CN106046106A - 具有hiv成熟抑制活性的c‑3环烯三萜类化合物 - Google Patents
具有hiv成熟抑制活性的c‑3环烯三萜类化合物 Download PDFInfo
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- CN106046106A CN106046106A CN201610397768.6A CN201610397768A CN106046106A CN 106046106 A CN106046106 A CN 106046106A CN 201610397768 A CN201610397768 A CN 201610397768A CN 106046106 A CN106046106 A CN 106046106A
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- Prior art keywords
- alkyl
- base
- alkene
- substituted
- cyclopenta
- Prior art date
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- -1 cycloalkenyl triterpenoids Chemical class 0.000 title abstract description 118
- 230000035800 maturation Effects 0.000 title abstract description 10
- 230000002401 inhibitory effect Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 265
- 150000001875 compounds Chemical class 0.000 claims abstract description 174
- 239000003814 drug Substances 0.000 claims abstract description 22
- 208000030507 AIDS Diseases 0.000 claims abstract description 20
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000003443 antiviral agent Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 230000002924 anti-infective effect Effects 0.000 claims description 6
- 239000002955 immunomodulating agent Substances 0.000 claims description 6
- 229940121354 immunomodulator Drugs 0.000 claims description 6
- 230000002584 immunomodulator Effects 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000002835 hiv fusion inhibitor Substances 0.000 claims description 5
- 125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 229940126154 HIV entry inhibitor Drugs 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 16
- 229940079593 drug Drugs 0.000 abstract description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 239000002585 base Substances 0.000 description 838
- 239000000203 mixture Substances 0.000 description 317
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 314
- 238000002360 preparation method Methods 0.000 description 253
- 239000002253 acid Substances 0.000 description 199
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 186
- 238000005160 1H NMR spectroscopy Methods 0.000 description 164
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 144
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 141
- 239000000047 product Substances 0.000 description 136
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 115
- 235000019439 ethyl acetate Nutrition 0.000 description 113
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 109
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 109
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 102
- 230000002829 reductive effect Effects 0.000 description 101
- 239000000376 reactant Substances 0.000 description 100
- 239000000243 solution Substances 0.000 description 100
- 238000000746 purification Methods 0.000 description 97
- 239000007787 solid Substances 0.000 description 88
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 87
- 229910052796 boron Inorganic materials 0.000 description 83
- 239000012141 concentrate Substances 0.000 description 81
- 235000008504 concentrate Nutrition 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 77
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
- 239000000741 silica gel Substances 0.000 description 64
- 229910002027 silica gel Inorganic materials 0.000 description 64
- 229960001866 silicon dioxide Drugs 0.000 description 64
- 150000002148 esters Chemical class 0.000 description 63
- 229910052757 nitrogen Inorganic materials 0.000 description 60
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 59
- 125000004494 ethyl ester group Chemical group 0.000 description 54
- 150000002118 epoxides Chemical class 0.000 description 52
- 239000002904 solvent Substances 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 44
- 238000003756 stirring Methods 0.000 description 42
- 150000001335 aliphatic alkanes Chemical class 0.000 description 41
- 150000004702 methyl esters Chemical class 0.000 description 41
- 239000000284 extract Substances 0.000 description 39
- 241000725303 Human immunodeficiency virus Species 0.000 description 37
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 description 37
- 239000012044 organic layer Substances 0.000 description 37
- 238000004128 high performance liquid chromatography Methods 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 29
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 239000000706 filtrate Substances 0.000 description 27
- 238000003818 flash chromatography Methods 0.000 description 27
- 239000000725 suspension Substances 0.000 description 27
- 235000011121 sodium hydroxide Nutrition 0.000 description 26
- 239000012043 crude product Substances 0.000 description 25
- 238000004293 19F NMR spectroscopy Methods 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 24
- 239000000126 substance Substances 0.000 description 24
- 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 23
- 238000010790 dilution Methods 0.000 description 23
- 239000012895 dilution Substances 0.000 description 23
- TXKMVPPZCYKFAC-UHFFFAOYSA-N disulfur monoxide Inorganic materials O=S=S TXKMVPPZCYKFAC-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 238000010438 heat treatment Methods 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 125000003700 epoxy group Chemical group 0.000 description 21
- 239000000463 material Substances 0.000 description 21
- 239000011780 sodium chloride Substances 0.000 description 21
- 229910021529 ammonia Inorganic materials 0.000 description 20
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 230000008859 change Effects 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 229910052799 carbon Inorganic materials 0.000 description 17
- 238000005406 washing Methods 0.000 description 17
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- 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 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 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 14
- 235000019253 formic acid Nutrition 0.000 description 14
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- 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 13
- 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 13
- 239000005711 Benzoic acid Substances 0.000 description 13
- 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 13
- 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 13
- 235000010233 benzoic acid Nutrition 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 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 13
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 13
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000003513 alkali Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 239000012948 isocyanate Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 229910000160 potassium phosphate Inorganic materials 0.000 description 12
- 235000011009 potassium phosphates Nutrition 0.000 description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 12
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 11
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 11
- 229960001220 amsacrine Drugs 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000002274 desiccant Substances 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 11
- 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 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 229910052717 sulfur Inorganic materials 0.000 description 11
- 239000011593 sulfur Substances 0.000 description 11
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 238000005352 clarification Methods 0.000 description 10
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 125000004093 cyano group Chemical group *C#N 0.000 description 9
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 9
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 9
- 229960002555 zidovudine Drugs 0.000 description 9
- 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 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- KWGFISNERABFPJ-UHFFFAOYSA-N 4-(2-chloroethyl)-1,4-thiazinane 1,1-dioxide Chemical compound ClCCN1CCS(=O)(=O)CC1 KWGFISNERABFPJ-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 description 6
- 229960001936 indinavir Drugs 0.000 description 6
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 6
- 235000011056 potassium acetate Nutrition 0.000 description 6
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- LZOZLBFZGFLFBV-UHFFFAOYSA-N sulfene Chemical compound C=S(=O)=O LZOZLBFZGFLFBV-UHFFFAOYSA-N 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- BKSHRYOTCPWATO-UHFFFAOYSA-N sulfonylmethanesulfonamide Chemical compound NS(=O)(=O)C=S(=O)=O BKSHRYOTCPWATO-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 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 description 1
- 229960001355 tenofovir disoproxil Drugs 0.000 description 1
- JFVZFKDSXNQEJW-CQSZACIVSA-N tenofovir disoproxil Chemical compound N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N JFVZFKDSXNQEJW-CQSZACIVSA-N 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229940096998 ursolic acid Drugs 0.000 description 1
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
- 238000002061 vacuum sublimation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261599040P | 2012-02-15 | 2012-02-15 | |
| US61/599,040 | 2012-02-15 | ||
| US13/760,726 | 2013-02-06 | ||
| US13/760,726 US8906889B2 (en) | 2012-02-15 | 2013-02-06 | C-3 cycloalkenyl triterpenoids with HIV maturation inhibitory activity |
| CN201380019696.6A CN104220451B (zh) | 2012-02-15 | 2013-02-13 | 具有hiv成熟抑制活性的c-3环烯三萜类化合物 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380019696.6A Division CN104220451B (zh) | 2012-02-15 | 2013-02-13 | 具有hiv成熟抑制活性的c-3环烯三萜类化合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106046106A true CN106046106A (zh) | 2016-10-26 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610397768.6A Pending CN106046106A (zh) | 2012-02-15 | 2013-02-13 | 具有hiv成熟抑制活性的c‑3环烯三萜类化合物 |
| CN201380019696.6A Expired - Fee Related CN104220451B (zh) | 2012-02-15 | 2013-02-13 | 具有hiv成熟抑制活性的c-3环烯三萜类化合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380019696.6A Expired - Fee Related CN104220451B (zh) | 2012-02-15 | 2013-02-13 | 具有hiv成熟抑制活性的c-3环烯三萜类化合物 |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US8906889B2 (https=) |
| EP (1) | EP2814834B1 (https=) |
| JP (1) | JP6155285B2 (https=) |
| KR (1) | KR20140123584A (https=) |
| CN (2) | CN106046106A (https=) |
| AR (1) | AR089996A1 (https=) |
| AU (1) | AU2013221725B2 (https=) |
| BR (1) | BR112014019672A8 (https=) |
| CA (1) | CA2864656A1 (https=) |
| CL (1) | CL2014002141A1 (https=) |
| CO (1) | CO7061077A2 (https=) |
| EA (1) | EA024361B1 (https=) |
| ES (1) | ES2656984T3 (https=) |
| HK (1) | HK1204608A1 (https=) |
| IL (1) | IL234077A (https=) |
| MX (1) | MX2014009235A (https=) |
| MY (1) | MY166793A (https=) |
| NZ (1) | NZ631408A (https=) |
| PE (1) | PE20142315A1 (https=) |
| PH (1) | PH12014501816A1 (https=) |
| PT (1) | PT2814834T (https=) |
| SG (1) | SG11201404748XA (https=) |
| TW (1) | TW201336863A (https=) |
| UY (1) | UY34627A (https=) |
| WO (1) | WO2013123019A1 (https=) |
| ZA (1) | ZA201406724B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109705189A (zh) * | 2018-12-29 | 2019-05-03 | 中国医学科学院药用植物研究所 | 具有式i所示结构的三萜衍生物及其制备方法和应用 |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8889854B2 (en) | 2012-05-07 | 2014-11-18 | Bristol-Myers Squibb Company | C-17 bicyclic amines of triterpenoids with HIV maturation inhibitory activity |
| SG11201505639SA (en) | 2013-02-06 | 2015-08-28 | Bristol Myers Squibb Co | C-19 modified triterpenoids with hiv maturation inhibitory activity |
| SI3129392T1 (sl) * | 2014-04-11 | 2020-11-30 | VIIV Healthcare UK(No.4) Limited | Triterpenoidi z inhibitorno aktivnostjo maturacije HIV-a, substituirani na položaju 3 z nearomatskim obročem, ki nosi haloalkilni substituent |
| WO2015195776A1 (en) | 2014-06-19 | 2015-12-23 | Bristol-Myers Squibb Company | Betulinic acid derivatives with hiv maturation inhibitory activity |
| EP3218388A1 (en) | 2014-11-14 | 2017-09-20 | VIIV Healthcare UK (No.5) Limited | C17-aryl substituted betulinic acid analogs |
| KR20170092580A (ko) * | 2014-11-14 | 2017-08-11 | 비브 헬스케어 유케이 (넘버5) 리미티드 | 연장된 베툴린산 유사체 |
| CN107250153A (zh) * | 2014-11-14 | 2017-10-13 | Viiv保健英国第五有限公司 | 氧代羽扇豆烯衍生物 |
| RU2017134461A (ru) * | 2015-04-14 | 2019-05-14 | ВАЙВ ХЕЛТКЕР ЮКей (N4) ЛИМИТЕД | Способы получения ингибитора созревания HIV |
| RU2018105352A (ru) | 2015-07-28 | 2019-08-29 | ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед | Производные бетулина для предупреждения или лечения ВИЧ-инфекций |
| WO2017017609A1 (en) | 2015-07-28 | 2017-02-02 | Glaxosmithkline Intellectual Property (No.2) Limited | Betuin derivatives for preventing or treating hiv infections |
| RU2018112958A (ru) | 2015-09-24 | 2019-10-28 | ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед | Соединения с ингибирующей созревание ВИЧ активностью |
| WO2017125870A1 (en) * | 2016-01-20 | 2017-07-27 | Glaxosmithkline Intellectual Property (No.2) Limited | Amine derivatives of lupanes with hiv maturation inhibitory activity |
| AR107512A1 (es) * | 2016-02-04 | 2018-05-09 | VIIV HEALTHCARE UK Nº 5 LTD | Triterpenoides modificados en c-3 y c-17 como inhibidores del vih-1 |
| CN106905264B (zh) * | 2017-04-12 | 2019-06-07 | 连云港杰瑞药业有限公司 | 一种合成阿扎拉韦中间体的方法 |
| WO2019055280A1 (en) | 2017-09-13 | 2019-03-21 | Emmyon, Inc. | DIETHANOLAMINE SALTS AND URSOLIC ACID MORPHOLIN |
| ES2970042T3 (es) | 2018-04-24 | 2024-05-24 | Viiv Healthcare Uk No 5 Ltd | Compuestos con actividad inhibidora de la maduración del VIH |
| SI3924361T1 (sl) | 2019-02-11 | 2024-02-29 | Hetero Labs Limited | Novi derivati triterpena kot zaviralci virusa hiv |
| WO2020229398A1 (de) | 2019-05-14 | 2020-11-19 | Bayer Aktiengesellschaft | (1-alkenyl)-substituierte pyrazole und triazole als schädlingsbekämpfungsmittel |
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| WO2009020732A1 (en) * | 2007-08-03 | 2009-02-12 | Advanced Life Sciences, Inc. | Lupane-type triterpenoids modified at 30-position and analogues thereof |
| WO2011153319A1 (en) * | 2010-06-04 | 2011-12-08 | Bristol-Myers Squibb Company | C-28 amides of modified c-3 betulinic acid derivatives as hiv maturation inhibitors |
| WO2011153315A1 (en) * | 2010-06-04 | 2011-12-08 | Bristol-Myers Squibb Company | Modified c-3 betulinic acid derivatives as hiv maturation inhibitors |
| CN103429607A (zh) * | 2011-01-31 | 2013-12-04 | 百时美施贵宝公司 | 具有hiv成熟抑制活性的c-17和c-3经修饰的三萜系化合物 |
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| US5869535A (en) | 1995-03-21 | 1999-02-09 | The Board Of Trustees Of The University Of Illinois | Method and composition for selectively inhibiting melanoma |
| US5679828A (en) | 1995-06-05 | 1997-10-21 | Biotech Research Labs, Inc. | Betulinic acid and dihydrobetulinic acid derivatives and uses therefor |
| US20040110785A1 (en) | 2001-02-02 | 2004-06-10 | Tao Wang | Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives |
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| US20050014730A1 (en) | 2003-04-02 | 2005-01-20 | Carlson Robert M. | Anti-fungal formulation of triterpene and essential oil |
| US7745625B2 (en) | 2004-03-15 | 2010-06-29 | Bristol-Myers Squibb Company | Prodrugs of piperazine and substituted piperidine antiviral agents |
| EP1730163A4 (en) | 2004-03-17 | 2009-12-30 | Panacos Pharmaceuticals Inc | Pharmaceutical salts of 3-O- (3,3-dimethylsuccinyl) betulinic acid |
| TW200628161A (en) | 2004-11-12 | 2006-08-16 | Panacos Pharmaceuticals Inc | Novel betulin derivatives, preparation thereof and use thereof |
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| SG11201505639SA (en) * | 2013-02-06 | 2015-08-28 | Bristol Myers Squibb Co | C-19 modified triterpenoids with hiv maturation inhibitory activity |
-
2013
- 2013-02-06 US US13/760,726 patent/US8906889B2/en active Active
- 2013-02-08 TW TW102105203A patent/TW201336863A/zh unknown
- 2013-02-13 CA CA2864656A patent/CA2864656A1/en not_active Abandoned
- 2013-02-13 WO PCT/US2013/025897 patent/WO2013123019A1/en not_active Ceased
- 2013-02-13 NZ NZ631408A patent/NZ631408A/en not_active IP Right Cessation
- 2013-02-13 PT PT137074936T patent/PT2814834T/pt unknown
- 2013-02-13 HK HK15105069.8A patent/HK1204608A1/xx unknown
- 2013-02-13 PE PE2014001279A patent/PE20142315A1/es not_active Application Discontinuation
- 2013-02-13 MX MX2014009235A patent/MX2014009235A/es unknown
- 2013-02-13 SG SG11201404748XA patent/SG11201404748XA/en unknown
- 2013-02-13 MY MYPI2014702277A patent/MY166793A/en unknown
- 2013-02-13 ES ES13707493.6T patent/ES2656984T3/es active Active
- 2013-02-13 CN CN201610397768.6A patent/CN106046106A/zh active Pending
- 2013-02-13 EP EP13707493.6A patent/EP2814834B1/en active Active
- 2013-02-13 CN CN201380019696.6A patent/CN104220451B/zh not_active Expired - Fee Related
- 2013-02-13 BR BR112014019672A patent/BR112014019672A8/pt not_active Application Discontinuation
- 2013-02-13 JP JP2014557739A patent/JP6155285B2/ja not_active Expired - Fee Related
- 2013-02-13 KR KR1020147025339A patent/KR20140123584A/ko not_active Ceased
- 2013-02-13 AU AU2013221725A patent/AU2013221725B2/en not_active Ceased
- 2013-02-13 EA EA201491531A patent/EA024361B1/ru not_active IP Right Cessation
- 2013-02-14 AR ARP130100466A patent/AR089996A1/es unknown
- 2013-02-14 UY UY0001034627A patent/UY34627A/es not_active Application Discontinuation
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2014
- 2014-08-12 PH PH12014501816A patent/PH12014501816A1/en unknown
- 2014-08-12 IL IL234077A patent/IL234077A/en not_active IP Right Cessation
- 2014-08-13 CL CL2014002141A patent/CL2014002141A1/es unknown
- 2014-08-28 CO CO14189685A patent/CO7061077A2/es unknown
- 2014-09-12 ZA ZA2014/06724A patent/ZA201406724B/en unknown
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| WO2009020732A1 (en) * | 2007-08-03 | 2009-02-12 | Advanced Life Sciences, Inc. | Lupane-type triterpenoids modified at 30-position and analogues thereof |
| WO2011153319A1 (en) * | 2010-06-04 | 2011-12-08 | Bristol-Myers Squibb Company | C-28 amides of modified c-3 betulinic acid derivatives as hiv maturation inhibitors |
| WO2011153315A1 (en) * | 2010-06-04 | 2011-12-08 | Bristol-Myers Squibb Company | Modified c-3 betulinic acid derivatives as hiv maturation inhibitors |
| CN103429607A (zh) * | 2011-01-31 | 2013-12-04 | 百时美施贵宝公司 | 具有hiv成熟抑制活性的c-17和c-3经修饰的三萜系化合物 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109705189A (zh) * | 2018-12-29 | 2019-05-03 | 中国医学科学院药用植物研究所 | 具有式i所示结构的三萜衍生物及其制备方法和应用 |
| CN109705189B (zh) * | 2018-12-29 | 2020-06-05 | 中国医学科学院药用植物研究所 | 具有式i所示结构的三萜衍生物及其制备方法和应用 |
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Application publication date: 20161026 |