MX2008015662A - Nuevos receptores antagonistas de la hormona concentradora de melanina (mch). - Google Patents
Nuevos receptores antagonistas de la hormona concentradora de melanina (mch).Info
- Publication number
- MX2008015662A MX2008015662A MX2008015662A MX2008015662A MX2008015662A MX 2008015662 A MX2008015662 A MX 2008015662A MX 2008015662 A MX2008015662 A MX 2008015662A MX 2008015662 A MX2008015662 A MX 2008015662A MX 2008015662 A MX2008015662 A MX 2008015662A
- Authority
- MX
- Mexico
- Prior art keywords
- phenyl
- methoxy
- chloro
- thieno
- pyridin
- Prior art date
Links
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 title description 2
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title description 2
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 243
- 239000000203 mixture Substances 0.000 claims abstract description 149
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 208000008589 Obesity Diseases 0.000 claims abstract description 16
- 235000020824 obesity Nutrition 0.000 claims abstract description 16
- -1 -OR6 Chemical group 0.000 claims description 225
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 145
- 229910052757 nitrogen Inorganic materials 0.000 claims description 91
- 239000001257 hydrogen Substances 0.000 claims description 86
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 83
- 125000000623 heterocyclic group Chemical group 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 60
- 125000001153 fluoro group Chemical group F* 0.000 claims description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- 150000002431 hydrogen Chemical group 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 33
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 31
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 27
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 21
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 14
- 125000004193 piperazinyl group Chemical group 0.000 claims description 14
- 229910052701 rubidium Inorganic materials 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000002393 azetidinyl group Chemical group 0.000 claims description 11
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- RIYCFWXOWRQFFK-UHFFFAOYSA-N 6h-thieno[2,3-c]pyridin-7-one Chemical compound O=C1NC=CC2=C1SC=C2 RIYCFWXOWRQFFK-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000005959 diazepanyl group Chemical group 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
- 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 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- BZZWVAIHDUQQFR-UHFFFAOYSA-N COC1=C(C(C(N)=O)N2CCCC2)C=CC(N(CCC2=C3SC(C(C=C4)=CC=C4Cl)=C2)C3=O)=C1 Chemical compound COC1=C(C(C(N)=O)N2CCCC2)C=CC(N(CCC2=C3SC(C(C=C4)=CC=C4Cl)=C2)C3=O)=C1 BZZWVAIHDUQQFR-UHFFFAOYSA-N 0.000 claims description 3
- 239000002830 appetite depressant Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- QGZSTDQCFJYIOI-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(3-fluoro-4-piperazin-1-ylphenyl)thieno[2,3-c]pyridin-7-one hydrochloride Chemical compound Cl.FC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CCNCC1 QGZSTDQCFJYIOI-UHFFFAOYSA-N 0.000 claims 1
- JJKPBTAVSUKHIZ-ZMBIFBSDSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-1-methylpiperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one;hydrochloride Chemical compound Cl.COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCN(C)C1 JJKPBTAVSUKHIZ-ZMBIFBSDSA-N 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- LLMKLOUFMKLTIZ-UHFFFAOYSA-N 4h-thieno[2,3-c]pyridin-7-one Chemical compound O=C1N=CCC2=C1SC=C2 LLMKLOUFMKLTIZ-UHFFFAOYSA-N 0.000 claims 1
- YBBIWGPWUVGUFK-UHFFFAOYSA-N COC1=C(C=CC(=C1)N2C=CC3=C(C2=O)SC(=C3)C4=CC=C(C=C4)Cl)C(C(=O)N)N5CCCC5 Chemical compound COC1=C(C=CC(=C1)N2C=CC3=C(C2=O)SC(=C3)C4=CC=C(C=C4)Cl)C(C(=O)N)N5CCCC5 YBBIWGPWUVGUFK-UHFFFAOYSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 101800002739 Melanin-concentrating hormone Proteins 0.000 abstract description 2
- 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 abstract description 2
- 102000047659 melanin-concentrating hormone Human genes 0.000 abstract description 2
- 239000003667 hormone antagonist Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 225
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 176
- 238000002360 preparation method Methods 0.000 description 127
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
- 238000006243 chemical reaction Methods 0.000 description 118
- 239000000243 solution Substances 0.000 description 115
- 235000019439 ethyl acetate Nutrition 0.000 description 103
- 229910001868 water Inorganic materials 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 49
- 239000007787 solid Substances 0.000 description 49
- 238000004587 chromatography analysis Methods 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000013058 crude material Substances 0.000 description 40
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 239000012267 brine Substances 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 239000000725 suspension Substances 0.000 description 29
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
- 239000002904 solvent Substances 0.000 description 27
- 239000007832 Na2SO4 Substances 0.000 description 26
- 239000011734 sodium Substances 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 239000002253 acid Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 229940093499 ethyl acetate Drugs 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 239000012458 free base Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 8
- 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 7
- 239000005711 Benzoic acid Substances 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 238000006880 cross-coupling reaction Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 150000002596 lactones Chemical class 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 229930192474 thiophene Natural products 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- 230000010933 acylation Effects 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 150000003951 lactams Chemical class 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 150000001543 aryl boronic acids Chemical class 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 4
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 3-methylthiophene-2-carboxylic acid Chemical compound CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 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
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 3
- FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 3
- SMVVBGGWBKSALK-UHFFFAOYSA-N 2-(4-chlorophenyl)-4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)OCC2 SMVVBGGWBKSALK-UHFFFAOYSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 3
- VBPMITJBSXBGOI-UHFFFAOYSA-N 3-methoxy-4-(2-pyrrolidin-1-ylethoxy)aniline Chemical compound COC1=CC(N)=CC=C1OCCN1CCCC1 VBPMITJBSXBGOI-UHFFFAOYSA-N 0.000 description 3
- PJPKCICWTWFJTK-UHFFFAOYSA-N 5-(4-chlorophenyl)-N-(2,2-diethoxyethyl)thiophene-2-carboxamide Chemical compound CCOC(CNC(=O)c1ccc(s1)-c1ccc(Cl)cc1)OCC PJPKCICWTWFJTK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000006254 arylation reaction Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 150000003140 primary amides Chemical group 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000002821 scintillation proximity assay Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 3
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000005406 washing Methods 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
- XEYLTFFHAJZTJG-UHFFFAOYSA-N (4-bromophenyl)-(1-methylpyrrolidin-3-yl)methanone Chemical compound C1N(C)CCC1C(=O)C1=CC=C(Br)C=C1 XEYLTFFHAJZTJG-UHFFFAOYSA-N 0.000 description 2
- OVUOTZUANLDTCA-UHFFFAOYSA-N (4-bromophenyl)-pyrrolidin-3-ylmethanone Chemical compound C1=CC(Br)=CC=C1C(=O)C1CNCC1 OVUOTZUANLDTCA-UHFFFAOYSA-N 0.000 description 2
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 2
- VARQKLKKURHTHL-RXMQYKEDSA-N (5r)-5-(hydroxymethyl)-4-methylmorpholin-3-one Chemical compound CN1[C@H](CO)COCC1=O VARQKLKKURHTHL-RXMQYKEDSA-N 0.000 description 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 2
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 2
- VYCIHDBIKGRENI-UHFFFAOYSA-N 1,3-bis[2,6-di(propan-2-yl)phenyl]-2h-imidazol-1-ium-2-ide Chemical group CC(C)C1=CC=CC(C(C)C)=C1N1C=CN(C=2C(=CC=CC=2C(C)C)C(C)C)[C]1 VYCIHDBIKGRENI-UHFFFAOYSA-N 0.000 description 2
- OBPFHJKEIFNNHY-UHFFFAOYSA-N 1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCN1CCCC1 OBPFHJKEIFNNHY-UHFFFAOYSA-N 0.000 description 2
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 2
- HWKWUTRHKIRYTH-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(4-hydroxy-3-methoxyphenyl)-3a,7a-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=C(O)C(OC)=CC(N2C(C3SC(=CC3C=C2)C=2C=CC(Cl)=CC=2)=O)=C1 HWKWUTRHKIRYTH-UHFFFAOYSA-N 0.000 description 2
- PLMQRYVQWOWZQJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 PLMQRYVQWOWZQJ-UHFFFAOYSA-N 0.000 description 2
- UGYGGUSKVPGNOC-UHFFFAOYSA-N 2-(4-chlorophenyl)-6h-thieno[2,3-c]pyridin-7-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)NC=C2 UGYGGUSKVPGNOC-UHFFFAOYSA-N 0.000 description 2
- HPHZIECUWRMAOQ-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)NCC2 HPHZIECUWRMAOQ-UHFFFAOYSA-N 0.000 description 2
- WCHRPSHIMRQFRS-UHFFFAOYSA-N 2-bromo-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one Chemical compound C1CNC(=O)C2=C1C=C(Br)S2 WCHRPSHIMRQFRS-UHFFFAOYSA-N 0.000 description 2
- VLLHNQHEIOOCSY-UHFFFAOYSA-N 3-(2-hydroxyethyl)-5-iodo-n-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound C=1C=C(OCCN2CCCC2)C(OC)=CC=1NC(=O)C=1SC(I)=CC=1CCO VLLHNQHEIOOCSY-UHFFFAOYSA-N 0.000 description 2
- UUYBKHZVYJDKGE-UHFFFAOYSA-N 4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound O=C1OCCC2=C1SC=C2 UUYBKHZVYJDKGE-UHFFFAOYSA-N 0.000 description 2
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 2
- MYBCIGYUYNICKH-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)-7-oxo-4,5-dihydrothieno[2,3-c]pyridin-6-yl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=C1 MYBCIGYUYNICKH-UHFFFAOYSA-N 0.000 description 2
- WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 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
- ORPWXKFFXAOFCU-UHFFFAOYSA-N 5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one Chemical compound O=C1NCCC2=C1SC=C2 ORPWXKFFXAOFCU-UHFFFAOYSA-N 0.000 description 2
- GWLCYLPZQKOCTB-UHFFFAOYSA-N 5-(4-chlorophenyl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(Cl)C=C1 GWLCYLPZQKOCTB-UHFFFAOYSA-N 0.000 description 2
- KJGOICMDNIIVOW-UHFFFAOYSA-N 6-(4-hydroxy-3-methoxyphenyl)-2-(4-methoxyphenyl)-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(O)=CC=1)CC2 KJGOICMDNIIVOW-UHFFFAOYSA-N 0.000 description 2
- MLGPKMGGYIHVJU-UHFFFAOYSA-N 6-(4-hydroxyphenyl)-2-(4-methoxyphenyl)-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=CC(O)=CC=1)CC2 MLGPKMGGYIHVJU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 240000000786 Margyricarpus pinnatus Species 0.000 description 2
- 235000010838 Margyricarpus pinnatus Nutrition 0.000 description 2
- 229920001410 Microfiber Polymers 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- DFRTZSWEZDHGLB-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-3-(2-trimethylsilylethynyl)thiophene-2-carboxylate Chemical compound C[Si](C)(C)C#CC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 DFRTZSWEZDHGLB-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000003658 microfiber Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- CSTIYCZYBJMJBA-UHFFFAOYSA-N n-(4-bromo-2-methoxyphenyl)-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(Br)=CC=C1NC(=O)CN1CCCC1 CSTIYCZYBJMJBA-UHFFFAOYSA-N 0.000 description 2
- ILCQYORZHHFLNL-UHFFFAOYSA-N n-bromoaniline Chemical compound BrNC1=CC=CC=C1 ILCQYORZHHFLNL-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Chemical group 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- RPCWHOFDACENQM-UHFFFAOYSA-N tert-butyl 3-[methoxy(methyl)carbamoyl]azetidine-1-carboxylate Chemical compound CON(C)C(=O)C1CN(C(=O)OC(C)(C)C)C1 RPCWHOFDACENQM-UHFFFAOYSA-N 0.000 description 2
- LAAAMOQBIKIHLV-UHFFFAOYSA-N tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)C1 LAAAMOQBIKIHLV-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- QNEGDGPAXKYZHZ-UHFFFAOYSA-N (2,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1Cl QNEGDGPAXKYZHZ-UHFFFAOYSA-N 0.000 description 1
- ARAWNUIHRHZFRP-UHFFFAOYSA-N (2-methoxy-4-nitrophenoxy)-tri(propan-2-yl)silane Chemical compound COC1=CC([N+]([O-])=O)=CC=C1O[Si](C(C)C)(C(C)C)C(C)C ARAWNUIHRHZFRP-UHFFFAOYSA-N 0.000 description 1
- BJWHQBTUHVIRJJ-PPHPATTJSA-N (2s)-2-amino-3-phenylmethoxypropan-1-ol;hydrochloride Chemical compound Cl.OC[C@H](N)COCC1=CC=CC=C1 BJWHQBTUHVIRJJ-PPHPATTJSA-N 0.000 description 1
- MMNOBTOOAAADKJ-SECBINFHSA-N (3r)-1-(2-methoxy-4-nitrophenyl)pyrrolidin-3-ol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N1C[C@H](O)CC1 MMNOBTOOAAADKJ-SECBINFHSA-N 0.000 description 1
- UTUPESZTMCQTJC-RXMQYKEDSA-N (3r)-3-hydroxypiperidine-1-carboxylic acid Chemical compound O[C@@H]1CCCN(C(O)=O)C1 UTUPESZTMCQTJC-RXMQYKEDSA-N 0.000 description 1
- FUJRVEOGUZAIIZ-BXKDBHETSA-N (3r,4r)-4-(4-bromo-2-methoxyphenoxy)-1-methylpyrrolidin-3-ol Chemical compound COC1=CC(Br)=CC=C1O[C@H]1[C@H](O)CN(C)C1 FUJRVEOGUZAIIZ-BXKDBHETSA-N 0.000 description 1
- MOTWSOSQDFIZCN-LDYMZIIASA-N (3r,4r)-4-(4-bromo-2-methoxyphenoxy)pyrrolidin-3-ol Chemical compound COC1=CC(Br)=CC=C1O[C@H]1[C@H](O)CNC1 MOTWSOSQDFIZCN-LDYMZIIASA-N 0.000 description 1
- JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
- JXQRPZPHNYDWNE-UHFFFAOYSA-N (4-bromophenyl)-(1-methylazetidin-3-yl)methanone Chemical compound C1N(C)CC1C(=O)C1=CC=C(Br)C=C1 JXQRPZPHNYDWNE-UHFFFAOYSA-N 0.000 description 1
- IZOOGQYKHWNGOK-UHFFFAOYSA-N (4-cyclopropyloxyphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1OC1CC1 IZOOGQYKHWNGOK-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 1
- PKEHWYKDQTXBIT-GFCCVEGCSA-N (5r)-4-methyl-5-(phenylmethoxymethyl)morpholin-3-one Chemical compound C1OCC(=O)N(C)[C@@H]1COCC1=CC=CC=C1 PKEHWYKDQTXBIT-GFCCVEGCSA-N 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- WNSNPGHNIJOOPM-UHFFFAOYSA-N 1,4-dibromo-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1Br WNSNPGHNIJOOPM-UHFFFAOYSA-N 0.000 description 1
- RMGFLMXDCGQKPS-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine Chemical compound ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- JXIJUAWSDBACEB-UHFFFAOYSA-N 1-chloro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1Cl JXIJUAWSDBACEB-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- YVSNGCKSQOSQJR-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6-dihydro-4h-1-benzothiophen-7-one Chemical compound COC1=CC(C2C(C=3SC(=CC=3CC2)C=2C(=CC(Cl)=CC=2)Cl)=O)=CC=C1OCCN1CCCC1 YVSNGCKSQOSQJR-UHFFFAOYSA-N 0.000 description 1
- LXWDLMNDLTVQAO-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-methylthiophene Chemical compound CC1=CSC(C=2C=CC(Cl)=CC=2)=C1 LXWDLMNDLTVQAO-UHFFFAOYSA-N 0.000 description 1
- NPPPNNPYWMVJBH-UHFFFAOYSA-N 2-(4-chlorophenyl)-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)NCC2 NPPPNNPYWMVJBH-UHFFFAOYSA-N 0.000 description 1
- UXGKGCYVJOCDHZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(4-hydroxy-3-methoxyphenyl)-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=C(O)C(OC)=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=C1 UXGKGCYVJOCDHZ-UHFFFAOYSA-N 0.000 description 1
- UZBNHZZHRUCOIV-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(4-hydroxy-3-methoxyphenyl)thieno[2,3-c]pyridin-7-one Chemical compound C1=C(O)C(OC)=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=C1 UZBNHZZHRUCOIV-UHFFFAOYSA-N 0.000 description 1
- DANNXIYTSPUKNZ-HXUWFJFHSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-piperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCNC1 DANNXIYTSPUKNZ-HXUWFJFHSA-N 0.000 description 1
- LQTOEBBZSKBFRQ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-tri(propan-2-yl)silyloxyphenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=C(O[Si](C(C)C)(C(C)C)C(C)C)C(OC)=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=C1 LQTOEBBZSKBFRQ-UHFFFAOYSA-N 0.000 description 1
- PVKPANQDSFNJKN-UHFFFAOYSA-N 2-(4-fluorophenyl)-6h-thieno[2,3-c]pyridin-7-one Chemical compound C1=CC(F)=CC=C1C(S1)=CC2=C1C(=O)NC=C2 PVKPANQDSFNJKN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- WQCPSNAAWLHQAE-UHFFFAOYSA-N 2-bromo-4-methylthiophene Chemical compound CC1=CSC(Br)=C1 WQCPSNAAWLHQAE-UHFFFAOYSA-N 0.000 description 1
- FCXQFXIRTUMUOI-UHFFFAOYSA-N 2-bromo-6-[3-methoxy-4-tri(propan-2-yl)silyloxyphenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=C(O[Si](C(C)C)(C(C)C)C(C)C)C(OC)=CC(N2C(C=3SC(Br)=CC=3CC2)=O)=C1 FCXQFXIRTUMUOI-UHFFFAOYSA-N 0.000 description 1
- QBRRKBBDPKCJFZ-UHFFFAOYSA-N 2-bromo-6h-thieno[2,3-c]pyridin-7-one Chemical compound C1=CNC(=O)C2=C1C=C(Br)S2 QBRRKBBDPKCJFZ-UHFFFAOYSA-N 0.000 description 1
- AZBVIMDRJLBPGA-UHFFFAOYSA-N 2-bromothieno[3,2-b]pyridine 1-oxide Chemical compound C1=CC=C2S(=O)C(Br)=CC2=N1 AZBVIMDRJLBPGA-UHFFFAOYSA-N 0.000 description 1
- WCICCXZIFBFBFU-NSHDSACASA-N 2-chloro-n-[(2s)-1-hydroxy-3-phenylmethoxypropan-2-yl]acetamide Chemical compound ClCC(=O)N[C@@H](CO)COCC1=CC=CC=C1 WCICCXZIFBFBFU-NSHDSACASA-N 0.000 description 1
- KKZUMAMOMRDVKA-UHFFFAOYSA-N 2-chloropropane Chemical group [CH2]C(C)Cl KKZUMAMOMRDVKA-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- VJVMORHSPGSHMV-UHFFFAOYSA-N 2-iodo-3-methyl-4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound C1COC(=O)C2=C1C(C)=C(I)S2 VJVMORHSPGSHMV-UHFFFAOYSA-N 0.000 description 1
- SUBKTBCIDIOSLO-UHFFFAOYSA-N 2-iodo-4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound C1COC(=O)C2=C1C=C(I)S2 SUBKTBCIDIOSLO-UHFFFAOYSA-N 0.000 description 1
- FZGDYKHIXZFFFK-UHFFFAOYSA-N 2-iodo-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(I)=CC=3CC2)=O)=CC=C1OCCN1CCCC1 FZGDYKHIXZFFFK-UHFFFAOYSA-N 0.000 description 1
- PXOQKEMFUUMHHQ-UHFFFAOYSA-N 2-methoxy-4-[2-(4-methoxyphenyl)-7-oxo-4,5-dihydrothieno[2,3-c]pyridin-6-yl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(C(=O)NCCN3CCCC3)=CC=1)CC2 PXOQKEMFUUMHHQ-UHFFFAOYSA-N 0.000 description 1
- LBTUTDYXOOUODJ-UHFFFAOYSA-N 2-pyrrolidin-1-ylacetamide Chemical compound NC(=O)CN1CCCC1 LBTUTDYXOOUODJ-UHFFFAOYSA-N 0.000 description 1
- HIGULTVOVROJID-UHFFFAOYSA-N 2-pyrrolidin-1-ylacetic acid;hydrochloride Chemical compound Cl.OC(=O)CN1CCCC1 HIGULTVOVROJID-UHFFFAOYSA-N 0.000 description 1
- GWZCLMWEJWPFFA-UHFFFAOYSA-N 2-thiophen-3-ylacetonitrile Chemical compound N#CCC=1C=CSC=1 GWZCLMWEJWPFFA-UHFFFAOYSA-N 0.000 description 1
- PYUCPHDVJORSMA-UHFFFAOYSA-N 2-thiophen-3-ylethanamine;hydrochloride Chemical compound Cl.NCCC=1C=CSC=1 PYUCPHDVJORSMA-UHFFFAOYSA-N 0.000 description 1
- YYPNNBPPDFTQFX-UHFFFAOYSA-N 2-thiophen-3-ylethanol Chemical compound OCCC=1C=CSC=1 YYPNNBPPDFTQFX-UHFFFAOYSA-N 0.000 description 1
- MDISPYSGEXWDAQ-UHFFFAOYSA-N 3-(2-hydroxyethyl)-n-[3-methoxy-4-tri(propan-2-yl)silyloxyphenyl]thiophene-2-carboxamide Chemical compound C1=C(O[Si](C(C)C)(C(C)C)C(C)C)C(OC)=CC(NC(=O)C2=C(C=CS2)CCO)=C1 MDISPYSGEXWDAQ-UHFFFAOYSA-N 0.000 description 1
- MZVQRVGNTHJVOT-UHFFFAOYSA-N 3-(2-hydroxyethyl)thiophene-2-carboxylic acid Chemical compound OCCC=1C=CSC=1C(O)=O MZVQRVGNTHJVOT-UHFFFAOYSA-N 0.000 description 1
- HCGTXBIYYPUJKK-UHFFFAOYSA-N 3-(4-bromobenzoyl)pyrrolidine-1-carboxylic acid Chemical compound BrC1=CC=C(C(=O)C2CN(CC2)C(=O)O)C=C1 HCGTXBIYYPUJKK-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
- WTVXITPNPRFQLL-UHFFFAOYSA-N 3-(methoxymethylcarbamoyl)pyrrolidine-1-carboxylic acid Chemical compound COCNC(=O)C1CCN(C(O)=O)C1 WTVXITPNPRFQLL-UHFFFAOYSA-N 0.000 description 1
- JNNWPVNKOZCNKR-UHFFFAOYSA-N 3-[(4-bromophenyl)-difluoromethyl]-1-methylpyrrolidine Chemical compound C1N(C)CCC1C(F)(F)C1=CC=C(Br)C=C1 JNNWPVNKOZCNKR-UHFFFAOYSA-N 0.000 description 1
- IHYVCHGREKNHDD-UHFFFAOYSA-N 3-[(4-bromophenyl)-fluoromethyl]-1-methylpyrrolidine Chemical compound C1N(C)CCC1C(F)C1=CC=C(Br)C=C1 IHYVCHGREKNHDD-UHFFFAOYSA-N 0.000 description 1
- UXJOLSDBAVDZJS-UHFFFAOYSA-N 3-carbamoylpyrrolidine-1-carboxylic acid Chemical compound NC(=O)C1CCN(C(O)=O)C1 UXJOLSDBAVDZJS-UHFFFAOYSA-N 0.000 description 1
- SNBYDHCSBZIOQL-UHFFFAOYSA-N 3-hydroxyazetidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)C1 SNBYDHCSBZIOQL-UHFFFAOYSA-N 0.000 description 1
- GQEDUQWBJAARRG-UHFFFAOYSA-N 3-iodo-4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound C1COC(=O)C2=C1C(I)=CS2 GQEDUQWBJAARRG-UHFFFAOYSA-N 0.000 description 1
- WWSOKTYKPQVQDT-GOSISDBHSA-N 3-methoxy-4-[(3r)-3-tri(propan-2-yl)silyloxypyrrolidin-1-yl]aniline Chemical compound COC1=CC(N)=CC=C1N1C[C@H](O[Si](C(C)C)(C(C)C)C(C)C)CC1 WWSOKTYKPQVQDT-GOSISDBHSA-N 0.000 description 1
- JJIKJZWPFBTFGQ-UHFFFAOYSA-N 3-methoxy-4-tri(propan-2-yl)silyloxyaniline Chemical compound COC1=CC(N)=CC=C1O[Si](C(C)C)(C(C)C)C(C)C JJIKJZWPFBTFGQ-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- JDIDRYPFTQYNGT-UHFFFAOYSA-N 3-methyl-4,5-dihydrothieno[2,3-c]pyran-7-one Chemical compound C1COC(=O)C2=C1C(C)=CS2 JDIDRYPFTQYNGT-UHFFFAOYSA-N 0.000 description 1
- QHZITEHQKWPDJE-UHFFFAOYSA-N 4,5-dihydrocyclopenta[b]thiophen-6-one Chemical compound C1=CSC2=C1CCC2=O QHZITEHQKWPDJE-UHFFFAOYSA-N 0.000 description 1
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical group [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 1
- SAAQPHIYUULWRE-UHFFFAOYSA-N 4-benzylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1CC1=CC=CC=C1 SAAQPHIYUULWRE-UHFFFAOYSA-N 0.000 description 1
- WHSIIJQOEGXWSN-UHFFFAOYSA-N 4-bromo-2-methoxyphenol Chemical compound COC1=CC(Br)=CC=C1O WHSIIJQOEGXWSN-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- CEEIJOOHMCRBMH-UHFFFAOYSA-N 4-methylthiophene Chemical compound CC1=[C]SC=C1 CEEIJOOHMCRBMH-UHFFFAOYSA-N 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- KHRJIKKOUZQGPS-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-(2-hydroxyethyl)thiophene-2-carboxylic acid Chemical compound S1C(C(O)=O)=C(CCO)C=C1C1=CC=C(Cl)C=C1 KHRJIKKOUZQGPS-UHFFFAOYSA-N 0.000 description 1
- OMXYXOIKYRALRC-UHFFFAOYSA-N 5-(chloromethyl)-1-methylimidazole;hydrochloride Chemical compound Cl.CN1C=NC=C1CCl OMXYXOIKYRALRC-UHFFFAOYSA-N 0.000 description 1
- ZVCPOVBXJHZQBV-UHFFFAOYSA-N 5-chloro-n-(2,2-diethoxyethyl)thiophene-2-carboxamide Chemical compound CCOC(OCC)CNC(=O)C1=CC=C(Cl)S1 ZVCPOVBXJHZQBV-UHFFFAOYSA-N 0.000 description 1
- FKXPVGDHNWWMMM-UHFFFAOYSA-N 6-[3-methoxy-4-tri(propan-2-yl)silyloxyphenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=C(O[Si](C(C)C)(C(C)C)C(C)C)C(OC)=CC(N2C(C=3SC=CC=3CC2)=O)=C1 FKXPVGDHNWWMMM-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
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- QTHSRHLRAAPURJ-UHFFFAOYSA-N COC1=C(C=CC(=C1)N)C(C(=O)N)N2CCCC2 Chemical compound COC1=C(C=CC(=C1)N)C(C(=O)N)N2CCCC2 QTHSRHLRAAPURJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 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
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension 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
- 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
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 102000044674 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 1
- QENGPZGAWFQWCZ-UHFFFAOYSA-N Methylthiophene Natural products CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 244000124853 Perilla frutescens Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- OPNGALFCKMOIRM-UHFFFAOYSA-N S1C=C(C=C1)CCO.S1C=CC2=C1C(OCC2)=O Chemical compound S1C=C(C=C1)CCO.S1C=CC2=C1C(OCC2)=O OPNGALFCKMOIRM-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- 108010084455 Zeocin Proteins 0.000 description 1
- NSEGYKKILYPFSW-GOSISDBHSA-N [(3r)-1-(2-methoxy-4-nitrophenyl)pyrrolidin-3-yl]oxy-tri(propan-2-yl)silane Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N1C[C@H](O[Si](C(C)C)(C(C)C)C(C)C)CC1 NSEGYKKILYPFSW-GOSISDBHSA-N 0.000 description 1
- NSEGYKKILYPFSW-SFHVURJKSA-N [(3s)-1-(2-methoxy-4-nitrophenyl)pyrrolidin-3-yl]oxy-tri(propan-2-yl)silane Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N1C[C@@H](O[Si](C(C)C)(C(C)C)C(C)C)CC1 NSEGYKKILYPFSW-SFHVURJKSA-N 0.000 description 1
- RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001539 anorectic effect Effects 0.000 description 1
- 230000000578 anorexic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- CGPAHSQPUFYIAT-UHFFFAOYSA-N azetidin-3-yl-(4-bromophenyl)methanone Chemical compound C1=CC(Br)=CC=C1C(=O)C1CNC1 CGPAHSQPUFYIAT-UHFFFAOYSA-N 0.000 description 1
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 125000006378 chloropyridyl group Chemical group 0.000 description 1
- 101150113676 chr1 gene Proteins 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000047277 human MCHR1 Human genes 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 230000003166 hypermetabolic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003796 lateral hypothalamic area Anatomy 0.000 description 1
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000013289 male long evans rat Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 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 1
- KDDGDLZSTSJJPE-UHFFFAOYSA-N methyl 3-bromo-5-(4-chlorophenyl)thiophene-2-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 KDDGDLZSTSJJPE-UHFFFAOYSA-N 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- FRZKCMCCQAJIBN-UHFFFAOYSA-N n-(4-bromophenyl)-2-chloroacetamide Chemical compound ClCC(=O)NC1=CC=C(Br)C=C1 FRZKCMCCQAJIBN-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-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
- 229960004927 neomycin Drugs 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- XITQUSLLOSKDTB-UHFFFAOYSA-N nitrofen Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C(Cl)C=C1Cl XITQUSLLOSKDTB-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000001956 orexigenic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- ADPQWEGXWVSSKZ-UHFFFAOYSA-N pyrrolidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)C1 ADPQWEGXWVSSKZ-UHFFFAOYSA-N 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 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
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RHFDLMVXCXVPBB-CYBMUJFWSA-N tert-butyl (3r)-3-(2-methoxy-4-nitrophenoxy)piperidine-1-carboxylate Chemical compound COC1=CC([N+]([O-])=O)=CC=C1O[C@H]1CN(C(=O)OC(C)(C)C)CCC1 RHFDLMVXCXVPBB-CYBMUJFWSA-N 0.000 description 1
- NUYWPLSBEHXOHO-UHFFFAOYSA-N tert-butyl 2-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1O NUYWPLSBEHXOHO-UHFFFAOYSA-N 0.000 description 1
- AWPBKPMUHXEWRV-UHFFFAOYSA-N tert-butyl 3-(4-amino-2-fluorophenoxy)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1OC1=CC=C(N)C=C1F AWPBKPMUHXEWRV-UHFFFAOYSA-N 0.000 description 1
- CDFYNOOXQDBKKV-UHFFFAOYSA-N tert-butyl 3-(4-bromobenzoyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1C(=O)C1=CC=C(Br)C=C1 CDFYNOOXQDBKKV-UHFFFAOYSA-N 0.000 description 1
- XRRXRQJQQKMFBC-UHFFFAOYSA-N tert-butyl 3-hydroxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(O)C1 XRRXRQJQQKMFBC-UHFFFAOYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- YOLVWCABLVHASL-UHFFFAOYSA-N tert-butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1F YOLVWCABLVHASL-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81184106P | 2006-06-08 | 2006-06-08 | |
| PCT/US2007/070662 WO2007146758A2 (en) | 2006-06-08 | 2007-06-08 | Novel mch receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2008015662A true MX2008015662A (es) | 2009-01-12 |
Family
ID=38651254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2008015662A MX2008015662A (es) | 2006-06-08 | 2007-06-08 | Nuevos receptores antagonistas de la hormona concentradora de melanina (mch). |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US8263772B2 (https=) |
| EP (1) | EP2029609A2 (https=) |
| JP (1) | JP5198439B2 (https=) |
| CN (1) | CN101454328A (https=) |
| AU (1) | AU2007257922A1 (https=) |
| BR (1) | BRPI0712680A2 (https=) |
| CA (1) | CA2652385A1 (https=) |
| EA (1) | EA015127B1 (https=) |
| MX (1) | MX2008015662A (https=) |
| WO (1) | WO2007146758A2 (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2740193A1 (en) | 2008-12-23 | 2010-07-01 | Abbott Laboratories | Anti-viral compounds |
| EP2367823A1 (en) | 2008-12-23 | 2011-09-28 | Abbott Laboratories | Anti-viral compounds |
| BRPI0923527A2 (pt) * | 2008-12-24 | 2016-08-09 | Syngenta Ltd | métodos de preparo de fungicidas |
| CN102459165B (zh) * | 2009-04-15 | 2015-09-02 | Abbvie公司 | 抗病毒化合物 |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| US9394279B2 (en) | 2009-06-11 | 2016-07-19 | Abbvie Inc. | Anti-viral compounds |
| UA118080C2 (uk) | 2009-06-11 | 2018-11-26 | Еббві Айрленд Анлімітед Компані | Противірусні сполуки |
| US8716454B2 (en) | 2009-06-11 | 2014-05-06 | Abbvie Inc. | Solid compositions |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| US9034832B2 (en) | 2011-12-29 | 2015-05-19 | Abbvie Inc. | Solid compositions |
| US20150065343A1 (en) | 2012-04-02 | 2015-03-05 | Basf Se | Acrylamide compounds for combating invertebrate pests |
| BR112014027133A2 (pt) | 2012-05-09 | 2017-06-27 | Basf Se | compostos, composição agrícola ou veterinária, método para o controle das pragas de invertebrados, material de propagação dos vegetais e método para o tratamento ou proteção de um animal. |
| MX394360B (es) | 2013-03-14 | 2025-03-24 | Sumitomo Pharma Oncology Inc | Inhibidores de jak2 y alk2 y metodos para su uso. |
| US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
| EP3089757A1 (en) | 2014-01-03 | 2016-11-09 | AbbVie Inc. | Solid antiviral dosage forms |
| AR102849A1 (es) * | 2015-03-09 | 2017-03-29 | Astellas Pharma Inc | Compuesto de piridina bicíclica |
| ES2849951T3 (es) | 2015-06-18 | 2021-08-24 | 89Bio Ltd | Derivados de piperidina 4-bencil y 4-benzoil sustituidos |
| EA201890086A1 (ru) | 2015-06-18 | 2018-06-29 | Сефалон, Инк. | 1,4-замещенные производные пиперидина |
| MX2021000977A (es) | 2018-07-26 | 2021-04-12 | Sumitomo Pharma Oncology Inc | Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos. |
| CN113226322A (zh) | 2018-10-30 | 2021-08-06 | 诺维逊生物股份有限公司 | 作为bet抑制剂的杂环化合物 |
| EP3997070A4 (en) | 2019-07-02 | 2023-07-26 | Nuvation Bio Inc. | HETEROCYCLIC COMPOUNDS AS BET INHIBITORS |
| US20260028336A1 (en) * | 2022-07-20 | 2026-01-29 | Arcus Biosciences, Inc. | Cbl-b inhibitors and methods of use thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002003370A (ja) * | 1999-09-20 | 2002-01-09 | Takeda Chem Ind Ltd | メラニン凝集ホルモン拮抗剤 |
| US20020099073A1 (en) * | 2000-07-07 | 2002-07-25 | Andersen Henrik Sune | Modulators of protein tyrosine phosphatases (PTPases) |
| GB0124627D0 (en) * | 2001-10-15 | 2001-12-05 | Smithkline Beecham Plc | Novel compounds |
| US20060194871A1 (en) * | 2003-04-11 | 2006-08-31 | Barvian Kevin K | Heterocyclic mchr1 antagoists |
| US20070078125A1 (en) * | 2003-10-23 | 2007-04-05 | Glaxo Group Limited | Arylamine mch r1 antagonists |
| WO2005047293A1 (en) * | 2003-11-07 | 2005-05-26 | Neurocrine Biosciences, Inc. | Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto |
| UA83416C2 (en) * | 2004-02-13 | 2008-07-10 | Баниу Фармасьютикал Ко., Лтд. | Fused ring 4-oxopyrimidine derivative |
| US20050256124A1 (en) * | 2004-04-15 | 2005-11-17 | Neurocrine Biosciences, Inc. | Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto |
| MXPA06014535A (es) | 2004-06-18 | 2007-06-05 | Biolipox Ab | Indoles utiles en el tratamiento de la inflamacion. |
| US7902356B2 (en) * | 2004-12-17 | 2011-03-08 | Eli Lilly And Company | Thiazolopyridinone derivates as MCH receptor antagonists |
| EP1987020B1 (en) * | 2006-02-15 | 2012-10-03 | Sanofi | Azacyclyl-substituted aryldihydroisoquinolinones, process for their preparation and their use as medicaments |
| KR20080094699A (ko) * | 2006-02-15 | 2008-10-23 | 사노피-아벤티스 | 신규 아미노알콜-치환된 아릴디하이드로이소퀴놀리논, 이의제조 방법 및 이의 약물로서의 용도 |
-
2007
- 2007-06-08 MX MX2008015662A patent/MX2008015662A/es unknown
- 2007-06-08 WO PCT/US2007/070662 patent/WO2007146758A2/en not_active Ceased
- 2007-06-08 EA EA200870517A patent/EA015127B1/ru not_active IP Right Cessation
- 2007-06-08 EP EP07798258A patent/EP2029609A2/en not_active Withdrawn
- 2007-06-08 CN CNA2007800195489A patent/CN101454328A/zh active Pending
- 2007-06-08 CA CA002652385A patent/CA2652385A1/en not_active Abandoned
- 2007-06-08 AU AU2007257922A patent/AU2007257922A1/en not_active Abandoned
- 2007-06-08 JP JP2009514544A patent/JP5198439B2/ja not_active Expired - Fee Related
- 2007-06-08 US US12/298,792 patent/US8263772B2/en not_active Expired - Fee Related
- 2007-06-08 BR BRPI0712680-8A patent/BRPI0712680A2/pt not_active IP Right Cessation
-
2012
- 2012-08-08 US US13/569,899 patent/US20120302547A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20090093456A1 (en) | 2009-04-09 |
| JP5198439B2 (ja) | 2013-05-15 |
| BRPI0712680A2 (pt) | 2012-11-20 |
| EP2029609A2 (en) | 2009-03-04 |
| WO2007146758A3 (en) | 2008-02-07 |
| EA200870517A1 (ru) | 2009-04-28 |
| WO2007146758A2 (en) | 2007-12-21 |
| CA2652385A1 (en) | 2007-12-21 |
| US8263772B2 (en) | 2012-09-11 |
| EA015127B1 (ru) | 2011-06-30 |
| JP2009539875A (ja) | 2009-11-19 |
| AU2007257922A1 (en) | 2007-12-21 |
| CN101454328A (zh) | 2009-06-10 |
| US20120302547A1 (en) | 2012-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2008015662A (es) | Nuevos receptores antagonistas de la hormona concentradora de melanina (mch). | |
| AU2005316314B2 (en) | Thiazolopyridinone derivates as MCH receptor antagonists | |
| ES2373680T3 (es) | Derivados de tiazol condensados como inhibidores de cinasa. | |
| CZ2004498A3 (cs) | Pyrimidinonové deriváty, způsob výroby a farmaceutický prostředek | |
| US20040024210A1 (en) | New compounds | |
| CN121568930A (zh) | 化合物及其作为抗癌药的用途 | |
| RU2418803C2 (ru) | Конденсированное гетероциклическое производное, содержащая его лечебная композиция и ее применение в медицине | |
| NZ552283A (en) | New compounds useful for the treatment of obesity, type II diabetes and CNS disorders | |
| WO2010002802A1 (en) | Pyrrolidine-substituted azaindole compounds having 5-ht6 receptor affinity | |
| AU2008256859A1 (en) | 4' substituted compounds having 5-HT6 receptor affinity | |
| US20080200471A1 (en) | 6' substituted compounds having 5-ht6 receptor affinity | |
| CA2536107A1 (en) | Substituted piperazines of azepines, oxazepines, and thiazepines | |
| NZ549386A (en) | (Indol-3-yl)-heterocycle derivatives as agonists of the cannabinoid CB1 receptor | |
| MX2008015486A (es) | Nuevos receptores antagonistas de la hormona concentrador de melanina (mch). | |
| TW201116531A (en) | Ring-annulated dihydropyrrolo[2,1-a]isoquinolines | |
| EP1897881A2 (en) | Compounds useful for the treatment of obesity, type II diabetes and CNS disorders |