DE60218721T2 - Pyrimidione als Melanin-konzentrierenden Hormonrezeptor 1 - Google Patents
Pyrimidione als Melanin-konzentrierenden Hormonrezeptor 1 Download PDFInfo
- 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
- 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
Links
- 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
- FZGSRDKXDBSKDY-UHFFFAOYSA-N 3-[4-[2-[benzyl(methyl)amino]ethoxy]-3-methoxyphenyl]-6-(4-chlorophenyl)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=C1OCCN(C)CC1=CC=CC=C1 FZGSRDKXDBSKDY-UHFFFAOYSA-N 0.000 description 3
- CDDGNGVFPQRJJM-UHFFFAOYSA-N 3-fluoropyrrolidine Chemical compound FC1CCNC1 CDDGNGVFPQRJJM-UHFFFAOYSA-N 0.000 description 3
- RTTZXTNJMQSHLZ-UHFFFAOYSA-N 4-(2,2-diethoxyethoxy)-3-methoxyaniline Chemical compound CCOC(OCC)COC1=CC=C(N)C=C1OC RTTZXTNJMQSHLZ-UHFFFAOYSA-N 0.000 description 3
- DGEIDETWOGABOM-UHFFFAOYSA-N 4-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1OCCN1CC(F)(F)CC1 DGEIDETWOGABOM-UHFFFAOYSA-N 0.000 description 3
- GGZGIZHZCJERAA-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(1-methylpiperidin-4-yl)oxyphenyl]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=C1OC1CCN(C)CC1 GGZGIZHZCJERAA-UHFFFAOYSA-N 0.000 description 3
- GTBVUCDFNJKBHP-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethylamino)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=C1NCCN1CCCC1 GTBVUCDFNJKBHP-UHFFFAOYSA-N 0.000 description 3
- LWTHZRWQJIOEQZ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(3-hydroxypyrrolidin-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(O)C1 LWTHZRWQJIOEQZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- VGCASWIYXYUVSE-UHFFFAOYSA-N 1-[1-(2-methoxy-4-nitrophenoxy)-2-methylpropan-2-yl]pyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCC(C)(C)N1CCCC1 VGCASWIYXYUVSE-UHFFFAOYSA-N 0.000 description 2
- JFJDBJXORBKDIV-UHFFFAOYSA-N 1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidin-3-ol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCN1CC(O)CC1 JFJDBJXORBKDIV-UHFFFAOYSA-N 0.000 description 2
- ATKHSJCMFOGKDU-UHFFFAOYSA-N 1-[2-(4-amino-2-methoxyphenoxy)ethyl]pyrrolidin-3-ol Chemical compound COC1=CC(N)=CC=C1OCCN1CC(O)CC1 ATKHSJCMFOGKDU-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AYOWDZLGGRUSCF-UHFFFAOYSA-N 2-amino-4-chloro-n-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]benzamide Chemical compound C=1C=C(OCCN2CCCC2)C(OC)=CC=1NC(=O)C1=CC=C(Cl)C=C1N AYOWDZLGGRUSCF-UHFFFAOYSA-N 0.000 description 2
- NRXIXDFFYWZZNL-UHFFFAOYSA-N 2-methyl-2-pyrrolidin-1-ylpropan-1-ol Chemical compound OCC(C)(C)N1CCCC1 NRXIXDFFYWZZNL-UHFFFAOYSA-N 0.000 description 2
- KBLVKJOYSZOHOJ-UHFFFAOYSA-N 3,3-difluoro-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCN1CC(F)(F)CC1 KBLVKJOYSZOHOJ-UHFFFAOYSA-N 0.000 description 2
- IKPYVPOMHMMERM-UHFFFAOYSA-N 3-(4-amino-3-methoxyphenyl)-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(N)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 IKPYVPOMHMMERM-UHFFFAOYSA-N 0.000 description 2
- FPWBJZYTTWDKGY-UHFFFAOYSA-N 3-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN1CCOCC1 FPWBJZYTTWDKGY-UHFFFAOYSA-N 0.000 description 2
- IVRCHBYBKXRNIC-UHFFFAOYSA-N 3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-6-phenylthieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN1CCCC1 IVRCHBYBKXRNIC-UHFFFAOYSA-N 0.000 description 2
- SPBCBHQCDZVPAO-UHFFFAOYSA-N 3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-7-[4-(trifluoromethyl)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(=CC=2)C(F)(F)F)=O)=CC=C1OCCN1CCCC1 SPBCBHQCDZVPAO-UHFFFAOYSA-N 0.000 description 2
- AFMVAWLHNDKNEM-UHFFFAOYSA-N 3-[4-(3-bromopropoxy)-3-methoxyphenyl]-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCCCBr)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 AFMVAWLHNDKNEM-UHFFFAOYSA-N 0.000 description 2
- SZYJTOFVJRBPMR-ZDUSSCGKSA-N 3-[4-[(2s)-2-aminopropoxy]-3-methoxyphenyl]-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC[C@H](C)N)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 SZYJTOFVJRBPMR-ZDUSSCGKSA-N 0.000 description 2
- OENYWTXSWLCGIW-UHFFFAOYSA-N 3-[4-[2-[benzyl(methyl)amino]ethoxy]-3-methoxyphenyl]-7-(4-fluorophenyl)quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1OCCN(C)CC1=CC=CC=C1 OENYWTXSWLCGIW-UHFFFAOYSA-N 0.000 description 2
- URDOBXAPPNIYPN-UHFFFAOYSA-N 3-[4-[3-(dimethylamino)-2,2-dimethylpropoxy]-3-methoxyphenyl]-6-(4-fluorophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCC(C)(C)CN(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(F)=CC=2)=O)=C1 URDOBXAPPNIYPN-UHFFFAOYSA-N 0.000 description 2
- BCLXISHZOIMOBX-UHFFFAOYSA-N 3-fluoro-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCN1CC(F)CC1 BCLXISHZOIMOBX-UHFFFAOYSA-N 0.000 description 2
- JLZQYWSJMSPOEC-UHFFFAOYSA-N 3-methoxy-4-(1-methylpiperidin-4-yl)oxyaniline Chemical compound COC1=CC(N)=CC=C1OC1CCN(C)CC1 JLZQYWSJMSPOEC-UHFFFAOYSA-N 0.000 description 2
- ZKBJEIWSBBXLJG-UHFFFAOYSA-N 3-methoxy-4-(2-methyl-2-pyrrolidin-1-ylpropoxy)aniline Chemical compound COC1=CC(N)=CC=C1OCC(C)(C)N1CCCC1 ZKBJEIWSBBXLJG-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- LONHIKNRVFLWFP-UHFFFAOYSA-N 4-[2-(diethylamino)ethylsulfanyl]aniline Chemical compound CCN(CC)CCSC1=CC=C(N)C=C1 LONHIKNRVFLWFP-UHFFFAOYSA-N 0.000 description 2
- CCYGYZQEMUYDTJ-UHFFFAOYSA-N 4-chloro-n-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2-nitrobenzamide Chemical compound C=1C=C(OCCN2CCCC2)C(OC)=CC=1NC(=O)C1=CC=C(Cl)C=C1[N+]([O-])=O CCYGYZQEMUYDTJ-UHFFFAOYSA-N 0.000 description 2
- HJCDDONOCCNMLW-UHFFFAOYSA-N 5-bromo-3-nitrothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(Br)=CC=1[N+]([O-])=O HJCDDONOCCNMLW-UHFFFAOYSA-N 0.000 description 2
- WPRCCQVZAFUAMJ-UHFFFAOYSA-N 5-bromo-n-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-nitrothiophene-2-carboxamide Chemical compound C=1C=C(OCCN2CCCC2)C(OC)=CC=1NC(=O)C=1SC(Br)=CC=1[N+]([O-])=O WPRCCQVZAFUAMJ-UHFFFAOYSA-N 0.000 description 2
- ADDGGQMXFXRHCR-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(2-methyl-2-pyrrolidin-1-ylpropoxy)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=C1OCC(C)(C)N1CCCC1 ADDGGQMXFXRHCR-UHFFFAOYSA-N 0.000 description 2
- HCKJCTZRNNIPCG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2-methylthieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2C)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 HCKJCTZRNNIPCG-UHFFFAOYSA-N 0.000 description 2
- HBFKTLVPSULPMJ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-[[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]amino]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=C1OCCNC(O1)=NN=C1C1=CC=C(C)C=C1 HBFKTLVPSULPMJ-UHFFFAOYSA-N 0.000 description 2
- UONHRKJTUKYJOB-IBGZPJMESA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[[(2s)-1-methylpyrrolidin-2-yl]methoxy]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=C1OC[C@@H]1CCCN1C UONHRKJTUKYJOB-IBGZPJMESA-N 0.000 description 2
- MJYYVJHJPLMVPV-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(diethylamino)ethylsulfanyl]phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(SCCN(CC)CC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 MJYYVJHJPLMVPV-UHFFFAOYSA-N 0.000 description 2
- LWTHZRWQJIOEQZ-LJQANCHMSA-N 6-(4-chlorophenyl)-3-[4-[2-[(3r)-3-hydroxypyrrolidin-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=C1OCCN1CC[C@@H](O)C1 LWTHZRWQJIOEQZ-LJQANCHMSA-N 0.000 description 2
- MKINIOIDVIDSPM-UHFFFAOYSA-N 6-bromo-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(Br)=CC=3N=C2)=O)=CC=C1OCCN1CCCC1 MKINIOIDVIDSPM-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 150000001500 aryl chlorides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000013583 drug formulation Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- CJPGWIJUHQBYJT-UHFFFAOYSA-N ethyl 2-methyl-2-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)C(C)(C)N1CCCC1 CJPGWIJUHQBYJT-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- MWULMTACIBZPGN-UHFFFAOYSA-N gw-803,430 Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 MWULMTACIBZPGN-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 description 2
- QJZWJXHEFMMBHE-UHFFFAOYSA-N methyl 4-amino-2-(4-chlorophenyl)-1,3-thiazole-5-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC(Cl)=CC=2)=N1 QJZWJXHEFMMBHE-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- WLJZINGKRZGNSA-UHFFFAOYSA-N n-(3-bromopropyl)-n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-4-methylbenzenesulfonamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(CCCBr)S(=O)(=O)C1=CC=C(C)C=C1 WLJZINGKRZGNSA-UHFFFAOYSA-N 0.000 description 2
- BNPOXCUQIOPISW-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NC(=O)CN1CCCC1 BNPOXCUQIOPISW-UHFFFAOYSA-N 0.000 description 2
- YVOQUDHRKZOLQT-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-4-methylbenzenesulfonamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 YVOQUDHRKZOLQT-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 235000003270 potassium fluoride Nutrition 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 239000001119 stannous chloride Substances 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 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 2
- 239000012588 trypsin Substances 0.000 description 2
- JRQQUMKTXWEXDF-NSHDSACASA-N (2s)-2-[(2-methoxy-4-nitrophenoxy)methyl]-1-methylpyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OC[C@H]1N(C)CCC1 JRQQUMKTXWEXDF-NSHDSACASA-N 0.000 description 1
- JFJDBJXORBKDIV-LLVKDONJSA-N (3r)-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidin-3-ol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCN1C[C@H](O)CC1 JFJDBJXORBKDIV-LLVKDONJSA-N 0.000 description 1
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-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
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- METPQQHVRNLTRX-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-fluoropyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](F)CN1C(=O)OC(C)(C)C METPQQHVRNLTRX-YUMQZZPRSA-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
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- IKKUKDZKIIIKJK-UHFFFAOYSA-N 2,2-diethoxyethanol Chemical compound CCOC(CO)OCC IKKUKDZKIIIKJK-UHFFFAOYSA-N 0.000 description 1
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BGYBCXUHQOXSCU-UHFFFAOYSA-N 2-(4-chloro-n-methylanilino)ethyl 4-methylbenzenesulfonate Chemical compound C=1C=C(Cl)C=CC=1N(C)CCOS(=O)(=O)C1=CC=C(C)C=C1 BGYBCXUHQOXSCU-UHFFFAOYSA-N 0.000 description 1
- VVBMGZYZYBRLCY-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-one Chemical compound COC1=CC(N2C(C=3SC(=NC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 VVBMGZYZYBRLCY-UHFFFAOYSA-N 0.000 description 1
- OYCDJBDFAWTHPV-UHFFFAOYSA-N 2-(4-cyano-n-methylanilino)ethyl 4-methylbenzenesulfonate Chemical compound C=1C=C(C#N)C=CC=1N(C)CCOS(=O)(=O)C1=CC=C(C)C=C1 OYCDJBDFAWTHPV-UHFFFAOYSA-N 0.000 description 1
- GKCQYXFDGRHHKD-UHFFFAOYSA-N 2-[2-(2-methoxy-4-nitrophenoxy)ethyl]-1-methylpyrrolidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OCCC1N(C)CCC1 GKCQYXFDGRHHKD-UHFFFAOYSA-N 0.000 description 1
- QPYWTEPJJSGXST-UHFFFAOYSA-N 2-chloro-4-methylbenzenesulfonyl bromide Chemical compound ClC1=C(S(=O)(=O)Br)C=CC(=C1)C QPYWTEPJJSGXST-UHFFFAOYSA-N 0.000 description 1
- RAGSWDIQBBZLLL-UHFFFAOYSA-N 2-chloroethyl(diethyl)azanium;chloride Chemical compound Cl.CCN(CC)CCCl RAGSWDIQBBZLLL-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- HGUYBLVGLMAUFF-UHFFFAOYSA-N 2-methoxybenzene-1,4-diamine Chemical compound COC1=CC(N)=CC=C1N HGUYBLVGLMAUFF-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- RZIYRKYHMDDHCK-UHFFFAOYSA-N 265654-77-1 Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCN1CCCC1 RZIYRKYHMDDHCK-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- FFOIFAAVWJZLFE-UHFFFAOYSA-N 3-(chloromethyl)-1-methylpiperidine Chemical compound CN1CCCC(CCl)C1 FFOIFAAVWJZLFE-UHFFFAOYSA-N 0.000 description 1
- OGWTWNVPPNFBEC-UHFFFAOYSA-N 3-[3-chloro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-7-(4-fluorophenyl)quinazolin-4-one Chemical compound C1=CC(F)=CC=C1C1=CC=C2C(=O)N(C=3C=C(Cl)C(OCCN4CCCC4)=CC=3)C=NC2=C1 OGWTWNVPPNFBEC-UHFFFAOYSA-N 0.000 description 1
- ZCAWEOSGRAIYEU-UHFFFAOYSA-N 3-[3-chloro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-7-phenylquinazolin-4-one Chemical compound ClC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN1CCCC1 ZCAWEOSGRAIYEU-UHFFFAOYSA-N 0.000 description 1
- ICKGONQJJDEDEB-UHFFFAOYSA-N 3-[3-methoxy-4-(2-piperidin-1-ylethoxy)phenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN1CCCCC1 ICKGONQJJDEDEB-UHFFFAOYSA-N 0.000 description 1
- UBBXNKMTSHKIHZ-UHFFFAOYSA-N 3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-7-(4-methylphenyl)quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(C)=CC=2)=O)=CC=C1OCCN1CCCC1 UBBXNKMTSHKIHZ-UHFFFAOYSA-N 0.000 description 1
- QINSFGJODVXLBB-UHFFFAOYSA-N 3-[3-methoxy-4-[2-(4-phenylpiperidin-1-yl)ethoxy]phenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN(CC1)CCC1C1=CC=CC=C1 QINSFGJODVXLBB-UHFFFAOYSA-N 0.000 description 1
- YEAQAYWYFLMJTF-UHFFFAOYSA-N 3-[3-methoxy-4-[2-[methyl(2-phenylethyl)amino]ethoxy]phenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN(C)CCC1=CC=CC=C1 YEAQAYWYFLMJTF-UHFFFAOYSA-N 0.000 description 1
- VFUZKBABFYOEER-LJQANCHMSA-N 3-[3-methoxy-4-[[(2r)-1-methylpyrrolidin-2-yl]methoxy]phenyl]-6-phenylthieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC=CC=2)=O)=CC=C1OC[C@H]1CCCN1C VFUZKBABFYOEER-LJQANCHMSA-N 0.000 description 1
- PIKUZHPVMYYORI-UHFFFAOYSA-N 3-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]-7-(4-fluorophenyl)quinazolin-4-one Chemical compound C1=C(OC)C(OCC(OCC)OCC)=CC=C1N1C(=O)C2=CC=C(C=3C=CC(F)=CC=3)C=C2N=C1 PIKUZHPVMYYORI-UHFFFAOYSA-N 0.000 description 1
- GUBYDYRUSSOGJM-UHFFFAOYSA-N 3-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]-7-phenylquinazolin-4-one Chemical compound C1=C(OC)C(OCC(OCC)OCC)=CC=C1N1C(=O)C2=CC=C(C=3C=CC=CC=3)C=C2N=C1 GUBYDYRUSSOGJM-UHFFFAOYSA-N 0.000 description 1
- GPWLASBMJRFNSI-UHFFFAOYSA-N 3-[4-(2-aminoethoxy)-3-methoxyphenyl]-6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(OCCN)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 GPWLASBMJRFNSI-UHFFFAOYSA-N 0.000 description 1
- NONWZAKHBBRYSD-UHFFFAOYSA-N 3-[4-[2-(azepan-1-yl)ethoxy]-3-methoxyphenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN1CCCCCC1 NONWZAKHBBRYSD-UHFFFAOYSA-N 0.000 description 1
- HJNPUIGBTVMOCJ-UHFFFAOYSA-N 3-[4-[2-(diethylamino)ethylamino]-3-methoxyphenyl]-6-(4-fluorophenyl)thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC)C(NCCN(CC)CC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(F)=CC=3)=C2N=C1 HJNPUIGBTVMOCJ-UHFFFAOYSA-N 0.000 description 1
- VTAYQHNDOUGKKJ-UHFFFAOYSA-N 3-[4-[2-(dimethylamino)ethoxy]-3-methoxyphenyl]-7-(4-fluorophenyl)quinazolin-4-one Chemical compound C1=C(OCCN(C)C)C(OC)=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(F)=CC=2)=O)=C1 VTAYQHNDOUGKKJ-UHFFFAOYSA-N 0.000 description 1
- FXUJCVRFNDAKFO-UHFFFAOYSA-N 3-[4-[2-[4-(4-chlorophenyl)piperidin-1-yl]ethoxy]-3-methoxyphenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN(CC1)CCC1C1=CC=C(Cl)C=C1 FXUJCVRFNDAKFO-UHFFFAOYSA-N 0.000 description 1
- LCVZNGTXXFABPR-UHFFFAOYSA-N 3-[4-[2-[cyclohexyl(methyl)amino]ethoxy]-3-methoxyphenyl]-7-phenylquinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC=CC=2)=O)=CC=C1OCCN(C)C1CCCCC1 LCVZNGTXXFABPR-UHFFFAOYSA-N 0.000 description 1
- PKCRBFVMGVPQHZ-UHFFFAOYSA-N 3-[4-[2-[ethyl(methyl)amino]ethoxy]-3-methoxyphenyl]-7-phenylquinazolin-4-one Chemical compound C1=C(OC)C(OCCN(C)CC)=CC=C1N1C(=O)C2=CC=C(C=3C=CC=CC=3)C=C2N=C1 PKCRBFVMGVPQHZ-UHFFFAOYSA-N 0.000 description 1
- MAUZMOMALBDIHE-UHFFFAOYSA-N 3-[4-[3-[benzyl(methyl)amino]propoxy]-3-methoxyphenyl]-6-(4-chlorophenyl)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=C1OCCCN(C)CC1=CC=CC=C1 MAUZMOMALBDIHE-UHFFFAOYSA-N 0.000 description 1
- ODUVFBUXTFLIKB-UHFFFAOYSA-N 3-amino-5-(4-chlorophenyl)-n-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thiophene-2-carboxamide Chemical compound C=1C=C(OCCN2CCCC2)C(OC)=CC=1NC(=O)C(=C(C=1)N)SC=1C1=CC=C(Cl)C=C1 ODUVFBUXTFLIKB-UHFFFAOYSA-N 0.000 description 1
- GJSCPTFOPWQABH-UHFFFAOYSA-N 4-(2-methoxy-4-nitrophenoxy)-1-methylpiperidine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OC1CCN(C)CC1 GJSCPTFOPWQABH-UHFFFAOYSA-N 0.000 description 1
- OTYZNDKWNPQQJP-UHFFFAOYSA-N 4-(2-pyrrolidin-1-ylethoxy)aniline Chemical compound C1=CC(N)=CC=C1OCCN1CCCC1 OTYZNDKWNPQQJP-UHFFFAOYSA-N 0.000 description 1
- GYPHGCDLYJOIHJ-UHFFFAOYSA-N 4-[2-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]ethyl-methylamino]benzonitrile Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN(C)C1=CC=C(C#N)C=C1 GYPHGCDLYJOIHJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JPPRLSRXIXXHFB-UHFFFAOYSA-N 4-[[2-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]ethylamino]methyl]benzonitrile Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCNCC1=CC=C(C#N)C=C1 JPPRLSRXIXXHFB-UHFFFAOYSA-N 0.000 description 1
- WCDSVWRUXWCYFN-UHFFFAOYSA-N 4-aminobenzenethiol Chemical compound NC1=CC=C(S)C=C1 WCDSVWRUXWCYFN-UHFFFAOYSA-N 0.000 description 1
- JAHIPDTWWVYVRV-UHFFFAOYSA-N 4-chloro-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1[N+]([O-])=O JAHIPDTWWVYVRV-UHFFFAOYSA-N 0.000 description 1
- MMJYSVRCFSCVCI-UHFFFAOYSA-N 4-chloro-2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C(Cl)=O MMJYSVRCFSCVCI-UHFFFAOYSA-N 0.000 description 1
- XSSLDBLGZJJFAQ-UHFFFAOYSA-N 4-chloro-n-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]-2-nitrobenzamide Chemical compound C1=C(OC)C(OCC(OCC)OCC)=CC=C1NC(=O)C1=CC=C(Cl)C=C1[N+]([O-])=O XSSLDBLGZJJFAQ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- MFFVZXOPRXMVET-UHFFFAOYSA-N 4-methylbenzohydrazide Chemical compound CC1=CC=C(C(=O)NN)C=C1 MFFVZXOPRXMVET-UHFFFAOYSA-N 0.000 description 1
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
- ILAXZPDKSKVBRP-UHFFFAOYSA-N 4h-[1,3]thiazolo[4,5-d]pyrimidin-7-one Chemical compound O=C1N=CNC2=C1SC=N2 ILAXZPDKSKVBRP-UHFFFAOYSA-N 0.000 description 1
- CJQLWGHXINNBHL-UHFFFAOYSA-N 5-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-(2-pyrrolidin-1-ylethoxy)benzonitrile Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(C(OCCN3CCCC3)=CC=1)C#N)C=N2 CJQLWGHXINNBHL-UHFFFAOYSA-N 0.000 description 1
- RVPBRKPMATWEMT-UHFFFAOYSA-N 5-[6-(4-fluorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-(2-pyrrolidin-1-ylethoxy)benzonitrile Chemical compound C1=CC(F)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(C(OCCN3CCCC3)=CC=1)C#N)C=N2 RVPBRKPMATWEMT-UHFFFAOYSA-N 0.000 description 1
- GIMGDUAANSGEKN-UHFFFAOYSA-N 5-bromo-3-nitrothiophene-2-carbaldehyde Chemical compound [O-][N+](=O)C=1C=C(Br)SC=1C=O GIMGDUAANSGEKN-UHFFFAOYSA-N 0.000 description 1
- BLUAIVROTZBRAO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-fluoro-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound FC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 BLUAIVROTZBRAO-UHFFFAOYSA-N 0.000 description 1
- NDOXLGFXBPKRBR-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(1-methylpyrrolidin-3-yl)oxyphenyl]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=C1OC1CCN(C)C1 NDOXLGFXBPKRBR-UHFFFAOYSA-N 0.000 description 1
- MDKYEFRJXGNSOE-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(3-morpholin-4-ylpropoxy)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=C1OCCCN1CCOCC1 MDKYEFRJXGNSOE-UHFFFAOYSA-N 0.000 description 1
- CYPAEQPUFNOLRR-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(3-piperidin-1-ylpropoxy)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=C1OCCCN1CCCCC1 CYPAEQPUFNOLRR-UHFFFAOYSA-N 0.000 description 1
- NEJMVUINSJRNOB-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-(3-pyrrolidin-1-ylpropoxy)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=C1OCCCN1CCCC1 NEJMVUINSJRNOB-UHFFFAOYSA-N 0.000 description 1
- OJRHDVOJINZRRO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-(1-methylpyrrolidin-2-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=C1OCCC1CCCN1C OJRHDVOJINZRRO-UHFFFAOYSA-N 0.000 description 1
- MZCJGEVQDMTBKO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-(n-methylanilino)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=C1OCCN(C)C1=CC=CC=C1 MZCJGEVQDMTBKO-UHFFFAOYSA-N 0.000 description 1
- AUZFYADZUMKYGU-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[2-[(4-propan-2-ylphenyl)methylamino]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=C1OCCNCC1=CC=C(C(C)C)C=C1 AUZFYADZUMKYGU-UHFFFAOYSA-N 0.000 description 1
- CUNLTIUNXMGHDT-QGZVFWFLSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[[(2r)-pyrrolidin-2-yl]methylamino]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=C1NC[C@H]1CCCN1 CUNLTIUNXMGHDT-QGZVFWFLSA-N 0.000 description 1
- CUNLTIUNXMGHDT-KRWDZBQOSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[[(2s)-pyrrolidin-2-yl]methylamino]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=C1NC[C@@H]1CCCN1 CUNLTIUNXMGHDT-KRWDZBQOSA-N 0.000 description 1
- VTRYQKKGEQBYMO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[3-methoxy-4-[methyl(2-pyrrolidin-1-ylethyl)amino]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=C1N(C)CCN1CCCC1 VTRYQKKGEQBYMO-UHFFFAOYSA-N 0.000 description 1
- UBBUOIAMIOBSQF-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC)C(OCC(OCC)OCC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 UBBUOIAMIOBSQF-UHFFFAOYSA-N 0.000 description 1
- ZZSMJTYVSUILMQ-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2-isothiocyanatoethoxy)-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCCN=C=S)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 ZZSMJTYVSUILMQ-UHFFFAOYSA-N 0.000 description 1
- UWTRWNHARUVTAF-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2-morpholin-4-ylethylamino)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=CC(NCCN3CCOCC3)=CC=1)C=N2 UWTRWNHARUVTAF-UHFFFAOYSA-N 0.000 description 1
- WTWJKXYKYTZGLG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2-morpholin-4-ylethylsulfanyl)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=CC(SCCN3CCOCC3)=CC=1)C=N2 WTWJKXYKYTZGLG-UHFFFAOYSA-N 0.000 description 1
- JEOGMBMGVGRYLK-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=CC(OCCN3CCCC3)=CC=1)C=N2 JEOGMBMGVGRYLK-UHFFFAOYSA-N 0.000 description 1
- WUHFAEBGFJLAGR-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(2-pyrrolidin-1-ylethylamino)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=CC(NCCN3CCCC3)=CC=1)C=N2 WUHFAEBGFJLAGR-UHFFFAOYSA-N 0.000 description 1
- ODSHKSOSUIFDBW-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-(4-methylpiperazin-1-yl)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CC=C(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 ODSHKSOSUIFDBW-UHFFFAOYSA-N 0.000 description 1
- IPXHLEWQJSZAPK-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(3,3-difluoropyrrolidin-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)(F)C1 IPXHLEWQJSZAPK-UHFFFAOYSA-N 0.000 description 1
- IEUVEBOSNSXVOW-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(diethylamino)ethoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC)C(OCCN(CC)CC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 IEUVEBOSNSXVOW-UHFFFAOYSA-N 0.000 description 1
- XUTNCXQUYLZAQD-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCCN(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 XUTNCXQUYLZAQD-UHFFFAOYSA-N 0.000 description 1
- XIGIWPMSBFGHFG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(dimethylamino)ethyl-methylamino]phenyl]thieno[3,2-d]pyrimidin-4-one;hydrochloride Chemical compound Cl.C1=CC(N(C)CCN(C)C)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 XIGIWPMSBFGHFG-UHFFFAOYSA-N 0.000 description 1
- HUMPSADFMPCABD-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(dimethylamino)ethylamino]phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(NCCN(C)C)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 HUMPSADFMPCABD-UHFFFAOYSA-N 0.000 description 1
- QBYBRHVXAUUXMI-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-(n-ethyl-3-methylanilino)ethoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C=1C=CC(C)=CC=1N(CC)CCOC(C(=C1)OC)=CC=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 QBYBRHVXAUUXMI-UHFFFAOYSA-N 0.000 description 1
- FYALQXNFTWSLTG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-[(4-chlorophenyl)methylamino]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=C1OCCNCC1=CC=C(Cl)C=C1 FYALQXNFTWSLTG-UHFFFAOYSA-N 0.000 description 1
- FMAFKBLQMUVADX-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-[(4-fluorophenyl)methylamino]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=C1OCCNCC1=CC=C(F)C=C1 FMAFKBLQMUVADX-UHFFFAOYSA-N 0.000 description 1
- OQLROCIJAVSRKX-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[2-[ethyl(methyl)amino]ethoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC)C(OCCN(C)CC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 OQLROCIJAVSRKX-UHFFFAOYSA-N 0.000 description 1
- CQLNVQKONQRZEO-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(cyclobutylamino)propoxy]-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=C1OCCCNC1CCC1 CQLNVQKONQRZEO-UHFFFAOYSA-N 0.000 description 1
- XUEKXWKDHYCPGS-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(cyclohexylamino)propoxy]-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=C1OCCCNC1CCCCC1 XUEKXWKDHYCPGS-UHFFFAOYSA-N 0.000 description 1
- CLQAAKYHVSPYFC-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(cyclopentylamino)propoxy]-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=C1OCCCNC1CCCC1 CLQAAKYHVSPYFC-UHFFFAOYSA-N 0.000 description 1
- VJHOGKUNJMJIBW-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(diethylamino)propoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OC)C(OCCCN(CC)CC)=CC=C1N1C(=O)C(SC(=C2)C=3C=CC(Cl)=CC=3)=C2N=C1 VJHOGKUNJMJIBW-UHFFFAOYSA-N 0.000 description 1
- NFTYPDKDUPOASG-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(dimethylamino)-2,2-dimethylpropoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCC(C)(C)CN(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 NFTYPDKDUPOASG-UHFFFAOYSA-N 0.000 description 1
- ZYIJYEBJRJFIAM-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=C(OCCCN(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 ZYIJYEBJRJFIAM-UHFFFAOYSA-N 0.000 description 1
- XSJVJKAZIZJJMV-HXUWFJFHSA-N 6-(4-chlorophenyl)-3-[4-[3-[(3r)-3-hydroxypyrrolidin-1-yl]propoxy]-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=C1OCCCN1CC[C@@H](O)C1 XSJVJKAZIZJJMV-HXUWFJFHSA-N 0.000 description 1
- GXTGYXVQZPDOFX-RBUKOAKNSA-N 6-(4-chlorophenyl)-3-[4-[[(2s,4r)-4-hydroxy-1-methylpyrrolidin-2-yl]methoxy]-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=C1OC[C@@H]1C[C@@H](O)CN1C GXTGYXVQZPDOFX-RBUKOAKNSA-N 0.000 description 1
- SJDMQUVJEWXXON-HKUYNNGSSA-N 6-(4-chlorophenyl)-3-[4-[[(2s,4s)-4-fluoro-1-methylpyrrolidin-2-yl]methoxy]-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=C1OC[C@@H]1C[C@H](F)CN1C SJDMQUVJEWXXON-HKUYNNGSSA-N 0.000 description 1
- YYOUGWYAYZJOPM-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[3-methoxy-4-(2-piperidin-1-ylethylamino)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1NCCN1CCCCC1 YYOUGWYAYZJOPM-UHFFFAOYSA-N 0.000 description 1
- CKTNCLCDSHGEKS-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1OCCN1CCCC1 CKTNCLCDSHGEKS-UHFFFAOYSA-N 0.000 description 1
- ZDLWNIPGFMPNTQ-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[3-methoxy-4-(4-methylpiperazin-1-yl)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1N1CCN(C)CC1 ZDLWNIPGFMPNTQ-UHFFFAOYSA-N 0.000 description 1
- UOCYXWRAFVJXPJ-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-[3-methoxy-4-[3-(2-oxopyrrolidin-1-yl)propylamino]phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1NCCCN1CCCC1=O UOCYXWRAFVJXPJ-UHFFFAOYSA-N 0.000 description 1
- ZTNBIEKDJCSBRV-UHFFFAOYSA-N 6-(4-methoxyphenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(OCCN3CCCC3)=CC=1)C=N2 ZTNBIEKDJCSBRV-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- LJUXTOWEAHWJAH-UHFFFAOYSA-N 7-(3-chloro-4-fluorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=C(Cl)C(F)=CC=2)=O)=CC=C1OCCN1CCCC1 LJUXTOWEAHWJAH-UHFFFAOYSA-N 0.000 description 1
- AIEUHHJDSGYASO-UHFFFAOYSA-N 7-(3-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=C(Cl)C=CC=2)=O)=CC=C1OCCN1CCCC1 AIEUHHJDSGYASO-UHFFFAOYSA-N 0.000 description 1
- OBSIOMOXXPNZMC-UHFFFAOYSA-N 7-(3-fluorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=C(F)C=CC=2)=O)=CC=C1OCCN1CCCC1 OBSIOMOXXPNZMC-UHFFFAOYSA-N 0.000 description 1
- QVFFMGLKNMKANX-UHFFFAOYSA-N 7-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 QVFFMGLKNMKANX-UHFFFAOYSA-N 0.000 description 1
- QVMQWNXUASPOGN-UHFFFAOYSA-N 7-(4-ethylphenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound C1=CC(CC)=CC=C1C1=CC=C2C(=O)N(C=3C=C(OC)C(OCCN4CCCC4)=CC=3)C=NC2=C1 QVMQWNXUASPOGN-UHFFFAOYSA-N 0.000 description 1
- GYDNKTHVAINWEC-UHFFFAOYSA-N 7-(4-fluoro-3-methylphenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=C(C)C(F)=CC=2)=O)=CC=C1OCCN1CCCC1 GYDNKTHVAINWEC-UHFFFAOYSA-N 0.000 description 1
- CQTMFLZAHNTVCR-UHFFFAOYSA-N 7-(4-fluorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(C=C3N=C2)C=2C=CC(F)=CC=2)=O)=CC=C1OCCN1CCCC1 CQTMFLZAHNTVCR-UHFFFAOYSA-N 0.000 description 1
- USMXJLWIOVWARK-UHFFFAOYSA-N 7-(4-methoxyphenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CC=C2C(=O)N(C=3C=C(OC)C(OCCN4CCCC4)=CC=3)C=NC2=C1 USMXJLWIOVWARK-UHFFFAOYSA-N 0.000 description 1
- IKDHIARCZPTXAS-UHFFFAOYSA-N 7-chloro-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-4-one Chemical compound COC1=CC(N2C(C3=CC=C(Cl)C=C3N=C2)=O)=CC=C1OCCN1CCCC1 IKDHIARCZPTXAS-UHFFFAOYSA-N 0.000 description 1
- OJKKREXNIVCJGW-UHFFFAOYSA-N 7-chloro-3-[4-(2,2-diethoxyethoxy)-3-methoxyphenyl]quinazolin-4-one Chemical compound C1=C(OC)C(OCC(OCC)OCC)=CC=C1N1C(=O)C2=CC=C(Cl)C=C2N=C1 OJKKREXNIVCJGW-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
- 244000215068 Acacia senegal Species 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- KTEWFARDTVPTNR-UHFFFAOYSA-N CC(C)c1ccc(CNCCOc(c(OC)c2)ccc2N(C=Nc2c3[s]c(-c(cc4)ccc4N)c2)C3=O)cc1 Chemical compound CC(C)c1ccc(CNCCOc(c(OC)c2)ccc2N(C=Nc2c3[s]c(-c(cc4)ccc4N)c2)C3=O)cc1 KTEWFARDTVPTNR-UHFFFAOYSA-N 0.000 description 1
- PMSRTMFNKFBABQ-UHFFFAOYSA-N COc1cc(N(C=Nc2c3[s]c(-c(cc4)ccc4Cl)c2)C3=O)ccc1OCCN(Cc1ccccc1)N Chemical compound COc1cc(N(C=Nc2c3[s]c(-c(cc4)ccc4Cl)c2)C3=O)ccc1OCCN(Cc1ccccc1)N PMSRTMFNKFBABQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 241001480079 Corymbia calophylla Species 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000015580 Increased body weight Diseases 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 239000003810 Jones reagent Substances 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
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 description 1
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010057362 Underdose Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- VCOJPHPOVDIRJK-LURJTMIESA-N [(2s)-1-methylpyrrolidin-2-yl]methanol Chemical compound CN1CCC[C@H]1CO VCOJPHPOVDIRJK-LURJTMIESA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 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
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003667 hormone antagonist Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- UDKHRMACSCPJNV-UHFFFAOYSA-N methyl 4-chlorobenzenecarbodithioate Chemical compound CSC(=S)C1=CC=C(Cl)C=C1 UDKHRMACSCPJNV-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- DLRPOOIAFCOLII-UHFFFAOYSA-N n-(2-chloroethyl)-n-ethyl-3-methylaniline Chemical compound ClCCN(CC)C1=CC=CC(C)=C1 DLRPOOIAFCOLII-UHFFFAOYSA-N 0.000 description 1
- UYEQVTRZRUPPKR-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-4-methyl-n-(3-piperidin-1-ylpropyl)benzenesulfonamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(S(=O)(=O)C=1C=CC(C)=CC=1)CCCN1CCCCC1 UYEQVTRZRUPPKR-UHFFFAOYSA-N 0.000 description 1
- XHYGFOUOMNRCMB-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-4-methyl-n-(3-pyrrolidin-1-ylpropyl)benzenesulfonamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(S(=O)(=O)C=1C=CC(C)=CC=1)CCCN1CCCC1 XHYGFOUOMNRCMB-UHFFFAOYSA-N 0.000 description 1
- NIOIZAMBRXYSDK-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-n-(2-pyrrolidin-1-ylethyl)formamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(C=O)CCN1CCCC1 NIOIZAMBRXYSDK-UHFFFAOYSA-N 0.000 description 1
- NIQLNQAGXQBXHH-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-n-(2-pyrrolidin-1-ylethyl)furan-2-carboxamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(C(=O)C=1OC=CC=1)CCN1CCCC1 NIQLNQAGXQBXHH-UHFFFAOYSA-N 0.000 description 1
- YZPWHDPNKYUFSF-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-n-[3-(diethylamino)propyl]-4-methylbenzenesulfonamide Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(CCCN(CC)CC)C(C(=C1)OC)=CC=C1N(C(C=1S2)=O)C=NC=1C=C2C1=CC=C(Cl)C=C1 YZPWHDPNKYUFSF-UHFFFAOYSA-N 0.000 description 1
- GCDFBWYZYKJIHR-UHFFFAOYSA-N n-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenyl]-n-[3-(dimethylamino)propyl]-4-methylbenzenesulfonamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N(CCCN(C)C)S(=O)(=O)C1=CC=C(C)C=C1 GCDFBWYZYKJIHR-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
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000001956 orexigenic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- HXOFRBVHQQOXNL-UHFFFAOYSA-N phenyl(trifluoromethoxy)borinic acid Chemical compound FC(F)(F)OB(O)C1=CC=CC=C1 HXOFRBVHQQOXNL-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000644 propagated effect Effects 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
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 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
- 238000007789 sealing Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- UJOHRABSLHWXJA-LEWJYISDSA-N tert-butyl (2s,4r)-2-[[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]methyl]-4-hydroxypyrrolidine-1-carboxylate Chemical compound COC1=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C UJOHRABSLHWXJA-LEWJYISDSA-N 0.000 description 1
- ROEMZCLHRRRKGF-YUMQZZPRSA-N tert-butyl (2s,4s)-4-fluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](F)C[C@H]1CO ROEMZCLHRRRKGF-YUMQZZPRSA-N 0.000 description 1
- GMBNMLPPFZNYCQ-KBPBESRZSA-N tert-butyl (2s,4s)-4-fluoro-2-[(4-methylphenyl)sulfonyloxymethyl]pyrrolidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1N(C(=O)OC(C)(C)C)C[C@@H](F)C1 GMBNMLPPFZNYCQ-KBPBESRZSA-N 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- KDITUFRWDUIUMY-INIZCTEOSA-N tert-butyl n-[(2s)-1-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]propan-2-yl]carbamate Chemical compound C1=C(OC[C@H](C)NC(=O)OC(C)(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 KDITUFRWDUIUMY-INIZCTEOSA-N 0.000 description 1
- HCBBKZXNRKVVPP-UHFFFAOYSA-N tert-butyl n-[2-(4-amino-2-methoxyphenoxy)ethyl]carbamate Chemical compound COC1=CC(N)=CC=C1OCCNC(=O)OC(C)(C)C HCBBKZXNRKVVPP-UHFFFAOYSA-N 0.000 description 1
- GOLKKBJLKVVHDF-UHFFFAOYSA-N tert-butyl n-[2-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]ethyl]carbamate Chemical compound C1=C(OCCNC(=O)OC(C)(C)C)C(OC)=CC(N2C(C=3SC(=CC=3N=C2)C=2C=CC(Cl)=CC=2)=O)=C1 GOLKKBJLKVVHDF-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000012773 waffles Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/10—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D257/12—Six-membered rings having four nitrogen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0124627.1A GB0124627D0 (en) | 2001-10-15 | 2001-10-15 | Novel compounds |
| GB0124627 | 2001-10-15 | ||
| PCT/US2002/032739 WO2003033476A1 (en) | 2001-10-15 | 2002-10-15 | Pyrimidinones as melanin concentrating hormone receptor 1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60218721D1 DE60218721D1 (en) | 2007-04-19 |
| DE60218721T2 true DE60218721T2 (de) | 2007-11-15 |
Family
ID=9923785
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60218721T Expired - Fee Related DE60218721T2 (de) | 2001-10-15 | 2002-10-15 | Pyrimidione als Melanin-konzentrierenden Hormonrezeptor 1 |
| DE60217147T Expired - Fee Related DE60217147T2 (de) | 2001-10-15 | 2002-10-15 | Lactamderivate zur verwendung als humane 11cby rezeptorantagonisten |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60217147T Expired - Fee Related DE60217147T2 (de) | 2001-10-15 | 2002-10-15 | Lactamderivate zur verwendung als humane 11cby rezeptorantagonisten |
Country Status (21)
Families Citing this family (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1592739A (zh) | 2001-11-26 | 2005-03-09 | 先灵公司 | 用于治疗肥胖和cns疾病的基于哌啶的mch拮抗剂 |
| US7084156B2 (en) | 2001-11-27 | 2006-08-01 | Merck & Co., Inc. | 2-Aminoquinoline compounds |
| DE10238865A1 (de) * | 2002-08-24 | 2004-03-11 | Boehringer Ingelheim International Gmbh | Neue Carbonsäureamid-Verbindungen mit MCH-antagonistischer Wirkung, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US7351719B2 (en) | 2002-10-31 | 2008-04-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Amide compounds having MCH-antagonistic activity and medicaments comprising these compounds |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2004092181A1 (en) * | 2003-04-11 | 2004-10-28 | Smithkline Beecham Corporation | Heterocyclic mchr1 antagonists |
| WO2005016928A1 (ja) * | 2003-08-15 | 2005-02-24 | Banyu Pharmaceutical Co., Ltd. | イミダゾピリジン誘導体 |
| KR100747042B1 (ko) * | 2003-08-19 | 2007-08-07 | 솔젠트 (주) | 신물질６-메틸-３-펜에틸-３,４-디히드로-１ｈ-큐나졸린-２-티온,이의 제조방법 및 이를 유효성분으로 포함하는 미백 효능조성물 |
| CA2543122A1 (en) * | 2003-10-23 | 2005-05-12 | Glaxo Group Limited | 3-(4-aminophenyl) thienopyrimid-4-one derivatives as mch r1 antagonists for the treatment of obesity, diabetes, depression and anxiety |
| US7592373B2 (en) | 2003-12-23 | 2009-09-22 | Boehringer Ingelheim International Gmbh | Amide compounds with MCH antagonistic activity and medicaments comprising these compounds |
| UA83416C2 (en) | 2004-02-13 | 2008-07-10 | Баниу Фармасьютикал Ко., Лтд. | Fused ring 4-oxopyrimidine derivative |
| DE102004010893A1 (de) * | 2004-03-06 | 2005-09-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue ß-Ketoamid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| US7605176B2 (en) | 2004-03-06 | 2009-10-20 | Boehringer Ingelheim International Gmbh | β-ketoamide compounds with MCH antagonistic activity |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| DE102004017934A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| US7524862B2 (en) | 2004-04-14 | 2009-04-28 | Boehringer Ingelheim International Gmbh | Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds |
| MX2007007227A (es) | 2004-12-17 | 2007-08-21 | Lilly Co Eli | Derivados de tiazolopiridinona como antagonistas del receptor mch. |
| WO2006085692A1 (ja) * | 2005-02-14 | 2006-08-17 | Banyu Pharmaceutical Co., Ltd | ４（３ｈ）－キナゾリノン誘導体の結晶 |
| WO2006118320A1 (ja) | 2005-04-28 | 2006-11-09 | Takeda Pharmaceutical Company Limited | チエノピリミドン化合物 |
| WO2007011286A1 (en) * | 2005-07-15 | 2007-01-25 | Astrazeneca Ab | Therapeutic agents |
| KR20080042158A (ko) * | 2005-08-31 | 2008-05-14 | 셀진 코포레이션 | 이소인돌-이미드 화합물과 이를 포함하는 조성물 및 이를이용한 방법 |
| BRPI0617436B8 (pt) * | 2005-10-19 | 2021-05-25 | Kissei Pharmaceutical | derivado heterocíclico fundido, composição farmacêutica compreendendo o mesmo e usos do dito derivado na prevenção ou tratamento de doença dependente de hormônio sexual e na regulação da reprodução, contracepção ou indução de ovulação |
| US7745447B2 (en) | 2005-10-26 | 2010-06-29 | Bristol-Myers Squibb Company | Substituted thieno[3,2-D]pyrimidines as non-basic melanin concentrating hormone receptor-1 antagonists |
| US8618115B2 (en) | 2005-10-26 | 2013-12-31 | Bristol-Myers Squibb Company | Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them |
| JP5193878B2 (ja) | 2005-12-21 | 2013-05-08 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｍｃｈ−１が媒介する疾患における使用のための新規な置換ピラジノン誘導体 |
| US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
| RU2008136898A (ru) | 2006-02-15 | 2010-03-20 | Санофи-Авентис (Fr) | Азациклил-замещенные арилдигидроизохинолиноны, способ их получения и их применение в качестве лекарственных средств |
| JP2009526794A (ja) | 2006-02-15 | 2009-07-23 | サノフィ−アベンティス | 新規なアミノアルコール置換アリールチエノピリミジノン、それらの製造方法及び薬剤としてそれらの使用 |
| JP2009526795A (ja) | 2006-02-15 | 2009-07-23 | サノフィ−アベンティス | 新規なアミノアルコール置換アリールジヒドロイソキノリノン、それらの製造方法及び薬剤としてそれらの使用 |
| WO2007093363A1 (en) | 2006-02-15 | 2007-08-23 | Sanofi-Aventis | Novel azacycly-substituted arylthienopyrimidinones, process for their preparation and their use as medicaments |
| WO2007142217A1 (ja) * | 2006-06-07 | 2007-12-13 | Banyu Pharmaceutical Co., Ltd. | １－フェニルピリドン誘導体 |
| CA2652524A1 (en) | 2006-06-08 | 2007-12-21 | Eli Lilly And Company | Novel mch receptor antagonists |
| JP5198439B2 (ja) * | 2006-06-08 | 2013-05-15 | イーライ リリー アンド カンパニー | 新規なｍｃｈ受容体アンタゴニスト |
| CA2666193A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, process for preparing them, medicaments comprising these compounds, and their use |
| WO2008020799A1 (en) * | 2006-08-18 | 2008-02-21 | Astrazeneca Ab | Thienopyrimidin-4-one and thienopyridazin-7-one derivatives as mch rl antagonists |
| WO2008068265A1 (en) | 2006-12-05 | 2008-06-12 | Janssen Pharmaceutica N.V. | Novel substituted diaza spiro pyridinone derivatives for use in mch-1 mediated diseases |
| JP5269804B2 (ja) * | 2006-12-14 | 2013-08-21 | イーライ リリー アンド カンパニー | 新規なｍｃｈ受容体拮抗薬 |
| BRPI0806537A2 (pt) | 2007-01-10 | 2014-04-22 | Albany Molecular Res Inc | Indazóis substituídos por 5-piridinona |
| CN101687882A (zh) | 2007-04-25 | 2010-03-31 | 百时美施贵宝公司 | 非碱性黑色素浓集激素受体-1拮抗剂 |
| MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| DE102007028925A1 (de) | 2007-06-22 | 2008-12-24 | Saltigo Gmbh | Verfahren zur Herstellung von 2-Phenoxyacetalen und den daraus korrespondierenden 2-Phenoxycarbaldehyden |
| ATE544759T1 (de) | 2007-07-21 | 2012-02-15 | Albany Molecular Res Inc | 5-pyridinon-substituierte indazole und pharmazeutische zusammensetzungen davon |
| JP5632612B2 (ja) * | 2007-12-05 | 2014-11-26 | あすか製薬株式会社 | ラクタム化合物又はその塩及びｐｐａｒ活性化剤 |
| PE20091928A1 (es) | 2008-05-29 | 2009-12-31 | Bristol Myers Squibb Co | Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos |
| CA2930674A1 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AR072707A1 (es) | 2008-07-09 | 2010-09-15 | Sanofi Aventis | Compuestos heterociclicos, procesos para su preparacion, medicamentos que comprenden estos compuestos y el uso de los mismos |
| JP2011528375A (ja) | 2008-07-16 | 2011-11-17 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト |
| AU2009307884B2 (en) | 2008-10-22 | 2014-07-31 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US8329914B2 (en) | 2008-10-31 | 2012-12-11 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| CA2689707A1 (en) | 2009-11-16 | 2011-05-16 | Jean-Simon Diallo | Identification of the novel small molecule viral sensitizer vse1 using high-throughput screening |
| AU2010288523A1 (en) | 2009-08-26 | 2012-03-15 | Sanofi | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
| CA2786314A1 (en) | 2010-02-25 | 2011-09-01 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2012036233A1 (ja) * | 2010-09-17 | 2012-03-22 | 塩野義製薬株式会社 | メラニン凝集ホルモン受容体アンタゴニスト活性を有する縮合へテロ環誘導体 |
| BR122021002201A8 (pt) | 2011-02-25 | 2023-04-11 | Merck Sharp & Dohme | Composto, composição, uso de um composto, e, método de tratamento de um distúrbio, condição ou doença |
| US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2683701B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120057A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8809325B2 (en) | 2011-03-08 | 2014-08-19 | Sanofi | Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683700B1 (de) | 2011-03-08 | 2015-02-18 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| KR101236188B1 (ko) * | 2011-03-10 | 2013-02-22 | 한국화학연구원 | 신규한 피롤로피리디논 유도체 및 그의 ｍｃｈ 수용체-1 관련 질환에 대한 치료학적 용도 |
| HUP1100241A3 (en) | 2011-05-06 | 2013-12-30 | Richter Gedeon Nyrt | Oxetane substituted pyrimidones |
| TWI549944B (zh) | 2011-07-01 | 2016-09-21 | 吉李德科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| NO3175985T3 (cg-RX-API-DMAC7.html) | 2011-07-01 | 2018-04-28 | ||
| AU2013296470B2 (en) | 2012-08-02 | 2016-03-17 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| KR20150118158A (ko) | 2013-02-22 | 2015-10-21 | 머크 샤프 앤드 돔 코포레이션 | 항당뇨병 비시클릭 화합물 |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP4424697A3 (en) | 2013-06-05 | 2024-12-25 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| JP6615791B2 (ja) * | 2014-06-05 | 2019-12-04 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 殺虫剤としての二環式化合物 |
| CA3008171A1 (en) | 2015-12-22 | 2017-06-29 | SHY Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| EP3497089B1 (de) * | 2016-08-12 | 2020-07-29 | Bayer CropScience Aktiengesellschaft | Verfahren zur herstellung von 4-substituierten 2,3-dihydro-1-benzofuranderivaten durch zyklisierung von 2-(2-diazonium-6-substituierten-phenyl)ethanol salzen |
| KR102537985B1 (ko) | 2016-09-12 | 2023-05-30 | 인테그랄 헬스 인코퍼레이티드 | Gpr120 조정제로서 유용한 단환형 화합물 |
| CN110121343B (zh) | 2016-09-12 | 2023-11-03 | 整体健康 | 用作gpr120调节剂的双环化合物 |
| WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298A4 (en) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | ANTIDIABETIC SPIROCHROMAN COMPOUNDS |
| WO2018237084A1 (en) | 2017-06-21 | 2018-12-27 | SHY Therapeutics LLC | COMPOUNDS INTERACTING WITH RAS SUPERFAMIL FOR USE IN THE TREATMENT OF CANCERS, INFLAMMATORY DISEASES, RASOPATHIES AND FIBROTIC DISEASES |
| WO2019063708A1 (en) | 2017-09-29 | 2019-04-04 | Bayer Aktiengesellschaft | SUBSTITUTED 3-PHENYLQUINAZOLIN-4 (3H) -ONES AND USES THEREOF |
| UY37907A (es) | 2017-09-29 | 2019-04-30 | Bayer Ag | 3-fenilquinazolin-4 (3h)-onas sustituidas y sus usos |
| JP7407461B2 (ja) | 2018-12-19 | 2024-01-04 | シャイ・セラピューティクス・エルエルシー | がん、炎症性疾患、ｒａｓ病、及び線維性疾患の処置のためのｒａｓスーパーファミリーと相互作用する化合物 |
| CN110563730B (zh) * | 2019-07-29 | 2022-03-25 | 江苏理工学院 | 高纯度n10-三氟乙酰蝶酸的制备方法 |
| JP2023539663A (ja) | 2020-08-28 | 2023-09-15 | アルビナス・オペレーションズ・インコーポレイテッド | 急速進行性線維肉腫タンパク質分解化合物及び関連する使用方法 |
| CN113651800B (zh) * | 2021-09-07 | 2022-08-19 | 山东铂源药业股份有限公司 | 一种甲磺酸奥希替尼的制备方法 |
| EP4584258A1 (en) | 2022-09-07 | 2025-07-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL137227B2 (en) * | 1984-03-28 | 1986-05-31 | Univ Lodzki | Process for preparing novel n-/dialkylaminoalkoxyphenyl/-imides of tetrahydrophtalic acids |
| DE69723869T2 (de) * | 1996-12-31 | 2004-04-22 | Dr. Reddy's Laboratories Ltd. | Heterozyklische verbindungen, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen die diese enthalten und ihre anwendung in der behandlung von diabetis und verwandten krankheiten |
| CA2386474A1 (en) * | 1999-09-20 | 2001-03-29 | Takeda Chemical Industries, Ltd. | Melanin concentrating hormone antagonist |
-
2001
- 2001-10-15 GB GBGB0124627.1A patent/GB0124627D0/en not_active Ceased
-
2002
- 2002-10-15 MX MXPA04003534A patent/MXPA04003534A/es unknown
- 2002-10-15 CN CNA028235932A patent/CN1596247A/zh active Pending
- 2002-10-15 MX MXPA04003532A patent/MXPA04003532A/es unknown
- 2002-10-15 CA CA002463509A patent/CA2463509A1/en not_active Abandoned
- 2002-10-15 DE DE60218721T patent/DE60218721T2/de not_active Expired - Fee Related
- 2002-10-15 EP EP02801692A patent/EP1442025B1/en not_active Expired - Lifetime
- 2002-10-15 ES ES02801693T patent/ES2279009T3/es not_active Expired - Lifetime
- 2002-10-15 WO PCT/US2002/032740 patent/WO2003033480A1/en not_active Ceased
- 2002-10-15 EP EP02801693A patent/EP1436267B1/en not_active Expired - Lifetime
- 2002-10-15 PL PL02370138A patent/PL370138A1/xx not_active Application Discontinuation
- 2002-10-15 JP JP2003536220A patent/JP2005508966A/ja active Pending
- 2002-10-15 BR BR0213242-7A patent/BR0213242A/pt not_active Application Discontinuation
- 2002-10-15 NZ NZ531911A patent/NZ531911A/en unknown
- 2002-10-15 KR KR1020047005548A patent/KR20050043724A/ko not_active Withdrawn
- 2002-10-15 HU HU0402346A patent/HUP0402346A2/hu unknown
- 2002-10-15 ES ES02801692T patent/ES2283647T3/es not_active Expired - Lifetime
- 2002-10-15 AT AT02801693T patent/ATE349434T1/de not_active IP Right Cessation
- 2002-10-15 AT AT02801692T patent/ATE356119T1/de not_active IP Right Cessation
- 2002-10-15 IL IL16107402A patent/IL161074A0/xx unknown
- 2002-10-15 CZ CZ2004499A patent/CZ2004499A3/cs unknown
- 2002-10-15 JP JP2003536216A patent/JP2005510487A/ja active Pending
- 2002-10-15 CN CNA028204522A patent/CN1571774A/zh active Pending
- 2002-10-15 BR BR0213040-8A patent/BR0213040A/pt not_active IP Right Cessation
- 2002-10-15 IL IL16087202A patent/IL160872A0/xx unknown
- 2002-10-15 HU HU0402335A patent/HUP0402335A3/hu unknown
- 2002-10-15 KR KR10-2004-7005546A patent/KR20040045833A/ko not_active Withdrawn
- 2002-10-15 CA CA002463508A patent/CA2463508A1/en not_active Abandoned
- 2002-10-15 PL PL02370587A patent/PL370587A1/xx not_active Application Discontinuation
- 2002-10-15 CZ CZ2004498A patent/CZ2004498A3/cs unknown
- 2002-10-15 RU RU2004110053/04A patent/RU2004110053A/ru not_active Application Discontinuation
- 2002-10-15 DE DE60217147T patent/DE60217147T2/de not_active Expired - Fee Related
- 2002-10-15 WO PCT/US2002/032739 patent/WO2003033476A1/en not_active Ceased
-
2004
- 2004-04-05 ZA ZA200402672A patent/ZA200402672B/en unknown
- 2004-04-13 ZA ZA200402814A patent/ZA200402814B/en unknown
- 2004-04-13 NO NO20041504A patent/NO20041504L/no not_active Application Discontinuation
- 2004-04-13 NO NO20041503A patent/NO20041503L/no not_active Application Discontinuation
- 2004-04-14 CO CO04034243A patent/CO5580778A2/es not_active Application Discontinuation
- 2004-04-14 CO CO04034241A patent/CO5580779A2/es not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60218721T2 (de) | Pyrimidione als Melanin-konzentrierenden Hormonrezeptor 1 | |
| DE60315615T2 (de) | Tricyclische verbindungen basierend auf thiophen und arzneimittel, die diese umfassen | |
| JP5916700B2 (ja) | アミド化合物、組成物およびそれらの使用 | |
| JP2006522812A (ja) | 複素環ｍｃｈｒ１アンタゴニスト | |
| DE60313634T2 (de) | Piperazinsubstituierte arylbenzodiazepine | |
| KR102650565B1 (ko) | Pde9 억제제 및 이의 용도 | |
| JP2012502986A (ja) | Ｐ２ｘ３受容体活性のモジュレーター | |
| EA015127B1 (ru) | Антагонисты мсн-рецепторов | |
| AU2010202008A1 (en) | Substituted 2,4-dihydro-pyrrolo (3,4-b) -quinolin-9-one derivatives useful as phosphodiesterase inhibitors | |
| KR20110094355A (ko) | 피부 질환 치료용 포스포디에스테라제 억제제로서의 트리아졸로피리딘 | |
| KR20060100412A (ko) | 비만, 당뇨, 우울증 및 불안증을 치료하기 위한 ｍｃｈｒ１ 길항제로서의 3-(4-아미노페닐)티에노피리미드-4-온유도체 | |
| WO2023081859A1 (en) | Triazine amino derivatives for treating sca3 | |
| JP2009509928A (ja) | カリウムチャンネル開口剤としての新規ベンゾピラン誘導体 | |
| JP4890446B2 (ja) | ドーパミンｄ３受容体に対してアフィニティーを有する化合物およびその使用 | |
| US7285557B2 (en) | Pyrimidinones as melanin concentrating hormone receptor 1 | |
| DK155007B (da) | Imidazo(1,5-a)quinazolinforbindelse, praeparat indeholdende samme samt isocyanomethyl-oxadiazol til brug som udgangsmateriale ved fremstillingen af forbindelsen | |
| CA2669447A1 (en) | Allosteric modulators of the a1 adenosine receptor | |
| JP2022502484A (ja) | キナーゼ阻害活性を有する芳香族複素環式化合物 | |
| DE10004157A1 (de) | 4-Pyridyl-und 2,4-Pyrimidinyl-substituierte Pyrrolderivate und ihre Anwendung in der Pharmazie | |
| AU2002335004A1 (en) | Pyrimidinones as melanin concentrating hormone receptor 1 | |
| US4431657A (en) | Analgesic compositions consisting of 2H-benzothieno[3,2-c]pyrazol-3-amine derivatives | |
| CN119143780A (zh) | Lp-PLA2抑制剂、其制备方法、其药物组合物和用途 | |
| AU605822B2 (en) | Tricyclic benzimidazoles, processes for the preparation thereof and pharmaceutical compositions containing them | |
| JP2020011902A (ja) | 縮環ピロール誘導体およびその医薬用途 | |
| WO2025080609A1 (en) | Isotryptamine tetracycles for treating brain disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |