BRPI0712680A2 - antagonistas de receptor de mch - Google Patents

Info

Publication number

BRPI0712680A2

BRPI0712680A2 BRPI0712680-8A BRPI0712680A BRPI0712680A2 BR PI0712680 A2 BRPI0712680 A2 BR PI0712680A2 BR PI0712680 A BRPI0712680 A BR PI0712680A BR PI0712680 A2 BRPI0712680 A2 BR PI0712680A2

Authority

BR

Brazil

Prior art keywords

phenyl

methoxy

chloro

thieno

pyridin

Prior art date

2006-06-08

Links

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• 239000002464 receptor antagonist Substances 0.000 title abstract 2
• 229940044551 receptor antagonist Drugs 0.000 title abstract 2
• 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title description 2
• 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 242
• 239000000203 mixture Substances 0.000 claims abstract description 151
• 208000008589 Obesity Diseases 0.000 claims abstract description 16
• 235000020824 obesity Nutrition 0.000 claims abstract description 16
• 150000003839 salts Chemical class 0.000 claims abstract description 11
• 239000000460 chlorine Substances 0.000 claims description 198
• -1 -OR6 Chemical group 0.000 claims description 108
• 229910052739 hydrogen Inorganic materials 0.000 claims description 87
• 239000001257 hydrogen Substances 0.000 claims description 86
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 69
• 125000000623 heterocyclic group Chemical group 0.000 claims description 65
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 64
• 238000000034 method Methods 0.000 claims description 62
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 57
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 49
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 42
• 229910052801 chlorine Inorganic materials 0.000 claims description 39
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 36
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 36
• 239000011737 fluorine Substances 0.000 claims description 31
• 229910052731 fluorine Inorganic materials 0.000 claims description 31
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• 229910052701 rubidium Inorganic materials 0.000 claims description 20
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 125000004043 oxo group Chemical group O=* 0.000 claims description 15
• 125000004193 piperazinyl group Chemical group 0.000 claims description 14
• 125000003386 piperidinyl group Chemical group 0.000 claims description 14
• 125000002393 azetidinyl group Chemical group 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 125000002883 imidazolyl group Chemical group 0.000 claims description 11
• 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 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000003545 alkoxy 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
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 6
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
• CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical group FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 claims description 6
• 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 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
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 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 4
• XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 239000002830 appetite depressant Substances 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• MRPMZDZHOMJYJI-FQEVSTJZSA-N (5s)-5-[[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-methoxyphenoxy]methyl]-4-methylmorpholin-3-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC[C@@H]1COCC(=O)N1C MRPMZDZHOMJYJI-FQEVSTJZSA-N 0.000 claims description 2
• 125000000753 cycloalkyl 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
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 13
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims 1
• 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
• RDXDDIURVFTSGG-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-fluoro-4-(1-methylazetidin-3-yl)oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CC1OC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1F RDXDDIURVFTSGG-UHFFFAOYSA-N 0.000 claims 1
• DANNXIYTSPUKNZ-FQEVSTJZSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-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-FQEVSTJZSA-N 0.000 claims 1
• NEQYTWHZDNXZAF-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[4-(1-methylpyrrolidine-3-carbonyl)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CCC1C(=O)C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 NEQYTWHZDNXZAF-UHFFFAOYSA-N 0.000 claims 1
• GYBQZUCJAUWRPG-FSRHSHDFSA-N 2-(4-chlorophenyl)-6-[4-[(3r)-3-hydroxypyrrolidin-1-yl]-3-methoxyphenyl]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=C1N1CC[C@@H](O)C1 GYBQZUCJAUWRPG-FSRHSHDFSA-N 0.000 claims 1
• CZRGFNLUHBYQMI-DENIHFKCSA-N 2-(4-chlorophenyl)-6-[4-[(3r,4r)-4-hydroxy-1-methylpyrrolidin-3-yl]oxy-3-methoxyphenyl]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]1CN(C)C[C@H]1O CZRGFNLUHBYQMI-DENIHFKCSA-N 0.000 claims 1
• ROFZYMVRJQBSBY-BOXHHOBZSA-N 2-(4-chlorophenyl)-6-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-3-methoxyphenyl]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=C1N1CC[C@H](N(C)C)C1 ROFZYMVRJQBSBY-BOXHHOBZSA-N 0.000 claims 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
• 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 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
• YMWUTSHORUIBBG-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]phenyl]-1-methylpyrrolidine-3-carboxamide Chemical compound C1N(C)CCC1C(=O)NC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 YMWUTSHORUIBBG-UHFFFAOYSA-N 0.000 claims 1
• 101800002739 Melanin-concentrating hormone Proteins 0.000 abstract description 22
• 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 21
• 201000010099 disease Diseases 0.000 abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
• 102400001132 Melanin-concentrating hormone Human genes 0.000 abstract 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 221
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 166
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
• 238000002360 preparation method Methods 0.000 description 132
• 239000012141 concentrate Substances 0.000 description 120
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 119
• 238000003756 stirring Methods 0.000 description 118
• 239000000243 solution Substances 0.000 description 114
• 235000019439 ethyl acetate Nutrition 0.000 description 99
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
• 238000006243 chemical reaction Methods 0.000 description 84
• 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 78
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
• 239000011734 sodium Substances 0.000 description 78
• 239000000284 extract Substances 0.000 description 70
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 239000007787 solid Substances 0.000 description 50
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 44
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 44
• 239000013058 crude material Substances 0.000 description 39
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
• 239000012044 organic layer Substances 0.000 description 33
• 238000004587 chromatography analysis Methods 0.000 description 31
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
• 239000012267 brine Substances 0.000 description 29
• 239000000047 product Substances 0.000 description 29
• 239000000725 suspension Substances 0.000 description 29
• 239000002904 solvent Substances 0.000 description 26
• 238000010898 silica gel chromatography Methods 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 238000010791 quenching Methods 0.000 description 22
• 238000010992 reflux Methods 0.000 description 22
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 21
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 102000047659 melanin-concentrating hormone Human genes 0.000 description 20
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 18
• 239000002253 acid Substances 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 239000012458 free base Substances 0.000 description 16
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 15
• 238000003818 flash chromatography Methods 0.000 description 15
• 239000000543 intermediate Substances 0.000 description 15
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• 229910052763 palladium Inorganic materials 0.000 description 14
• 239000000463 material Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
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• 239000002585 base Substances 0.000 description 10
• 150000003840 hydrochlorides Chemical class 0.000 description 10
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 9
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• 238000001914 filtration Methods 0.000 description 9
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• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 150000001408 amides Chemical class 0.000 description 8
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• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 210000003739 neck Anatomy 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 238000010926 purge Methods 0.000 description 8
• 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 8
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• 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 description 7
• 239000005557 antagonist Substances 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 238000005859 coupling reaction Methods 0.000 description 7
• 238000006880 cross-coupling reaction Methods 0.000 description 7
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
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• 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-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
• 230000015572 biosynthetic process Effects 0.000 description 6
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• 239000003153 chemical reaction reagent Substances 0.000 description 6
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• NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
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• 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
• 238000003828 vacuum filtration Methods 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
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