TW201336863A - 具有ｈｉｖ成熟抑制活性之ｃ－３環烯三萜類化合物 - Google Patents

Info

Publication number

TW201336863A

TW201336863A TW102105203A TW102105203A TW201336863A TW 201336863 A TW201336863 A TW 201336863A TW 102105203 A TW102105203 A TW 102105203A TW 102105203 A TW102105203 A TW 102105203A TW 201336863 A TW201336863 A TW 201336863A

Authority

TW

Taiwan

Prior art keywords

alkyl

group

mmol

substituted

cyclopenta

Prior art date

2012-02-15

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• -1 cycloalkenyl triterpenoids Chemical class 0.000 title abstract description 99
• 230000035800 maturation Effects 0.000 title abstract description 11
• 230000002401 inhibitory effect Effects 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 196
• 208000030507 AIDS Diseases 0.000 claims abstract description 20
• 239000003814 drug Substances 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
• 230000000840 anti-viral effect Effects 0.000 claims abstract description 12
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 142
• 229910052739 hydrogen Inorganic materials 0.000 claims description 78
• 125000001072 heteroaryl group Chemical group 0.000 claims description 64
• 125000003118 aryl group Chemical group 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 239000003085 diluting agent Substances 0.000 claims description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 8
• 208000031886 HIV Infections Diseases 0.000 claims description 7
• 208000037357 HIV infectious disease Diseases 0.000 claims description 7
• 239000003443 antiviral agent Substances 0.000 claims description 7
• 239000002835 hiv fusion inhibitor Substances 0.000 claims description 7
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 7
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 6
• 125000003107 substituted aryl group Chemical group 0.000 claims description 6
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
• 229960005475 antiinfective agent Drugs 0.000 claims description 5
• 239000004599 antimicrobial Substances 0.000 claims description 5
• 125000001475 halogen functional group Chemical group 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 229940124597 therapeutic agent Drugs 0.000 claims description 4
• 229940126154 HIV entry inhibitor Drugs 0.000 claims description 3
• 239000002955 immunomodulating agent Substances 0.000 claims description 3
• 230000002584 immunomodulator Effects 0.000 claims description 3
• 229940121354 immunomodulator Drugs 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 239000002552 dosage form Substances 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 374
• 239000003112 inhibitor Substances 0.000 abstract description 20
• 229940079593 drug Drugs 0.000 abstract description 9
• 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 350
• 239000000203 mixture Substances 0.000 description 295
• 238000002360 preparation method Methods 0.000 description 285
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 213
• 238000005481 NMR spectroscopy Methods 0.000 description 210
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 173
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 163
• 235000019439 ethyl acetate Nutrition 0.000 description 156
• 239000000047 product Substances 0.000 description 128
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 118
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 103
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 102
• 238000004949 mass spectrometry Methods 0.000 description 97
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 95
• 239000000243 solution Substances 0.000 description 92
• 239000002904 solvent Substances 0.000 description 91
• 229910052796 boron Inorganic materials 0.000 description 88
• 230000002829 reductive effect Effects 0.000 description 87
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 71
• VUSWCWPCANWBFG-UHFFFAOYSA-N cyclohex-3-ene-1-carboxylic acid Chemical compound OC(=O)C1CCC=CC1 VUSWCWPCANWBFG-UHFFFAOYSA-N 0.000 description 70
• 125000003003 spiro group Chemical group 0.000 description 68
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 59
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 59
• 229910052757 nitrogen Inorganic materials 0.000 description 57
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 56
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
• 239000007787 solid Substances 0.000 description 55
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 52
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
• ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 47
• 239000000376 reactant Substances 0.000 description 43
• 239000012044 organic layer Substances 0.000 description 38
• 150000001412 amines Chemical class 0.000 description 36
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 36
• 239000002253 acid Substances 0.000 description 35
• 241000725303 Human immunodeficiency virus Species 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 33
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 32
• 238000003818 flash chromatography Methods 0.000 description 31
• 238000000746 purification Methods 0.000 description 31
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
• 238000010438 heat treatment Methods 0.000 description 30
• 238000002953 preparative HPLC Methods 0.000 description 30
• 239000000706 filtrate Substances 0.000 description 29
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 239000000725 suspension Substances 0.000 description 27
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
• QGJZLNKBHJESQX-FZFNOLFKSA-N betulinic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C QGJZLNKBHJESQX-FZFNOLFKSA-N 0.000 description 26
• 238000001914 filtration Methods 0.000 description 24
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• 235000011121 sodium hydroxide Nutrition 0.000 description 24
• 239000012043 crude product Substances 0.000 description 23
• 239000000741 silica gel Substances 0.000 description 22
• 229910002027 silica gel Inorganic materials 0.000 description 22
• 239000007795 chemical reaction product Substances 0.000 description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 18
• 239000013058 crude material Substances 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• QTBSBXVTEAMEQO-GUEYOVJQSA-N acetic acid-d4 Chemical compound [2H]OC(=O)C([2H])([2H])[2H] QTBSBXVTEAMEQO-GUEYOVJQSA-N 0.000 description 17
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• 239000000543 intermediate Substances 0.000 description 16
• 229910000160 potassium phosphate Inorganic materials 0.000 description 16
• 235000011009 potassium phosphates Nutrition 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 15
• 239000000460 chlorine Substances 0.000 description 15
• 239000003921 oil Substances 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 125000003396 thiol group Chemical group [H]S* 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 13
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 13
• 239000007858 starting material Substances 0.000 description 13
• SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 12
• MNLVCBKWEVXHGE-UHFFFAOYSA-N [CH]1[CH]CC[CH]1 Chemical group [CH]1[CH]CC[CH]1 MNLVCBKWEVXHGE-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 239000002274 desiccant Substances 0.000 description 12
• 125000004494 ethyl ester group Chemical group 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 239000000463 material Substances 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• OSNPFTFAUNVQMS-UHFFFAOYSA-N spiro[3.3]heptane-2,2-dicarboxylic acid Chemical compound C1C(C(=O)O)(C(O)=O)CC11CCC1 OSNPFTFAUNVQMS-UHFFFAOYSA-N 0.000 description 12
• QGJZLNKBHJESQX-UHFFFAOYSA-N 3-Epi-Betulin-Saeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(=C)C)C5C4CCC3C21C QGJZLNKBHJESQX-UHFFFAOYSA-N 0.000 description 11
• CLOUCVRNYSHRCF-UHFFFAOYSA-N 3beta-Hydroxy-20(29)-Lupen-3,27-oic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C(O)=O)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C CLOUCVRNYSHRCF-UHFFFAOYSA-N 0.000 description 11
• DIZWSDNSTNAYHK-XGWVBXMLSA-N Betulinic acid Natural products CC(=C)[C@@H]1C[C@H]([C@H]2CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(=O)O DIZWSDNSTNAYHK-XGWVBXMLSA-N 0.000 description 11
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 11
• PZXJOHSZQAEJFE-UHFFFAOYSA-N dihydrobetulinic acid Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C(C)C)C5C4CCC3C21C PZXJOHSZQAEJFE-UHFFFAOYSA-N 0.000 description 11
• MQYXUWHLBZFQQO-UHFFFAOYSA-N nepehinol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=C)C)C5C4CCC3C21C MQYXUWHLBZFQQO-UHFFFAOYSA-N 0.000 description 11
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 11
• 241000700605 Viruses Species 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 10
• 239000005711 Benzoic acid Substances 0.000 description 9
• 235000010233 benzoic acid Nutrition 0.000 description 9
• 125000004093 cyano group Chemical group *C#N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 150000004702 methyl esters Chemical class 0.000 description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 8
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• 230000014759 maintenance of location Effects 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• 239000003643 water by type Substances 0.000 description 8
• 229960002555 zidovudine Drugs 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 7
• MQRJBSHKWOFOGF-UHFFFAOYSA-L disodium;carbonate;hydrate Chemical compound O.[Na+].[Na+].[O-]C([O-])=O MQRJBSHKWOFOGF-UHFFFAOYSA-L 0.000 description 7
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
• 238000006069 Suzuki reaction reaction Methods 0.000 description 6
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 6
• 125000004104 aryloxy group Chemical group 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• APGFPQCBDNWQSB-UHFFFAOYSA-N cyclohexa-1,3-diene-1-carboxylic acid Chemical compound OC(=O)C1=CC=CCC1 APGFPQCBDNWQSB-UHFFFAOYSA-N 0.000 description 6
• XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 6
• 229960001936 indinavir Drugs 0.000 description 6
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• 208000015181 infectious disease Diseases 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 235000011056 potassium acetate Nutrition 0.000 description 6
• 150000003141 primary amines Chemical class 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• 125000001424 substituent group Chemical group 0.000 description 6
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 6
• 125000005296 thioaryloxy group Chemical group 0.000 description 6
• 125000005404 thioheteroaryloxy group Chemical group 0.000 description 6
• 229940122440 HIV protease inhibitor Drugs 0.000 description 5
• 108060001084 Luciferase Proteins 0.000 description 5
• 239000005089 Luciferase Substances 0.000 description 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• RUSTYNDGQSCBHW-UHFFFAOYSA-N cyclohex-3-ene-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC=CC1 RUSTYNDGQSCBHW-UHFFFAOYSA-N 0.000 description 5
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 5
• JGDYSYLLIATOOX-UHFFFAOYSA-N diethyl cyclohex-3-ene-1,1-dicarboxylate Chemical compound CCOC(=O)C1(C(=O)OCC)CCC=CC1 JGDYSYLLIATOOX-UHFFFAOYSA-N 0.000 description 5
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