ZA200402359B - Quinoline derivatives as neuropeptide Y antagonists. - Google Patents
Quinoline derivatives as neuropeptide Y antagonists. Download PDFInfo
- Publication number
- ZA200402359B ZA200402359B ZA200402359A ZA200402359A ZA200402359B ZA 200402359 B ZA200402359 B ZA 200402359B ZA 200402359 A ZA200402359 A ZA 200402359A ZA 200402359 A ZA200402359 A ZA 200402359A ZA 200402359 B ZA200402359 B ZA 200402359B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyrrolidin
- quinolin
- methyl
- alkyl
- benzonitrile
- Prior art date
Links
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 10
- 101710151321 Melanostatin Proteins 0.000 title claims description 7
- 102400000064 Neuropeptide Y Human genes 0.000 title 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 title description 5
- 239000005557 antagonist Substances 0.000 title description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- -1 amino, acetylamino Chemical group 0.000 claims description 47
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-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
- 208000008589 Obesity Diseases 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 229960001243 orlistat Drugs 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Chemical group 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Chemical group 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 208000030814 Eating disease Diseases 0.000 claims description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 235000014632 disordered eating Nutrition 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 201000006370 kidney failure Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical group C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- CHRSSSYOZYZOFK-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 CHRSSSYOZYZOFK-UHFFFAOYSA-N 0.000 claims description 3
- XATCREPNDSEOGK-UHFFFAOYSA-N 2-chloro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(Cl)C(C#N)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 XATCREPNDSEOGK-UHFFFAOYSA-N 0.000 claims description 3
- SNRXFJAQZXURJY-UHFFFAOYSA-N 2-methyl-7-(pyridin-4-yloxymethyl)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCC1 SNRXFJAQZXURJY-UHFFFAOYSA-N 0.000 claims description 3
- OSHRLFZAABJWIA-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=C(C)C(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 OSHRLFZAABJWIA-UHFFFAOYSA-N 0.000 claims description 3
- FBJUQLXTVWMSMQ-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]benzonitrile Chemical compound C=12C=C(C)C(CNC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 FBJUQLXTVWMSMQ-UHFFFAOYSA-N 0.000 claims description 3
- FQMBNIOZTFMQEB-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 FQMBNIOZTFMQEB-UHFFFAOYSA-N 0.000 claims description 3
- VORUYQGEUJBGHH-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzene-1,2-dicarbonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 VORUYQGEUJBGHH-UHFFFAOYSA-N 0.000 claims description 3
- YRGQRXMURUGZDN-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YRGQRXMURUGZDN-UHFFFAOYSA-N 0.000 claims description 3
- ZETVYJWZAJSNLN-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(CNC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 ZETVYJWZAJSNLN-UHFFFAOYSA-N 0.000 claims description 3
- RVEDDNXDVZBQNM-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 RVEDDNXDVZBQNM-UHFFFAOYSA-N 0.000 claims description 3
- UXMOAHLHPOHSPS-QFIPXVFZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methoxy]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=C(C)C=C12 UXMOAHLHPOHSPS-QFIPXVFZSA-N 0.000 claims description 3
- SELLRXHGEKIKKL-UHFFFAOYSA-N [4-(azepan-1-yl)-2-methylquinolin-7-yl]methanol Chemical compound C=12C=CC(CO)=CC2=NC(C)=CC=1N1CCCCCC1 SELLRXHGEKIKKL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- BHJULLBAVAZKLV-UHFFFAOYSA-N n-butyl-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=1C(C)=NC2=CC(C(=O)NCCCC)=CC=C2C=1N1CCCC1 BHJULLBAVAZKLV-UHFFFAOYSA-N 0.000 claims description 3
- OFCMJTXCXQZZHQ-UHFFFAOYSA-N (2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CCCC1 OFCMJTXCXQZZHQ-UHFFFAOYSA-N 0.000 claims description 2
- DGEQVTJQZRYCHX-QFIPXVFZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methylamino]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(CNC=3C=CC(=CC=3)C#N)=C(C)C=C12 DGEQVTJQZRYCHX-QFIPXVFZSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 125000002346 iodo group Chemical group I* 0.000 claims 2
- BZCCJWGPBJXSFD-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]benzonitrile Chemical compound C=12C=CC(CNC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 BZCCJWGPBJXSFD-UHFFFAOYSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- FRONIFQNPCAWAG-UHFFFAOYSA-N (4-chloroquinolin-7-yl)methanol Chemical class ClC1=CC=NC2=CC(CO)=CC=C21 FRONIFQNPCAWAG-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000006880 cross-coupling reaction Methods 0.000 description 4
- 235000012631 food intake Nutrition 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 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 4
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 206010020710 Hyperphagia Diseases 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- 239000004367 Lipase Substances 0.000 description 3
- SIKWOTFNWURSAY-UHFFFAOYSA-N Lipstatin Natural products CCCCCCC1C(CC(CC=CCC=CCCCCC)C(=O)OC(CC(C)C)NC=O)OC1=O SIKWOTFNWURSAY-UHFFFAOYSA-N 0.000 description 3
- 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 description 3
- 101710198055 Neuropeptide Y receptor type 5 Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- OQMAKWGYQLJJIA-CUOOPAIESA-N lipstatin Chemical compound CCCCCC[C@H]1[C@H](C[C@H](C\C=C/C\C=C/CCCCC)OC(=O)[C@H](CC(C)C)NC=O)OC1=O OQMAKWGYQLJJIA-CUOOPAIESA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- BPGXUIVWLQTVLZ-OFGSCBOVSA-N neuropeptide y(npy) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 BPGXUIVWLQTVLZ-OFGSCBOVSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229940127470 Lipase Inhibitors Drugs 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
- 108090000189 Neuropeptides Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000021407 appetite control Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000001302 tertiary amino group Chemical group 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- HOTUXSIVLXHYAG-UHFFFAOYSA-N (2-chloro-6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=C(Cl)N=C2C=C(CO)C(C)=CC2=C1N1CCCC1 HOTUXSIVLXHYAG-UHFFFAOYSA-N 0.000 description 1
- LESWSBYGMHSGBZ-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)-pyrrolidin-1-ylmethanone Chemical compound C=12C=CC(C(=O)N3CCCC3)=CC2=NC(C)=CC=1N1CCCC1 LESWSBYGMHSGBZ-UHFFFAOYSA-N 0.000 description 1
- KALINDFRXWSFSG-UHFFFAOYSA-N (2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=CC(CO)=CC2=NC(C)=CC=1N1CCCC1 KALINDFRXWSFSG-UHFFFAOYSA-N 0.000 description 1
- BSDVWBISVNDMEB-ZDUSSCGKSA-N (3s)-1-[7-(hydroxymethyl)-2,6-dimethylquinolin-4-yl]pyrrolidin-3-ol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 BSDVWBISVNDMEB-ZDUSSCGKSA-N 0.000 description 1
- HZFRNCVZSHOIGY-UHFFFAOYSA-N (6-bromo-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C=12C=C(Br)C(CO)=CC2=NC(C)=CC=1N1CCCC1 HZFRNCVZSHOIGY-UHFFFAOYSA-N 0.000 description 1
- GATMSTWMFBCCGA-UHFFFAOYSA-N (6-methoxy-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=C(C)N=C2C=C(CO)C(OC)=CC2=C1N1CCCC1 GATMSTWMFBCCGA-UHFFFAOYSA-N 0.000 description 1
- KLGIOJHTZBSJTC-UHFFFAOYSA-N (6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methanol Chemical compound C1=CN=C2C=C(CO)C(C)=CC2=C1N1CCCC1 KLGIOJHTZBSJTC-UHFFFAOYSA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 description 1
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical group CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
- KORMWSBLSJUAKF-UHFFFAOYSA-N 2-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=C(C)C(COC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 KORMWSBLSJUAKF-UHFFFAOYSA-N 0.000 description 1
- HEKBGUOFDSCSBJ-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-5-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 HEKBGUOFDSCSBJ-UHFFFAOYSA-N 0.000 description 1
- DVNYSCUIDIGYPN-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-6-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=C(C=CC=3)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 DVNYSCUIDIGYPN-UHFFFAOYSA-N 0.000 description 1
- 150000005013 2-aminoquinolines Chemical class 0.000 description 1
- ZLGYFHNGOIEULT-UHFFFAOYSA-N 2-chloro-6-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=C(Cl)C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ZLGYFHNGOIEULT-UHFFFAOYSA-N 0.000 description 1
- GREJUAIIYPUSGP-UHFFFAOYSA-N 2-fluoro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(F)C(C#N)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 GREJUAIIYPUSGP-UHFFFAOYSA-N 0.000 description 1
- YCRWUXYRSACDBI-UHFFFAOYSA-N 2-iodo-6-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=C(I)C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 YCRWUXYRSACDBI-UHFFFAOYSA-N 0.000 description 1
- WWSYBBDZQRYWJF-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-(pyrrolidin-1-ylmethyl)quinoline Chemical compound C=12C=CC(CN3CCCC3)=CC2=NC(C)=CC=1N1CCCC1 WWSYBBDZQRYWJF-UHFFFAOYSA-N 0.000 description 1
- KYBIBARYJXLJSU-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 KYBIBARYJXLJSU-UHFFFAOYSA-N 0.000 description 1
- TYXJCGQGRUXPPD-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-yl-7-[[4-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 TYXJCGQGRUXPPD-UHFFFAOYSA-N 0.000 description 1
- XWOKDQGJISYYDI-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=12C=CC(C(N)=O)=CC2=NC(C)=CC=1N1CCCC1 XWOKDQGJISYYDI-UHFFFAOYSA-N 0.000 description 1
- DVCLTMIFEHEKLU-UHFFFAOYSA-N 2-methyl-7-(phenoxymethyl)-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CCCC1 DVCLTMIFEHEKLU-UHFFFAOYSA-N 0.000 description 1
- GNVKPJJTMMKXCV-UHFFFAOYSA-N 2-methyl-7-[(2-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C(=CC=CC=3)C)=CC2=NC(C)=CC=1N1CCCC1 GNVKPJJTMMKXCV-UHFFFAOYSA-N 0.000 description 1
- QVYCJMJBMKODFM-UHFFFAOYSA-N 2-methyl-7-[(3-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound CC1=CC=CC(OCC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 QVYCJMJBMKODFM-UHFFFAOYSA-N 0.000 description 1
- FZJQNXJRMQBCQA-UHFFFAOYSA-N 2-methyl-7-[(4-methylphenoxy)methyl]-4-pyrrolidin-1-ylquinoline Chemical compound C1=CC(C)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 FZJQNXJRMQBCQA-UHFFFAOYSA-N 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-M 2-methylbutyrate Chemical compound CCC(C)C([O-])=O WLAMNBDJUVNPJU-UHFFFAOYSA-M 0.000 description 1
- AGUZXFZMKJPLSX-UHFFFAOYSA-N 3,5-difluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(F)=CC=3F)C#N)=CC2=NC(C)=CC=1N1CCCC1 AGUZXFZMKJPLSX-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 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
- WROYXEJEURABQE-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 WROYXEJEURABQE-UHFFFAOYSA-N 0.000 description 1
- BYWDCMQRVTUUPY-UHFFFAOYSA-N 3-chloro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C#N)Cl)=CC2=NC(C)=CC=1N1CCCC1 BYWDCMQRVTUUPY-UHFFFAOYSA-N 0.000 description 1
- XMTFHHGBBFFOHD-UHFFFAOYSA-N 3-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-4-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(C=3F)C(F)(F)F)C#N)=CC2=NC(C)=CC=1N1CCCC1 XMTFHHGBBFFOHD-UHFFFAOYSA-N 0.000 description 1
- XMBLFMQJNDATJQ-UHFFFAOYSA-N 3-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=CC=3F)C#N)=CC2=NC(C)=CC=1N1CCCC1 XMBLFMQJNDATJQ-UHFFFAOYSA-N 0.000 description 1
- SIICUYTYQMVCBA-UHFFFAOYSA-N 3-fluoro-4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C#N)F)=CC2=NC(C)=CC=1N1CCCC1 SIICUYTYQMVCBA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HRXSZSYQFGVUCL-YSYXNDDBSA-N 4-(3-methoxypyrrolidin-1-yl)-2,6-dimethyl-7-[[(2s)-oxan-2-yl]oxymethyl]quinoline Chemical compound C1C(OC)CCN1C1=CC(C)=NC2=CC(CO[C@@H]3OCCCC3)=C(C)C=C12 HRXSZSYQFGVUCL-YSYXNDDBSA-N 0.000 description 1
- PWAZWPHCWIWQHS-UHFFFAOYSA-N 4-(azepan-1-yl)-2-chloro-6-methyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound CC1=CC2=C(N3CCCCCC3)C=C(Cl)N=C2C=C1COC1=CC=CC(C(F)(F)F)=C1 PWAZWPHCWIWQHS-UHFFFAOYSA-N 0.000 description 1
- CSCCGZCPGBQTMN-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinoline Chemical compound C=12C=CC(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCCCC1 CSCCGZCPGBQTMN-UHFFFAOYSA-N 0.000 description 1
- UNRZSWGCDDVUDS-UHFFFAOYSA-N 4-(azepan-1-yl)-7-(2-methoxyethoxymethyl)-2-methylquinoline Chemical compound C=1C(C)=NC2=CC(COCCOC)=CC=C2C=1N1CCCCCC1 UNRZSWGCDDVUDS-UHFFFAOYSA-N 0.000 description 1
- ABDJRZPMOKRWTJ-UHFFFAOYSA-N 4-(azepan-1-yl)-7-(methoxymethyl)-2-methylquinoline Chemical compound C=1C(C)=NC2=CC(COC)=CC=C2C=1N1CCCCCC1 ABDJRZPMOKRWTJ-UHFFFAOYSA-N 0.000 description 1
- PLAWARAAQGAMFW-UHFFFAOYSA-N 4-(azepan-1-yl)-n,6-dimethyl-7-[[3-(trifluoromethyl)phenoxy]methyl]quinolin-2-amine Chemical compound C=12C=C(C)C(COC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(NC)=CC=1N1CCCCCC1 PLAWARAAQGAMFW-UHFFFAOYSA-N 0.000 description 1
- PFWRJJVQJOIMCZ-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-3-(trifluoromethyl)benzonitrile Chemical compound C=12C=C(C)C(COC=3C(=CC(=CC=3)C#N)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 PFWRJJVQJOIMCZ-UHFFFAOYSA-N 0.000 description 1
- UUJRPJPWYOIWTP-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl-methylamino]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1N(C)CC(C(=CC1=2)C)=CC1=NC(C)=CC=2N1CCCC1 UUJRPJPWYOIWTP-UHFFFAOYSA-N 0.000 description 1
- ZWACIOSTVPBAPF-UHFFFAOYSA-N 4-[(2,6-dimethyl-4-pyrrolidin-1-ylquinolin-7-yl)methylamino]-2-(trifluoromethyl)benzonitrile Chemical compound C=12C=C(C)C(CNC=3C=C(C(C#N)=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 ZWACIOSTVPBAPF-UHFFFAOYSA-N 0.000 description 1
- PORCTTYQFJTLCB-UHFFFAOYSA-N 4-[(2-methyl-4-piperidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCC1 PORCTTYQFJTLCB-UHFFFAOYSA-N 0.000 description 1
- MBDBJBMKQYJGAQ-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-2-nitrobenzonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)[N+]([O-])=O)=CC2=NC(C)=CC=1N1CCCC1 MBDBJBMKQYJGAQ-UHFFFAOYSA-N 0.000 description 1
- PGDWOHFKILYROS-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]-3-(trifluoromethyl)benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(=CC=3)C#N)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 PGDWOHFKILYROS-UHFFFAOYSA-N 0.000 description 1
- BVHRDVCQSTZZGH-BWDMCYIDSA-N 4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2,6-dimethyl-7-(oxan-2-yloxymethyl)quinoline Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(COC3OCCCC3)C(C)=CC2=1)C)CC1CC1 BVHRDVCQSTZZGH-BWDMCYIDSA-N 0.000 description 1
- VOROVDVRLLHAAV-UHFFFAOYSA-N 4-[(6-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound CC1=CC2=C(N3CCCC3)C=CN=C2C=C1COC1=CC=C(C#N)C=C1 VOROVDVRLLHAAV-UHFFFAOYSA-N 0.000 description 1
- DGJVALRZAYWWSE-UHFFFAOYSA-N 4-[[2-methyl-4-(4-methyl-1,4-diazepan-1-yl)quinolin-7-yl]methoxy]benzonitrile Chemical compound C1CN(C)CCCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=CC=C12 DGJVALRZAYWWSE-UHFFFAOYSA-N 0.000 description 1
- FJSZFDSFTZKCGA-UHFFFAOYSA-N 4-[[2-methyl-4-(4-methylpiperazin-1-yl)quinolin-7-yl]methoxy]benzonitrile Chemical compound C1CN(C)CCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=CC=C12 FJSZFDSFTZKCGA-UHFFFAOYSA-N 0.000 description 1
- QXGCCWDMSOEPGI-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-(dimethylamino)-6-methylquinolin-7-yl]methoxy]benzonitrile Chemical compound C=12C=C(C)C(COC=3C=CC(=CC=3)C#N)=CC2=NC(N(C)C)=CC=1N1CCCCCC1 QXGCCWDMSOEPGI-UHFFFAOYSA-N 0.000 description 1
- RXHLLKWUIAGWCN-OAQYLSRUSA-N 4-[[4-[(2r)-2-(methoxymethyl)pyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methoxy]benzonitrile Chemical compound COC[C@H]1CCCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=C(C)C=C12 RXHLLKWUIAGWCN-OAQYLSRUSA-N 0.000 description 1
- XMJSVKUVCYWIIR-FQEVSTJZSA-N 4-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]methoxy]benzene-1,2-dicarbonitrile Chemical compound C=12C=CC(COC=3C=C(C(C#N)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO XMJSVKUVCYWIIR-FQEVSTJZSA-N 0.000 description 1
- UGVHJGUBNSGOCJ-DEOSSOPVSA-N 4-[[4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methoxy]benzonitrile Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(COC=3C=CC(=CC=3)C#N)C(C)=CC2=1)C)CC1CC1 UGVHJGUBNSGOCJ-DEOSSOPVSA-N 0.000 description 1
- WGWIUXKCFQXCJF-FQEVSTJZSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-6-methylquinolin-7-yl]methylamino]-2-(trifluoromethyl)benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC=NC2=CC(CNC=3C=C(C(C#N)=CC=3)C(F)(F)F)=C(C)C=C12 WGWIUXKCFQXCJF-FQEVSTJZSA-N 0.000 description 1
- CDMDNVPJWXDRCJ-NRFANRHFSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-6-methylquinolin-7-yl]methylamino]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC=NC2=CC(CNC=3C=CC(=CC=3)C#N)=C(C)C=C12 CDMDNVPJWXDRCJ-NRFANRHFSA-N 0.000 description 1
- MEWQPDIXVANNDM-NRFANRHFSA-N 4-[[4-[(3s)-3-methoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methoxy]benzonitrile Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(COC=3C=CC(=CC=3)C#N)=C(C)C=C12 MEWQPDIXVANNDM-NRFANRHFSA-N 0.000 description 1
- ULOMPSGOQQSFAN-UHFFFAOYSA-N 4-aminoquinoline-7-carbonitrile Chemical class N#CC1=CC=C2C(N)=CC=NC2=C1 ULOMPSGOQQSFAN-UHFFFAOYSA-N 0.000 description 1
- DRNOUAUANPKLON-UHFFFAOYSA-N 4-aminoquinoline-7-carboxamide Chemical class NC1=CC=NC2=CC(C(=O)N)=CC=C21 DRNOUAUANPKLON-UHFFFAOYSA-N 0.000 description 1
- CHTDXTLZBDJJFV-UHFFFAOYSA-N 4-bromo-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(Br)C=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 CHTDXTLZBDJJFV-UHFFFAOYSA-N 0.000 description 1
- UKTYNFPTZDSBLR-UHFFFAOYSA-N 4-chloro-7-methoxyquinoline Chemical compound ClC1=CC=NC2=CC(OC)=CC=C21 UKTYNFPTZDSBLR-UHFFFAOYSA-N 0.000 description 1
- KNDOFJFSHZCKGT-UHFFFAOYSA-N 4-chloroquinoline Chemical compound C1=CC=C2C(Cl)=CC=NC2=C1 KNDOFJFSHZCKGT-UHFFFAOYSA-N 0.000 description 1
- NTLCAGGRCRJARZ-UHFFFAOYSA-N 4-chloroquinoline-7-carbaldehyde Chemical compound O=CC1=CC=C2C(Cl)=CC=NC2=C1 NTLCAGGRCRJARZ-UHFFFAOYSA-N 0.000 description 1
- NFCSRTCOMSRFOC-UHFFFAOYSA-N 4-chloroquinoline-7-carbonitrile Chemical compound N#CC1=CC=C2C(Cl)=CC=NC2=C1 NFCSRTCOMSRFOC-UHFFFAOYSA-N 0.000 description 1
- VMGVGPMZWPOPJP-UHFFFAOYSA-N 4-chloroquinoline-7-carboxylic acid Chemical compound ClC1=CC=NC2=CC(C(=O)O)=CC=C21 VMGVGPMZWPOPJP-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- IHOAJTUJVJUNII-UHFFFAOYSA-N 4-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC=C(F)C=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 IHOAJTUJVJUNII-UHFFFAOYSA-N 0.000 description 1
- ADQOOTSUKUZXTL-UHFFFAOYSA-N 5-bromo-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(Br)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ADQOOTSUKUZXTL-UHFFFAOYSA-N 0.000 description 1
- ZDMJKIPIHILMCC-UHFFFAOYSA-N 5-chloro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(Cl)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 ZDMJKIPIHILMCC-UHFFFAOYSA-N 0.000 description 1
- DQVFTFADMFYATF-UHFFFAOYSA-N 5-fluoro-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound C=12C=CC(COC=3C(=CC(F)=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 DQVFTFADMFYATF-UHFFFAOYSA-N 0.000 description 1
- NKKFQEBSLZDISC-UHFFFAOYSA-N 5-methyl-2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methoxy]benzonitrile Chemical compound N#CC1=CC(C)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 NKKFQEBSLZDISC-UHFFFAOYSA-N 0.000 description 1
- AYNKSWTVVXGZOH-UHFFFAOYSA-N 7-(aminomethyl)quinolin-4-amine Chemical class NC1=CC=NC2=CC(CN)=CC=C21 AYNKSWTVVXGZOH-UHFFFAOYSA-N 0.000 description 1
- BXDKEBOAEQYWLL-UHFFFAOYSA-N 7-(quinolin-7-ylmethoxymethyl)quinoline Chemical compound C1=CC=NC2=CC(COCC=3C=C4N=CC=CC4=CC=3)=CC=C21 BXDKEBOAEQYWLL-UHFFFAOYSA-N 0.000 description 1
- NKQXWXCDYBQSQZ-UHFFFAOYSA-N 7-[(2-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C(=CC=CC=3)F)=CC2=NC(C)=CC=1N1CCCC1 NKQXWXCDYBQSQZ-UHFFFAOYSA-N 0.000 description 1
- RHSJUIIVCCKPLQ-UHFFFAOYSA-N 7-[(2-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 RHSJUIIVCCKPLQ-UHFFFAOYSA-N 0.000 description 1
- UDXITQOJMCZFES-UHFFFAOYSA-N 7-[(3-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=C(F)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 UDXITQOJMCZFES-UHFFFAOYSA-N 0.000 description 1
- LQMTXSODFQPYKS-UHFFFAOYSA-N 7-[(3-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(OCC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 LQMTXSODFQPYKS-UHFFFAOYSA-N 0.000 description 1
- ZKAIWVFOSMRDEE-UHFFFAOYSA-N 7-[(4-fluorophenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(COC=3C=CC(F)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 ZKAIWVFOSMRDEE-UHFFFAOYSA-N 0.000 description 1
- SEIKATQWLFCPFW-UHFFFAOYSA-N 7-[(4-methoxyphenoxy)methyl]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C1=CC(OC)=CC=C1OCC1=CC=C(C(=CC(C)=N2)N3CCCC3)C2=C1 SEIKATQWLFCPFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- QYOVMAREBTZLBT-KTKRTIGZSA-N CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO QYOVMAREBTZLBT-KTKRTIGZSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 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
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 229940116685 Neuropeptide receptor antagonist Drugs 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 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 1
- XXCWACRBJGYUBN-ZDUSSCGKSA-N [(2s)-1-[7-(hydroxymethyl)-2-methylquinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(CO)=CC2=NC(C)=CC=1N1CCC[C@H]1CO XXCWACRBJGYUBN-ZDUSSCGKSA-N 0.000 description 1
- IOPQYDKQISFMJI-UHFFFAOYSA-N [1-[2-bis(4-methylphenyl)phosphanylnaphthalen-1-yl]naphthalen-2-yl]-bis(4-methylphenyl)phosphane Chemical group C1=CC(C)=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC(C)=CC=1)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 IOPQYDKQISFMJI-UHFFFAOYSA-N 0.000 description 1
- UEZAQHNVTWKJPD-PBVYKCSPSA-N [2-methyl-4-[(2s)-2-(oxan-2-yloxymethyl)pyrrolidin-1-yl]quinolin-7-yl]methanol Chemical compound C([C@@H]1CCCN1C=1C=C(N=C2C=C(CO)C=CC2=1)C)OC1CCCCO1 UEZAQHNVTWKJPD-PBVYKCSPSA-N 0.000 description 1
- MXAWUMMTIJTJRY-UHFFFAOYSA-N [4-(azepan-1-yl)-2,6-dimethylquinolin-7-yl]methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(C)=CC=1N1CCCCCC1 MXAWUMMTIJTJRY-UHFFFAOYSA-N 0.000 description 1
- XXDMNRLCGQNDEH-UHFFFAOYSA-N [4-(azepan-1-yl)-2-(dimethylamino)-6-methylquinolin-7-yl]methanol Chemical compound C=12C=C(C)C(CO)=CC2=NC(N(C)C)=CC=1N1CCCCCC1 XXDMNRLCGQNDEH-UHFFFAOYSA-N 0.000 description 1
- FIZCOXUNHFSRKU-UHFFFAOYSA-N [4-(azepan-1-yl)-2-chloro-6-methylquinolin-7-yl]methanol Chemical compound C1=C(Cl)N=C2C=C(CO)C(C)=CC2=C1N1CCCCCC1 FIZCOXUNHFSRKU-UHFFFAOYSA-N 0.000 description 1
- MJZGGCLYPSOQME-KRWDZBQOSA-N [4-[(3s)-3-(cyclopropylmethoxy)pyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methanol Chemical compound O([C@H]1CCN(C1)C=1C=C(N=C2C=C(CO)C(C)=CC2=1)C)CC1CC1 MJZGGCLYPSOQME-KRWDZBQOSA-N 0.000 description 1
- LGQODQYMJCBWSG-HNNXBMFYSA-N [4-[(3s)-3-ethoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methanol Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(CO)=C(C)C=C12 LGQODQYMJCBWSG-HNNXBMFYSA-N 0.000 description 1
- MFIMFBWTLPDYIT-AWEZNQCLSA-N [4-[(3s)-3-methoxypyrrolidin-1-yl]-2,6-dimethylquinolin-7-yl]methanol Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(CO)=C(C)C=C12 MFIMFBWTLPDYIT-AWEZNQCLSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids 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
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 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
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125890 compound Ia Drugs 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical group C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- DDCLCVPHNUWYRZ-UHFFFAOYSA-N methyl 6-bromo-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxylate Chemical compound C=12C=C(Br)C(C(=O)OC)=CC2=NC(C)=CC=1N1CCCC1 DDCLCVPHNUWYRZ-UHFFFAOYSA-N 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- RNBRGFBBPVFNQJ-UHFFFAOYSA-N n-(4-cyanophenyl)-2-methyl-4-pyrrolidin-1-ylquinoline-7-carboxamide Chemical compound C=12C=CC(C(=O)NC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 RNBRGFBBPVFNQJ-UHFFFAOYSA-N 0.000 description 1
- DXHPEXGXMQTFLJ-UHFFFAOYSA-N n-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl]-3-(trifluoromethyl)aniline Chemical compound C=12C=CC(CNC=3C=C(C=CC=3)C(F)(F)F)=CC2=NC(C)=CC=1N1CCCC1 DXHPEXGXMQTFLJ-UHFFFAOYSA-N 0.000 description 1
- IBQQZUFOYSTLFX-UHFFFAOYSA-N n-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)methyl]butan-1-amine Chemical compound C=1C(C)=NC2=CC(CNCCCC)=CC=C2C=1N1CCCC1 IBQQZUFOYSTLFX-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- MMCIXNVRVDTQSG-UHFFFAOYSA-N quinoline-7-carboxamide Chemical class C1=CC=NC2=CC(C(=O)N)=CC=C21 MMCIXNVRVDTQSG-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000002829 reductive effect Effects 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
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 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
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004360 trifluorophenyl group Chemical group 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Manufacturing & Machinery (AREA)
- Ceramic Engineering (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Structural Engineering (AREA)
- Physical Education & Sports Medicine (AREA)
- Materials Engineering (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Vascular Medicine (AREA)
- Nutrition Science (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Quinoline Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01123496 | 2001-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200402359B true ZA200402359B (en) | 2005-05-03 |
Family
ID=8178804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200402359A ZA200402359B (en) | 2001-09-28 | 2004-03-25 | Quinoline derivatives as neuropeptide Y antagonists. |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US6787558B2 (enExample) |
| EP (1) | EP1432421A1 (enExample) |
| JP (1) | JP4187652B2 (enExample) |
| KR (1) | KR100605765B1 (enExample) |
| CN (1) | CN1289087C (enExample) |
| AR (1) | AR040626A1 (enExample) |
| AU (1) | AU2002342735B2 (enExample) |
| BR (1) | BR0212929A (enExample) |
| CA (1) | CA2460865C (enExample) |
| GT (1) | GT200200197A (enExample) |
| HR (1) | HRP20040272A2 (enExample) |
| HU (1) | HUP0401481A2 (enExample) |
| IL (1) | IL160750A0 (enExample) |
| MX (1) | MXPA04002825A (enExample) |
| NO (1) | NO20041235L (enExample) |
| NZ (1) | NZ531517A (enExample) |
| PA (1) | PA8555401A1 (enExample) |
| PE (1) | PE20030603A1 (enExample) |
| PL (1) | PL370414A1 (enExample) |
| RU (1) | RU2300531C2 (enExample) |
| UY (1) | UY27462A1 (enExample) |
| WO (1) | WO2003028726A1 (enExample) |
| ZA (1) | ZA200402359B (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| PT2182950T (pt) * | 2007-05-17 | 2017-09-11 | Helperby Therapeutics Ltd | Uso de compostos 4-(pirrolidin-1-il)quinolina para eliminação de microrganismos clinicamente latentes |
| CN101772513B (zh) | 2007-06-04 | 2013-11-13 | 协同医药品公司 | 有效用于胃肠功能紊乱、炎症、癌症和其他疾病治疗的鸟苷酸环化酶激动剂 |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| RU2497821C2 (ru) * | 2008-01-28 | 2013-11-10 | Янссен Фармацевтика Нв | ПРОИЗВОДНЫЕ 6-ЗАМЕЩЕННОГО-ТИО (ИЛИ -ОКСО-)-2-АМИНО-ХИНОЛИНА, ПРИМЕНЯЕМЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ β-СЕКРЕТАЗЫ (BACE) |
| CA2726917C (en) | 2008-06-04 | 2018-06-26 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2010009319A2 (en) | 2008-07-16 | 2010-01-21 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| WO2010047982A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| EP2362731B1 (en) | 2008-10-31 | 2016-04-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| EP2538784B1 (en) | 2010-02-25 | 2015-09-09 | Merck Sharp & Dohme Corp. | Benzimidazole derivatives useful anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CA2826649C (en) | 2011-02-25 | 2016-07-26 | Merck Sharp & Dohme Corp. | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| CA2880901A1 (en) | 2012-08-02 | 2014-02-06 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| CN104994848A (zh) | 2013-02-22 | 2015-10-21 | 默沙东公司 | 抗糖尿病二环化合物 |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| AU2014235215A1 (en) | 2013-03-15 | 2015-10-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| HK1220611A1 (zh) | 2013-03-15 | 2017-05-12 | Bausch Health Ireland Limited | 用於治疗胃肠道病症的组成物 |
| HRP20240805T1 (hr) | 2013-06-05 | 2024-09-27 | Bausch Health Ireland Limited | Ultra-pročišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i uporabe |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| US9663468B2 (en) | 2014-01-10 | 2017-05-30 | Northwestern University | 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition |
| US9212144B2 (en) * | 2014-01-10 | 2015-12-15 | Northwestern University | 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition |
| JP6969800B2 (ja) * | 2016-05-04 | 2021-11-24 | ジェノシアンス ファルマ | 増殖性疾患の治療に使用される置換２，４−ジアミノ−キノリン誘導体 |
| WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298A4 (en) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | ANTIDIABETIC SPIROCHROMAN COMPOUNDS |
| WO2020160151A1 (en) * | 2019-01-31 | 2020-08-06 | Kyorin Pharmaceutical Co., Ltd. | 15-pgdh inhibitors |
| WO2020231739A2 (en) * | 2019-05-10 | 2020-11-19 | Antidote Ip Holdings, Llc | Compounds and methods for treating cancer |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3272824A (en) | 1962-12-06 | 1966-09-13 | Norwich Pharma Co | 4-amino-6, 7-di(lower) alkoxyquinolines |
| US4035367A (en) | 1974-09-09 | 1977-07-12 | Sandoz, Inc. | Hydroxyalkyl-substituted-amino-quinolines |
| CA1247547A (en) | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
| CA1270837A (en) | 1984-12-21 | 1990-06-26 | Hoffmann-La Roche Limited | Oxetanones |
| CA1328881C (en) | 1984-12-21 | 1994-04-26 | Pierre Barbier | Process for the manufacture of oxetanones |
| JPH068292B2 (ja) * | 1985-05-07 | 1994-02-02 | アルカロイダ ベギエスゼティ ギャル | トリアゾリルキノリン誘導体 |
| CA2035972C (en) | 1990-02-23 | 2006-07-11 | Martin Karpf | Process for the preparation of oxetanones |
| US5274143A (en) | 1991-07-23 | 1993-12-28 | Hoffmann-La Roche Inc. | Process for the preparation of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-pyran-2-one and (R)-5,6-dihydro-6-undecyl-2H-pyran-2,4(3H)-dione |
| AU719392B2 (en) | 1996-10-01 | 2000-05-11 | Kyowa Hakko Kirin Co., Ltd. | Nitrogen-containing heterocyclic compounds |
| US6004996A (en) | 1997-02-05 | 1999-12-21 | Hoffman-La Roche Inc. | Tetrahydrolipstatin containing compositions |
| US6267952B1 (en) | 1998-01-09 | 2001-07-31 | Geltex Pharmaceuticals, Inc. | Lipase inhibiting polymers |
| US6199042B1 (en) * | 1998-06-19 | 2001-03-06 | L&H Applications Usa, Inc. | Reading system |
| ATE293970T1 (de) | 1998-08-14 | 2005-05-15 | Hoffmann La Roche | Lipasehemmer enthaltende pharmazeutische zusammensetzungen |
| PT1105123E (pt) | 1998-08-14 | 2004-08-31 | Hoffmann La Roche | Composicoes farmaceuticas contendo inibidores da lipase e quitosano |
| FR2795726A1 (fr) * | 1999-06-30 | 2001-01-05 | Aventis Cropscience Sa | Nouveaux pyrazoles fongicides |
| CN1377356A (zh) | 1999-09-30 | 2002-10-30 | 纽罗杰有限公司 | 亚烷基二胺取代的杂环 |
| US6900226B2 (en) | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
-
2002
- 2002-09-19 US US10/247,009 patent/US6787558B2/en not_active Expired - Fee Related
- 2002-09-20 CN CNB028191919A patent/CN1289087C/zh not_active Expired - Fee Related
- 2002-09-20 PL PL02370414A patent/PL370414A1/xx not_active Application Discontinuation
- 2002-09-20 WO PCT/EP2002/010618 patent/WO2003028726A1/en not_active Ceased
- 2002-09-20 EP EP02779399A patent/EP1432421A1/en not_active Withdrawn
- 2002-09-20 HU HU0401481A patent/HUP0401481A2/hu unknown
- 2002-09-20 MX MXPA04002825A patent/MXPA04002825A/es active IP Right Grant
- 2002-09-20 KR KR1020047004591A patent/KR100605765B1/ko not_active Expired - Fee Related
- 2002-09-20 AU AU2002342735A patent/AU2002342735B2/en not_active Ceased
- 2002-09-20 CA CA002460865A patent/CA2460865C/en not_active Expired - Fee Related
- 2002-09-20 JP JP2003532058A patent/JP4187652B2/ja not_active Expired - Fee Related
- 2002-09-20 HR HR20040272A patent/HRP20040272A2/hr not_active Application Discontinuation
- 2002-09-20 IL IL16075002A patent/IL160750A0/xx unknown
- 2002-09-20 NZ NZ531517A patent/NZ531517A/en unknown
- 2002-09-20 BR BR0212929-9A patent/BR0212929A/pt not_active IP Right Cessation
- 2002-09-20 RU RU2004113207/04A patent/RU2300531C2/ru not_active IP Right Cessation
- 2002-09-25 PA PA20028555401A patent/PA8555401A1/es unknown
- 2002-09-26 PE PE2002000952A patent/PE20030603A1/es not_active Application Discontinuation
- 2002-09-27 GT GT200200197A patent/GT200200197A/es unknown
- 2002-09-27 AR AR20020103663A patent/AR040626A1/es not_active Application Discontinuation
- 2002-09-27 UY UY27462A patent/UY27462A1/es not_active Application Discontinuation
-
2004
- 2004-03-24 NO NO20041235A patent/NO20041235L/no not_active Application Discontinuation
- 2004-03-25 ZA ZA200402359A patent/ZA200402359B/en unknown
- 2004-07-22 US US10/896,445 patent/US7012073B2/en not_active Expired - Fee Related
-
2005
- 2005-11-10 US US11/272,207 patent/US7064134B2/en not_active Expired - Fee Related
-
2006
- 2006-03-16 US US11/376,976 patent/US7166589B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200402359B (en) | Quinoline derivatives as neuropeptide Y antagonists. | |
| AU2002342735A1 (en) | Quinoline derivatives as neuropeptide Y antagonists | |
| KR102662358B1 (ko) | Egfr 돌연변이 키나아제 활성을 조절하기 위한 화합물 및 조성물 | |
| JP4216196B2 (ja) | Ｎｐｙアンタゴニストとしてのキノリン誘導体 | |
| RU2573834C2 (ru) | ФАРМАЦЕВТИЧЕСКИ АКТИВНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ Axl | |
| NZ520005A (en) | 2-amino-nicotinamide derivatives and their use as VEGF- receptor tyrosine kinase inhibitors for treating disease such as neoplastic, retinopathy or age related macular degeneration | |
| ZA200308783B (en) | Quinoline derivatives as ligands for the neuropeptide Y receptor. | |
| CA2860765A1 (en) | Pyrazinecarboxamide compound | |
| AU2016317806A1 (en) | Heteroaryl compounds and their use as therapeutic drugs | |
| RU2296757C2 (ru) | Производные хиназолина |