DE60218721T2 - Pyrimidione als Melanin-konzentrierenden Hormonrezeptor 1 - Google Patents

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Publication number

DE60218721T2

DE60218721T2 DE60218721T DE60218721T DE60218721T2 DE 60218721 T2 DE60218721 T2 DE 60218721T2 DE 60218721 T DE60218721 T DE 60218721T DE 60218721 T DE60218721 T DE 60218721T DE 60218721 T2 DE60218721 T2 DE 60218721T2

Authority

DE

Germany

Prior art keywords

group

formula

alkyl

compound according

nmr

Prior art date

2001-10-15

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

Expired - Fee Related

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• 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 title description 7
• 102000044674 Melanin-concentrating hormone receptor 1 Human genes 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 177
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• 239000012453 solvate Substances 0.000 claims abstract description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 89
• 238000006243 chemical reaction Methods 0.000 claims description 71
• 239000001257 hydrogen Substances 0.000 claims description 70
• 229910052739 hydrogen Inorganic materials 0.000 claims description 70
• 239000000203 mixture Substances 0.000 claims description 70
• 238000000034 method Methods 0.000 claims description 52
• 229910052736 halogen Inorganic materials 0.000 claims description 49
• 150000002367 halogens Chemical class 0.000 claims description 46
• -1 C 1 6- dialkylamino Chemical group 0.000 claims description 39
• 125000003545 alkoxy group Chemical group 0.000 claims description 38
• 150000002431 hydrogen Chemical class 0.000 claims description 35
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 238000002360 preparation method Methods 0.000 claims description 32
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
• 229910052717 sulfur Inorganic materials 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 239000002904 solvent Substances 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 24
• 125000004043 oxo group Chemical group O=* 0.000 claims description 24
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 23
• 239000000460 chlorine Substances 0.000 claims description 23
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 22
• 125000000623 heterocyclic group Chemical group 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 19
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 150000001412 amines Chemical class 0.000 claims description 12
• 239000003054 catalyst Substances 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
• 229910052763 palladium Inorganic materials 0.000 claims description 11
• 208000008589 Obesity Diseases 0.000 claims description 10
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 235000020824 obesity Nutrition 0.000 claims description 10
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
• 125000003282 alkyl amino group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000004122 cyclic group Chemical group 0.000 claims description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims description 7
• 239000002168 alkylating agent Substances 0.000 claims description 6
• 229940100198 alkylating agent Drugs 0.000 claims description 6
• 239000003638 chemical reducing agent Substances 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 230000029936 alkylation Effects 0.000 claims description 5
• 238000005804 alkylation reaction Methods 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• SPTWLZKLYBNOIM-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(3-fluoropyrrolidin-1-yl)ethoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCC(F)C1 SPTWLZKLYBNOIM-UHFFFAOYSA-N 0.000 claims description 4
• 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
• 239000003153 chemical reaction reagent Substances 0.000 claims description 4
• 239000011737 fluorine Substances 0.000 claims description 4
• 238000005932 reductive alkylation reaction Methods 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• 206010020772 Hypertension Diseases 0.000 claims description 3
• 241000124008 Mammalia Species 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 150000001413 amino acids Chemical class 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 230000008878 coupling Effects 0.000 claims description 3
• 238000010168 coupling process Methods 0.000 claims description 3
• 238000005859 coupling reaction Methods 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 238000006268 reductive amination reaction Methods 0.000 claims description 3
• 239000011593 sulfur Substances 0.000 claims description 3
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 2
• GNYADONDNGUVHO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-(3-oxopyrrolidin-1-yl)ethoxy]phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCC(=O)C1 GNYADONDNGUVHO-UHFFFAOYSA-N 0.000 claims description 2
• 208000019901 Anxiety disease Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 239000007868 Raney catalyst Substances 0.000 claims description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
• 229910000564 Raney nickel Inorganic materials 0.000 claims description 2
• 238000006619 Stille reaction Methods 0.000 claims description 2
• 238000006069 Suzuki reaction reaction Methods 0.000 claims description 2
• 230000036506 anxiety Effects 0.000 claims description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
• 238000010438 heat treatment Methods 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 241000894007 species Species 0.000 claims description 2
• 125000004952 trihaloalkoxy group Chemical group 0.000 claims description 2
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 2
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
• 230000010933 acylation Effects 0.000 claims 1
• 238000005917 acylation reaction Methods 0.000 claims 1
• 239000007822 coupling agent Substances 0.000 claims 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 228
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 222
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 194
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 89
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
• 239000000243 solution Substances 0.000 description 60
• 239000000047 product Substances 0.000 description 55
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• 235000019439 ethyl acetate Nutrition 0.000 description 36
• 239000007787 solid Substances 0.000 description 34
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 22
• 235000002639 sodium chloride Nutrition 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
• 238000002390 rotary evaporation Methods 0.000 description 19
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 239000002244 precipitate Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 14
• 239000011734 sodium Substances 0.000 description 14
• 239000000543 intermediate Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 11
• WEKBYHGPOQSONW-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(O)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 WEKBYHGPOQSONW-UHFFFAOYSA-N 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
• 229910000024 caesium carbonate Inorganic materials 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 9
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 229910052799 carbon Inorganic materials 0.000 description 9
• 239000011976 maleic acid Substances 0.000 description 9
• ALWFLYMKFZJTBB-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-3-(dimethylaminomethylideneamino)thiophene-2-carboxylate Chemical compound CN(C)C=NC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=C1 ALWFLYMKFZJTBB-UHFFFAOYSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
• 101800002739 Melanin-concentrating hormone Proteins 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 239000005557 antagonist Substances 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 239000002609 medium Substances 0.000 description 8
• 238000010898 silica gel chromatography Methods 0.000 description 8
• PZMKGWRBZNOIPQ-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1SC=C2 PZMKGWRBZNOIPQ-UHFFFAOYSA-N 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
• 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 6
• 238000002156 mixing Methods 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• OYRKCMGKJLZIQO-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCBr OYRKCMGKJLZIQO-UHFFFAOYSA-N 0.000 description 5
• 0 C*C(C1=O)=C(C)N=C(*)N1C(C=CC(N)=C1)=CC1(C)I*=* Chemical compound C*C(C1=O)=C(C)N=C(*)N1C(C=CC(N)=C1)=CC1(C)I*=* 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 238000010792 warming Methods 0.000 description 5
• JXIJUAWSDBACEB-UHFFFAOYSA-N 1-chloro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1Cl JXIJUAWSDBACEB-UHFFFAOYSA-N 0.000 description 4
• VBPMITJBSXBGOI-UHFFFAOYSA-N 3-methoxy-4-(2-pyrrolidin-1-ylethoxy)aniline Chemical compound COC1=CC(N)=CC=C1OCCN1CCCC1 VBPMITJBSXBGOI-UHFFFAOYSA-N 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
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-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
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 150000001409 amidines Chemical class 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 4
• 102000047659 melanin-concentrating hormone Human genes 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• IZLVFLOBTPURLP-UHFFFAOYSA-N 2-Methoxy-4-nitrophenol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1O IZLVFLOBTPURLP-UHFFFAOYSA-N 0.000 description 3
• KVTUSMPNLUCCQO-UHFFFAOYSA-N 3,3-difluoropyrrolidine Chemical compound FC1(F)CCNC1 KVTUSMPNLUCCQO-UHFFFAOYSA-N 0.000 description 3
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