CA2521832A1 - Heterocyclic mchr1 antagonists - Google Patents
Heterocyclic mchr1 antagonists Download PDFInfo
- Publication number
- CA2521832A1 CA2521832A1 CA002521832A CA2521832A CA2521832A1 CA 2521832 A1 CA2521832 A1 CA 2521832A1 CA 002521832 A CA002521832 A CA 002521832A CA 2521832 A CA2521832 A CA 2521832A CA 2521832 A1 CA2521832 A1 CA 2521832A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- compound
- chlorophenyl
- thieno
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 33
- 239000005557 antagonist Substances 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 357
- 238000000034 method Methods 0.000 claims abstract description 89
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 123
- -1 amino ester Chemical class 0.000 claims description 116
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 110
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 107
- 229910052757 nitrogen Inorganic materials 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 66
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 52
- 125000005843 halogen group Chemical group 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 47
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 45
- 239000002904 solvent Substances 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 29
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 208000008589 Obesity Diseases 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 235000020824 obesity Nutrition 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 6
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000003367 polycyclic group Chemical group 0.000 claims description 4
- 241000894007 species Species 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 3
- XYCZXPVVNCEPEF-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(4-methylpiperazin-1-yl)methyl]-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1CN(C)CCN1CC1=CC2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2S1 XYCZXPVVNCEPEF-UHFFFAOYSA-N 0.000 claims description 2
- ATILBCJMFACSLA-UHFFFAOYSA-N 6-phenyl-3-[2-(pyrrolidin-1-ylmethyl)quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound S1C=2C(=O)N(C=3C=C4C=CC(CN5CCCC5)=NC4=CC=3)C=NC=2C=C1C1=CC=CC=C1 ATILBCJMFACSLA-UHFFFAOYSA-N 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 229940124802 CB1 antagonist Drugs 0.000 claims description 2
- 108010016122 Ghrelin Receptors Proteins 0.000 claims description 2
- 102100039256 Growth hormone secretagogue receptor type 1 Human genes 0.000 claims description 2
- 101000993364 Homo sapiens Ciliary neurotrophic factor Proteins 0.000 claims description 2
- 101000978418 Homo sapiens Melanocortin receptor 4 Proteins 0.000 claims description 2
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 2
- 102100023724 Melanocortin receptor 4 Human genes 0.000 claims description 2
- 239000007868 Raney catalyst Substances 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000007822 coupling agent Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 229940125425 inverse agonist Drugs 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 230000001561 neurotransmitter reuptake Effects 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 239000000018 receptor agonist Substances 0.000 claims description 2
- 229940044601 receptor agonist Drugs 0.000 claims description 2
- 229940044551 receptor antagonist Drugs 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims description 2
- 239000002485 serotonin 2C agonist Substances 0.000 claims description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 4
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical group C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical group C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical group C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical group C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- YMDKGGMAMAEFNG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(dimethylamino)-3-methylbenzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C2N(C)C(N(C)C)=NC2=CC=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 YMDKGGMAMAEFNG-UHFFFAOYSA-N 0.000 claims 1
- RJPPIDAXEMYCJF-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(2,2,6,6-tetramethylpiperidin-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound CC1(C)CCCC(C)(C)N1CC1=CC=C(C=C(C=C2)N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)C2=N1 RJPPIDAXEMYCJF-UHFFFAOYSA-N 0.000 claims 1
- FDIBWJRZRJTTOK-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(2-methyl-4,5-dihydroimidazol-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound CC1=NCCN1CC1=CC=C(C=C(C=C2)N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)C2=N1 FDIBWJRZRJTTOK-UHFFFAOYSA-N 0.000 claims 1
- HTLJHDQWVDIZCQ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[6-[(4-hydroxypiperidin-1-yl)methyl]naphthalen-2-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1CC(O)CCN1CC1=CC=C(C=C(C=C2)N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)C2=C1 HTLJHDQWVDIZCQ-UHFFFAOYSA-N 0.000 claims 1
- SANXLPAIECKXLI-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[2-(piperidin-1-ylmethyl)quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCCCC4)=NC3=CC=1)C=N2 SANXLPAIECKXLI-UHFFFAOYSA-N 0.000 claims 1
- HJFIRBMYMDXWII-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[2-(pyrrolidin-1-ylmethyl)quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCCC4)=NC3=CC=1)C=N2 HJFIRBMYMDXWII-UHFFFAOYSA-N 0.000 claims 1
- 238000006619 Stille reaction Methods 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 12
- 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 102000044674 Melanin-concentrating hormone receptor 1 Human genes 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 352
- 238000005481 NMR spectroscopy Methods 0.000 description 270
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 239
- 239000000203 mixture Substances 0.000 description 196
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 190
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- 239000007787 solid Substances 0.000 description 147
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 133
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 123
- 239000000243 solution Substances 0.000 description 122
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 107
- 239000000543 intermediate Substances 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- 229910001868 water Inorganic materials 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 238000002474 experimental method Methods 0.000 description 51
- ZJOXWRFJOUWUKX-GOSISDBHSA-N 2-[[4-[(3R)-1-oxo-3,4-dihydroisochromene-3-carbonyl]piperazin-1-yl]methyl]-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-4-one Chemical compound C1CCCC2=C1SC1=C2C(=O)NC(CN2CCN(CC2)C([C@@H]2OC(=O)C3=CC=CC=C3C2)=O)=N1 ZJOXWRFJOUWUKX-GOSISDBHSA-N 0.000 description 46
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 44
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 41
- 239000000047 product Substances 0.000 description 40
- 235000002639 sodium chloride Nutrition 0.000 description 39
- 238000010992 reflux Methods 0.000 description 38
- 229940093499 ethyl acetate Drugs 0.000 description 37
- 238000010898 silica gel chromatography Methods 0.000 description 37
- PZMKGWRBZNOIPQ-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1SC=C2 PZMKGWRBZNOIPQ-UHFFFAOYSA-N 0.000 description 36
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 36
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 34
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 34
- 239000002244 precipitate Substances 0.000 description 32
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 30
- 229910002027 silica gel Inorganic materials 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 25
- 235000019441 ethanol Nutrition 0.000 description 24
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 17
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910021529 ammonia Inorganic materials 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- 150000002431 hydrogen Chemical class 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- ALWFLYMKFZJTBB-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-3-(dimethylaminomethylideneamino)thiophene-2-carboxylate Chemical compound CN(C)C=NC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 ALWFLYMKFZJTBB-UHFFFAOYSA-N 0.000 description 11
- 125000001624 naphthyl group Chemical group 0.000 description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 11
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 10
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical group NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 238000001816 cooling Methods 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- FXVPQFWEVKYLME-UHFFFAOYSA-N 2-(bromomethyl)-6-nitroquinoline Chemical compound N1=C(CBr)C=CC2=CC([N+](=O)[O-])=CC=C21 FXVPQFWEVKYLME-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 8
- 125000004535 benzothien-5-yl group Chemical group S1C=CC2=C1C=CC(=C2)* 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 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 7
- 239000012043 crude product Substances 0.000 description 7
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 6
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 6
- PTEJPYNTLJOJBM-UHFFFAOYSA-N 2-chloro-1-methylbenzimidazol-5-amine Chemical compound NC1=CC=C2N(C)C(Cl)=NC2=C1 PTEJPYNTLJOJBM-UHFFFAOYSA-N 0.000 description 6
- VMRHKCAEQFYIBE-UHFFFAOYSA-N 2-chloro-3-methylbenzimidazol-5-amine Chemical compound C1=C(N)C=C2N(C)C(Cl)=NC2=C1 VMRHKCAEQFYIBE-UHFFFAOYSA-N 0.000 description 6
- NKAPXWIFLZNFAE-UHFFFAOYSA-N 2-piperidin-1-yl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1N1CCCCC1 NKAPXWIFLZNFAE-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical group CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229940098779 methanesulfonic acid Drugs 0.000 description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 6
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 6
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 5
- HCPPGSITODINMJ-UHFFFAOYSA-N 2-chloro-3h-benzimidazol-5-amine Chemical compound NC1=CC=C2N=C(Cl)NC2=C1 HCPPGSITODINMJ-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 5
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- XTSJODSVIJVJPS-UHFFFAOYSA-N 1-phenylbenzimidazole-2,5-diamine Chemical compound NC1=NC2=CC(N)=CC=C2N1C1=CC=CC=C1 XTSJODSVIJVJPS-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 4
- OBFVWUKSMRIYJJ-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound NC1=CC=C2OC(CN(C)C)COC2=C1 OBFVWUKSMRIYJJ-UHFFFAOYSA-N 0.000 description 4
- AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 4
- YRUBIFAMCRFPPC-UHFFFAOYSA-N 2-chloro-7-fluoro-1h-quinazolin-4-one Chemical compound N1C(Cl)=NC(=O)C=2C1=CC(F)=CC=2 YRUBIFAMCRFPPC-UHFFFAOYSA-N 0.000 description 4
- BOUDHYSDNNTOQD-UHFFFAOYSA-N 6-nitroquinoline-2-carbaldehyde Chemical compound N1=C(C=O)C=CC2=CC([N+](=O)[O-])=CC=C21 BOUDHYSDNNTOQD-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000002688 maleic acid derivatives Chemical class 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 4
- 102000047659 melanin-concentrating hormone Human genes 0.000 description 4
- MELGGDOYSMRBGA-UHFFFAOYSA-N methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 MELGGDOYSMRBGA-UHFFFAOYSA-N 0.000 description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- GYGYDOOXVKDZCF-UHFFFAOYSA-N n-methyl-2-pyrrolidin-1-ylethanamine Chemical compound CNCCN1CCCC1 GYGYDOOXVKDZCF-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003756 stirring Methods 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
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical group O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 3
- LOTKRQAVGJMPNV-UHFFFAOYSA-N 1-fluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C([N+]([O-])=O)=C1 LOTKRQAVGJMPNV-UHFFFAOYSA-N 0.000 description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- HRXMMARNIZKHLR-UHFFFAOYSA-N 2-(methoxymethoxy)-5-nitrophenol Chemical compound COCOC1=CC=C([N+]([O-])=O)C=C1O HRXMMARNIZKHLR-UHFFFAOYSA-N 0.000 description 3
- KHLTXMUSFLOCCS-UHFFFAOYSA-N 2-(piperidin-1-ylmethyl)quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN1CCCCC1 KHLTXMUSFLOCCS-UHFFFAOYSA-N 0.000 description 3
- LANVKIOYLOBIJU-UHFFFAOYSA-N 2-[(4-phenylpiperazin-1-yl)methyl]quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN(CC1)CCN1C1=CC=CC=C1 LANVKIOYLOBIJU-UHFFFAOYSA-N 0.000 description 3
- FKDWIFDBEKDYPT-UHFFFAOYSA-N 2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN(CC1)CCC1C1=CC=CC=C1 FKDWIFDBEKDYPT-UHFFFAOYSA-N 0.000 description 3
- POULBABPILHZQH-UHFFFAOYSA-N 2-[[4-[4-(trifluoromethyl)phenyl]piperidin-1-yl]methyl]quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN(CC1)CCC1C1=CC=C(C(F)(F)F)C=C1 POULBABPILHZQH-UHFFFAOYSA-N 0.000 description 3
- DXDPHHQJZWWAEH-UHFFFAOYSA-N 2-methyl-6-nitroquinoline Chemical compound C1=C([N+]([O-])=O)C=CC2=NC(C)=CC=C21 DXDPHHQJZWWAEH-UHFFFAOYSA-N 0.000 description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- GJEWXBDQJPCQOR-UHFFFAOYSA-N 5-amino-n,n-dimethyl-1-benzothiophene-2-carboxamide Chemical compound NC1=CC=C2SC(C(=O)N(C)C)=CC2=C1 GJEWXBDQJPCQOR-UHFFFAOYSA-N 0.000 description 3
- PZJPGXPFQBLOHQ-UHFFFAOYSA-N 6-(piperidin-1-ylmethyl)naphthalen-2-amine Chemical compound C1=CC2=CC(N)=CC=C2C=C1CN1CCCCC1 PZJPGXPFQBLOHQ-UHFFFAOYSA-N 0.000 description 3
- NZTPZUIIYNYZKT-UHFFFAOYSA-N 6-aminonaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(N)=CC=C21 NZTPZUIIYNYZKT-UHFFFAOYSA-N 0.000 description 3
- LYRLHBRLOOFCON-UHFFFAOYSA-N 6-nitro-2-[(4-phenylpiperazin-1-yl)methyl]quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN(CC1)CCN1C1=CC=CC=C1 LYRLHBRLOOFCON-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 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
- 230000037396 body weight Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- NRNFKRFWZQQDMD-UHFFFAOYSA-M dichloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=C(Cl)Cl NRNFKRFWZQQDMD-UHFFFAOYSA-M 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- LPXVPYIHRFOTJZ-UHFFFAOYSA-N methyl 6-aminonaphthalene-2-carboxylate Chemical compound C1=C(N)C=CC2=CC(C(=O)OC)=CC=C21 LPXVPYIHRFOTJZ-UHFFFAOYSA-N 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- CHPRFKYDQRKRRK-ZCFIWIBFSA-N (2r)-2-(methoxymethyl)pyrrolidine Chemical compound COC[C@H]1CCCN1 CHPRFKYDQRKRRK-ZCFIWIBFSA-N 0.000 description 2
- XCKDLEDCGWEDOQ-SECBINFHSA-N (2r)-2-[[2-(methoxymethoxy)-5-nitrophenoxy]methyl]oxirane Chemical compound COCOC1=CC=C([N+]([O-])=O)C=C1OC[C@@H]1OC1 XCKDLEDCGWEDOQ-SECBINFHSA-N 0.000 description 2
- XCKDLEDCGWEDOQ-VIFPVBQESA-N (2s)-2-[[2-(methoxymethoxy)-5-nitrophenoxy]methyl]oxirane Chemical compound COCOC1=CC=C([N+]([O-])=O)C=C1OC[C@H]1OC1 XCKDLEDCGWEDOQ-VIFPVBQESA-N 0.000 description 2
- STFCEHQRFPIJQR-VIFPVBQESA-N (3s)-1-(6-amino-1-methylbenzimidazol-2-yl)pyrrolidin-3-ol Chemical compound N=1C2=CC=C(N)C=C2N(C)C=1N1CC[C@H](O)C1 STFCEHQRFPIJQR-VIFPVBQESA-N 0.000 description 2
- JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical group O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 2
- CWRRKRGYQNLVBU-UHFFFAOYSA-N (5-amino-1-benzothiophen-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC2=CC(N)=CC=C2S1 CWRRKRGYQNLVBU-UHFFFAOYSA-N 0.000 description 2
- RZJDNTBSGPAANZ-UHFFFAOYSA-N (5-amino-1-benzothiophen-2-yl)-piperidin-1-ylmethanone Chemical compound C=1C2=CC(N)=CC=C2SC=1C(=O)N1CCCCC1 RZJDNTBSGPAANZ-UHFFFAOYSA-N 0.000 description 2
- UDSJBTQHEYUGMF-BTJKTKAUSA-N (z)-but-2-enedioic acid;6-(4-methylphenyl)-3-[2-(pyrrolidin-1-ylmethyl)-1-benzofuran-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound OC(=O)\C=C/C(O)=O.C1=CC(C)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=C(CN4CCCC4)OC3=CC=1)C=N2 UDSJBTQHEYUGMF-BTJKTKAUSA-N 0.000 description 2
- TWYNWMMHDUDLKS-UHFFFAOYSA-N 1-(2-pyrrolidin-1-ylethyl)benzimidazol-2-amine Chemical compound NC1=NC2=CC=CC=C2N1CCN1CCCC1 TWYNWMMHDUDLKS-UHFFFAOYSA-N 0.000 description 2
- GIWDNSYJBPPKRQ-UHFFFAOYSA-N 1-(3-methoxypropyl)-n-methyl-5-nitrobenzimidazol-2-amine Chemical compound [O-][N+](=O)C1=CC=C2N(CCCOC)C(NC)=NC2=C1 GIWDNSYJBPPKRQ-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- GEBIDLYXGZLTOJ-UHFFFAOYSA-N 1-[(6-aminonaphthalen-2-yl)methyl]piperidin-4-ol Chemical compound C1=CC2=CC(N)=CC=C2C=C1CN1CCC(O)CC1 GEBIDLYXGZLTOJ-UHFFFAOYSA-N 0.000 description 2
- CKQWIXDWKBDYDL-UHFFFAOYSA-N 1-methyl-2-pyrrolidin-1-ylbenzimidazol-5-amine Chemical compound N=1C2=CC(N)=CC=C2N(C)C=1N1CCCC1 CKQWIXDWKBDYDL-UHFFFAOYSA-N 0.000 description 2
- DEHTZQXUGULDPE-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-3h-benzimidazol-5-amine Chemical compound C1CN(C)CCN1C1=NC2=CC=C(N)C=C2N1 DEHTZQXUGULDPE-UHFFFAOYSA-N 0.000 description 2
- FSZCVSHQVWJBGB-UHFFFAOYSA-N 2-(morpholin-4-ylmethyl)-1-benzothiophen-5-amine Chemical compound C=1C2=CC(N)=CC=C2SC=1CN1CCOCC1 FSZCVSHQVWJBGB-UHFFFAOYSA-N 0.000 description 2
- UTTPTRRZAYUUPN-UHFFFAOYSA-N 2-(morpholin-4-ylmethyl)quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN1CCOCC1 UTTPTRRZAYUUPN-UHFFFAOYSA-N 0.000 description 2
- NITRGJVFBJCZRU-UHFFFAOYSA-N 2-(piperidin-1-ylmethyl)-1-benzothiophen-5-amine Chemical compound C=1C2=CC(N)=CC=C2SC=1CN1CCCCC1 NITRGJVFBJCZRU-UHFFFAOYSA-N 0.000 description 2
- VJKXQVIKIJCJQZ-UHFFFAOYSA-N 2-(pyrrolidin-1-ylmethyl)quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN1CCCC1 VJKXQVIKIJCJQZ-UHFFFAOYSA-N 0.000 description 2
- RNBVCCIKTUIEQF-UHFFFAOYSA-N 2-[(dimethylamino)methyl]quinolin-6-amine Chemical compound C1=C(N)C=CC2=NC(CN(C)C)=CC=C21 RNBVCCIKTUIEQF-UHFFFAOYSA-N 0.000 description 2
- SUDHYNMZBNIDBW-UHFFFAOYSA-N 2-[2-(dimethylamino)-5-nitrobenzimidazol-1-yl]ethanol Chemical group [O-][N+](=O)C1=CC=C2N(CCO)C(N(C)C)=NC2=C1 SUDHYNMZBNIDBW-UHFFFAOYSA-N 0.000 description 2
- AALAFRCTXXQRKK-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)piperidin-1-yl]methyl]-6-nitroquinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN(CC1)CCC1C1=CC=C(F)C=C1 AALAFRCTXXQRKK-UHFFFAOYSA-N 0.000 description 2
- BAAUCXCLMDAZEL-UHFFFAOYSA-N 2-bromo-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1Br BAAUCXCLMDAZEL-UHFFFAOYSA-N 0.000 description 2
- UXZYKSFMGDWHGJ-UHFFFAOYSA-N 2-chloro-1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C(Cl)=NC2=C1 UXZYKSFMGDWHGJ-UHFFFAOYSA-N 0.000 description 2
- ILYJVWRIZRFLCK-UHFFFAOYSA-N 2-chloro-1-methylbenzimidazole dimethyl sulfate Chemical compound COS(=O)(=O)OC.ClC1=NC2=C(N1C)C=CC=C2 ILYJVWRIZRFLCK-UHFFFAOYSA-N 0.000 description 2
- KJVBJICWGQIMOZ-UHFFFAOYSA-N 2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1F KJVBJICWGQIMOZ-UHFFFAOYSA-N 0.000 description 2
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 2
- TYJFYUVDUUACKX-UHFFFAOYSA-N 2-methylquinolin-6-amine Chemical compound C1=C(N)C=CC2=NC(C)=CC=C21 TYJFYUVDUUACKX-UHFFFAOYSA-N 0.000 description 2
- ATSINGARJSBJPD-UHFFFAOYSA-N 2-morpholin-4-yl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1N1CCOCC1 ATSINGARJSBJPD-UHFFFAOYSA-N 0.000 description 2
- LZOWVCCALXJHCX-UHFFFAOYSA-N 2-n,2-n,1-trimethylbenzimidazole-2,5-diamine Chemical compound NC1=CC=C2N(C)C(N(C)C)=NC2=C1 LZOWVCCALXJHCX-UHFFFAOYSA-N 0.000 description 2
- CFLGSXQNLPVSMG-UHFFFAOYSA-N 2-n,2-n,3-trimethylbenzimidazole-2,5-diamine Chemical compound C1=C(N)C=C2N(C)C(N(C)C)=NC2=C1 CFLGSXQNLPVSMG-UHFFFAOYSA-N 0.000 description 2
- LDNMFBVTFGBUQE-UHFFFAOYSA-N 2-n-(2-pyrrolidin-1-ylethyl)-3h-benzimidazole-2,5-diamine Chemical compound N1C2=CC(N)=CC=C2N=C1NCCN1CCCC1 LDNMFBVTFGBUQE-UHFFFAOYSA-N 0.000 description 2
- QACKLJSVCAYRNI-UHFFFAOYSA-N 2-n-methyl-3h-benzimidazole-2,5-diamine Chemical compound C1=C(N)C=C2NC(NC)=NC2=C1 QACKLJSVCAYRNI-UHFFFAOYSA-N 0.000 description 2
- OEWXPUJPUSCQMA-UHFFFAOYSA-N 3-(2-amino-1-phenylbenzimidazol-5-yl)-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC1=NC2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2N1C1=CC=CC=C1 OEWXPUJPUSCQMA-UHFFFAOYSA-N 0.000 description 2
- FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 2
- IFNLHIRHJNDMBM-UHFFFAOYSA-N 3h-benzimidazole-2,5-diamine Chemical compound C1=C(N)C=C2NC(N)=NC2=C1 IFNLHIRHJNDMBM-UHFFFAOYSA-N 0.000 description 2
- AFYALJSDFPSAAZ-UHFFFAOYSA-N 4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1CCNCC1 AFYALJSDFPSAAZ-UHFFFAOYSA-N 0.000 description 2
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-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
- YLNMKOAPZKIZAU-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(4-methylpiperazin-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1CN(C)CCN1CC1=CC=C(C=C(C=C2)N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)C2=N1 YLNMKOAPZKIZAU-UHFFFAOYSA-N 0.000 description 2
- ODMRZHCWTPHENJ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCC(CC4)C=4C=CC=CC=4)=NC3=CC=1)C=N2 ODMRZHCWTPHENJ-UHFFFAOYSA-N 0.000 description 2
- RAXCDNRFFLXBJM-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(dimethylamino)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC2=NC(CN(C)C)=CC=C2C=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 RAXCDNRFFLXBJM-UHFFFAOYSA-N 0.000 description 2
- XDACWJTYIVEDBG-UHFFFAOYSA-N 6-(pyrrolidin-1-ylmethyl)naphthalen-2-amine Chemical compound C1=CC2=CC(N)=CC=C2C=C1CN1CCCC1 XDACWJTYIVEDBG-UHFFFAOYSA-N 0.000 description 2
- SOIJOIZOKGTWKB-UHFFFAOYSA-N 7-chloro-3-[2-(chloromethyl)quinolin-6-yl]quinazolin-4-one Chemical compound C1=NC2=CC(Cl)=CC=C2C(=O)N1C1=CC2=CC=C(CCl)N=C2C=C1 SOIJOIZOKGTWKB-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- HDUHGHUBQYHGRV-UHFFFAOYSA-N [N+](=O)([O-])CC1=CC=C(C=C1)S(=O)(=O)O.C1(CCCCC1)N=C=NCCN1CCOCC1 Chemical compound [N+](=O)([O-])CC1=CC=C(C=C1)S(=O)(=O)O.C1(CCCCC1)N=C=NCCN1CCOCC1 HDUHGHUBQYHGRV-UHFFFAOYSA-N 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229910000086 alane Inorganic materials 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
- 229960001058 bupropion Drugs 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 235000015220 hamburgers Nutrition 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- BKIUKKCYXXNBIP-UHFFFAOYSA-N morpholin-4-yl-(5-nitro-1-benzothiophen-2-yl)methanone Chemical compound C=1C2=CC([N+](=O)[O-])=CC=C2SC=1C(=O)N1CCOCC1 BKIUKKCYXXNBIP-UHFFFAOYSA-N 0.000 description 2
- AAIJIFVGZFZMOW-UHFFFAOYSA-N n,n-dimethylcarbamimidoyl chloride Chemical compound CN(C)C(Cl)=N AAIJIFVGZFZMOW-UHFFFAOYSA-N 0.000 description 2
- NZYUIUZGOFCPLB-UHFFFAOYSA-N n-(2-morpholin-4-ylethyl)-2,4-dinitroaniline Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC=C1NCCN1CCOCC1 NZYUIUZGOFCPLB-UHFFFAOYSA-N 0.000 description 2
- QDYPYXXYHITULK-UHFFFAOYSA-N n-[6-(chloromethyl)naphthalen-2-yl]-2,2-dimethylpropanamide Chemical compound C1=C(CCl)C=CC2=CC(NC(=O)C(C)(C)C)=CC=C21 QDYPYXXYHITULK-UHFFFAOYSA-N 0.000 description 2
- KEQNUFACDKGLKQ-UHFFFAOYSA-N n-[6-(hydroxymethyl)naphthalen-2-yl]-2,2-dimethylpropanamide Chemical compound C1=C(CO)C=CC2=CC(NC(=O)C(C)(C)C)=CC=C21 KEQNUFACDKGLKQ-UHFFFAOYSA-N 0.000 description 2
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical group NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000006501 nitrophenyl group Chemical group 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- OIHLDTCGGKKINI-UHFFFAOYSA-N tert-butyl N-[2-[5-amino-2-(dimethylamino)benzimidazol-1-yl]ethyl]carbamate Chemical compound NC1=CC2=C(N(C(=N2)N(C)C)CCNC(OC(C)(C)C)=O)C=C1 OIHLDTCGGKKINI-UHFFFAOYSA-N 0.000 description 2
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical group CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- OBFVWUKSMRIYJJ-SECBINFHSA-N (2r)-2-[(dimethylamino)methyl]-2,3-dihydro-1,4-benzodioxin-6-amine Chemical group NC1=CC=C2O[C@H](CN(C)C)COC2=C1 OBFVWUKSMRIYJJ-SECBINFHSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical group OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- SJZMIZIVYIOMIW-UHFFFAOYSA-N (4-methylcyclohexen-1-yl)boronic acid Chemical compound CC1CCC(B(O)O)=CC1 SJZMIZIVYIOMIW-UHFFFAOYSA-N 0.000 description 1
- ZGOFWQZAPZRBSR-UHFFFAOYSA-N (5-amino-1-benzothiophen-2-yl)-(4-phenylpiperazin-1-yl)methanone Chemical compound C=1C2=CC(N)=CC=C2SC=1C(=O)N(CC1)CCN1C1=CC=CC=C1 ZGOFWQZAPZRBSR-UHFFFAOYSA-N 0.000 description 1
- UDFINEKTIZVXIB-UHFFFAOYSA-N (5-amino-1-benzothiophen-2-yl)-(4-phenylpiperidin-1-yl)methanone Chemical compound C=1C2=CC(N)=CC=C2SC=1C(=O)N(CC1)CCC1C1=CC=CC=C1 UDFINEKTIZVXIB-UHFFFAOYSA-N 0.000 description 1
- GXPNBHVGVOPTET-SNVBAGLBSA-N (5-amino-1-benzothiophen-2-yl)-[(3r)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound C=1C2=CC(N)=CC=C2SC=1C(=O)N1CC[C@@H](O)C1 GXPNBHVGVOPTET-SNVBAGLBSA-N 0.000 description 1
- QLLFUMWZSKLVAI-UHFFFAOYSA-N (5-amino-1-benzothiophen-2-yl)-morpholin-4-ylmethanone Chemical compound C=1C2=CC(N)=CC=C2SC=1C(=O)N1CCOCC1 QLLFUMWZSKLVAI-UHFFFAOYSA-N 0.000 description 1
- KKQLJJHKFRREOT-UHFFFAOYSA-N (5-nitro-1-benzothiophen-2-yl)-(4-phenylpiperidin-1-yl)methanone Chemical compound C=1C2=CC([N+](=O)[O-])=CC=C2SC=1C(=O)N(CC1)CCC1C1=CC=CC=C1 KKQLJJHKFRREOT-UHFFFAOYSA-N 0.000 description 1
- XWMQCYNSLNSYDQ-UHFFFAOYSA-N (6-aminonaphthalen-2-yl)-pyrrolidin-1-ylmethanone Chemical compound C1=CC2=CC(N)=CC=C2C=C1C(=O)N1CCCC1 XWMQCYNSLNSYDQ-UHFFFAOYSA-N 0.000 description 1
- CZPGEXFVAUMAID-UHFFFAOYSA-N (6-aminonaphthalen-2-yl)methanol Chemical compound C1=C(CO)C=CC2=CC(N)=CC=C21 CZPGEXFVAUMAID-UHFFFAOYSA-N 0.000 description 1
- CTKINSOISVBQLD-GSVOUGTGSA-N (R)-Glycidol Chemical compound OC[C@@H]1CO1 CTKINSOISVBQLD-GSVOUGTGSA-N 0.000 description 1
- CTKINSOISVBQLD-VKHMYHEASA-N (S)-Glycidol Chemical group OC[C@H]1CO1 CTKINSOISVBQLD-VKHMYHEASA-N 0.000 description 1
- PWJDADFQYZTUAQ-UITAMQMPSA-N (z)-3-chloro-3-(4-nitrophenyl)prop-2-enenitrile Chemical compound [O-][N+](=O)C1=CC=C(C(\Cl)=C\C#N)C=C1 PWJDADFQYZTUAQ-UITAMQMPSA-N 0.000 description 1
- KUEHNDLYGQZCDU-UHFFFAOYSA-N 1,4-dimethyl-5-nitrobenzimidazol-2-amine Chemical compound CC1=C([N+]([O-])=O)C=CC2=C1N=C(N)N2C KUEHNDLYGQZCDU-UHFFFAOYSA-N 0.000 description 1
- RMGFLMXDCGQKPS-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine Chemical compound ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 1
- ZDOYHCIRUPHUHN-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Cl ZDOYHCIRUPHUHN-UHFFFAOYSA-N 0.000 description 1
- AQMHBKNDKRGOFD-UHFFFAOYSA-N 1-(2-pyrrolidin-1-ylethyl)benzimidazol-5-amine Chemical compound C1=NC2=CC(N)=CC=C2N1CCN1CCCC1 AQMHBKNDKRGOFD-UHFFFAOYSA-N 0.000 description 1
- NRSHDCXOQUDIEI-UHFFFAOYSA-N 1-(3-chloropropyl)-n,n-dimethyl-5-nitrobenzimidazol-2-amine Chemical compound [O-][N+](=O)C1=CC=C2N(CCCCl)C(N(C)C)=NC2=C1 NRSHDCXOQUDIEI-UHFFFAOYSA-N 0.000 description 1
- DRSAOTYHHCWSOL-UHFFFAOYSA-N 1-(3-methoxypropyl)-2-n-methylbenzimidazole-2,5-diamine Chemical compound NC1=CC=C2N(CCCOC)C(NC)=NC2=C1 DRSAOTYHHCWSOL-UHFFFAOYSA-N 0.000 description 1
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- RHTVQEPJVKUMPI-UHFFFAOYSA-N 2,4-dinitro-n-phenylaniline Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC=C1NC1=CC=CC=C1 RHTVQEPJVKUMPI-UHFFFAOYSA-N 0.000 description 1
- SPMLMLQATWNZEE-UHFFFAOYSA-N 2-(chloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CCl)=NC2=C1 SPMLMLQATWNZEE-UHFFFAOYSA-N 0.000 description 1
- SQTDRFSBROPENI-UHFFFAOYSA-N 2-N,2-N-dimethyl-1-(2-morpholin-4-ylethyl)benzimidazole-2,5-diamine Chemical compound CN(C1=NC2=C(N1CCN1CCOCC1)C=CC(=C2)N)C SQTDRFSBROPENI-UHFFFAOYSA-N 0.000 description 1
- YLTFKOCWNQBGNP-UHFFFAOYSA-N 2-N,3-dimethyl-2-N-(2-pyrrolidin-1-ylethyl)benzimidazole-2,5-diamine Chemical compound CN(C1=NC2=C(N1C)C=C(C=C2)N)CCN2CCCC2 YLTFKOCWNQBGNP-UHFFFAOYSA-N 0.000 description 1
- ALSKYUJVXULHBQ-UHFFFAOYSA-N 2-[(4-methylpiperazin-1-yl)methyl]-1-benzothiophen-5-amine Chemical compound C1CN(C)CCN1CC1=CC2=CC(N)=CC=C2S1 ALSKYUJVXULHBQ-UHFFFAOYSA-N 0.000 description 1
- GMJZGJFAMURIMD-UHFFFAOYSA-N 2-[(4-methylpiperazin-1-yl)methyl]quinolin-6-amine Chemical compound C1CN(C)CCN1CC1=CC=C(C=C(N)C=C2)C2=N1 GMJZGJFAMURIMD-UHFFFAOYSA-N 0.000 description 1
- WSZQNEFKZKGHJD-UHFFFAOYSA-N 2-[(4-phenylpiperazin-1-yl)methyl]-1-benzothiophen-5-amine Chemical compound C=1C2=CC(N)=CC=C2SC=1CN(CC1)CCN1C1=CC=CC=C1 WSZQNEFKZKGHJD-UHFFFAOYSA-N 0.000 description 1
- VSRBDXNMFGFCDJ-UHFFFAOYSA-N 2-[(4-phenylpiperidin-1-yl)methyl]-1-benzothiophen-5-amine Chemical compound C=1C2=CC(N)=CC=C2SC=1CN(CC1)CCC1C1=CC=CC=C1 VSRBDXNMFGFCDJ-UHFFFAOYSA-N 0.000 description 1
- NSWIQZJMXNVPAF-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-benzothiophen-5-amine Chemical compound NC1=CC=C2SC(CN(C)C)=CC2=C1 NSWIQZJMXNVPAF-UHFFFAOYSA-N 0.000 description 1
- RGNOTAVFDJWYLE-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-3,4-dihydro-2h-1,4-benzoxazin-6-amine Chemical group NC1=CC=C2OC(CN(C)C)CNC2=C1 RGNOTAVFDJWYLE-UHFFFAOYSA-N 0.000 description 1
- YSQPDQWTQJTPQT-UHFFFAOYSA-N 2-[(dimethylamino)methyl]quinolin-6-amine N,N-dimethyl-1-(6-nitroquinolin-2-yl)methanamine Chemical compound CN(CC1=NC2=CC=C(C=C2C=C1)[N+](=O)[O-])C.CN(C)CC1=NC2=CC=C(C=C2C=C1)N YSQPDQWTQJTPQT-UHFFFAOYSA-N 0.000 description 1
- YDJMSLGMROYGTC-UHFFFAOYSA-N 2-[2-(dimethylamino)-6-nitrobenzimidazol-1-yl]ethanol Chemical group C1=C([N+]([O-])=O)C=C2N(CCO)C(N(C)C)=NC2=C1 YDJMSLGMROYGTC-UHFFFAOYSA-N 0.000 description 1
- QIMWOOBHVIUZIP-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)piperidin-1-yl]methyl]quinolin-6-amine Chemical compound C1=CC2=CC(N)=CC=C2N=C1CN(CC1)CCC1C1=CC=C(F)C=C1 QIMWOOBHVIUZIP-UHFFFAOYSA-N 0.000 description 1
- GYSVCGUNMIZIAD-UHFFFAOYSA-N 2-amino-4-chloro-n-(2-methylquinolin-6-yl)benzamide Chemical compound C1=CC2=NC(C)=CC=C2C=C1NC(=O)C1=CC=C(Cl)C=C1N GYSVCGUNMIZIAD-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical group OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- QNYFEUMEQHKASR-UHFFFAOYSA-N 2-chloro-1-methyl-5-nitrobenzimidazole Chemical compound [O-][N+](=O)C1=CC=C2N(C)C(Cl)=NC2=C1 QNYFEUMEQHKASR-UHFFFAOYSA-N 0.000 description 1
- QLHVJBXAQWPEDI-UHFFFAOYSA-N 2-chloro-3,5-dinitropyridine Chemical group [O-][N+](=O)C1=CN=C(Cl)C([N+]([O-])=O)=C1 QLHVJBXAQWPEDI-UHFFFAOYSA-N 0.000 description 1
- VFVHWCKUHAEDMY-UHFFFAOYSA-N 2-chloro-5-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=O)=C1 VFVHWCKUHAEDMY-UHFFFAOYSA-N 0.000 description 1
- GWSMACGSFHRVFA-UHFFFAOYSA-N 2-chloro-6-nitro-1h-benzimidazole Chemical compound [O-][N+](=O)C1=CC=C2N=C(Cl)NC2=C1 GWSMACGSFHRVFA-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical group COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- QHBIGTKXNYVNMD-UHFFFAOYSA-N 2-n-(2-methoxyethyl)-2-n,1-dimethylbenzimidazole-2,5-diamine Chemical compound NC1=CC=C2N(C)C(N(C)CCOC)=NC2=C1 QHBIGTKXNYVNMD-UHFFFAOYSA-N 0.000 description 1
- PJPWWFOTVSPFFE-UHFFFAOYSA-N 2-n-methyl-1-phenylbenzimidazole-2,5-diamine Chemical compound CNC1=NC2=CC(N)=CC=C2N1C1=CC=CC=C1 PJPWWFOTVSPFFE-UHFFFAOYSA-N 0.000 description 1
- MRBQLPFDEIEQGP-UHFFFAOYSA-N 2-pyrrolidin-1-yl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1N1CCCC1 MRBQLPFDEIEQGP-UHFFFAOYSA-N 0.000 description 1
- LCLYWJDPJMDAQN-UHFFFAOYSA-N 3-(4-methoxyphenyl)-1,1-dimethylurea Chemical compound COC1=CC=C(NC(=O)N(C)C)C=C1 LCLYWJDPJMDAQN-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- GYUUGQVCEFOBMA-UHFFFAOYSA-N 3-[2-(dimethylamino)-3-methylbenzimidazol-5-yl]-6-(4-nitrophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C2N(C)C(N(C)C)=NC2=CC=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C([N+]([O-])=O)C=C1 GYUUGQVCEFOBMA-UHFFFAOYSA-N 0.000 description 1
- MTPKKZOKDAJSHL-UHFFFAOYSA-N 3-[2-[(dimethylamino)methyl]quinolin-6-yl]-7-(4-fluorophenyl)quinazolin-4-one Chemical compound C1=CC2=NC(CN(C)C)=CC=C2C=C1N(C(C1=CC=2)=O)C=NC1=CC=2C1=CC=C(F)C=C1 MTPKKZOKDAJSHL-UHFFFAOYSA-N 0.000 description 1
- GBOBZKIXDFDVRH-UHFFFAOYSA-N 3-amino-5-(4-fluorophenyl)thiophene-2-carboxylic acid Chemical group S1C(C(O)=O)=C(N)C=C1C1=CC=C(F)C=C1 GBOBZKIXDFDVRH-UHFFFAOYSA-N 0.000 description 1
- PSUXTZLDBVEZTD-UHFFFAOYSA-N 3-bromopropoxymethylbenzene Chemical compound BrCCCOCC1=CC=CC=C1 PSUXTZLDBVEZTD-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- VPBWZBGZWHDNKL-UHFFFAOYSA-N 3-pyrrolidin-1-ylpropan-1-amine Chemical compound NCCCN1CCCC1 VPBWZBGZWHDNKL-UHFFFAOYSA-N 0.000 description 1
- RSSIMZHMCQZVMX-UHFFFAOYSA-N 4-[2-(5-nitrobenzimidazol-1-yl)ethyl]morpholine Chemical group C1=NC2=CC([N+](=O)[O-])=CC=C2N1CCN1CCOCC1 RSSIMZHMCQZVMX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- MMJYSVRCFSCVCI-UHFFFAOYSA-N 4-chloro-2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C(Cl)=O MMJYSVRCFSCVCI-UHFFFAOYSA-N 0.000 description 1
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 description 1
- XJNPNXSISMKQEX-UHFFFAOYSA-N 4-nitrocatechol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1O XJNPNXSISMKQEX-UHFFFAOYSA-N 0.000 description 1
- LXJRAFNQLZHUFK-UHFFFAOYSA-N 5-nitro-1-benzofuran-2-carboxylic acid (5-nitro-1-benzofuran-2-yl)-pyrrolidin-1-ylmethanone Chemical compound [N+](=O)([O-])C=1C=CC2=C(C=C(O2)C(=O)O)C1.[N+](=O)([O-])C=1C=CC2=C(C=C(O2)C(=O)N2CCCC2)C1 LXJRAFNQLZHUFK-UHFFFAOYSA-N 0.000 description 1
- DASVYRORIVFNNR-UHFFFAOYSA-N 5-nitro-1-phenylbenzimidazol-2-amine Chemical compound NC1=NC2=CC([N+]([O-])=O)=CC=C2N1C1=CC=CC=C1 DASVYRORIVFNNR-UHFFFAOYSA-N 0.000 description 1
- CDUDDFAXMJGYHS-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-(2-morpholin-4-yl-3h-benzimidazol-5-yl)thieno[3,2-d]pyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3NC(=NC3=CC=1)N1CCOCC1)C=N2 CDUDDFAXMJGYHS-UHFFFAOYSA-N 0.000 description 1
- YDLGNVWJHFYQGT-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[1-(2-morpholin-4-ylethyl)benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3N=CN(CCN4CCOCC4)C3=CC=1)C=N2 YDLGNVWJHFYQGT-UHFFFAOYSA-N 0.000 description 1
- LAOLAICCPSJBOW-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(2-pyrrolidin-1-ylethylamino)-3h-benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3N=C(NCCN4CCCC4)NC3=CC=1)C=N2 LAOLAICCPSJBOW-UHFFFAOYSA-N 0.000 description 1
- NFJNDCDJCMFMRC-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(dimethylamino)-1-(2-hydroxyethyl)benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C=1C=C2N(CCO)C(N(C)C)=NC2=CC=1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 NFJNDCDJCMFMRC-UHFFFAOYSA-N 0.000 description 1
- PFFMJYGFJRSMTK-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(dimethylamino)-1-(2-morpholin-4-ylethyl)benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound CN(C)C1=NC2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2N1CCN1CCOCC1 PFFMJYGFJRSMTK-UHFFFAOYSA-N 0.000 description 1
- SIMIMDQKZHJQIP-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(methylamino)-1-(2-morpholin-4-ylethyl)benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CNC1=NC2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2N1CCN1CCOCC1 SIMIMDQKZHJQIP-UHFFFAOYSA-N 0.000 description 1
- QUPILHSZFLDDLG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(morpholin-4-ylmethyl)-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=C(CN4CCOCC4)SC3=CC=1)C=N2 QUPILHSZFLDDLG-UHFFFAOYSA-N 0.000 description 1
- UBGBTGVLKSVQKG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(morpholin-4-ylmethyl)quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCOCC4)=NC3=CC=1)C=N2 UBGBTGVLKSVQKG-UHFFFAOYSA-N 0.000 description 1
- PVFOJNGXRJKDMG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-(piperidin-1-ylmethyl)-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=C(CN4CCCCC4)SC3=CC=1)C=N2 PVFOJNGXRJKDMG-UHFFFAOYSA-N 0.000 description 1
- CSIWZRJTSWJCKM-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(4-phenylpiperazin-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCN(CC4)C=4C=CC=CC=4)=NC3=CC=1)C=N2 CSIWZRJTSWJCKM-UHFFFAOYSA-N 0.000 description 1
- NRMDDYSFIYWXTP-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(4-phenylpiperidin-1-yl)methyl]-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=C(CN4CCC(CC4)C=4C=CC=CC=4)SC3=CC=1)C=N2 NRMDDYSFIYWXTP-UHFFFAOYSA-N 0.000 description 1
- XJMIODNDCXPYKT-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(dimethylamino)methyl]-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C=1C=C2SC(CN(C)C)=CC2=CC=1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 XJMIODNDCXPYKT-UHFFFAOYSA-N 0.000 description 1
- WWPGTYXGCMWETG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[(dimethylamino)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C=1C=C2OC(CN(C)C)COC2=CC=1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 WWPGTYXGCMWETG-UHFFFAOYSA-N 0.000 description 1
- NYCMABQJWBVKHY-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[2-methoxyethyl(methyl)amino]-1-methylbenzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.C=1C=C2N(C)C(N(C)CCOC)=NC2=CC=1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 NYCMABQJWBVKHY-UHFFFAOYSA-N 0.000 description 1
- ZDFHQJRHOKOKEF-LJQANCHMSA-N 6-(4-chlorophenyl)-3-[2-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-1-benzothiophen-5-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1[C@H](O)CCN1CC1=CC2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2S1 ZDFHQJRHOKOKEF-LJQANCHMSA-N 0.000 description 1
- RQJWJHHGWVZDIQ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[[4-(4-fluorophenyl)piperidin-1-yl]methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C1CCN(CC=2N=C3C=CC(=CC3=CC=2)N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)CC1 RQJWJHHGWVZDIQ-UHFFFAOYSA-N 0.000 description 1
- SKNZPZRUVKYVNL-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[2-[methyl(2-pyrrolidin-1-ylethyl)amino]-3h-benzimidazol-5-yl]thieno[3,2-d]pyrimidin-4-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.N=1C2=CC(N3C(C=4SC(=CC=4N=C3)C=3C=CC(Cl)=CC=3)=O)=CC=C2NC=1N(C)CCN1CCCC1 SKNZPZRUVKYVNL-UHFFFAOYSA-N 0.000 description 1
- LGQRXFXMSKWBCD-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[6-(hydroxymethyl)naphthalen-2-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC2=CC(CO)=CC=C2C=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 LGQRXFXMSKWBCD-UHFFFAOYSA-N 0.000 description 1
- UODVREUPOUDRNR-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[6-(pyrrolidin-1-ylmethyl)naphthalen-2-yl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C3C=CC(CN4CCCC4)=CC3=CC=1)C=N2 UODVREUPOUDRNR-UHFFFAOYSA-N 0.000 description 1
- LOMNCPDMOWHWMC-UHFFFAOYSA-N 6-[(dimethylamino)methyl]naphthalen-2-amine Chemical compound C1=C(N)C=CC2=CC(CN(C)C)=CC=C21 LOMNCPDMOWHWMC-UHFFFAOYSA-N 0.000 description 1
- FZCMEXXHMHFHRR-UHFFFAOYSA-N 6-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-n,n-dimethylquinoline-2-carboxamide Chemical compound C1=CC2=NC(C(=O)N(C)C)=CC=C2C=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 FZCMEXXHMHFHRR-UHFFFAOYSA-N 0.000 description 1
- UEPWMGSYZCLGTA-UHFFFAOYSA-N 6-nitro-2-(piperidin-1-ylmethyl)quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN1CCCCC1 UEPWMGSYZCLGTA-UHFFFAOYSA-N 0.000 description 1
- DDIHBRSLYYKIDQ-UHFFFAOYSA-N 6-nitro-2-(pyrrolidin-1-ylmethyl)quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN1CCCC1 DDIHBRSLYYKIDQ-UHFFFAOYSA-N 0.000 description 1
- ACDCXROWTQJSBF-UHFFFAOYSA-N 6-nitro-2-[(4-phenylpiperidin-1-yl)methyl]quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN(CC1)CCC1C1=CC=CC=C1 ACDCXROWTQJSBF-UHFFFAOYSA-N 0.000 description 1
- QMBQXTXZWWUHDK-UHFFFAOYSA-N 6-nitro-2-[[4-[4-(trifluoromethyl)phenyl]piperidin-1-yl]methyl]quinoline Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N=C1CN(CC1)CCC1C1=CC=C(C(F)(F)F)C=C1 QMBQXTXZWWUHDK-UHFFFAOYSA-N 0.000 description 1
- OLVIMDBYIORTQQ-UHFFFAOYSA-N 6-nitro-n-(2-pyrrolidin-1-ylethyl)-1h-benzimidazol-2-amine Chemical compound N1C2=CC([N+](=O)[O-])=CC=C2N=C1NCCN1CCCC1 OLVIMDBYIORTQQ-UHFFFAOYSA-N 0.000 description 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
- LHFFMAAGRIIVQV-UHFFFAOYSA-N 7-(4-chlorophenyl)-3-[2-[(dimethylamino)methyl]quinolin-6-yl]quinazolin-4-one Chemical compound C1=CC2=NC(CN(C)C)=CC=C2C=C1N(C(C1=CC=2)=O)C=NC1=CC=2C1=CC=C(Cl)C=C1 LHFFMAAGRIIVQV-UHFFFAOYSA-N 0.000 description 1
- FQBRCNWQFPWNAY-UHFFFAOYSA-N 7-chloro-3-(2-methyl-1-oxidoquinolin-1-ium-6-yl)quinazolin-4-one Chemical compound C1=NC2=CC(Cl)=CC=C2C(=O)N1C1=CC2=CC=C(C)[N+]([O-])=C2C=C1 FQBRCNWQFPWNAY-UHFFFAOYSA-N 0.000 description 1
- KXXVCAUNRXWQND-UHFFFAOYSA-N 7-chloro-3-(2-methylquinolin-6-yl)quinazolin-4-one Chemical compound C1=NC2=CC(Cl)=CC=C2C(=O)N1C1=CC2=CC=C(C)N=C2C=C1 KXXVCAUNRXWQND-UHFFFAOYSA-N 0.000 description 1
- PORJLQKWTXZDBE-UHFFFAOYSA-N 7-chloro-3-[2-[(dimethylamino)methyl]quinolin-6-yl]quinazolin-4-one Chemical compound C1=NC2=CC(Cl)=CC=C2C(=O)N1C1=CC2=CC=C(CN(C)C)N=C2C=C1 PORJLQKWTXZDBE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- ALWFLYMKFZJTBB-RQZCQDPDSA-N CN(C)/C=N/C1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 Chemical compound CN(C)/C=N/C1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 ALWFLYMKFZJTBB-RQZCQDPDSA-N 0.000 description 1
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical group NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 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
- 208000020401 Depressive disease Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- CZYYYDWBZQAEIA-UHFFFAOYSA-N FC(C(=O)O)(F)F.ClC1=CC=C(C=C1)C1=CC=2N=CN(C(C2S1)=O)C=1C=C2C=CC(=NC2=CC1)CNC Chemical compound FC(C(=O)O)(F)F.ClC1=CC=C(C=C1)C1=CC=2N=CN(C(C2S1)=O)C=1C=C2C=CC(=NC2=CC1)CNC CZYYYDWBZQAEIA-UHFFFAOYSA-N 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 241000206672 Gelidium Species 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
- 239000007821 HATU Substances 0.000 description 1
- 101700012268 Holin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101500028288 Homo sapiens Melanin-concentrating hormone Proteins 0.000 description 1
- 206010020710 Hyperphagia 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
- 208000015580 Increased body weight Diseases 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 101150104680 MCH1 gene Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 description 1
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SLKXGTOMVBNIJZ-UHFFFAOYSA-N N-[6-[(4-hydroxypiperidin-1-yl)methyl]naphthalen-2-yl]-2,2-dimethylpropanamide Chemical compound OC1CCN(CC1)CC=1C=C2C=CC(=CC2=CC1)NC(C(C)(C)C)=O SLKXGTOMVBNIJZ-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- WMGIJMCZOFMTPY-UHFFFAOYSA-N OC(=O)C(F)(F)F.CNc1nc2cc(ccc2[nH]1)-n1cnc2cc(sc2c1=O)-c1ccc(Cl)cc1 Chemical compound OC(=O)C(F)(F)F.CNc1nc2cc(ccc2[nH]1)-n1cnc2cc(sc2c1=O)-c1ccc(Cl)cc1 WMGIJMCZOFMTPY-UHFFFAOYSA-N 0.000 description 1
- DDVFXZIOVDVBOI-UHFFFAOYSA-N OC(=O)C(F)(F)F.Clc1ccc(cc1)-c1cc2ncn(-c3ccc4[nH]c(nc4c3)N3CCCC3)c(=O)c2s1 Chemical compound OC(=O)C(F)(F)F.Clc1ccc(cc1)-c1cc2ncn(-c3ccc4[nH]c(nc4c3)N3CCCC3)c(=O)c2s1 DDVFXZIOVDVBOI-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101100382379 Rattus norvegicus Cap1 gene Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 239000005864 Sulphur Substances 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 201000002380 X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2 Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JHZCHEBIMQDHGT-UHFFFAOYSA-N [N+](=O)([O-])C=1C=C(C(=CC1)N)N.CN(C1=NC2=C(N1)C=CC(=C2)[N+](=O)[O-])C Chemical compound [N+](=O)([O-])C=1C=C(C(=CC1)N)N.CN(C1=NC2=C(N1)C=CC(=C2)[N+](=O)[O-])C JHZCHEBIMQDHGT-UHFFFAOYSA-N 0.000 description 1
- JQZFPGMPLPZPFE-UHFFFAOYSA-N [N+](=O)([O-])C=1C=CC2=C(C=C(O2)C(=O)N2CCCC2)C1.[N+](=O)([O-])C=1C=CC2=C(C=C(O2)CN2CCCC2)C1 Chemical compound [N+](=O)([O-])C=1C=CC2=C(C=C(O2)C(=O)N2CCCC2)C1.[N+](=O)([O-])C=1C=CC2=C(C=C(O2)CN2CCCC2)C1 JQZFPGMPLPZPFE-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N anhydrous methyl chloride Natural products ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 230000001539 anorectic effect Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 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
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- CJYQQUPRURWLOW-YDLUHMIOSA-M dmsc Chemical compound [Na+].OP(=O)=O.OP(=O)=O.OP(=O)=O.[O-]P(=O)=O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O CJYQQUPRURWLOW-YDLUHMIOSA-M 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000005686 eating Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 150000002390 heteroarenes Chemical class 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
- 239000003667 hormone antagonist Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 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
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 208000024714 major depressive disease Diseases 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- UOZZOCYYLNLMSF-UHFFFAOYSA-N methanamine (6-nitroquinolin-2-yl)methanamine Chemical compound CN.[N+](=O)([O-])C=1C=C2C=CC(=NC2=CC1)CN UOZZOCYYLNLMSF-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- YIBRKYVKVWTHEM-UHFFFAOYSA-N methyl 3-amino-5-(4-fluorophenyl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC(F)=CC=2)=C1 YIBRKYVKVWTHEM-UHFFFAOYSA-N 0.000 description 1
- NVUFFVPGEHZJFW-UHFFFAOYSA-N methyl 3-amino-5-(4-nitrophenyl)thiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1 NVUFFVPGEHZJFW-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- CURJNMSGPBXOGK-UHFFFAOYSA-N n',n'-di(propan-2-yl)ethane-1,2-diamine Chemical group CC(C)N(C(C)C)CCN CURJNMSGPBXOGK-UHFFFAOYSA-N 0.000 description 1
- XXZNFWHGOMHWCO-UHFFFAOYSA-N n,n-diethylthiohydroxylamine Chemical compound CCN(S)CC XXZNFWHGOMHWCO-UHFFFAOYSA-N 0.000 description 1
- ZURKMSRAZZOXGT-UHFFFAOYSA-N n,n-dimethyl-1-(6-nitroquinolin-2-yl)methanamine Chemical compound C1=C([N+]([O-])=O)C=CC2=NC(CN(C)C)=CC=C21 ZURKMSRAZZOXGT-UHFFFAOYSA-N 0.000 description 1
- JYDFEZZIGCAYBA-UHFFFAOYSA-N n,n-dimethyl-6-nitro-1h-benzimidazol-2-amine Chemical compound C1=C([N+]([O-])=O)C=C2NC(N(C)C)=NC2=C1 JYDFEZZIGCAYBA-UHFFFAOYSA-N 0.000 description 1
- SGBUHGQBGANFIV-UHFFFAOYSA-N n-(6-formylnaphthalen-2-yl)-2,2-dimethylpropanamide Chemical compound C1=C(C=O)C=CC2=CC(NC(=O)C(C)(C)C)=CC=C21 SGBUHGQBGANFIV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IZZHTEJYHVCMDF-UHFFFAOYSA-N n-methylbenzimidazol-1-amine Chemical compound C1=CC=C2N(NC)C=NC2=C1 IZZHTEJYHVCMDF-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940099990 ogen Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000001956 orexigenic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- UOJMTSCORVQOHS-UHFFFAOYSA-N pachypodol Natural products COc1cc(ccc1O)C2=C(C)C(=O)c3c(O)cc(C)cc3O2 UOJMTSCORVQOHS-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 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
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- JTTWNTXHFYNETH-UHFFFAOYSA-N propyl 4-methylbenzenesulfonate Chemical compound CCCOS(=O)(=O)C1=CC=C(C)C=C1 JTTWNTXHFYNETH-UHFFFAOYSA-N 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- RJSRSRITMWVIQT-UHFFFAOYSA-N quinolin-6-amine Chemical compound N1=CC=CC2=CC(N)=CC=C21 RJSRSRITMWVIQT-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 1
- 229960003015 rimonabant Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 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
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000004722 stifle Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005750 substituted cyclic group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- PTVRCUVHYMGECC-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)piperidine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCCCC1CN PTVRCUVHYMGECC-UHFFFAOYSA-N 0.000 description 1
- GEJPLVOHYPGIAY-UHFFFAOYSA-N tert-butyl N-[(6-aminoquinolin-2-yl)methyl]-N-methylcarbamate Chemical compound NC=1C=C2C=CC(=NC2=CC1)CN(C(OC(C)(C)C)=O)C GEJPLVOHYPGIAY-UHFFFAOYSA-N 0.000 description 1
- OITFYTCMMXPDPM-UHFFFAOYSA-N tert-butyl N-[2-[2-(dimethylamino)-5-nitrobenzimidazol-1-yl]ethyl]carbamate Chemical compound CN(C1=NC2=C(N1CCNC(OC(C)(C)C)=O)C=CC(=C2)[N+](=O)[O-])C OITFYTCMMXPDPM-UHFFFAOYSA-N 0.000 description 1
- GRFXJRYAOWIDIE-UHFFFAOYSA-N tert-butyl N-[2-[5-amino-2-(dimethylamino)benzimidazol-1-yl]ethyl]-N-methylcarbamate Chemical compound NC1=CC2=C(N(C(=N2)N(C)C)CCN(C(OC(C)(C)C)=O)C)C=C1 GRFXJRYAOWIDIE-UHFFFAOYSA-N 0.000 description 1
- QYJVBVKFXDHFPQ-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)-n-methylcarbamate Chemical group NCCN(C)C(=O)OC(C)(C)C QYJVBVKFXDHFPQ-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- HNDGEYCCZGRMTN-UHFFFAOYSA-N thieno[3,2-f:4,5-f]bis[1]benzothiophene Chemical compound S1C2=CC=3SC=CC=3C=C2C2=C1C=C(SC=C1)C1=C2 HNDGEYCCZGRMTN-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 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
- 238000001665 trituration Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46229203P | 2003-04-11 | 2003-04-11 | |
| US60/462,292 | 2003-04-11 | ||
| PCT/US2004/010518 WO2004092181A1 (en) | 2003-04-11 | 2004-04-06 | Heterocyclic mchr1 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2521832A1 true CA2521832A1 (en) | 2004-10-28 |
Family
ID=33299933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002521832A Abandoned CA2521832A1 (en) | 2003-04-11 | 2004-04-06 | Heterocyclic mchr1 antagonists |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20060194871A1 (enExample) |
| EP (1) | EP1618112A1 (enExample) |
| JP (1) | JP2006522812A (enExample) |
| AR (1) | AR044011A1 (enExample) |
| CA (1) | CA2521832A1 (enExample) |
| MX (1) | MXPA05010859A (enExample) |
| TW (1) | TW200510429A (enExample) |
| WO (1) | WO2004092181A1 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5000490B2 (ja) * | 2005-04-28 | 2012-08-15 | 武田薬品工業株式会社 | チエノピリミドン化合物 |
| WO2007011285A1 (en) * | 2005-07-15 | 2007-01-25 | Astrazeneca Ab | Therapeutic agents |
| EP1937683A4 (en) * | 2005-09-23 | 2010-08-25 | Coley Pharm Group Inc | PROCESS FOR 1H-IMIDAZO [4,5-C] PYRIDINES AND ANALOGUE THEREOF |
| KR101020333B1 (ko) | 2005-09-30 | 2011-03-09 | 에프. 호프만-라 로슈 아게 | Ｍｃｈ 수용체 길항제로서의 인단 유도체 |
| AR056155A1 (es) * | 2005-10-26 | 2007-09-19 | Bristol Myers Squibb Co | Antagonistas del receptor 1 de la hormona de concentracion de melanina no basica |
| US7745447B2 (en) * | 2005-10-26 | 2010-06-29 | Bristol-Myers Squibb Company | Substituted thieno[3,2-D]pyrimidines as non-basic melanin concentrating hormone receptor-1 antagonists |
| US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
| WO2007093364A1 (en) * | 2006-02-15 | 2007-08-23 | Sanofi-Aventis | Azacyclyl-substituted aryldihydroisoquinolinones, process for their preparation and their use as medicaments |
| CA2636617A1 (en) * | 2006-02-15 | 2007-08-23 | Lothar Schwink | Novel aminoalcohol-substituted aryldihydroisoquinolinones, process for their preparation and their use as medicaments |
| WO2007146758A2 (en) * | 2006-06-08 | 2007-12-21 | Eli Lilly And Company | Novel mch receptor antagonists |
| CN101460503A (zh) * | 2006-06-08 | 2009-06-17 | 伊莱利利公司 | 新的mch受体拮抗剂 |
| US20070299062A1 (en) * | 2006-06-26 | 2007-12-27 | The Procter & Gamble Company | Melanin concentrating hormone antagonists |
| BRPI0715160A2 (pt) | 2006-08-08 | 2013-06-11 | Sanofi Aventis | imidazolidina-2,4-dionas substituÍdas por arilamimoaril-alquil-, processo para preparÁ-las, medicamentos compeendendo estes compostos, e seu uso |
| JP2010501553A (ja) | 2006-08-18 | 2010-01-21 | アストラゼネカ アクチボラグ | Ｍｃｈｒ１アンタゴニストとしてのチエノピリミジン−４−オン誘導体およびチエノピリダジン−７−オン誘導体 |
| CN101679348A (zh) | 2007-01-10 | 2010-03-24 | 阿尔巴尼分子研究公司 | 5-吡啶酮取代的吲唑 |
| US8198307B2 (en) * | 2007-05-11 | 2012-06-12 | Korea Research Institute Of Chemical Technology | Imidazole derivatives having aryl piperidine substituent, method for preparation thereof and pharmaceutical compositions containing same |
| ATE544759T1 (de) | 2007-07-21 | 2012-02-15 | Albany Molecular Res Inc | 5-pyridinon-substituierte indazole und pharmazeutische zusammensetzungen davon |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| PE20091928A1 (es) | 2008-05-29 | 2009-12-31 | Bristol Myers Squibb Co | Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| AR075401A1 (es) | 2009-02-13 | 2011-03-30 | Sanofi Aventis | Indanos sustituidos, procesos para su preparacion y uso de los mismos como un medicamento |
| UY32443A (es) | 2009-02-13 | 2010-09-30 | Sanofi Aventis | Nuevos tetrahidronaftalenos, procesos para su preparación y uso de los mismos como medicamento. |
| ES2443016T3 (es) | 2009-08-26 | 2014-02-17 | Sanofi | Nuevos hidratos cristalinos de fluoroglicósidos heteroaromáticos, productos farmacéuticos que comprenden estos compuestos, y su empleo |
| WO2012120053A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| HUP1100241A3 (en) | 2011-05-06 | 2013-12-30 | Richter Gedeon Nyrt | Oxetane substituted pyrimidones |
| EP2848621A4 (en) * | 2012-05-10 | 2016-06-01 | Takeda Pharmaceutical | AROMATIC RING CONNECTION |
| KR101551313B1 (ko) * | 2014-07-28 | 2015-09-09 | 충남대학교산학협력단 | 신규한 인덴 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 망막 질환의 예방 또는 치료용 약학적 조성물 |
| US11447486B2 (en) | 2014-07-31 | 2022-09-20 | Institut Pasteur Korea | 2-amino-benzimidazole derivatives and their use as 5-lipoxygenase and/or prostaglandin E synthase inhibitors |
| CN106866545B (zh) * | 2017-03-31 | 2019-07-09 | 枣庄学院 | 1-环烷烃-5-硝基-1h-苯并[d]咪唑类化合物及其制备方法 |
| CN107445899A (zh) * | 2017-07-19 | 2017-12-08 | 枣庄学院 | 一种苯并咪唑类化合物及其制备方法 |
| CN109020895B (zh) * | 2018-08-07 | 2020-04-24 | 枣庄学院 | 一种金属催化的1-苄胺基取代苯并咪唑的合成方法 |
| EP4132935A1 (en) * | 2020-04-08 | 2023-02-15 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1285651B1 (en) * | 2000-04-28 | 2010-09-01 | Takeda Pharmaceutical Company Limited | Melanin concentrating hormone antagonists |
| WO2002006245A1 (en) * | 2000-07-05 | 2002-01-24 | Synaptic Pharmarceutical Corporation | Selective melanin concentrating hormone-1 (mch1) receptor antagonists and uses thereof |
| GB0124627D0 (en) * | 2001-10-15 | 2001-12-05 | Smithkline Beecham Plc | Novel compounds |
-
2004
- 2004-04-06 EP EP04759148A patent/EP1618112A1/en not_active Withdrawn
- 2004-04-06 MX MXPA05010859A patent/MXPA05010859A/es unknown
- 2004-04-06 CA CA002521832A patent/CA2521832A1/en not_active Abandoned
- 2004-04-06 JP JP2006509727A patent/JP2006522812A/ja active Pending
- 2004-04-06 WO PCT/US2004/010518 patent/WO2004092181A1/en not_active Ceased
- 2004-04-06 US US10/552,232 patent/US20060194871A1/en not_active Abandoned
- 2004-04-07 AR ARP040101194A patent/AR044011A1/es not_active Application Discontinuation
- 2004-04-09 TW TW093109839A patent/TW200510429A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200510429A (en) | 2005-03-16 |
| WO2004092181A9 (en) | 2005-01-27 |
| MXPA05010859A (es) | 2005-12-14 |
| AR044011A1 (es) | 2005-08-24 |
| WO2004092181A1 (en) | 2004-10-28 |
| US20060194871A1 (en) | 2006-08-31 |
| EP1618112A1 (en) | 2006-01-25 |
| JP2006522812A (ja) | 2006-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2521832A1 (en) | Heterocyclic mchr1 antagonists | |
| EP1442025B1 (en) | Pyrimidinones as melanin concentrating hormone receptor 1 | |
| CA2312885C (en) | 2-aryl-8-oxodihydropurine derivatives, process for producing the same, medicinal compositions containing the same, and intermediates thereof | |
| JP5324437B2 (ja) | ５−ｈｔ６モジュレーターとしてのインドール | |
| US20050261333A1 (en) | Use of and some novel imidazopyridines | |
| AU660799B2 (en) | 2,3 (1H,4H)-quinoxalinediones | |
| CA2740262C (en) | 1-(arylsulfonyl)-4-(piperazin-1-yl)-1h-benzimidazoles as 5-hydroxytryptamine-6 ligands | |
| HUP0402576A2 (hu) | 5-HT antagonista tulajdonságú, gyógyászatilag hasznosítható kinolonvegyületek | |
| AU2007332440A1 (en) | Quinoxaline derivative | |
| JP2006528186A (ja) | ５−ヒドロキシトリプタミン−６リガンドとしてのスルホニルジヒドロベンゾイミダゾロン化合物 | |
| CA2417082C (en) | New benzimidazolone derivatives displaying affinity at the serotonin and dopamine receptors | |
| FI67550C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 2,10-dihydro-4-piperazinyl-pyrazolo(3,4-b)(1,5)bensodiazepinderivat | |
| AU2017379024A1 (en) | Condensed ring group azacyclobutyl triazole derivative, preparation method therefor and use thereof in medicine | |
| FI92203C (fi) | Menetelmä terapeuttisesti aktiivisten 4-okso-imidatso/1,5-a/kinoksaliinijohdannaisten valmistamiseksi | |
| CZ2000320A3 (cs) | Deriváty 4-oxo-3,5dihydro-4H-pyridazino[4,5-b]indol-1-acetamidu a farmaceutický prostředek, který je obsahuje | |
| DD255344A5 (de) | Heteroaryl-oxy-beta-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel | |
| US5512590A (en) | 5,6-dihydro-4h-imidazo 2',1':2,3!imidazo- 4,5,1-ij!quinoline and 4,5-dihydroimidazo- 1,2-a!pyrolo 1,2,3-cd!benzimidazole derivatives, their preparation and application in therapeutics | |
| US5466706A (en) | 9H-imidazo[1,2-A]benzimidazole-3-acetamide derivatives, their preparation and their therapeutic application | |
| CA2543627A1 (en) | Sulfonyltetrahydro-3h-benzo(e)indole-8-amine compounds as 5-hydroxytryptamine-6 ligands | |
| AU2003230869B2 (en) | 2-(quinolonyl)-fused heterocycles as androgen receptor modulators | |
| IE922342A1 (en) | Imidazo[2,1-b]benzothiazole-3-acetamide derivatives, their¹preparation and their use in therapeutics | |
| CA2417081C (en) | New n, n'-disubstituted benzimidazolone derivatives with affinity at the serotonin and dopamine receptors | |
| AU716199B2 (en) | Use of tricyclic derivatives of 1,4-dihydro-1,4-dioxo-1H-nap-hthalene, novel compounds obtained and their application in therapy | |
| US7291736B2 (en) | Sulfonyldihydroimidazopyridinone compounds as 5-hydroxytryptamine-6 ligands | |
| AU747543B2 (en) | Process for converting propargylic amine-N-oxides to enaminones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |