TWI668217B - 二氫嘧啶類化合物及其在藥物中的應用 - Google Patents

Info

Publication number

TWI668217B

TWI668217B TW102130355A TW102130355A TWI668217B TW I668217 B TWI668217 B TW I668217B TW 102130355 A TW102130355 A TW 102130355A TW 102130355 A TW102130355 A TW 102130355A TW I668217 B TWI668217 B TW I668217B

Authority

TW

Taiwan

Prior art keywords

methyl

esi

mmol

independently

carboxylic acid

Prior art date

2012-08-24

Links

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• 239000003814 drug Substances 0.000 title claims abstract description 42
• WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical class C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 title description 3
• -1 dihydropyrimidine compound Chemical class 0.000 claims abstract description 367
• 150000001875 compounds Chemical class 0.000 claims abstract description 204
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• 208000002672 hepatitis B Diseases 0.000 claims abstract description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 102
• 229910052739 hydrogen Inorganic materials 0.000 claims description 83
• 239000001257 hydrogen Substances 0.000 claims description 80
• 150000002431 hydrogen Chemical class 0.000 claims description 70
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 34
• 239000000460 chlorine Substances 0.000 claims description 33
• 229910052801 chlorine Inorganic materials 0.000 claims description 29
• 229910052731 fluorine Inorganic materials 0.000 claims description 29
• 201000010099 disease Diseases 0.000 claims description 28
• 239000008194 pharmaceutical composition Substances 0.000 claims description 27
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
• 239000011737 fluorine Substances 0.000 claims description 20
• 238000002360 preparation method Methods 0.000 claims description 20
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
• 230000003612 virological effect Effects 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
• 206010016654 Fibrosis Diseases 0.000 claims description 9
• 230000007882 cirrhosis Effects 0.000 claims description 9
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
• LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 7
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 7
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
• 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 6
• 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 6
• 239000002671 adjuvant Substances 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 239000003981 vehicle Substances 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 3
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 3
• 125000001246 bromo group Chemical group Br* 0.000 claims description 2
• 125000001153 fluoro group Chemical group F* 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims 1
• 230000002265 prevention Effects 0.000 abstract description 10
• 239000012453 solvate Substances 0.000 abstract description 9
• 150000002500 ions Chemical class 0.000 description 298
• 238000005481 NMR spectroscopy Methods 0.000 description 288
• 239000007787 solid Substances 0.000 description 258
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
• 238000000034 method Methods 0.000 description 187
• 238000001308 synthesis method Methods 0.000 description 116
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 74
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
• 235000019439 ethyl acetate Nutrition 0.000 description 63
• 125000000217 alkyl group Chemical group 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 56
• 239000000203 mixture Substances 0.000 description 50
• 125000003118 aryl group Chemical group 0.000 description 49
• 239000002904 solvent Substances 0.000 description 48
• 230000002829 reductive effect Effects 0.000 description 47
• JUNOWSHJELIDQP-UHFFFAOYSA-N morpholin-4-ium-3-carboxylate Chemical compound OC(=O)C1COCCN1 JUNOWSHJELIDQP-UHFFFAOYSA-N 0.000 description 43
• 239000000243 solution Substances 0.000 description 43
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
• 239000000543 intermediate Substances 0.000 description 34
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 34
• 125000005997 bromomethyl group Chemical group 0.000 description 33
• 230000015572 biosynthetic process Effects 0.000 description 30
• 238000003786 synthesis reaction Methods 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• 238000004440 column chromatography Methods 0.000 description 27
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 27
• 125000001072 heteroaryl group Chemical group 0.000 description 27
• 125000000623 heterocyclic group Chemical group 0.000 description 26
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 229910052794 bromium Inorganic materials 0.000 description 25
• ACVCAKOXDIMMMW-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(C=2SC=CN=2)=NC1C1=CC=C(F)C=C1Br ACVCAKOXDIMMMW-UHFFFAOYSA-N 0.000 description 25
• 229910052757 nitrogen Inorganic materials 0.000 description 25
• 239000000047 product Substances 0.000 description 25
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 125000003831 tetrazolyl group Chemical group 0.000 description 23
• 125000001425 triazolyl group Chemical group 0.000 description 23
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
• 238000003756 stirring Methods 0.000 description 22
• 125000001424 substituent group Chemical group 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 21
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
• 239000012043 crude product Substances 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
• 125000003545 alkoxy group Chemical group 0.000 description 19
• 125000003710 aryl alkyl group Chemical group 0.000 description 19
• 239000003208 petroleum Substances 0.000 description 19
• 125000003342 alkenyl group Chemical group 0.000 description 18
• 125000003282 alkyl amino group Chemical group 0.000 description 18
• 239000000126 substance Substances 0.000 description 17
• OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 16
• 125000000304 alkynyl group Chemical group 0.000 description 16
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 16
• 125000000753 cycloalkyl group Chemical group 0.000 description 16
• 229940079593 drug Drugs 0.000 description 16
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 16
• 125000001188 haloalkyl group Chemical group 0.000 description 16
• 239000003921 oil Substances 0.000 description 16
• 235000019198 oils Nutrition 0.000 description 16
• 238000010189 synthetic method Methods 0.000 description 16
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 15
• UCDFBOLUCCNTDQ-YFKPBYRVSA-N [(3s)-morpholin-3-yl]methanol Chemical compound OC[C@H]1COCCN1 UCDFBOLUCCNTDQ-YFKPBYRVSA-N 0.000 description 15
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 15
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 14
• 108010050904 Interferons Proteins 0.000 description 14
• 102000014150 Interferons Human genes 0.000 description 14
• 239000012230 colorless oil Substances 0.000 description 13
• 125000002720 diazolyl group Chemical group 0.000 description 13
• 150000002148 esters Chemical class 0.000 description 13
• AZXCZFFBKKBGCH-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(Cl)cc1Cl)c1nccs1 AZXCZFFBKKBGCH-UHFFFAOYSA-N 0.000 description 13
• 229940079322 interferon Drugs 0.000 description 13
• 125000001786 isothiazolyl group Chemical group 0.000 description 13
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 13
• 125000003373 pyrazinyl group Chemical group 0.000 description 13
• 125000003226 pyrazolyl group Chemical group 0.000 description 13
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 13
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• 229960000583 acetic acid Drugs 0.000 description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
• 125000004432 carbon atom Chemical group C* 0.000 description 12
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 12
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 125000002541 furyl group Chemical group 0.000 description 12
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 12
• 239000012442 inert solvent Substances 0.000 description 12
• 125000002971 oxazolyl group Chemical group 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 239000000651 prodrug Substances 0.000 description 12
• 229940002612 prodrug Drugs 0.000 description 12
• 125000000714 pyrimidinyl group Chemical group 0.000 description 12
• 125000000168 pyrrolyl group Chemical group 0.000 description 12
• 125000000335 thiazolyl group Chemical group 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 11
• SVKWSVDFYWOGGU-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Cl)c1nccs1 SVKWSVDFYWOGGU-UHFFFAOYSA-N 0.000 description 11
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
• 208000015181 infectious disease Diseases 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
• 125000001113 thiadiazolyl group Chemical group 0.000 description 11
• JUNOWSHJELIDQP-BYPYZUCNSA-N (3s)-morpholin-4-ium-3-carboxylate Chemical compound OC(=O)[C@@H]1COCCN1 JUNOWSHJELIDQP-BYPYZUCNSA-N 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 235000019270 ammonium chloride Nutrition 0.000 description 10
• 229910052799 carbon Inorganic materials 0.000 description 10
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 10
• 229910052736 halogen Inorganic materials 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• 125000002883 imidazolyl group Chemical group 0.000 description 10
• 125000000842 isoxazolyl group Chemical group 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 230000002194 synthesizing effect Effects 0.000 description 10
• 125000001544 thienyl group Chemical group 0.000 description 10
• 125000004306 triazinyl group Chemical group 0.000 description 10
• 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 125000002619 bicyclic group Chemical group 0.000 description 9
• 125000004122 cyclic group Chemical group 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 150000002367 halogens Chemical class 0.000 description 9
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 9
• 125000001715 oxadiazolyl group Chemical group 0.000 description 9
• 125000002098 pyridazinyl group Chemical group 0.000 description 9
• 229910052717 sulfur Inorganic materials 0.000 description 9
• 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 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• 125000003277 amino group Chemical group 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 230000001684 chronic effect Effects 0.000 description 8
• 239000002552 dosage form Substances 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 238000004949 mass spectrometry Methods 0.000 description 8
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 8
• 230000009385 viral infection Effects 0.000 description 8
• FTVXLBDGIPTBCP-UHNVWZDZSA-N (2r,3s)-2-methylmorpholine-3-carboxylic acid Chemical compound C[C@H]1OCCN[C@@H]1C(O)=O FTVXLBDGIPTBCP-UHNVWZDZSA-N 0.000 description 7
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 7
• 125000001931 aliphatic group Chemical group 0.000 description 7
• 125000004103 aminoalkyl group Chemical group 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 125000005842 heteroatom Chemical group 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
• 241000700721 Hepatitis B virus Species 0.000 description 6
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
• 102100040018 Interferon alpha-2 Human genes 0.000 description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 241000700605 Viruses Species 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 230000001154 acute effect Effects 0.000 description 6
• 229910021529 ammonia Inorganic materials 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
• 239000000969 carrier Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 230000002401 inhibitory effect Effects 0.000 description 6
• 229960001627 lamivudine Drugs 0.000 description 6
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 6
• 239000002207 metabolite Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 235000021317 phosphate Nutrition 0.000 description 6
• 229910052698 phosphorus Inorganic materials 0.000 description 6
• 235000019260 propionic acid Nutrition 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 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 6
• 230000009467 reduction Effects 0.000 description 6
• 125000003396 thiol group Chemical class [H]S* 0.000 description 6
• FYCRNRZIEVLZDO-BYPYZUCNSA-N (2s)-morpholin-4-ium-2-carboxylate Chemical compound OC(=O)[C@@H]1CNCCO1 FYCRNRZIEVLZDO-BYPYZUCNSA-N 0.000 description 5
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
• WALYANWSNCYFRG-UHFFFAOYSA-N 1,3,4-thiadiazole-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NN=CS1 WALYANWSNCYFRG-UHFFFAOYSA-N 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
• KMQWNQKESAHDKD-UHFFFAOYSA-N 2-chloro-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Cl)=C1 KMQWNQKESAHDKD-UHFFFAOYSA-N 0.000 description 5
• 108020004414 DNA Proteins 0.000 description 5
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 150000001299 aldehydes Chemical class 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
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• PWGDBONJBVGOFE-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(5-fluoro-1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1ncc(F)s1 PWGDBONJBVGOFE-UHFFFAOYSA-N 0.000 description 2
• CDSFXSPOBQSNCY-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(5-methoxy-1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(C=2SC(OC)=CN=2)=NC1C1=CC=C(F)C=C1Br CDSFXSPOBQSNCY-UHFFFAOYSA-N 0.000 description 2
• XUFZPXCFFHTBIG-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(5-methyl-1,3,4-thiadiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(C=2SC(C)=NN=2)=NC1C1=CC=C(F)C=C1Br XUFZPXCFFHTBIG-UHFFFAOYSA-N 0.000 description 2
• PBAXUOXKRRYXPP-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[2-(3-hydroxypropyl)morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CN2CCOC(CCCO)C2)NC(=NC1c1ccc(F)cc1Br)c1nccs1 PBAXUOXKRRYXPP-UHFFFAOYSA-N 0.000 description 2
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• HJVAAIPZUCLXRN-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-[4-[2-oxo-2-(propan-2-ylamino)ethyl]-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Br)c1nc(CC(=O)NC(C)C)cs1 HJVAAIPZUCLXRN-UHFFFAOYSA-N 0.000 description 2
• IRWJUOOROOEPAC-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=O)NC1C1=CC=C(F)C=C1Br IRWJUOOROOEPAC-UHFFFAOYSA-N 0.000 description 2
• PHAWTGJUVTZXNS-UHFFFAOYSA-N ethyl 4-(2-chloro-4-fluorophenyl)-1,6-dimethyl-2-(1,3-thiazol-2-yl)-4h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)N(C)C(C=2SC=CN=2)=NC1C1=CC=C(F)C=C1Cl PHAWTGJUVTZXNS-UHFFFAOYSA-N 0.000 description 2
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• JHYBXGXGXWYKKX-UHFFFAOYSA-N ethyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-pyrazin-2-yl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Cl)c1cnccn1 JHYBXGXGXWYKKX-UHFFFAOYSA-N 0.000 description 2
• QDTMZXGMYXJIIA-UHFFFAOYSA-N ethyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-pyridin-3-yl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Cl)c1cccnc1 QDTMZXGMYXJIIA-UHFFFAOYSA-N 0.000 description 2
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• WUWZBLZTAIYTGK-UHFFFAOYSA-N ethyl 4-(2,4-dichlorophenyl)-6-methyl-2-(1,3-thiazol-4-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(Cl)cc1Cl)c1cscn1 WUWZBLZTAIYTGK-UHFFFAOYSA-N 0.000 description 1
• HRUHKMPETOAMQH-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-2-(3-chloropyridin-2-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Br)c1ncccc1Cl HRUHKMPETOAMQH-UHFFFAOYSA-N 0.000 description 1
• SCWHBLSIEZJJEC-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(2,4,6-trifluorophenyl)-1,4-dihydropyrimidine-5-carboxylate Chemical class CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1c(F)cc(F)cc1F SCWHBLSIEZJJEC-UHFFFAOYSA-N 0.000 description 1
• FQIRUDJAAFQBLX-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(3,5-difluoropyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound C(C)OC(=O)C=1C(N=C(NC1CBr)C1=NC=C(C=C1F)F)C1=C(C=C(C=C1)F)Br FQIRUDJAAFQBLX-UHFFFAOYSA-N 0.000 description 1
• YILGTVOUECPDHW-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(furan-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1ccco1 YILGTVOUECPDHW-UHFFFAOYSA-N 0.000 description 1
• MVKZGZPYXVAKMU-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-[4-(2-methoxy-2-oxoethyl)-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1nc(CC(=O)OC)cs1 MVKZGZPYXVAKMU-UHFFFAOYSA-N 0.000 description 1
• RVJLBOFXCDNBDF-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-[4-[2-(methylamino)-2-oxoethyl]-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1nc(CC(=O)NC)cs1 RVJLBOFXCDNBDF-UHFFFAOYSA-N 0.000 description 1
• KKVBCOXCAPOFAI-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-[4-[2-oxo-2-(propan-2-ylamino)ethyl]-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1nc(CC(=O)NC(C)C)cs1 KKVBCOXCAPOFAI-UHFFFAOYSA-N 0.000 description 1
• UTZYRDBNAAGMJV-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-[5-(trifluoromethyl)-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1ncc(s1)C(F)(F)F UTZYRDBNAAGMJV-UHFFFAOYSA-N 0.000 description 1
• WJFIHWKWNANLGC-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-phenyl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Br)c1ccccc1 WJFIHWKWNANLGC-UHFFFAOYSA-N 0.000 description 1
• HYJVRTKSJPFPHM-KKFHFHRHSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[(2S)-2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]methyl]-2-(1H-1,2,4-triazol-5-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CN2CCC[C@H]2C(C)(C)O)NC(=NC1c1ccc(F)cc1Br)c1nc[nH]n1 HYJVRTKSJPFPHM-KKFHFHRHSA-N 0.000 description 1
• FALCJTRGAIXAIJ-FVRDMJKUSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-2-(1h-1,2,4-triazol-5-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2NN=CN=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCC[C@H]1CO FALCJTRGAIXAIJ-FVRDMJKUSA-N 0.000 description 1
• PHBUSVOKJJVMSI-LROBGIAVSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[(3s)-3-(2-hydroxyethylcarbamoyl)morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2SC=CN=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCOC[C@H]1C(=O)NCCO PHBUSVOKJJVMSI-LROBGIAVSA-N 0.000 description 1
• NCVLPGCRWDGVBA-LROBGIAVSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[(3s)-3-[methoxy(methyl)carbamoyl]morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2SC=CN=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCOC[C@H]1C(=O)N(C)OC NCVLPGCRWDGVBA-LROBGIAVSA-N 0.000 description 1
• SNUFAGDQIIPPEC-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[2-[3-(methylamino)-3-oxopropyl]morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CN2CCOC(CCC(=O)NC)C2)NC(=NC1c1ccc(F)cc1Br)c1nccs1 SNUFAGDQIIPPEC-UHFFFAOYSA-N 0.000 description 1
• GOEGDCHDZBAASO-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[3-(hydroxymethyl)morpholin-4-yl]methyl]-2-(5-methoxy-1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2SC(OC)=CN=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCOCC1CO GOEGDCHDZBAASO-UHFFFAOYSA-N 0.000 description 1
• RBOAGVAUVHVDJT-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[3-(hydroxymethyl)morpholin-4-yl]methyl]-2-(6-methoxy-1,3-benzothiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2SC3=CC(OC)=CC=C3N=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCOCC1CO RBOAGVAUVHVDJT-UHFFFAOYSA-N 0.000 description 1
• XBDLZXRDUUUTJW-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[3-[(2-ethoxy-2-oxoethyl)carbamoyl]morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)CNC(=O)C1COCCN1CC1=C(C(=O)OCC)C(C=2C(=CC(F)=CC=2)Br)N=C(C=2SC=CN=2)N1 XBDLZXRDUUUTJW-UHFFFAOYSA-N 0.000 description 1
• ROKRLIKOSMKCBQ-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-[[3-[3-hydroxy-2-(hydroxymethyl)propyl]morpholin-4-yl]methyl]-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound N1C(C=2SC=CN=2)=NC(C=2C(=CC(F)=CC=2)Br)C(C(=O)OCC)=C1CN1CCOCC1CC(CO)CO ROKRLIKOSMKCBQ-UHFFFAOYSA-N 0.000 description 1
• KQVCCHCQKRBWNN-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(1,2,4-thiadiazol-5-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical class CCOC(=O)C1=C(C)NC(C=2SN=CN=2)=NC1C1=CC=C(F)C=C1Br KQVCCHCQKRBWNN-UHFFFAOYSA-N 0.000 description 1
• VJRFJEOXKOVEAD-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(2,4,6-trifluorophenyl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Br)c1c(F)cc(F)cc1F VJRFJEOXKOVEAD-UHFFFAOYSA-N 0.000 description 1
• RWWAXMXPJIMGKZ-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(5-methyl-1,3,4-thiadiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=2SC(C)=NN=2)=NC1C1=CC=C(F)C=C1Br RWWAXMXPJIMGKZ-UHFFFAOYSA-N 0.000 description 1
• GMGICTYUJNBRHH-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-[4-[2-(methylamino)-2-oxoethyl]-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Br)c1nc(CC(=O)NC)cs1 GMGICTYUJNBRHH-UHFFFAOYSA-N 0.000 description 1
• CLLMAWGNMHJFSD-UHFFFAOYSA-N ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-[5-(trifluoromethyl)-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1Br)c1ncc(s1)C(F)(F)F CLLMAWGNMHJFSD-UHFFFAOYSA-N 0.000 description 1
• KUNKHBQPUQEYFO-UHFFFAOYSA-N ethyl 4-(2-chloro-4-fluorophenyl)-2-(3-fluoropyridin-2-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=2C(=CC=CN=2)F)=NC1C1=CC=C(F)C=C1Cl KUNKHBQPUQEYFO-UHFFFAOYSA-N 0.000 description 1
• JIQRTJRFRXOOQE-UHFFFAOYSA-N ethyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=2SC=CN=2)=NC1C1=CC=C(F)C=C1Cl JIQRTJRFRXOOQE-UHFFFAOYSA-N 0.000 description 1
• ZSUSHFJJNWKISX-UHFFFAOYSA-N ethyl 4-[2-[3,5-bis(trifluoromethyl)phenyl]-4-fluorophenyl]-6-(bromomethyl)-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1-c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1nccs1 ZSUSHFJJNWKISX-UHFFFAOYSA-N 0.000 description 1
• LUMONRHBODHNGQ-UHFFFAOYSA-N ethyl 4-[2-[3,5-bis(trifluoromethyl)phenyl]-4-fluorophenyl]-6-methyl-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=NC1c1ccc(F)cc1-c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1nccs1 LUMONRHBODHNGQ-UHFFFAOYSA-N 0.000 description 1
• DSVTUOQLUPSPKD-UHFFFAOYSA-N ethyl 6-(bromomethyl)-2-(1,3-thiazol-2-yl)-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccccc1C(F)(F)F)c1nccs1 DSVTUOQLUPSPKD-UHFFFAOYSA-N 0.000 description 1
• OAOQPDTZGDHOIM-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(1,3-thiazol-4-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(Cl)cc1Cl)c1cscn1 OAOQPDTZGDHOIM-UHFFFAOYSA-N 0.000 description 1
• KPUKOGPVXXMSCY-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-[4-(trifluoromethyl)-1,3-thiazol-2-yl]-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(C=2SC=C(N=2)C(F)(F)F)=NC1C1=CC=C(Cl)C=C1Cl KPUKOGPVXXMSCY-UHFFFAOYSA-N 0.000 description 1
• IXDFHNPFDUIQRV-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-1-methyl-2-(1,3-thiazol-2-yl)-4H-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)N(C)C(=NC1c1ccc(F)cc1Cl)c1nccs1 IXDFHNPFDUIQRV-UHFFFAOYSA-N 0.000 description 1
• ASCKOACAMLZWAM-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoropyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Cl)c1ncc(F)cc1F ASCKOACAMLZWAM-UHFFFAOYSA-N 0.000 description 1
• OJTKFTYDYBOTOQ-UHFFFAOYSA-N ethyl 6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-pyridin-2-yl-1,4-dihydropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(CBr)NC(=NC1c1ccc(F)cc1Cl)c1ccccn1 OJTKFTYDYBOTOQ-UHFFFAOYSA-N 0.000 description 1
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