0.000 description 33
• 238000001816 cooling Methods 0.000 description 26
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• 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
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 238000001914 filtration Methods 0.000 description 16
• 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 16
• 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 14
• 239000006260 foam Substances 0.000 description 14
• 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 13
• 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
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 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 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 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 9
• AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 9
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 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 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 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
• 239000002244 precipitate Substances 0.000 description 8
• 229910052708 sodium Inorganic materials 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
• 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 7
• HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• VEFLZRCRHNLSIG-JJTBHEEUSA-N (3s)-1-[2,6-dimethyl-7-(oxan-2-yloxymethyl)quinolin-4-yl]pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C=12C=C(C)C(COC3OCCCC3)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 VEFLZRCRHNLSIG-JJTBHEEUSA-N 0.000 description 6
• RQHOXNWJPCOVNH-UHFFFAOYSA-N 4-[(4-chloro-2,6-dimethylquinolin-7-yl)methylamino]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=C(C)C=1CNC1=CC=C(C#N)C=C1 RQHOXNWJPCOVNH-UHFFFAOYSA-N 0.000 description 6
• 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
• 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 6
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