JP3715280B2 - ニューロペプチドｙレセプターのリガンドとしてのキノリン誘導体 - Google Patents

Info

Publication number

JP3715280B2

JP3715280B2 JP2002591462A JP2002591462A JP3715280B2 JP 3715280 B2 JP3715280 B2 JP 3715280B2 JP 2002591462 A JP2002591462 A JP 2002591462A JP 2002591462 A JP2002591462 A JP 2002591462A JP 3715280 B2 JP3715280 B2 JP 3715280B2

Authority

JP

Japan

Prior art keywords

methyl

pyrrolidin

quinolin

quinoline

yloxymethyl

Prior art date

2001-05-21

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

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 6
• 239000003446 ligand Substances 0.000 title description 6
• 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
• 108050002826 Neuropeptide Y Receptor Proteins 0.000 title 1
• 102000012301 Neuropeptide Y receptor Human genes 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 136
• -1 heteroarylalkylamino Chemical group 0.000 claims description 73
• 238000006243 chemical reaction Methods 0.000 claims description 72
• 125000000217 alkyl group Chemical group 0.000 claims description 68
• 239000001257 hydrogen Substances 0.000 claims description 51
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• HTWNTQBDROIOEZ-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCC1 HTWNTQBDROIOEZ-UHFFFAOYSA-N 0.000 claims description 50
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 49
• 125000003545 alkoxy group Chemical group 0.000 claims description 38
• 125000003118 aryl group Chemical group 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 30
• 238000000034 method Methods 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 28
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 25
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 22
• 125000000623 heterocyclic group Chemical group 0.000 claims description 21
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
• 208000008589 Obesity Diseases 0.000 claims description 19
• 235000020824 obesity Nutrition 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000000304 alkynyl group Chemical group 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
• 150000002148 esters Chemical class 0.000 claims description 15
• 229940086609 Lipase inhibitor Drugs 0.000 claims description 14
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
• 239000003054 catalyst Substances 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 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 14
• 229960001243 orlistat Drugs 0.000 claims description 14
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 208000030814 Eating disease Diseases 0.000 claims description 10
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 10
• 206010003246 arthritis Diseases 0.000 claims description 10
• 206010012601 diabetes mellitus Diseases 0.000 claims description 10
• 235000014632 disordered eating Nutrition 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 125000004104 aryloxy group Chemical group 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 125000001769 aryl amino group Chemical group 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 7
• 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 101710151321 Melanostatin Proteins 0.000 claims description 6
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
• 238000006664 bond formation reaction Methods 0.000 claims description 6
• 238000009833 condensation Methods 0.000 claims description 6
• 230000005494 condensation Effects 0.000 claims description 6
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
• 125000003725 azepanyl group Chemical group 0.000 claims description 5
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 5
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
• 229910052751 metal Inorganic materials 0.000 claims description 5
• 239000002184 metal Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 229920006395 saturated elastomer Polymers 0.000 claims description 5
• HFVCWXRIRISOEA-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HFVCWXRIRISOEA-UHFFFAOYSA-N 0.000 claims description 4
• NHZYJKKSOGTTMR-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NHZYJKKSOGTTMR-UHFFFAOYSA-N 0.000 claims description 4
• JAGFRBPZTHOFHK-IBGZPJMESA-N 4-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO JAGFRBPZTHOFHK-IBGZPJMESA-N 0.000 claims description 4
• OVIOWFMKGQXDFO-GOSISDBHSA-N 4-[[4-[(3r)-3-hydroxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CC[C@@H](O)C1 OVIOWFMKGQXDFO-GOSISDBHSA-N 0.000 claims description 4
• SZCZIXJRKAXDPV-SFHVURJKSA-N 4-[[6-fluoro-4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO SZCZIXJRKAXDPV-SFHVURJKSA-N 0.000 claims description 4
• AJOLWRGXBPZAIK-INIZCTEOSA-N [(2s)-1-[7-[(2-chloropyridin-3-yl)methoxy]-2-methylquinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCC[C@H]1CO AJOLWRGXBPZAIK-INIZCTEOSA-N 0.000 claims description 4
• HOVZPQYOIGUXKT-INIZCTEOSA-N [(2s)-1-[7-[(2-fluoropyridin-3-yl)methoxy]-2-methylquinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)F)=CC2=NC(C)=CC=1N1CCC[C@H]1CO HOVZPQYOIGUXKT-INIZCTEOSA-N 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 229910052763 palladium Inorganic materials 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 4
• ABWAKVYQYSRJEF-SFHVURJKSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-7-[(2-fluoropyridin-3-yl)methoxy]-2-methylquinoline Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)F)=CC=C12 ABWAKVYQYSRJEF-SFHVURJKSA-N 0.000 claims description 3
• NXANOKNNJGBJJU-UHFFFAOYSA-N 4-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NXANOKNNJGBJJU-UHFFFAOYSA-N 0.000 claims description 3
• DNCNFUQWEFNIKJ-NRFANRHFSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 DNCNFUQWEFNIKJ-NRFANRHFSA-N 0.000 claims description 3
• OVIOWFMKGQXDFO-SFHVURJKSA-N 4-[[4-[(3s)-3-hydroxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 OVIOWFMKGQXDFO-SFHVURJKSA-N 0.000 claims description 3
• QJPGZZBMFWSTCX-FQEVSTJZSA-N 4-[[4-[(3s)-3-methoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 QJPGZZBMFWSTCX-FQEVSTJZSA-N 0.000 claims description 3
• XHQZQRBRMJGODJ-UHFFFAOYSA-N 6-fluoro-7-[(2-fluoropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C(=NC=CC=3)F)=CC2=NC(C)=CC=1N1CCCC1 XHQZQRBRMJGODJ-UHFFFAOYSA-N 0.000 claims description 3
• KMROVFJWJQHRLB-KRWDZBQOSA-N 7-[(2-chloropyridin-3-yl)methoxy]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)Cl)=CC=C12 KMROVFJWJQHRLB-KRWDZBQOSA-N 0.000 claims description 3
• NHXYFTFKSJDZSH-SFHVURJKSA-N 7-[(2-chloropyridin-3-yl)methoxy]-4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinoline Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)Cl)=CC=C12 NHXYFTFKSJDZSH-SFHVURJKSA-N 0.000 claims description 3
• TYTFNCKBHQNAFN-UHFFFAOYSA-N 7-[(2-chloropyridin-3-yl)methoxy]-6-fluoro-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCCC1 TYTFNCKBHQNAFN-UHFFFAOYSA-N 0.000 claims description 3
• DHELLFMTWRQAKJ-KRWDZBQOSA-N 7-[(2-fluoropyridin-3-yl)methoxy]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)F)=CC=C12 DHELLFMTWRQAKJ-KRWDZBQOSA-N 0.000 claims description 3
• AGTMGARQEGRFBT-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 AGTMGARQEGRFBT-UHFFFAOYSA-N 0.000 claims description 3
• 229940127470 Lipase Inhibitors Drugs 0.000 claims description 3
• 239000013543 active substance Substances 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 150000004820 halides Chemical class 0.000 claims description 3
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
• SRCYQRXUBMEAPQ-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 SRCYQRXUBMEAPQ-UHFFFAOYSA-N 0.000 claims description 2
• DPMAQIWJJZJKLV-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-4-ylmethoxy)quinoline Chemical compound C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 DPMAQIWJJZJKLV-UHFFFAOYSA-N 0.000 claims description 2
• ZLJRLUWCTUDGGW-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 ZLJRLUWCTUDGGW-UHFFFAOYSA-N 0.000 claims description 2
• PBVJXDHCRUNAMA-UHFFFAOYSA-N 7-[(2-chloropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCCC1 PBVJXDHCRUNAMA-UHFFFAOYSA-N 0.000 claims description 2
• NFLYDVKEEWHEKP-UHFFFAOYSA-N 7-[(3-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NFLYDVKEEWHEKP-UHFFFAOYSA-N 0.000 claims description 2
• NUXDJOBRDWPOTK-UHFFFAOYSA-N 7-[(4-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NUXDJOBRDWPOTK-UHFFFAOYSA-N 0.000 claims description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
• 150000002440 hydroxy compounds Chemical class 0.000 claims 1
• 239000007787 solid Substances 0.000 description 174
• 238000001819 mass spectrum Methods 0.000 description 165
• 239000000047 product Substances 0.000 description 126
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
• 239000000243 solution Substances 0.000 description 46
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 36
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
• 239000002904 solvent Substances 0.000 description 25
• VVVUSVRZYKHWCX-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1OCC1=CC=C(C#N)C=C1 VVVUSVRZYKHWCX-UHFFFAOYSA-N 0.000 description 24
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 23
• 239000012458 free base Substances 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• 238000003756 stirring Methods 0.000 description 20
• 239000010410 layer Substances 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 18
• 239000000203 mixture Substances 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• OVZLPAGKKXUGNE-UHFFFAOYSA-N 6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=C(F)C(O)=CC2=NC(C)=CC=1N1CCCC1 OVZLPAGKKXUGNE-UHFFFAOYSA-N 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 10
• PVSTUKYIRRQGCP-UHFFFAOYSA-N 4-chloro-2-methyl-7-phenylmethoxyquinoline Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1OCC1=CC=CC=C1 PVSTUKYIRRQGCP-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 239000003610 charcoal Substances 0.000 description 10
• 235000019439 ethyl acetate Nutrition 0.000 description 10
• 238000004128 high performance liquid chromatography Methods 0.000 description 10
• SGSCTTZQIYSSSD-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCCCC1 SGSCTTZQIYSSSD-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 125000001072 heteroaryl group Chemical group 0.000 description 9
• 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 8
• 208000024172 Cardiovascular disease Diseases 0.000 description 8
• 208000001647 Renal Insufficiency Diseases 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 239000012300 argon atmosphere Substances 0.000 description 8
• 239000003480 eluent Substances 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• 201000006370 kidney failure Diseases 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• DOGYZJVTBGICNB-KRWDZBQOSA-N (3s)-1-(2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-3-ol Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 DOGYZJVTBGICNB-KRWDZBQOSA-N 0.000 description 7
• QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 7
• PSNCUSAUUATFDT-NSHDSACASA-N 4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCC[C@H]1CO PSNCUSAUUATFDT-NSHDSACASA-N 0.000 description 7
• GIBRMZKZDBMCTB-ZOWNYOTGSA-N 4-[(3S)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 GIBRMZKZDBMCTB-ZOWNYOTGSA-N 0.000 description 7
• CILNSTLMXGWWKH-UHFFFAOYSA-N 6-butyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C1=CN=C2C=C(O)C(CCCC)=CC2=C1N1CCCC1 CILNSTLMXGWWKH-UHFFFAOYSA-N 0.000 description 7
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
• 125000003282 alkyl amino group Chemical group 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 238000007429 general method Methods 0.000 description 7
• 239000005457 ice water Substances 0.000 description 7
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 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 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 239000002671 adjuvant Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
• KBZHAYBXUFJHNE-LBPRGKRZSA-N 4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(O)=CC=C12 KBZHAYBXUFJHNE-LBPRGKRZSA-N 0.000 description 5
• 102400000064 Neuropeptide Y Human genes 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000007903 gelatin capsule Substances 0.000 description 5
• 238000005984 hydrogenation reaction Methods 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 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 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 229920005862 polyol Polymers 0.000 description 5
• 150000003077 polyols Chemical class 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• OMSBSIXAZZRIRW-UHFFFAOYSA-N 2-methylpyridine;hydrochloride Chemical compound Cl.CC1=CC=CC=N1 OMSBSIXAZZRIRW-UHFFFAOYSA-N 0.000 description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
• HHEOOKPSFHYFOD-JTQLQIEISA-N 6-fluoro-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C=12C=C(F)C(O)=CC2=NC(C)=CC=1N1CCC[C@H]1CO HHEOOKPSFHYFOD-JTQLQIEISA-N 0.000 description 4
• 229920002261 Corn starch Polymers 0.000 description 4
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-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
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• 101100460785 Mus musculus Npy5r gene Proteins 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-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
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 239000008120 corn starch Substances 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 239000008298 dragée Substances 0.000 description 4
• 239000003925 fat Substances 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 239000000825 pharmaceutical preparation Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
• 229910000080 stannane Inorganic materials 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 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
• 239000001993 wax Substances 0.000 description 4
• DOGYZJVTBGICNB-QGZVFWFLSA-N (3r)-1-(2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-3-ol Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CC[C@@H](O)C1 DOGYZJVTBGICNB-QGZVFWFLSA-N 0.000 description 3
• 0 *c(c(OP)c1)ccc1N Chemical compound *c(c(OP)c1)ccc1N 0.000 description 3
• VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 3
• KGKBYUMMVCIGKX-UHFFFAOYSA-N 2-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxyethanol Chemical compound C=12C=CC(OCCO)=CC2=NC(C)=CC=1N1CCCC1 KGKBYUMMVCIGKX-UHFFFAOYSA-N 0.000 description 3
• LAQYREVCCIYNFW-UHFFFAOYSA-N 2-methyl-7-phenylmethoxy-1h-quinolin-4-one Chemical compound C=1C2=NC(C)=CC(O)=C2C=CC=1OCC1=CC=CC=C1 LAQYREVCCIYNFW-UHFFFAOYSA-N 0.000 description 3
• XNABVCNTZBHDAW-UHFFFAOYSA-N 2-methyl-7-phenylmethoxy-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 XNABVCNTZBHDAW-UHFFFAOYSA-N 0.000 description 3
• CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 3
• NREPAKQQAKWSBU-IBGZPJMESA-N 4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 NREPAKQQAKWSBU-IBGZPJMESA-N 0.000 description 3
• JUQPUEXSALIBJW-AWEZNQCLSA-N 4-[(3S)-3-(2-methoxyethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C1[C@@H](OCCOC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 JUQPUEXSALIBJW-AWEZNQCLSA-N 0.000 description 3
• QYQCYZAXJUSEJT-HNNXBMFYSA-N 4-[(3S)-3-(3-methoxypropoxy)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C1[C@@H](OCCCOC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 QYQCYZAXJUSEJT-HNNXBMFYSA-N 0.000 description 3
• GCBNADYDPAFXII-HNNXBMFYSA-N 4-[(3S)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(O)C=CC2=1)C)CC1CC1 GCBNADYDPAFXII-HNNXBMFYSA-N 0.000 description 3
• KJYDTXYTHVCRLY-LBPRGKRZSA-N 4-[(3S)-3-methoxypyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 KJYDTXYTHVCRLY-LBPRGKRZSA-N 0.000 description 3
• CBYSWKDGALCATF-NRFANRHFSA-N 4-[(3s)-3-(2-methoxyethoxy)pyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound C1[C@@H](OCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 CBYSWKDGALCATF-NRFANRHFSA-N 0.000 description 3
• PVNADSHSDFLKHQ-QFIPXVFZSA-N 4-[(3s)-3-(3-methoxypropoxy)pyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound C1[C@@H](OCCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 PVNADSHSDFLKHQ-QFIPXVFZSA-N 0.000 description 3
• KKLYYULYKZVYPL-QFIPXVFZSA-N 4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(OCC=3C=CC=CC=3)C=CC2=1)C)CC1CC1 KKLYYULYKZVYPL-QFIPXVFZSA-N 0.000 description 3
• ARHAUJBDNJGAPQ-IBGZPJMESA-N 4-[(3s)-3-methoxypyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 ARHAUJBDNJGAPQ-IBGZPJMESA-N 0.000 description 3
• JAGFRBPZTHOFHK-LJQANCHMSA-N 4-[[4-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@@H]1CO JAGFRBPZTHOFHK-LJQANCHMSA-N 0.000 description 3
• JUTKQVVEJIIULV-UHFFFAOYSA-N 6-bromo-4-chloro-7-methoxy-2-methylquinoline Chemical compound CC1=CC(Cl)=C2C=C(Br)C(OC)=CC2=N1 JUTKQVVEJIIULV-UHFFFAOYSA-N 0.000 description 3
• JMSAPWMSBCDURL-UHFFFAOYSA-N 6-butyl-4-chloro-7-phenylmethoxyquinoline;hydrochloride Chemical compound Cl.CCCCC1=CC2=C(Cl)C=CN=C2C=C1OCC1=CC=CC=C1 JMSAPWMSBCDURL-UHFFFAOYSA-N 0.000 description 3
• WFBCKOGMOVLURH-UHFFFAOYSA-N 6-butyl-7-phenylmethoxy-4-pyrrolidin-1-ylquinoline Chemical compound CCCCC1=CC2=C(N3CCCC3)C=CN=C2C=C1OCC1=CC=CC=C1 WFBCKOGMOVLURH-UHFFFAOYSA-N 0.000 description 3
• OXOQUVHYQRFEGV-UHFFFAOYSA-N 6-fluoro-2-methyl-7-phenylmethoxy-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 OXOQUVHYQRFEGV-UHFFFAOYSA-N 0.000 description 3
• 208000032841 Bulimia Diseases 0.000 description 3
• 206010006550 Bulimia nervosa Diseases 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
• 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 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
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
• 108090000189 Neuropeptides Proteins 0.000 description 3
• 102000003797 Neuropeptides Human genes 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• SGJOBMSHODRWLJ-SFHVURJKSA-N [(2s)-1-(2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCC[C@H]1CO SGJOBMSHODRWLJ-SFHVURJKSA-N 0.000 description 3
• SCVUAYSRWBVKJK-KRWDZBQOSA-N [(2s)-1-(6-fluoro-2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-2-yl]methanol Chemical compound C=12C=C(F)C(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCC[C@H]1CO SCVUAYSRWBVKJK-KRWDZBQOSA-N 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound 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 3
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000002299 complementary DNA Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• JQNNQJXVFCCBSL-UHFFFAOYSA-N ethyl 2-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxyacetate Chemical compound C=1C(C)=NC2=CC(OCC(=O)OCC)=CC=C2C=1N1CCCC1 JQNNQJXVFCCBSL-UHFFFAOYSA-N 0.000 description 3
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 125000001188 haloalkyl group Chemical group 0.000 description 3
• 239000008101 lactose 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
• 239000007788 liquid Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 238000002844 melting Methods 0.000 description 3
• 230000008018 melting Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
• 229920000642 polymer Polymers 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 description 3
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000011593 sulfur Chemical group 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• 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 2
• LLNKHPAEPMGSIY-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl) n,n-dimethylsulfamate Chemical compound C=1C(C)=NC2=CC(OS(=O)(=O)N(C)C)=CC=C2C=1N1CCCC1 LLNKHPAEPMGSIY-UHFFFAOYSA-N 0.000 description 2
• JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 2
• KEBOYHJEUFJZPE-LURJTMIESA-N (3s)-3-ethoxypyrrolidine Chemical compound CCO[C@H]1CCNC1 KEBOYHJEUFJZPE-LURJTMIESA-N 0.000 description 2
• CHPRFKYDQRKRRK-LURJTMIESA-N (S)-2-(methoxymethyl)pyrrolidine Chemical compound COC[C@@H]1CCCN1 CHPRFKYDQRKRRK-LURJTMIESA-N 0.000 description 2
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
• DDGRAFHHXYIQQR-UHFFFAOYSA-N 1-chloro-3-(chloromethyl)benzene Chemical compound ClCC1=CC=CC(Cl)=C1 DDGRAFHHXYIQQR-UHFFFAOYSA-N 0.000 description 2
• JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 2
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
• JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• GNNSGZZRRLGZNC-UHFFFAOYSA-N 2-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 GNNSGZZRRLGZNC-UHFFFAOYSA-N 0.000 description 2
• GQYNPZQREXFPHJ-IBGZPJMESA-N 2-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO GQYNPZQREXFPHJ-IBGZPJMESA-N 0.000 description 2
• VLAWRLXBRWVOHA-UHFFFAOYSA-N 2-methyl-7-(oxolan-3-yloxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OC3COCC3)=CC2=NC(C)=CC=1N1CCCC1 VLAWRLXBRWVOHA-UHFFFAOYSA-N 0.000 description 2
• UDXYZQHPSKBSOU-UHFFFAOYSA-N 2-methyl-7-(pyridin-2-ylmethoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3N=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 UDXYZQHPSKBSOU-UHFFFAOYSA-N 0.000 description 2
• XSRMUWXBTOQFMX-UHFFFAOYSA-N 2-methyl-7-(pyridin-3-ylmethoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=NC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 XSRMUWXBTOQFMX-UHFFFAOYSA-N 0.000 description 2
• NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 2
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
• CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• HPVQPASUKDEBHL-UHFFFAOYSA-N 4-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxybenzonitrile Chemical compound C=12C=CC(OC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HPVQPASUKDEBHL-UHFFFAOYSA-N 0.000 description 2
• UKCDQQHDCNGFHV-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-phenylmethoxyquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 UKCDQQHDCNGFHV-UHFFFAOYSA-N 0.000 description 2
• ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 2
• PHEKYYJZRXRWLO-UHFFFAOYSA-N 4-[(2-methyl-4-oxo-1h-quinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=1C2=NC(C)=CC(O)=C2C=CC=1OCC1=CC=C(C#N)C=C1 PHEKYYJZRXRWLO-UHFFFAOYSA-N 0.000 description 2
• LWRSPWIXSPLJMV-BDQAORGHSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 LWRSPWIXSPLJMV-BDQAORGHSA-N 0.000 description 2
• XFBKURUTJJKCKP-UHFFFAOYSA-N 4-[(6-butyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound CCCCC1=CC2=C(N3CCCC3)C=CN=C2C=C1OCC1=CC=C(C#N)C=C1 XFBKURUTJJKCKP-UHFFFAOYSA-N 0.000 description 2
• SVSNAAOBHMAMHA-UHFFFAOYSA-N 4-[2-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxyethyl]morpholine Chemical compound C=12C=CC(OCCN3CCOCC3)=CC2=NC(C)=CC=1N1CCCC1 SVSNAAOBHMAMHA-UHFFFAOYSA-N 0.000 description 2
• RVMWSFCYLTYURS-LJQANCHMSA-N 4-[[2-methyl-4-[(3r)-3-(methylamino)pyrrolidin-1-yl]quinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@H](NC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 RVMWSFCYLTYURS-LJQANCHMSA-N 0.000 description 2
• RVMWSFCYLTYURS-IBGZPJMESA-N 4-[[2-methyl-4-[(3s)-3-(methylamino)pyrrolidin-1-yl]quinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](NC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 RVMWSFCYLTYURS-IBGZPJMESA-N 0.000 description 2
• UIDMPHGKHHCVIB-HXUWFJFHSA-N 4-[[4-[(2r)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound COC[C@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 UIDMPHGKHHCVIB-HXUWFJFHSA-N 0.000 description 2
• UIDMPHGKHHCVIB-FQEVSTJZSA-N 4-[[4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 UIDMPHGKHHCVIB-FQEVSTJZSA-N 0.000 description 2
• IDDKJADQZPZLMR-HXUWFJFHSA-N 4-[[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@H](N(C)C)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 IDDKJADQZPZLMR-HXUWFJFHSA-N 0.000 description 2
• MJSVCBVXUQHWLZ-NRFANRHFSA-N 4-[[4-[(3s)-3-(2-hydroxyethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CC[C@H](OCCO)C1 MJSVCBVXUQHWLZ-NRFANRHFSA-N 0.000 description 2
• IDDKJADQZPZLMR-FQEVSTJZSA-N 4-[[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](N(C)C)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 IDDKJADQZPZLMR-FQEVSTJZSA-N 0.000 description 2
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
• VCXWKIQMINUCPK-UHFFFAOYSA-N 4-chloro-6-fluoro-2-methyl-7-phenylmethoxyquinoline Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=C(F)C=1OCC1=CC=CC=C1 VCXWKIQMINUCPK-UHFFFAOYSA-N 0.000 description 2
• LNYZXZVWQOHRPE-UHFFFAOYSA-N 4-chloro-7-methoxyquinolin-2-amine Chemical compound ClC1=CC(N)=NC2=CC(OC)=CC=C21 LNYZXZVWQOHRPE-UHFFFAOYSA-N 0.000 description 2
• QTOBKEAXSOGASJ-UHFFFAOYSA-N 4-fluoro-3-phenylmethoxyaniline Chemical compound NC1=CC=C(F)C(OCC=2C=CC=CC=2)=C1 QTOBKEAXSOGASJ-UHFFFAOYSA-N 0.000 description 2
• HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• FHMVOYGAZCZVOX-UHFFFAOYSA-N 5-(chloromethyl)pyridine-2-carbonitrile Chemical compound ClCC1=CC=C(C#N)N=C1 FHMVOYGAZCZVOX-UHFFFAOYSA-N 0.000 description 2
• HHHACGGZAGVVOZ-FQEVSTJZSA-N 5-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]pyridine-2-carbonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=NC(=CC=3)C#N)=CC=C12 HHHACGGZAGVVOZ-FQEVSTJZSA-N 0.000 description 2
• IUZDXTKOCBBWIT-KRWDZBQOSA-N 5-[[6-fluoro-4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]pyridine-2-carbonitrile Chemical compound C=12C=C(F)C(OCC=3C=NC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO IUZDXTKOCBBWIT-KRWDZBQOSA-N 0.000 description 2
• XQYICHLOAMMXKE-UHFFFAOYSA-N 5-amino-2-fluorophenol Chemical compound NC1=CC=C(F)C(O)=C1 XQYICHLOAMMXKE-UHFFFAOYSA-N 0.000 description 2
• TYDLFGQMWDLLTK-UHFFFAOYSA-N 6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-ol hydrochloride Chemical compound Cl.C=12C=C(Br)C(O)=CC2=NC(C)=CC=1N1CCCC1 TYDLFGQMWDLLTK-UHFFFAOYSA-N 0.000 description 2
• AYNMXUJMSXVSBU-UHFFFAOYSA-N 6-bromo-7-methoxy-2-methyl-1h-quinolin-4-one Chemical compound CC1=CC(O)=C2C=C(Br)C(OC)=CC2=N1 AYNMXUJMSXVSBU-UHFFFAOYSA-N 0.000 description 2
• MZMBNRDSVQTTQA-UHFFFAOYSA-N 6-butyl-7-phenylmethoxy-1h-quinolin-4-one Chemical compound CCCCC1=CC(C(C=CN2)=O)=C2C=C1OCC1=CC=CC=C1 MZMBNRDSVQTTQA-UHFFFAOYSA-N 0.000 description 2
• JJTUVMXXIZYZHL-UHFFFAOYSA-N 7-[(3,4-dimethoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C1=C(OC)C(OC)=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 JJTUVMXXIZYZHL-UHFFFAOYSA-N 0.000 description 2
• IGDRLYGAPUHJKU-UHFFFAOYSA-N 7-[(6-chloropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=NC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 IGDRLYGAPUHJKU-UHFFFAOYSA-N 0.000 description 2
• XYRMFPNSUMIFFF-UHFFFAOYSA-N 7-[[2-chloro-6-(trifluoromethyl)pyridin-3-yl]methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C(=NC(=CC=3)C(F)(F)F)Cl)=CC2=NC(C)=CC=1N1CCCC1 XYRMFPNSUMIFFF-UHFFFAOYSA-N 0.000 description 2
• PNOUWQOKJBWQCM-UHFFFAOYSA-N 7-ethoxy-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=1C(C)=NC2=CC(OCC)=CC=C2C=1N1CCCC1 PNOUWQOKJBWQCM-UHFFFAOYSA-N 0.000 description 2
• ADTPOIRZJFLNBY-UHFFFAOYSA-N 7-hydroxy-2-methyl-1h-quinolin-4-one Chemical compound C1=CC(O)=CC2=NC(C)=CC(O)=C21 ADTPOIRZJFLNBY-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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
• 239000001828 Gelatine Substances 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
• 102000028582 Neuropeptide Y5 receptor Human genes 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• 235000021355 Stearic acid Nutrition 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
• 229930006000 Sucrose Natural products 0.000 description 2
• 238000006069 Suzuki reaction reaction Methods 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
• 239000007983 Tris buffer Substances 0.000 description 2
• IACRSOKSJFPALK-KRWDZBQOSA-N [(2s)-1-[2-methyl-7-(pyridin-3-ylmethoxy)quinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C=NC=CC=3)=CC2=NC(C)=CC=1N1CCC[C@H]1CO IACRSOKSJFPALK-KRWDZBQOSA-N 0.000 description 2
• HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 150000001336 alkenes Chemical class 0.000 description 2
• 150000001345 alkine derivatives Chemical class 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 150000001448 anilines Chemical class 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 235000021407 appetite control Nutrition 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000027455 binding Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• QSXPTGKTXDBRIM-CLFYSBASSA-N ethyl (z)-3-(4-bromo-3-methoxyanilino)but-2-enoate Chemical compound CCOC(=O)\C=C(\C)NC1=CC=C(Br)C(OC)=C1 QSXPTGKTXDBRIM-CLFYSBASSA-N 0.000 description 2
• AQANIYMFBJFZKI-UHFFFAOYSA-N ethyl 3-(3-phenylmethoxyanilino)but-2-enoate Chemical compound CCOC(=O)C=C(C)NC1=CC=CC(OCC=2C=CC=CC=2)=C1 AQANIYMFBJFZKI-UHFFFAOYSA-N 0.000 description 2
• BNAVORYLMFPECT-UHFFFAOYSA-N ethyl 3-(4-fluoro-3-phenylmethoxyanilino)but-2-enoate Chemical compound CCOC(=O)C=C(C)NC1=CC=C(F)C(OCC=2C=CC=CC=2)=C1 BNAVORYLMFPECT-UHFFFAOYSA-N 0.000 description 2
• 230000001605 fetal effect Effects 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 235000003599 food sweetener Nutrition 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
• 238000010438 heat treatment Methods 0.000 description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
• 208000006278 hypochromic anemia Diseases 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• FAFKICGQLGAWII-QFIPXVFZSA-N methyl (2s)-1-[7-[(4-cyanophenyl)methoxy]-2-methylquinolin-4-yl]pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 FAFKICGQLGAWII-QFIPXVFZSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 229910017604 nitric acid Inorganic materials 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 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
• 150000007530 organic bases Chemical class 0.000 description 2
• 230000003204 osmotic effect Effects 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
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000005720 sucrose Substances 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
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 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 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 230000004584 weight gain Effects 0.000 description 2
• 235000019786 weight gain Nutrition 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• KJZLJGZZDNGGCA-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanol Chemical compound CN1CCC(CO)CC1 KJZLJGZZDNGGCA-UHFFFAOYSA-N 0.000 description 1
• JUPQABFQNIZLHE-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl) methanesulfonate Chemical compound C=12C=CC(OS(C)(=O)=O)=CC2=NC(C)=CC=1N1CCCC1 JUPQABFQNIZLHE-UHFFFAOYSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• CHPRFKYDQRKRRK-ZCFIWIBFSA-N (2r)-2-(methoxymethyl)pyrrolidine Chemical compound COC[C@H]1CCCN1 CHPRFKYDQRKRRK-ZCFIWIBFSA-N 0.000 description 1
• AVAWMINJNRAQFS-ZCFIWIBFSA-N (3r)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@@H]1CCNC1 AVAWMINJNRAQFS-ZCFIWIBFSA-N 0.000 description 1
• NGZYRKGJWYJGRS-RXMQYKEDSA-N (3r)-n-methylpyrrolidin-3-amine Chemical compound CN[C@@H]1CCNC1 NGZYRKGJWYJGRS-RXMQYKEDSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• AVAWMINJNRAQFS-LURJTMIESA-N (3s)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@H]1CCNC1 AVAWMINJNRAQFS-LURJTMIESA-N 0.000 description 1
• NGZYRKGJWYJGRS-YFKPBYRVSA-N (3s)-n-methylpyrrolidin-3-amine Chemical compound CN[C@H]1CCNC1 NGZYRKGJWYJGRS-YFKPBYRVSA-N 0.000 description 1
• JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 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 1
• GIPWMDPSGWDUGH-UHFFFAOYSA-N 1-(4-chloro-7-methoxyquinolin-2-yl)-3-phenylurea Chemical compound N=1C2=CC(OC)=CC=C2C(Cl)=CC=1NC(=O)NC1=CC=CC=C1 GIPWMDPSGWDUGH-UHFFFAOYSA-N 0.000 description 1
• BBXDMCQDLOCXRA-UHFFFAOYSA-N 1-(chloromethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CCl BBXDMCQDLOCXRA-UHFFFAOYSA-N 0.000 description 1
• UAWVMPOAIVZWFQ-UHFFFAOYSA-N 1-(chloromethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CCl UAWVMPOAIVZWFQ-UHFFFAOYSA-N 0.000 description 1
• CCAWDIFJOBKBSE-UHFFFAOYSA-N 1-(chloromethyl)-3,5-dimethoxybenzene Chemical compound COC1=CC(CCl)=CC(OC)=C1 CCAWDIFJOBKBSE-UHFFFAOYSA-N 0.000 description 1
• XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 1
• MCHDHQVROPEJJT-UHFFFAOYSA-N 1-(chloromethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CCl)C=C1 MCHDHQVROPEJJT-UHFFFAOYSA-N 0.000 description 1
• MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 1
• CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 1
• BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• QNBJYUUUYZVIJP-UHFFFAOYSA-N 2,4-dichloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC(Cl)=C21 QNBJYUUUYZVIJP-UHFFFAOYSA-N 0.000 description 1
• JSOHEMPXGOUNET-UHFFFAOYSA-N 2-(3-chloropropyl)pyridine Chemical compound ClCCCC1=CC=CC=N1 JSOHEMPXGOUNET-UHFFFAOYSA-N 0.000 description 1
• VOHILFSOWRNVJJ-UHFFFAOYSA-N 2-(bromomethyl)oxolane Chemical compound BrCC1CCCO1 VOHILFSOWRNVJJ-UHFFFAOYSA-N 0.000 description 1
• PFQYGHGKTNHYRQ-UHFFFAOYSA-N 2-(chloromethyl)-6-methylpyridine Chemical compound CC1=CC=CC(CCl)=N1 PFQYGHGKTNHYRQ-UHFFFAOYSA-N 0.000 description 1
• NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-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
• VWIYMZOBEBCEMW-UHFFFAOYSA-N 2-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile hydrochloride Chemical compound CC1=CC(=C2C=CC(=CC2=N1)COC3=CC=CC=C3C#N)N4CCCCCC4.Cl VWIYMZOBEBCEMW-UHFFFAOYSA-N 0.000 description 1
• JOSSSUIHWOPXBO-NRFANRHFSA-N 2-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=CC=CC=3)C#N)=CC=C12 JOSSSUIHWOPXBO-NRFANRHFSA-N 0.000 description 1
• FTKUUSXSOXTJFD-BOXHHOBZSA-N 2-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=CC=CC=3)C#N)=CC=C12 FTKUUSXSOXTJFD-BOXHHOBZSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• RAUCGVCCODJPPW-UHFFFAOYSA-N 2-chloro-3-(chloromethyl)-6-methylpyridine Chemical compound CC1=CC=C(CCl)C(Cl)=N1 RAUCGVCCODJPPW-UHFFFAOYSA-N 0.000 description 1
• QWIIJVGEBIQHSW-UHFFFAOYSA-N 2-chloro-3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1Cl QWIIJVGEBIQHSW-UHFFFAOYSA-N 0.000 description 1
• BAGKULABRRMPMK-UHFFFAOYSA-N 2-chloro-3-(chloromethyl)pyridine;hydrochloride Chemical compound Cl.ClCC1=CC=CN=C1Cl BAGKULABRRMPMK-UHFFFAOYSA-N 0.000 description 1
• SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 description 1
• MQTKXCOGYOYAMW-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)thiophene Chemical compound ClCC1=CC=C(Cl)S1 MQTKXCOGYOYAMW-UHFFFAOYSA-N 0.000 description 1
• OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical class C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
• BPNMARONMYYRAB-PBVYKCSPSA-N 2-methyl-4-[(3S)-3-[2-(oxan-2-yloxy)ethoxy]pyrrolidin-1-yl]quinolin-7-ol Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(O)C=CC2=1)C)CCOC1CCCCO1 BPNMARONMYYRAB-PBVYKCSPSA-N 0.000 description 1
• OYIZBZHNRUNJKY-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-(thiophen-3-ylmethoxy)quinoline Chemical compound C=12C=CC(OCC3=CSC=C3)=CC2=NC(C)=CC=1N1CCCC1 OYIZBZHNRUNJKY-UHFFFAOYSA-N 0.000 description 1
• JWPPSRMXFPBZPF-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-(thiophen-3-ylmethoxy)quinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC3=CSC=C3)=CC2=NC(C)=CC=1N1CCCC1 JWPPSRMXFPBZPF-UHFFFAOYSA-N 0.000 description 1
• BKKAVMPVRGYDSB-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[(6-pyrrolidin-1-ylpyridin-3-yl)methoxy]quinoline Chemical compound C=12C=CC(OCC=3C=NC(=CC=3)N3CCCC3)=CC2=NC(C)=CC=1N1CCCC1 BKKAVMPVRGYDSB-UHFFFAOYSA-N 0.000 description 1
• MCTIGJOTDFLALJ-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[2-(trifluoromethyl)phenyl]methoxy]quinoline Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 MCTIGJOTDFLALJ-UHFFFAOYSA-N 0.000 description 1
• BWYBSQOTKSEORL-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[3-(trifluoromethyl)phenyl]methoxy]quinoline Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 BWYBSQOTKSEORL-UHFFFAOYSA-N 0.000 description 1
• KBQVWLSVDGKWGD-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[4-(trifluoromethyl)phenyl]methoxy]quinoline Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 KBQVWLSVDGKWGD-UHFFFAOYSA-N 0.000 description 1
• WMLSNUMDKVCKHV-UHFFFAOYSA-N 2-methyl-7-(2-methylpropyl)-4-pyrrolidin-1-ylquinoline Chemical compound CC1=CC(=C2C=CC(=CC2=N1)CC(C)C)N3CCCC3 WMLSNUMDKVCKHV-UHFFFAOYSA-N 0.000 description 1
• BRPQWOQWAACAMK-UHFFFAOYSA-N 2-methyl-7-(3-pyridin-2-ylpropoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCCCC=3N=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 BRPQWOQWAACAMK-UHFFFAOYSA-N 0.000 description 1
• IDPAQJLOLYZOTG-UHFFFAOYSA-N 2-methyl-7-(oxolan-2-ylmethoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC3OCCC3)=CC2=NC(C)=CC=1N1CCCC1 IDPAQJLOLYZOTG-UHFFFAOYSA-N 0.000 description 1
• XHCVPQALAKCWNA-UHFFFAOYSA-N 2-methyl-7-(pyridin-4-ylmethoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCC1 XHCVPQALAKCWNA-UHFFFAOYSA-N 0.000 description 1
• ASUBKHJHCYYBSU-UHFFFAOYSA-N 2-methyl-7-[(1-methylpiperidin-4-yl)methoxy]-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C1CN(C)CCC1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 ASUBKHJHCYYBSU-UHFFFAOYSA-N 0.000 description 1
• LMBIJXFFBMNBNC-UHFFFAOYSA-N 2-methyl-7-[(2-methylpyridin-3-yl)methoxy]-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)C)=CC2=NC(C)=CC=1N1CCCC1 LMBIJXFFBMNBNC-UHFFFAOYSA-N 0.000 description 1
• SBCXTVACJOCLJH-UHFFFAOYSA-N 2-methyl-7-[(2-methylpyridin-3-yl)methoxy]-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C(=NC=CC=3)C)=CC2=NC(C)=CC=1N1CCCC1 SBCXTVACJOCLJH-UHFFFAOYSA-N 0.000 description 1
• DAEIAGGNKVFXFY-UHFFFAOYSA-N 2-methyl-7-[(6-methylpyridin-3-yl)methoxy]-4-pyrrolidin-1-ylquinoline Chemical compound C1=NC(C)=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 DAEIAGGNKVFXFY-UHFFFAOYSA-N 0.000 description 1
• GDRWSFWYLREJLB-UHFFFAOYSA-N 2-methyl-7-[(6-methylpyridin-3-yl)methoxy]-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C1=NC(C)=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 GDRWSFWYLREJLB-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• GEASZNBTMLEEGX-UHFFFAOYSA-N 3-(bromomethyl)-2-chloro-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(CBr)C(Cl)=N1 GEASZNBTMLEEGX-UHFFFAOYSA-N 0.000 description 1
• NDQQGQAFMKEMSD-UHFFFAOYSA-N 3-(bromomethyl)pyridin-1-ium;chloride Chemical compound Cl.BrCC1=CC=CN=C1 NDQQGQAFMKEMSD-UHFFFAOYSA-N 0.000 description 1
• HLNYUNAAFVNAMI-UHFFFAOYSA-N 3-(chloromethyl)-2-fluoropyridine Chemical compound FC1=NC=CC=C1CCl HLNYUNAAFVNAMI-UHFFFAOYSA-N 0.000 description 1
• LAUMZLJBVMYQLL-UHFFFAOYSA-N 3-(chloromethyl)-2-fluoropyridine;hydrochloride Chemical compound Cl.FC1=NC=CC=C1CCl LAUMZLJBVMYQLL-UHFFFAOYSA-N 0.000 description 1
• DYINCOADXUUIHA-UHFFFAOYSA-N 3-(chloromethyl)-2-methylpyridine Chemical compound CC1=NC=CC=C1CCl DYINCOADXUUIHA-UHFFFAOYSA-N 0.000 description 1
• IVKFTPSEDAPSSI-UHFFFAOYSA-N 3-(chloromethyl)-2-methylpyridine;hydrochloride Chemical compound Cl.CC1=NC=CC=C1CCl IVKFTPSEDAPSSI-UHFFFAOYSA-N 0.000 description 1
• WRXVOTDGLNPNND-UHFFFAOYSA-N 3-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=CC(C#N)=C1 WRXVOTDGLNPNND-UHFFFAOYSA-N 0.000 description 1
• UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
• KKWWFYAKOFXBEY-UHFFFAOYSA-N 3-(chloromethyl)thiophene Chemical compound ClCC=1C=CSC=1 KKWWFYAKOFXBEY-UHFFFAOYSA-N 0.000 description 1
• 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 1
• HWGPFDNEFUUCKN-UHFFFAOYSA-N 3-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HWGPFDNEFUUCKN-UHFFFAOYSA-N 0.000 description 1
• FMPGODFZPXPQMZ-UHFFFAOYSA-N 3-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 FMPGODFZPXPQMZ-UHFFFAOYSA-N 0.000 description 1
• MDFKMVCGZZBCCL-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile hydrochloride Chemical compound CC1=CC(=C2C=CC(=CC2=N1)COC3=CC=CC(=C3)C#N)N4CCCCCC4.Cl MDFKMVCGZZBCCL-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• XDPCNPCKDGQBAN-UHFFFAOYSA-N 3-hydroxytetrahydrofuran Chemical compound OC1CCOC1 XDPCNPCKDGQBAN-UHFFFAOYSA-N 0.000 description 1
• HWZUQAKHJDKBOE-UHFFFAOYSA-N 3-methoxypropyl 4-methylbenzenesulfonate Chemical compound COCCCOS(=O)(=O)C1=CC=C(C)C=C1 HWZUQAKHJDKBOE-UHFFFAOYSA-N 0.000 description 1
• WBXZCDIZXWDPBL-UHFFFAOYSA-N 3-methylpyridine-2-carbonitrile Chemical compound CC1=CC=CN=C1C#N WBXZCDIZXWDPBL-UHFFFAOYSA-N 0.000 description 1
• VZKSLWJLGAGPIU-UHFFFAOYSA-N 3-morpholin-4-ylpropan-1-ol Chemical compound OCCCN1CCOCC1 VZKSLWJLGAGPIU-UHFFFAOYSA-N 0.000 description 1
• IGPFOKFDBICQMC-UHFFFAOYSA-N 3-phenylmethoxyaniline Chemical compound NC1=CC=CC(OCC=2C=CC=CC=2)=C1 IGPFOKFDBICQMC-UHFFFAOYSA-N 0.000 description 1
• NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
• VJZKLTWJQIHBSP-UHFFFAOYSA-N 4-(2-methyl-7-phenylmethoxyquinolin-4-yl)morpholine Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCOCC1 VJZKLTWJQIHBSP-UHFFFAOYSA-N 0.000 description 1
• QPGPSFVOVKTUSK-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-2-ylmethoxy)quinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3N=CC=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 QPGPSFVOVKTUSK-UHFFFAOYSA-N 0.000 description 1
• MBSGQRLHUSOSSA-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-4-ylmethoxy)quinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 MBSGQRLHUSOSSA-UHFFFAOYSA-N 0.000 description 1
• WWHJLVMBXXXUFO-UHFFFAOYSA-N 4-(chloromethyl)-1,2-dimethoxybenzene Chemical compound COC1=CC=C(CCl)C=C1OC WWHJLVMBXXXUFO-UHFFFAOYSA-N 0.000 description 1
• CFRFWKYNMVPMKV-UHFFFAOYSA-N 4-[(2-methyl-4-morpholin-4-ylquinolin-7-yl)oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCOCC1 CFRFWKYNMVPMKV-UHFFFAOYSA-N 0.000 description 1
• XOINXGSOIJCZPY-UHFFFAOYSA-N 4-[(2-methyl-4-piperidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCC1 XOINXGSOIJCZPY-UHFFFAOYSA-N 0.000 description 1
• BSZYCCBUYXDANU-ZDUSSCGKSA-N 4-[(3S)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 BSZYCCBUYXDANU-ZDUSSCGKSA-N 0.000 description 1
• ARHAUJBDNJGAPQ-LJQANCHMSA-N 4-[(3r)-3-methoxypyrrolidin-1-yl]-2-methyl-7-phenylmethoxyquinoline Chemical compound C1[C@H](OC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC=CC=3)=CC=C12 ARHAUJBDNJGAPQ-LJQANCHMSA-N 0.000 description 1
• ABZTXQUYNILQIK-IBGZPJMESA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methyl-7-(pyridin-3-ylmethoxy)quinoline Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=NC=CC=3)=CC=C12 ABZTXQUYNILQIK-IBGZPJMESA-N 0.000 description 1
• AKLNGELRNJUNHP-FYZYNONXSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methyl-7-(pyridin-3-ylmethoxy)quinoline;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=NC=CC=3)=CC=C12 AKLNGELRNJUNHP-FYZYNONXSA-N 0.000 description 1
• JKTNEWBLWTWSLM-FERBBOLQSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-7-[(2-fluoropyridin-3-yl)methoxy]-2-methylquinoline;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)F)=CC=C12 JKTNEWBLWTWSLM-FERBBOLQSA-N 0.000 description 1
• QWHLDUQGSLASIV-NRFANRHFSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-7-[(3-methoxyphenyl)methoxy]-2-methylquinoline Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=C(OC)C=CC=3)=CC=C12 QWHLDUQGSLASIV-NRFANRHFSA-N 0.000 description 1
• FCUVDSOULYDWFJ-BOXHHOBZSA-N 4-[(3s)-3-ethoxypyrrolidin-1-yl]-7-[(3-methoxyphenyl)methoxy]-2-methylquinoline;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=C(OC)C=CC=3)=CC=C12 FCUVDSOULYDWFJ-BOXHHOBZSA-N 0.000 description 1
• NXYXRNQBYSNQPR-UHFFFAOYSA-N 4-[(6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(Br)C(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NXYXRNQBYSNQPR-UHFFFAOYSA-N 0.000 description 1
• LXKIWLHQXRDFPK-UHFFFAOYSA-N 4-[3-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxypropyl]morpholine;hydrochloride Chemical compound Cl.C=12C=CC(OCCCN3CCOCC3)=CC2=NC(C)=CC=1N1CCCC1 LXKIWLHQXRDFPK-UHFFFAOYSA-N 0.000 description 1
• MAZPPISNMYXNSY-UHFFFAOYSA-N 4-[5-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]pyridin-2-yl]morpholine Chemical compound C=12C=CC(OCC=3C=NC(=CC=3)N3CCOCC3)=CC2=NC(C)=CC=1N1CCCC1 MAZPPISNMYXNSY-UHFFFAOYSA-N 0.000 description 1
• YTKLLXIJNXJXGF-UHFFFAOYSA-N 4-[5-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]pyridin-2-yl]morpholine;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=NC(=CC=3)N3CCOCC3)=CC2=NC(C)=CC=1N1CCCC1 YTKLLXIJNXJXGF-UHFFFAOYSA-N 0.000 description 1
• ALWUHEODGYJMRG-QHCPKHFHSA-N 4-[[2-methyl-4-[(2s)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]quinolin-7-yl]oxymethyl]benzonitrile Chemical compound C([C@@H]1CCCN1C=1C=C(N=C2C=C(OCC=3C=CC(=CC=3)C#N)C=CC2=1)C)N1CCCC1 ALWUHEODGYJMRG-QHCPKHFHSA-N 0.000 description 1
• VFQCFLMFUDSLQC-BQAIUKQQSA-N 4-[[2-methyl-4-[(2s)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]quinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C([C@@H]1CCCN1C=1C=C(N=C2C=C(OCC=3C=CC(=CC=3)C#N)C=CC2=1)C)N1CCCC1 VFQCFLMFUDSLQC-BQAIUKQQSA-N 0.000 description 1
• QGTZVKWRBIPVMB-UHFFFAOYSA-N 4-[[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N(CC1)CCC21OCCO2 QGTZVKWRBIPVMB-UHFFFAOYSA-N 0.000 description 1
• KIQFHCQWIOWQPI-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile hydrochloride Chemical compound CC1=CC(=C2C=CC(=CC2=N1)COC3=CC=C(C=C3)C#N)N4CCCCCC4.Cl KIQFHCQWIOWQPI-UHFFFAOYSA-N 0.000 description 1
• OPRTZDVTKDZBCY-QFIPXVFZSA-N 4-[[4-[(3s)-3-(2-methoxyethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 OPRTZDVTKDZBCY-QFIPXVFZSA-N 0.000 description 1
• URCZZFVYNILKIB-FTBISJDPSA-N 4-[[4-[(3s)-3-(2-methoxyethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C1[C@@H](OCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 URCZZFVYNILKIB-FTBISJDPSA-N 0.000 description 1
• RDJNXCKGLTZUPB-QHCPKHFHSA-N 4-[[4-[(3s)-3-(3-methoxypropoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OCCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 RDJNXCKGLTZUPB-QHCPKHFHSA-N 0.000 description 1
• NTNFWJNKANIMTE-BQAIUKQQSA-N 4-[[4-[(3s)-3-(3-methoxypropoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C1[C@@H](OCCCOC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 NTNFWJNKANIMTE-BQAIUKQQSA-N 0.000 description 1
• VYDMPQALSDIXIQ-QHCPKHFHSA-N 4-[[4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(OCC=3C=CC(=CC=3)C#N)C=CC2=1)C)CC1CC1 VYDMPQALSDIXIQ-QHCPKHFHSA-N 0.000 description 1
• MGEUPFFZIRXGJM-BQAIUKQQSA-N 4-[[4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.O([C@H]1CCN(C1)C=1C=C(N=C2C=C(OCC=3C=CC(=CC=3)C#N)C=CC2=1)C)CC1CC1 MGEUPFFZIRXGJM-BQAIUKQQSA-N 0.000 description 1
• ORMAFQJRVDEJOI-BOXHHOBZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 ORMAFQJRVDEJOI-BOXHHOBZSA-N 0.000 description 1
• ICYAWHWCHBAHJT-BDQAORGHSA-N 4-[[4-[(3s)-3-methoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile;hydrochloride Chemical compound Cl.C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 ICYAWHWCHBAHJT-BDQAORGHSA-N 0.000 description 1
• RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 1
• HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-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
• XAACOEWSHBIFGJ-UHFFFAOYSA-N 4-fluoro-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1F XAACOEWSHBIFGJ-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
• QJALPIBEXWDDOX-UHFFFAOYSA-N 5-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]pyridine-2-carbonitrile;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=NC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 QJALPIBEXWDDOX-UHFFFAOYSA-N 0.000 description 1
• ZTVZIMAZBBAGCK-UHFFFAOYSA-N 5-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]pyridine-2-carbonitrile Chemical compound C=12C=C(F)C(OCC=3C=NC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ZTVZIMAZBBAGCK-UHFFFAOYSA-N 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• FFZVNTCWZPMHGM-SFHVURJKSA-N 5-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]pyridine-2-carbonitrile Chemical compound C=12C=CC(OCC=3C=NC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO FFZVNTCWZPMHGM-SFHVURJKSA-N 0.000 description 1
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XKEDIVOXXVGZHZ-UHFFFAOYSA-N 6-bromo-7-methoxy-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=C(Br)C(OC)=CC2=NC(C)=CC=1N1CCCC1 XKEDIVOXXVGZHZ-UHFFFAOYSA-N 0.000 description 1
• ZAEHYFHWOYSOPC-UHFFFAOYSA-N 6-butyl-7-ethoxy-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C1=CN=C2C=C(OCC)C(CCCC)=CC2=C1N1CCCC1 ZAEHYFHWOYSOPC-UHFFFAOYSA-N 0.000 description 1
• VNXJMBPWDKAZLP-UHFFFAOYSA-N 6-butyl-7-methoxy-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C1=CN=C2C=C(OC)C(CCCC)=CC2=C1N1CCCC1 VNXJMBPWDKAZLP-UHFFFAOYSA-N 0.000 description 1
• GSGNDEIEKJHNFT-UHFFFAOYSA-N 6-fluoro-2-methyl-7-(pyridin-3-ylmethoxy)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C=NC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 GSGNDEIEKJHNFT-UHFFFAOYSA-N 0.000 description 1
• ZFJLTHIOPSXQNB-UHFFFAOYSA-N 6-fluoro-2-methyl-7-[(2-methylpyridin-3-yl)methoxy]-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C(=NC=CC=3)C)=CC2=NC(C)=CC=1N1CCCC1 ZFJLTHIOPSXQNB-UHFFFAOYSA-N 0.000 description 1
• JHKAPLOQRUDNCL-UHFFFAOYSA-N 6-fluoro-2-methyl-7-phenylmethoxy-1h-quinolin-4-one Chemical compound C1=C2NC(C)=CC(=O)C2=CC(F)=C1OCC1=CC=CC=C1 JHKAPLOQRUDNCL-UHFFFAOYSA-N 0.000 description 1
• WJZNBYUUVYRKCN-UHFFFAOYSA-N 7-(2-methoxyethoxy)-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=1C(C)=NC2=CC(OCCOC)=CC=C2C=1N1CCCC1 WJZNBYUUVYRKCN-UHFFFAOYSA-N 0.000 description 1
• CCASEBWXHDWVNK-UHFFFAOYSA-N 7-(cyclopropylmethoxy)-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC3CC3)=CC2=NC(C)=CC=1N1CCCC1 CCASEBWXHDWVNK-UHFFFAOYSA-N 0.000 description 1
• REYRSAIXWIZEQH-INIZCTEOSA-N 7-(cyclopropylmethoxy)-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC3CC3)=CC=C12 REYRSAIXWIZEQH-INIZCTEOSA-N 0.000 description 1
• OSXPPQPPSWAUOR-NTISSMGPSA-N 7-(cyclopropylmethoxy)-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline;hydrochloride Chemical compound Cl.COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC3CC3)=CC=C12 OSXPPQPPSWAUOR-NTISSMGPSA-N 0.000 description 1
• JKPDZYQTUWZVGT-UHFFFAOYSA-N 7-[(2-chloro-6-methylpyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.ClC1=NC(C)=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 JKPDZYQTUWZVGT-UHFFFAOYSA-N 0.000 description 1
• QUDVDGXBCMKAFR-UHFFFAOYSA-N 7-[(2-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C(=CC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCCC1 QUDVDGXBCMKAFR-UHFFFAOYSA-N 0.000 description 1
• STPWJRWJQHWXHZ-LMOVPXPDSA-N 7-[(2-chloropyridin-3-yl)methoxy]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline;hydrochloride Chemical compound Cl.COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)Cl)=CC=C12 STPWJRWJQHWXHZ-LMOVPXPDSA-N 0.000 description 1
• TWFYCWXOOPIHHU-LMOVPXPDSA-N 7-[(2-fluoropyridin-3-yl)methoxy]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline;hydrochloride Chemical compound Cl.COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)F)=CC=C12 TWFYCWXOOPIHHU-LMOVPXPDSA-N 0.000 description 1
• LLYLIFLRNSBFJI-UHFFFAOYSA-N 7-[(2-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.COC1=CC=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 LLYLIFLRNSBFJI-UHFFFAOYSA-N 0.000 description 1
• PBRWDFKHAMWPJY-UHFFFAOYSA-N 7-[(3,5-dimethoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.COC1=CC(OC)=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 PBRWDFKHAMWPJY-UHFFFAOYSA-N 0.000 description 1
• RBNIDZCOVBHQJX-UHFFFAOYSA-N 7-[(3-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 RBNIDZCOVBHQJX-UHFFFAOYSA-N 0.000 description 1
• XQRUDFPTJMJBOG-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.COC1=CC=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 XQRUDFPTJMJBOG-UHFFFAOYSA-N 0.000 description 1
• JHGVHRYCRBWHCR-UHFFFAOYSA-N 7-[(4-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=12C=CC(OCC=3C=CC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 JHGVHRYCRBWHCR-UHFFFAOYSA-N 0.000 description 1
• YQTJGMPRKHCMQN-UHFFFAOYSA-N 7-[(4-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1COC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 YQTJGMPRKHCMQN-UHFFFAOYSA-N 0.000 description 1
• IMCGSRKRWIILQY-UHFFFAOYSA-N 7-methoxy-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=1C(C)=NC2=CC(OC)=CC=C2C=1N1CCCC1 IMCGSRKRWIILQY-UHFFFAOYSA-N 0.000 description 1
• HKRAHFCEOBHHJG-UHFFFAOYSA-N 7-methoxy-4-pyrrolidin-1-ylquinolin-2-amine;hydrochloride Chemical compound Cl.C=1C(N)=NC2=CC(OC)=CC=C2C=1N1CCCC1 HKRAHFCEOBHHJG-UHFFFAOYSA-N 0.000 description 1
• MHHXMFUTMMVENC-UHFFFAOYSA-N 7-methoxy-4-pyrrolidin-1-ylquinoline;hydrochloride Chemical compound Cl.C=1C=NC2=CC(OC)=CC=C2C=1N1CCCC1 MHHXMFUTMMVENC-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 240000006108 Allium ampeloprasum Species 0.000 description 1
• 235000005254 Allium ampeloprasum Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• JTAOASRKCLKRRJ-PBVYKCSPSA-N CC1=NC2=CC=CC=C2C(=C1)N3CC[C@@H](C3)OCCOC4CCCCO4 Chemical compound CC1=NC2=CC=CC=C2C(=C1)N3CC[C@@H](C3)OCCOC4CCCCO4 JTAOASRKCLKRRJ-PBVYKCSPSA-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
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 229910021591 Copper(I) chloride 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
• HVVNJUAVDAZWCB-RXMQYKEDSA-N D-prolinol Chemical compound OC[C@H]1CCCN1 HVVNJUAVDAZWCB-RXMQYKEDSA-N 0.000 description 1
• 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• 102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 239000005913 Maltodextrin Substances 0.000 description 1
• 229920002774 Maltodextrin Polymers 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 238000007126 N-alkylation reaction Methods 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• NNOPDLNHPOLRRE-UHFFFAOYSA-N Nequinate Chemical compound CCCCC1=CC(C(C(C(=O)OC)=CN2)=O)=C2C=C1OCC1=CC=CC=C1 NNOPDLNHPOLRRE-UHFFFAOYSA-N 0.000 description 1
• 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 description 1
• 101710198055 Neuropeptide Y receptor type 5 Proteins 0.000 description 1
• 108010046593 Neuropeptide Y5 receptor Proteins 0.000 description 1
• 229940116685 Neuropeptide receptor antagonist Drugs 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• 102100026459 POU domain, class 3, transcription factor 2 Human genes 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
• 206010037660 Pyrexia Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 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
• 230000015572 biosynthetic process Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 1
• LYXYLHLQHPZBEM-UHFFFAOYSA-N bromomethylcyclopropane;hydrochloride Chemical compound Cl.BrCC1CC1 LYXYLHLQHPZBEM-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 159000000007 calcium salts Chemical class 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
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000012875 competitive assay Methods 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 239000013078 crystal Substances 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
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 238000005661 deetherification reaction Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-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
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 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
• 239000002198 insoluble material Substances 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 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
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
• 239000011654 magnesium acetate Substances 0.000 description 1
• 235000011285 magnesium acetate Nutrition 0.000 description 1
• 229940069446 magnesium acetate Drugs 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 229940035034 maltodextrin Drugs 0.000 description 1
• 229960002510 mandelic acid 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
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• BLWYXBNNBYXPPL-YFKPBYRVSA-N methyl (2s)-pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1 BLWYXBNNBYXPPL-YFKPBYRVSA-N 0.000 description 1
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• JJIBACXWJHRORI-UHFFFAOYSA-N n,n,2,2-tetramethyl-3-(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxypropan-1-amine Chemical compound C=1C(C)=NC2=CC(OCC(C)(C)CN(C)C)=CC=C2C=1N1CCCC1 JJIBACXWJHRORI-UHFFFAOYSA-N 0.000 description 1
• JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 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
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000004430 oxygen atom 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
• 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
• 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
• 159000000001 potassium salts Chemical class 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000000926 separation method Methods 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
• 229910052708 sodium Inorganic materials 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000012453 solvate Substances 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
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 125000005415 substituted alkoxy group Chemical group 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 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
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000003786 synthesis reaction Methods 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
• 108010072897 transcription factor Brn-2 Proteins 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1