KR20150042830A - 인간 면역결핍 바이러스 복제의 억제제 - Google Patents
인간 면역결핍 바이러스 복제의 억제제 Download PDFInfo
- Publication number
- KR20150042830A KR20150042830A KR20157006290A KR20157006290A KR20150042830A KR 20150042830 A KR20150042830 A KR 20150042830A KR 20157006290 A KR20157006290 A KR 20157006290A KR 20157006290 A KR20157006290 A KR 20157006290A KR 20150042830 A KR20150042830 A KR 20150042830A
- Authority
- KR
- South Korea
- Prior art keywords
- tert
- acetic acid
- dioxa
- butoxy
- tree archon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 36
- 241000725303 Human immunodeficiency virus Species 0.000 title abstract description 31
- 230000029812 viral genome replication Effects 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 211
- 238000000034 method Methods 0.000 claims abstract description 138
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 15
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 15
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 564
- 241001566735 Archon Species 0.000 claims description 307
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 203
- -1 homopiperidinyl Chemical group 0.000 claims description 128
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 117
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 239000002777 nucleoside Substances 0.000 claims description 15
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 15
- 208000030507 AIDS Diseases 0.000 claims description 14
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 13
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- HQLILHPGWSURBT-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]acetic acid Chemical compound CC(C)(C)OCC(O)=O HQLILHPGWSURBT-UHFFFAOYSA-N 0.000 claims description 9
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 8
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 8
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 8
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 8
- 239000002835 hiv fusion inhibitor Substances 0.000 claims description 8
- 239000004030 hiv protease inhibitor Substances 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 229940122440 HIV protease inhibitor Drugs 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000005434 dihydrobenzoxazinyl group Chemical group O1N(CCC2=C1C=CC=C2)* 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 229940124524 integrase inhibitor Drugs 0.000 claims 1
- 239000002850 integrase inhibitor Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 208000015181 infectious disease Diseases 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 description 507
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 376
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 239
- 239000000243 solution Substances 0.000 description 224
- 235000019439 ethyl acetate Nutrition 0.000 description 183
- 238000006243 chemical reaction Methods 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 139
- 239000000047 product Substances 0.000 description 132
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 119
- 125000005336 allyloxy group Chemical group 0.000 description 118
- 239000007787 solid Substances 0.000 description 114
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 108
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 104
- 239000011734 sodium Substances 0.000 description 99
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 93
- 238000002360 preparation method Methods 0.000 description 81
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- 239000003921 oil Substances 0.000 description 59
- 235000019198 oils Nutrition 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 44
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 238000002953 preparative HPLC Methods 0.000 description 36
- 229920006395 saturated elastomer Polymers 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 230000002829 reductive effect Effects 0.000 description 31
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 28
- 238000000746 purification Methods 0.000 description 27
- 239000012043 crude product Substances 0.000 description 26
- 239000010410 layer Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 23
- 229910004298 SiO 2 Inorganic materials 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 19
- 239000011986 second-generation catalyst Substances 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000012230 colorless oil Substances 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 16
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 16
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 16
- IEMGWBMVQLVHEY-UHFFFAOYSA-N ethyl 2-(3-amino-6,7-dihydro-5h-cyclopenta[b]pyridin-7-yl)acetate Chemical compound NC1=CN=C2C(CC(=O)OCC)CCC2=C1 IEMGWBMVQLVHEY-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- ZHZCYWWNFQUZOR-RXMQYKEDSA-N (2r)-pent-4-en-2-ol Chemical compound C[C@@H](O)CC=C ZHZCYWWNFQUZOR-RXMQYKEDSA-N 0.000 description 13
- 241000700605 Viruses Species 0.000 description 13
- 238000005273 aeration Methods 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 229910052763 palladium Inorganic materials 0.000 description 12
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- HQLILHPGWSURBT-UHFFFAOYSA-M 2-[(2-methylpropan-2-yl)oxy]acetate Chemical compound CC(C)(C)OCC([O-])=O HQLILHPGWSURBT-UHFFFAOYSA-M 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 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 10
- 229910021653 sulphate ion Inorganic materials 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 235000010290 biphenyl Nutrition 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 8
- 239000005695 Ammonium acetate Substances 0.000 description 8
- 235000019257 ammonium acetate Nutrition 0.000 description 8
- 229940043376 ammonium acetate Drugs 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 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 7
- 229940099797 HIV integrase inhibitor Drugs 0.000 description 7
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000003084 hiv integrase inhibitor Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 239000007858 starting material Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000035800 maturation Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- MKHGVMIXRPGHOO-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-phenyloxaziridine Chemical compound C=1C=CC=CC=1S(=O)(=O)N1OC1C1=CC=CC=C1 MKHGVMIXRPGHOO-UHFFFAOYSA-N 0.000 description 4
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 4
- RPBFJMNEBQRVBS-UHFFFAOYSA-N 4-methyl-4-(prop-2-enoxymethyl)piperidine Chemical compound C=CCOCC1(C)CCNCC1 RPBFJMNEBQRVBS-UHFFFAOYSA-N 0.000 description 4
- XGOONJGQNKCWLR-UHFFFAOYSA-N 4-methyl-4-prop-2-enoxypiperidine Chemical compound C=CCOC1(C)CCNCC1 XGOONJGQNKCWLR-UHFFFAOYSA-N 0.000 description 4
- GVVSJGQBIZMKCC-UHFFFAOYSA-J C(C)(C)OC1=C(C=[Ru](Cl)(Cl)(Cl)Cl)C=CC=C1 Chemical compound C(C)(C)OC1=C(C=[Ru](Cl)(Cl)(Cl)Cl)C=CC=C1 GVVSJGQBIZMKCC-UHFFFAOYSA-J 0.000 description 4
- 101150003085 Pdcl gene Proteins 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 239000012259 ether extract Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- PUPAWTXNPAJCHR-UHFFFAOYSA-N oxazaborole Chemical compound O1C=CB=N1 PUPAWTXNPAJCHR-UHFFFAOYSA-N 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 235000011056 potassium acetate Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- MKZZJISUXHQQNU-BQYQJAHWSA-N tert-butyl 4-[(1e)-buta-1,3-dienyl]-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(\C=C\C=C)CC1 MKZZJISUXHQQNU-BQYQJAHWSA-N 0.000 description 4
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 4
- COECHZJTHZENSV-UHFFFAOYSA-N (1-methylcyclobutyl) acetate Chemical compound CC(=O)OC1(C)CCC1 COECHZJTHZENSV-UHFFFAOYSA-N 0.000 description 3
- XTYSXGHMTNTKFH-BDEHJDMKSA-N (2s)-1-[(2s,4r)-4-benzyl-2-hydroxy-5-[[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate Chemical compound O.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 XTYSXGHMTNTKFH-BDEHJDMKSA-N 0.000 description 3
- GGZASRFCRAZNPO-UHFFFAOYSA-N (5-chloro-2-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=CC=C1O GGZASRFCRAZNPO-UHFFFAOYSA-N 0.000 description 3
- BZLDVRIPHOINJB-UHFFFAOYSA-N 2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NC2=CC(=NN2C(=C1)I)C3=CC(=CC=C3)Br BZLDVRIPHOINJB-UHFFFAOYSA-N 0.000 description 3
- FPHDGFXDUXNKKF-UHFFFAOYSA-N 2-bromo-4-chloro-3-methylphenol Chemical compound CC1=C(Cl)C=CC(O)=C1Br FPHDGFXDUXNKKF-UHFFFAOYSA-N 0.000 description 3
- KKAZNBGOONSMFQ-UHFFFAOYSA-N 2-bromo-4-fluoro-3-methylphenol Chemical compound CC1=C(F)C=CC(O)=C1Br KKAZNBGOONSMFQ-UHFFFAOYSA-N 0.000 description 3
- OQDPFYLNWVPEDE-UHFFFAOYSA-N 2-bromo-4-fluoro-5-methylphenol Chemical compound CC1=CC(O)=C(Br)C=C1F OQDPFYLNWVPEDE-UHFFFAOYSA-N 0.000 description 3
- VBFNSHGLANEMRM-UHFFFAOYSA-N 3-(3-bromophenyl)-3-oxopropanenitrile Chemical compound BrC1=CC=CC(C(=O)CC#N)=C1 VBFNSHGLANEMRM-UHFFFAOYSA-N 0.000 description 3
- MRWWWZLJWNIEEJ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-propan-2-yloxy-1,3,2-dioxaborolane Chemical compound CC(C)OB1OC(C)(C)C(C)(C)O1 MRWWWZLJWNIEEJ-UHFFFAOYSA-N 0.000 description 3
- VFFPLRNGXGPLHH-SNAWJCMRSA-N 4-[(1e)-buta-1,3-dienyl]-4-methylpiperidine Chemical compound C=C/C=C/C1(C)CCNCC1 VFFPLRNGXGPLHH-SNAWJCMRSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 0 C**c1c(C(*)C(O)=*2)c2nc2c(C)c(*)n[n]12 Chemical compound C**c1c(C(*)C(O)=*2)c2nc2c(C)c(*)n[n]12 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- NLPRAJRHRHZCQQ-UHFFFAOYSA-N Epibatidine Natural products C1=NC(Cl)=CC=C1C1C(N2)CCC2C1 NLPRAJRHRHZCQQ-UHFFFAOYSA-N 0.000 description 3
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 3
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 3
- 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 3
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 229960001830 amprenavir Drugs 0.000 description 3
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 229940124522 antiretrovirals Drugs 0.000 description 3
- 239000003903 antiretrovirus agent Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229960005319 delavirdine Drugs 0.000 description 3
- 229960002656 didanosine Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960000366 emtricitabine Drugs 0.000 description 3
- NLPRAJRHRHZCQQ-IVZWLZJFSA-N epibatidine Chemical compound C1=NC(Cl)=CC=C1[C@@H]1[C@H](N2)CC[C@H]2C1 NLPRAJRHRHZCQQ-IVZWLZJFSA-N 0.000 description 3
- 229960003142 fosamprenavir Drugs 0.000 description 3
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229960001936 indinavir Drugs 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229960001627 lamivudine Drugs 0.000 description 3
- 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 3
- 229960004525 lopinavir Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960000689 nevirapine Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 3
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 229960000311 ritonavir Drugs 0.000 description 3
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- 229960001852 saquinavir Drugs 0.000 description 3
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229960001203 stavudine Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960004556 tenofovir Drugs 0.000 description 3
- 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 3
- YFYSPIRFZKBBAU-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(CO)CC1 YFYSPIRFZKBBAU-UHFFFAOYSA-N 0.000 description 3
- SWUCHJAQBNXPBO-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(O)CC1 SWUCHJAQBNXPBO-UHFFFAOYSA-N 0.000 description 3
- 229960000523 zalcitabine Drugs 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- 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 3
- JFVRQJFOBPBETM-UHFFFAOYSA-N (2-hydroxy-6-methylphenyl)boronic acid Chemical compound CC1=CC=CC(O)=C1B(O)O JFVRQJFOBPBETM-UHFFFAOYSA-N 0.000 description 2
- ZHZCYWWNFQUZOR-YFKPBYRVSA-N (2s)-pent-4-en-2-ol Chemical compound C[C@H](O)CC=C ZHZCYWWNFQUZOR-YFKPBYRVSA-N 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- ASSJTMUEFHUKMJ-UHFFFAOYSA-N 1-acetyl-n-[3-[4-[(4-carbamoylphenyl)methyl]piperidin-1-yl]propyl]-n-(3-chloro-4-methylphenyl)piperidine-4-carboxamide Chemical compound C1CN(C(=O)C)CCC1C(=O)N(C=1C=C(Cl)C(C)=CC=1)CCCN1CCC(CC=2C=CC(=CC=2)C(N)=O)CC1 ASSJTMUEFHUKMJ-UHFFFAOYSA-N 0.000 description 2
- BETCAKWIHGGEHB-UHFFFAOYSA-N 2-(3-but-3-enylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(CCC=C)=C1 BETCAKWIHGGEHB-UHFFFAOYSA-N 0.000 description 2
- GRQPDQPXSXQGBX-UHFFFAOYSA-N 2-bromo-4-chloro-5-methylphenol Chemical compound CC1=CC(O)=C(Br)C=C1Cl GRQPDQPXSXQGBX-UHFFFAOYSA-N 0.000 description 2
- JCCIFDCPHCKATH-UHFFFAOYSA-N 2-methylbutan-2-yl acetate Chemical compound CCC(C)(C)OC(C)=O JCCIFDCPHCKATH-UHFFFAOYSA-N 0.000 description 2
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 2
- YCOXTKKNXUZSKD-UHFFFAOYSA-N 3,4-xylenol Chemical compound CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 2
- UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 2
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 2
- JNETZJWWXCLUKM-UHFFFAOYSA-N 4-bromo-1-fluoro-2-iodobenzene Chemical compound FC1=CC=C(Br)C=C1I JNETZJWWXCLUKM-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- NQFSHBKZGKSELV-UHFFFAOYSA-N 5-(3-bromophenyl)-1h-pyrazol-3-amine Chemical compound N1N=C(N)C=C1C1=CC=CC(Br)=C1 NQFSHBKZGKSELV-UHFFFAOYSA-N 0.000 description 2
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 2
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229960004748 abacavir Drugs 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 229960003277 atazanavir Drugs 0.000 description 2
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- ZBPOCGOPSZYGNB-UHFFFAOYSA-N but-3-en-2-ol Chemical compound CC(C=C)O.CC(C=C)O ZBPOCGOPSZYGNB-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 239000002027 dichloromethane extract Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940121292 leronlimab Drugs 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- HDXFCMFLXFGXEI-UHFFFAOYSA-N methyl 2-[2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl]-2-hydroxyacetate Chemical compound N=1N2C(Cl)=C(C(O)C(=O)OC)C(C)=NC2=CC=1C1=CC=CC(Br)=C1 HDXFCMFLXFGXEI-UHFFFAOYSA-N 0.000 description 2
- WDDWDTRQOZNVNG-UHFFFAOYSA-N methyl 2-[2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl]-2-oxoacetate Chemical compound N=1N2C(Cl)=C(C(=O)C(=O)OC)C(C)=NC2=CC=1C1=CC=CC(Br)=C1 WDDWDTRQOZNVNG-UHFFFAOYSA-N 0.000 description 2
- ZGDIKFJUIUQECX-UHFFFAOYSA-N methyl 2-[2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl]-2-oxoacetate Chemical compound N=1N2C(I)=C(C(=O)C(=O)OC)C(C)=NC2=CC=1C1=CC=CC(Br)=C1 ZGDIKFJUIUQECX-UHFFFAOYSA-N 0.000 description 2
- MKUWVMRNQOOSAT-UHFFFAOYSA-N methylvinylmethanol Natural products CC(O)C=C MKUWVMRNQOOSAT-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical group C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 2
- 229960002169 plerixafor Drugs 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 229960004742 raltegravir Drugs 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 2
- LMKGOFDRKIAUPZ-UHFFFAOYSA-N tert-butyl 4-formyl-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(C=O)CC1 LMKGOFDRKIAUPZ-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- 235000015041 whisky Nutrition 0.000 description 2
- YIPPWSQPMKQSNL-UHFFFAOYSA-N (2-but-3-enylphenyl)-dimethoxyborane Chemical compound COB(OC)C1=CC=CC=C1CCC=C YIPPWSQPMKQSNL-UHFFFAOYSA-N 0.000 description 1
- HPTKHPAGOMESFW-UHFFFAOYSA-N (2-chloro-6-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=C(O)C=CC=C1Cl HPTKHPAGOMESFW-UHFFFAOYSA-N 0.000 description 1
- BSBYPAUPNICLEQ-UHFFFAOYSA-N (2-fluoro-6-hydroxy-3-methylphenyl)boronic acid Chemical compound CC1=CC=C(O)C(B(O)O)=C1F BSBYPAUPNICLEQ-UHFFFAOYSA-N 0.000 description 1
- FPXQHZPCFRQWCP-UHFFFAOYSA-N (2-fluoro-6-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=C(O)C=CC=C1F FPXQHZPCFRQWCP-UHFFFAOYSA-N 0.000 description 1
- YDMRDHQUQIVWBE-UHFFFAOYSA-N (2-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1O YDMRDHQUQIVWBE-UHFFFAOYSA-N 0.000 description 1
- TXIVUHPMDOHGON-UHFFFAOYSA-N (2-pent-4-enylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1CCCC=C TXIVUHPMDOHGON-UHFFFAOYSA-N 0.000 description 1
- LNPNXWKVAFKIBX-ZCFIWIBFSA-N (2r)-hex-5-en-2-ol Chemical compound C[C@@H](O)CCC=C LNPNXWKVAFKIBX-ZCFIWIBFSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- GEQJQQSCMWJDCW-UHFFFAOYSA-N (4-fluoro-2-hydroxy-5-methylphenyl)boronic acid Chemical compound CC1=CC(B(O)O)=C(O)C=C1F GEQJQQSCMWJDCW-UHFFFAOYSA-N 0.000 description 1
- KOFNQIAWWVBBJZ-UHFFFAOYSA-N (4-fluoro-2-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1O KOFNQIAWWVBBJZ-UHFFFAOYSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- NCWDBNBNYVVARF-UHFFFAOYSA-N 1,3,2-dioxaborolane Chemical compound B1OCCO1 NCWDBNBNYVVARF-UHFFFAOYSA-N 0.000 description 1
- LSMWOQFDLBIYPM-UHFFFAOYSA-N 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-2h-imidazol-1-ium-2-ide Chemical group CC1=CC(C)=CC(C)=C1N1[C-]=[N+](C=2C(=CC(C)=CC=2C)C)CC1 LSMWOQFDLBIYPM-UHFFFAOYSA-N 0.000 description 1
- ZRPFJAPZDXQHSM-UHFFFAOYSA-L 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole;dichloro-[(2-propan-2-yloxyphenyl)methylidene]ruthenium Chemical compound CC(C)OC1=CC=CC=C1C=[Ru](Cl)(Cl)=C1N(C=2C(=CC(C)=CC=2C)C)CCN1C1=C(C)C=C(C)C=C1C ZRPFJAPZDXQHSM-UHFFFAOYSA-L 0.000 description 1
- WQEKCOACXIDDRN-QMMMGPOBSA-N 1-bromo-4-chloro-2-[(2s)-pent-4-en-2-yl]oxybenzene Chemical compound C=CC[C@H](C)OC1=CC(Cl)=CC=C1Br WQEKCOACXIDDRN-QMMMGPOBSA-N 0.000 description 1
- LSUROFBGXMZYFZ-UHFFFAOYSA-N 1-fluoro-4-[(4-phenylphenyl)methyl]benzene Chemical compound C1=CC(F)=CC=C1CC1=CC=C(C=2C=CC=CC=2)C=C1 LSUROFBGXMZYFZ-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- DQWVUKFABWSFJD-UHFFFAOYSA-N 1-methylcyclobutan-1-ol Chemical compound CC1(O)CCC1 DQWVUKFABWSFJD-UHFFFAOYSA-N 0.000 description 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- VLROJECCXBBKPZ-UHFFFAOYSA-N 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC=C1O VLROJECCXBBKPZ-UHFFFAOYSA-N 0.000 description 1
- UWOMXMRZBJZRKM-NSHDSACASA-N 2-(5-bromo-2-fluorophenyl)-1-fluoro-3-[(2s)-pent-4-en-2-yl]oxybenzene Chemical group C=CC[C@H](C)OC1=CC=CC(F)=C1C1=CC(Br)=CC=C1F UWOMXMRZBJZRKM-NSHDSACASA-N 0.000 description 1
- MKQHUPIWRWGPDZ-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluorophenol Chemical compound OC1=CC=CC(F)=C1C1=CC(Br)=CC=C1F MKQHUPIWRWGPDZ-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- NVGOATMUHKIQQG-UHFFFAOYSA-N 2-Methyl-3-buten-1-ol Chemical compound OCC(C)C=C NVGOATMUHKIQQG-UHFFFAOYSA-N 0.000 description 1
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 1
- BROMJRLAHIONLD-LBPRGKRZSA-N 2-[4-chloro-2-[(2s)-pent-4-en-2-yl]oxyphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C=CC[C@H](C)OC1=CC(Cl)=CC=C1B1OC(C)(C)C(C)(C)O1 BROMJRLAHIONLD-LBPRGKRZSA-N 0.000 description 1
- GJLPLXXEHFEMBL-UHFFFAOYSA-N 2-bromo-4,5-dimethylphenol Chemical compound CC1=CC(O)=C(Br)C=C1C GJLPLXXEHFEMBL-UHFFFAOYSA-N 0.000 description 1
- OKMQOMMLPAIAON-UHFFFAOYSA-N 2-bromo-4-methyl-1-(3-methylpent-4-en-2-yloxy)benzene Chemical compound C=CC(C)C(C)OC1=CC=C(C)C=C1Br OKMQOMMLPAIAON-UHFFFAOYSA-N 0.000 description 1
- MTIDYGLTAOZOGU-UHFFFAOYSA-N 2-bromo-4-methylphenol Chemical compound CC1=CC=C(O)C(Br)=C1 MTIDYGLTAOZOGU-UHFFFAOYSA-N 0.000 description 1
- FMRKYXVZQWHGDA-UHFFFAOYSA-N 2-bromo-5-chlorophenol Chemical compound OC1=CC(Cl)=CC=C1Br FMRKYXVZQWHGDA-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- XMSQBHKHNKQPRJ-UHFFFAOYSA-N 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine Chemical compound CC1CNC2=C(O1)C=CC(=C2)B1OC(C(O1)(C)C)(C)C XMSQBHKHNKQPRJ-UHFFFAOYSA-N 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- PLHDSDPYRZFMJT-UHFFFAOYSA-N 2-phenyl-4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1C1=CC=CC=C1 PLHDSDPYRZFMJT-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZSPTYLOMNJNZNG-UHFFFAOYSA-N 3-Buten-1-ol Chemical compound OCCC=C ZSPTYLOMNJNZNG-UHFFFAOYSA-N 0.000 description 1
- JWHZKNRXTDYNJO-UHFFFAOYSA-N 3-bromo-1h-pyridin-4-one Chemical compound OC1=CC=NC=C1Br JWHZKNRXTDYNJO-UHFFFAOYSA-N 0.000 description 1
- MWPAHVGCBUBNMC-UHFFFAOYSA-N 3-bromo-4-but-3-enylpyridine Chemical compound BrC1=CN=CC=C1CCC=C MWPAHVGCBUBNMC-UHFFFAOYSA-N 0.000 description 1
- YPJHXRAHMUKXAE-UHFFFAOYSA-N 3-diethoxyphosphorylprop-1-ene Chemical compound CCOP(=O)(CC=C)OCC YPJHXRAHMUKXAE-UHFFFAOYSA-N 0.000 description 1
- COIPQIFWUIDWLU-UHFFFAOYSA-N 3-methylpent-4-en-2-ol Chemical compound CC(O)C(C)C=C COIPQIFWUIDWLU-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- FVYKRTYSGCRKPH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-[5-methyl-2-(3-methylpent-4-en-2-yloxy)phenyl]-1,3,2-dioxaborolane Chemical compound C=CC(C)C(C)OC1=CC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 FVYKRTYSGCRKPH-UHFFFAOYSA-N 0.000 description 1
- LRVKMSDCJCZTTB-UHFFFAOYSA-N 4-bromo-2-iodo-1-methylbenzene Chemical compound CC1=CC=C(Br)C=C1I LRVKMSDCJCZTTB-UHFFFAOYSA-N 0.000 description 1
- GQMUWGZQUWRFDG-VIFPVBQESA-N 4-bromo-3-[(2s)-pent-4-en-2-yl]oxybenzonitrile Chemical compound C=CC[C@H](C)OC1=CC(C#N)=CC=C1Br GQMUWGZQUWRFDG-VIFPVBQESA-N 0.000 description 1
- QBKXYSXQKRNVRQ-UHFFFAOYSA-N 4-bromo-3-fluorobenzonitrile Chemical compound FC1=CC(C#N)=CC=C1Br QBKXYSXQKRNVRQ-UHFFFAOYSA-N 0.000 description 1
- OKBNEDPOUYRYNP-UHFFFAOYSA-N 4-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C)(C(O)=O)CC1 OKBNEDPOUYRYNP-UHFFFAOYSA-N 0.000 description 1
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
- VIRFRHVDXNAETH-UHFFFAOYSA-N 4-methylpiperidine-1-carboxylic acid Chemical compound CC1CCN(C(O)=O)CC1 VIRFRHVDXNAETH-UHFFFAOYSA-N 0.000 description 1
- SJISCEAZUHNOMD-UHFFFAOYSA-N 4-phenylcyclohexan-1-amine Chemical compound C1CC(N)CCC1C1=CC=CC=C1 SJISCEAZUHNOMD-UHFFFAOYSA-N 0.000 description 1
- LPNANKDXVBMDKE-UHFFFAOYSA-N 5-bromopent-1-ene Chemical compound BrCCCC=C LPNANKDXVBMDKE-UHFFFAOYSA-N 0.000 description 1
- GWKYJFILHVNGEL-UHFFFAOYSA-N 5-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2h-1,4-benzoxazine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(OCCN2)C2=C1Cl GWKYJFILHVNGEL-UHFFFAOYSA-N 0.000 description 1
- UMYLXBFPUZVEIJ-UHFFFAOYSA-N 5-fluoro-2-phenylphenol Chemical compound OC1=CC(F)=CC=C1C1=CC=CC=C1 UMYLXBFPUZVEIJ-UHFFFAOYSA-N 0.000 description 1
- KKNJXLDMVHWJGM-UHFFFAOYSA-N 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound OC1=CC(C)=CC=C1B1OC(C)(C)C(C)(C)O1 KKNJXLDMVHWJGM-UHFFFAOYSA-N 0.000 description 1
- OISLTYSRSUFGPW-UHFFFAOYSA-N 7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2h-1,4-benzoxazine Chemical compound O1C(C)(C)C(C)(C)OB1C(C(=C1)F)=CC2=C1OCCN2 OISLTYSRSUFGPW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000349731 Afzelia bipindensis Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- LVOIWYBVYWHPKG-UHFFFAOYSA-N BrC1=C(C#N)C=CC=C1OC(C)CC=C Chemical compound BrC1=C(C#N)C=CC=C1OC(C)CC=C LVOIWYBVYWHPKG-UHFFFAOYSA-N 0.000 description 1
- VWHKRQZIQGLRAX-UHFFFAOYSA-N BrC=1C=CC(=C(C1)C1=CC=CC=C1Cl)C Chemical compound BrC=1C=CC(=C(C1)C1=CC=CC=C1Cl)C VWHKRQZIQGLRAX-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- QJTGECCOORMTHD-ALHVMVMPSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCCC4CCCCc3c-4cccc3)[n]1nc2-c1cccc-4c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCCC4CCCCc3c-4cccc3)[n]1nc2-c1cccc-4c1 QJTGECCOORMTHD-ALHVMVMPSA-N 0.000 description 1
- VIRUETIEIQIEEV-JIFWVNEYSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCC[C@H]4C/C=C\COc3c-4cccc3)[n]1nc2-c1cccc-4c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCC[C@H]4C/C=C\COc3c-4cccc3)[n]1nc2-c1cccc-4c1 VIRUETIEIQIEEV-JIFWVNEYSA-N 0.000 description 1
- YMYIWGJDAITAKD-BHVANESWSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3F)cc4c3OCCN4CCCCCc3c-4cccc3)[n]1nc2-c1cccc-4c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1c2)c(-c(cc3F)cc4c3OCCN4CCCCCc3c-4cccc3)[n]1nc2-c1cccc-4c1 YMYIWGJDAITAKD-BHVANESWSA-N 0.000 description 1
- BTXLUSNBQFLWMN-YWGMWZHNSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OC/C=C/COc1ccccc1-c1cccc-2c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OC/C=C/COc1ccccc1-c1cccc-2c1 BTXLUSNBQFLWMN-YWGMWZHNSA-N 0.000 description 1
- FDYCUPDVCNRFJG-DWDLGBGNSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OC/C=C\COc1cc(F)ccc1-c1cccc-2c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OC/C=C\COc1cc(F)ccc1-c1cccc-2c1 FDYCUPDVCNRFJG-DWDLGBGNSA-N 0.000 description 1
- HHYGFZYPSBMWPC-XIFFEERXSA-N CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OCCCCCCc(cccc1)c1-c1cccc-2c1 Chemical compound CC(C)(C)O[C@H](C(O)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)OCCCCCCc(cccc1)c1-c1cccc-2c1 HHYGFZYPSBMWPC-XIFFEERXSA-N 0.000 description 1
- QNHCUEYHMKHFHZ-WRAWZCCESA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCC[C@H]4CCCCOc3c-4cccc3)[n]1nc2-c1cc-4ccc1 Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(cc3)cc4c3OCC[C@H]4CCCCOc3c-4cccc3)[n]1nc2-c1cc-4ccc1 QNHCUEYHMKHFHZ-WRAWZCCESA-N 0.000 description 1
- JYNLTIMPMCALEO-KDXMTYKHSA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(cc3F)cc4c3OCCN4CC=C)[n]1nc2-c1cc(-c2ccccc2CCC=C)ccc1 Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(cc3F)cc4c3OCCN4CC=C)[n]1nc2-c1cc(-c2ccccc2CCC=C)ccc1 JYNLTIMPMCALEO-KDXMTYKHSA-N 0.000 description 1
- CIMJQPBNDCRELB-QNGWXLTQSA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(ccc(OCC3)c4N3CCCCCc3c-5cccc3)c4Cl)[n]1nc2-c1cccc-5c1 Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(ccc(OCC3)c4N3CCCCCc3c-5cccc3)c4Cl)[n]1nc2-c1cccc-5c1 CIMJQPBNDCRELB-QNGWXLTQSA-N 0.000 description 1
- CKRRIEUUIBQCNL-KDXMTYKHSA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(ccc3c4N(CC=C)CCO3)c4Cl)[n]1nc2-c1cc(-c2c(CCC=C)cccc2)ccc1 Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1c2)c(-c(ccc3c4N(CC=C)CCO3)c4Cl)[n]1nc2-c1cc(-c2c(CCC=C)cccc2)ccc1 CKRRIEUUIBQCNL-KDXMTYKHSA-N 0.000 description 1
- CXAIOJIHWSUYRD-HKBQPEDESA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3cc(C(F)(F)F)ccc3O)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3cc(C(F)(F)F)ccc3O)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C CXAIOJIHWSUYRD-HKBQPEDESA-N 0.000 description 1
- ZMQKAUYNBOXCLB-HKBQPEDESA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3cc(F)ccc3O)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3cc(F)ccc3O)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C ZMQKAUYNBOXCLB-HKBQPEDESA-N 0.000 description 1
- ANZHLIBXPHAHPQ-DHUJRADRSA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3ccccc3CCC=C)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(-c2cc(-c3ccccc3CCC=C)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C ANZHLIBXPHAHPQ-DHUJRADRSA-N 0.000 description 1
- KJZQWAFSLAGCOA-IBGZPJMESA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(Br)n[n]11)c1N(CC1)CCC1(C)OCC=C Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc(Br)n[n]11)c1N(CC1)CCC1(C)OCC=C KJZQWAFSLAGCOA-IBGZPJMESA-N 0.000 description 1
- QYRFWBZEHOWGKT-KAWHJGIGSA-N CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)/C=C/C=C\CCc1ccccc1-c1cc-2ccc1 Chemical compound CC(C)(C)O[C@H](C(OC)=O)c(c(C)nc1cc-2n[n]11)c1N(CC1)CCC1(C)/C=C/C=C\CCc1ccccc1-c1cc-2ccc1 QYRFWBZEHOWGKT-KAWHJGIGSA-N 0.000 description 1
- FCEPMBPRKFZEKD-DXSDROHOSA-N CC(CCCOC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)C(C)Oc1ccc(C)cc1-c1cc-3ccc1 Chemical compound CC(CCCOC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)C(C)Oc1ccc(C)cc1-c1cc-3ccc1 FCEPMBPRKFZEKD-DXSDROHOSA-N 0.000 description 1
- NKCVBHONPVHXDT-YRJBOYOSSA-N CC(COc1ccc(C)cc1-c1cccc(-c2n[n]3c(N(CC4)CCC4(C)OCC=C)c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc3c2)c1)C=C Chemical compound CC(COc1ccc(C)cc1-c1cccc(-c2n[n]3c(N(CC4)CCC4(C)OCC=C)c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc3c2)c1)C=C NKCVBHONPVHXDT-YRJBOYOSSA-N 0.000 description 1
- DFPPNLPOFAEHAZ-UHFFFAOYSA-N CCOC(Cc(c(C)nc1cc(-c2cc(Br)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C)=O Chemical compound CCOC(Cc(c(C)nc1cc(-c2cc(Br)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C)=O DFPPNLPOFAEHAZ-UHFFFAOYSA-N 0.000 description 1
- SICQPUFMIOCNMK-PDTOWJBFSA-N CCOC([C@H](c(c(C)nc1cc(-c2cc(-c3cc(C)ccc3OC(C)C(C)C=C)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C)OC(C)(C)C)=O Chemical compound CCOC([C@H](c(c(C)nc1cc(-c2cc(-c3cc(C)ccc3OC(C)C(C)C=C)ccc2)n[n]11)c1N(CC1)CCC1(C)OCC=C)OC(C)(C)C)=O SICQPUFMIOCNMK-PDTOWJBFSA-N 0.000 description 1
- RPBJAKCLYAXHCN-GGOOWQFJSA-N C[C@@H](C/C=C/COC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)Oc1ccc(C)c(F)c1-c1cccc-3c1 Chemical compound C[C@@H](C/C=C/COC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)Oc1ccc(C)c(F)c1-c1cccc-3c1 RPBJAKCLYAXHCN-GGOOWQFJSA-N 0.000 description 1
- PGELZYLOKZTIHE-DCUOSEHISA-N C[C@@H](C/C=C/COC(C)(CC1)CCN1c1c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc2cc(-c(cc3)c4)n[n]12)Oc1cccc(F)c1-c4c3F Chemical compound C[C@@H](C/C=C/COC(C)(CC1)CCN1c1c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc2cc(-c(cc3)c4)n[n]12)Oc1cccc(F)c1-c4c3F PGELZYLOKZTIHE-DCUOSEHISA-N 0.000 description 1
- GJCWZPJFVGAMNS-VIFPVBQESA-N C[C@@H](CC=C)Oc(c(Br)c1)cc(C)c1Cl Chemical compound C[C@@H](CC=C)Oc(c(Br)c1)cc(C)c1Cl GJCWZPJFVGAMNS-VIFPVBQESA-N 0.000 description 1
- FEJWZQLPRLZQNX-QMMMGPOBSA-N C[C@@H](CC=C)Oc(c(Br)c1C)ccc1Cl Chemical compound C[C@@H](CC=C)Oc(c(Br)c1C)ccc1Cl FEJWZQLPRLZQNX-QMMMGPOBSA-N 0.000 description 1
- DYCNCGVXEHGTAA-ZSQPVGNWSA-N C[C@@H](CC=C)Oc1cc(Cl)c(C)cc1-c1cccc(-c2n[n]3c(N(CC4)CCC4(C)OCC=C)c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc3c2)c1 Chemical compound C[C@@H](CC=C)Oc1cc(Cl)c(C)cc1-c1cccc(-c2n[n]3c(N(CC4)CCC4(C)OCC=C)c([C@@H](C(OC)=O)OC(C)(C)C)c(C)nc3c2)c1 DYCNCGVXEHGTAA-ZSQPVGNWSA-N 0.000 description 1
- ZOAZWXJCQSBOOU-UGDMGKLASA-N C[C@@H](CN(C)COC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)Oc1ccncc1-c1cc-3ccc1 Chemical compound C[C@@H](CN(C)COC(C)(CC1)CCN1c1c([C@@H](C(O)=O)OC(C)(C)C)c(C)nc2cc-3n[n]12)Oc1ccncc1-c1cc-3ccc1 ZOAZWXJCQSBOOU-UGDMGKLASA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- QXEAJQCJNALRFF-UHFFFAOYSA-N Cc(ccc(Br)c1)c1-c(c(O)ccc1)c1Cl Chemical compound Cc(ccc(Br)c1)c1-c(c(O)ccc1)c1Cl QXEAJQCJNALRFF-UHFFFAOYSA-N 0.000 description 1
- SRXDMAZDSKZYNV-UHFFFAOYSA-N Cc1nc2cc(-c3cccc(Br)c3)n[n]2c(O)c1CC(OC)=O Chemical compound Cc1nc2cc(-c3cccc(Br)c3)n[n]2c(O)c1CC(OC)=O SRXDMAZDSKZYNV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 238000003686 Davis oxidations reaction Methods 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061217 Infestation Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001139947 Mida Species 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000011225 antiretroviral therapy Methods 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- FCDPQMAOJARMTG-UHFFFAOYSA-M benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphanium Chemical compound C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-M 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 238000001023 centrifugal evaporation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- XREKLQOUFWBSFH-UHFFFAOYSA-N dimethyl 2-acetylbutanedioate Chemical compound COC(=O)CC(C(C)=O)C(=O)OC XREKLQOUFWBSFH-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FAMRKDQNMBBFBR-FPLPWBNLSA-N ethyl (nz)-n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)\N=N/C(=O)OCC FAMRKDQNMBBFBR-FPLPWBNLSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- PYGWGZALEOIKDF-UHFFFAOYSA-N etravirine Chemical compound CC1=CC(C#N)=CC(C)=C1OC1=NC(NC=2C=CC(=CC=2)C#N)=NC(N)=C1Br PYGWGZALEOIKDF-UHFFFAOYSA-N 0.000 description 1
- 229960002049 etravirine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- WCKWXPBDKSOVOK-UHFFFAOYSA-H hexachlororuthenium Chemical compound Cl[Ru](Cl)(Cl)(Cl)(Cl)Cl WCKWXPBDKSOVOK-UHFFFAOYSA-H 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229940111682 isentress Drugs 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HDXFCMFLXFGXEI-AWEZNQCLSA-N methyl (2s)-2-[2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl]-2-hydroxyacetate Chemical compound N=1N2C(Cl)=C([C@H](O)C(=O)OC)C(C)=NC2=CC=1C1=CC=CC(Br)=C1 HDXFCMFLXFGXEI-AWEZNQCLSA-N 0.000 description 1
- LXLAYZCOPUSIAB-AWEZNQCLSA-N methyl (2s)-2-[2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl]-2-hydroxyacetate Chemical compound N=1N2C(I)=C([C@H](O)C(=O)OC)C(C)=NC2=CC=1C1=CC=CC(Br)=C1 LXLAYZCOPUSIAB-AWEZNQCLSA-N 0.000 description 1
- QTTIYELOTIEZCH-UHFFFAOYSA-N methyl 2-(2-bromo-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate Chemical compound ClC1=C(CC(=O)OC)C(C)=NC2=CC(Br)=NN21 QTTIYELOTIEZCH-UHFFFAOYSA-N 0.000 description 1
- KMFJVYMFCAIRAN-UHFFFAOYSA-N methyl 3-bromobenzoate Chemical compound COC(=O)C1=CC=CC(Br)=C1 KMFJVYMFCAIRAN-UHFFFAOYSA-N 0.000 description 1
- YKFLJYAKACCWMH-UHFFFAOYSA-N methyl piperidine-1-carboxylate Chemical compound COC(=O)N1CCCCC1 YKFLJYAKACCWMH-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 108700004028 nef Genes Proteins 0.000 description 1
- 101150023385 nef gene Proteins 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- IRGRIOBZXRVYSW-UHFFFAOYSA-N tert-butyl 4-methyl-4-(prop-2-enoxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(COCC=C)CC1 IRGRIOBZXRVYSW-UHFFFAOYSA-N 0.000 description 1
- ZTVMKAWYUKNADP-UHFFFAOYSA-N tert-butyl 4-methyl-4-prop-2-enoxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(OCC=C)CC1 ZTVMKAWYUKNADP-UHFFFAOYSA-N 0.000 description 1
- SWAXTRYEYUTSAP-UHFFFAOYSA-N tert-butyl ethaneperoxoate Chemical compound CC(=O)OOC(C)(C)C SWAXTRYEYUTSAP-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/16—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261683772P | 2012-08-16 | 2012-08-16 | |
| US61/683,772 | 2012-08-16 | ||
| US201361818572P | 2013-05-02 | 2013-05-02 | |
| US61/818,572 | 2013-05-02 | ||
| US13/959,268 | 2013-08-05 | ||
| US13/959,268 US8906929B2 (en) | 2012-08-16 | 2013-08-05 | Inhibitors of human immunodeficiency virus replication |
| PCT/US2013/054532 WO2014028384A1 (en) | 2012-08-16 | 2013-08-12 | Inhibitors of human immunodeficiency virus replication |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20150042830A true KR20150042830A (ko) | 2015-04-21 |
Family
ID=50100460
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR20157006290A Withdrawn KR20150042830A (ko) | 2012-08-16 | 2013-08-12 | 인간 면역결핍 바이러스 복제의 억제제 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8906929B2 (https=) |
| EP (1) | EP2888266B1 (https=) |
| JP (1) | JP6214657B2 (https=) |
| KR (1) | KR20150042830A (https=) |
| CN (1) | CN104583214B (https=) |
| AU (1) | AU2013302873B2 (https=) |
| BR (1) | BR112015003175A2 (https=) |
| CA (1) | CA2882077A1 (https=) |
| EA (1) | EA201590358A1 (https=) |
| ES (1) | ES2619960T3 (https=) |
| IL (1) | IL237154A (https=) |
| MX (1) | MX2015001899A (https=) |
| SG (1) | SG11201500887QA (https=) |
| TW (1) | TW201412750A (https=) |
| WO (1) | WO2014028384A1 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP2013006706A0 (en) | 2010-07-02 | 2013-02-28 | Gilead Sciences Inc | Napht-2-ylacetic acid derivatives to treat AIDS |
| KR20130124291A (ko) | 2010-07-02 | 2013-11-13 | 길리애드 사이언시즈, 인코포레이티드 | Ｈｉｖ 항바이러스 화합물로서의 2-퀴놀리닐-아세트산 유도체 |
| BR112013027096A2 (pt) | 2011-04-21 | 2016-12-27 | Gilead Sciences Inc | compostos de benzotiazol e seu uso farmacêutico |
| WO2013103724A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | 2- (tert - butoxy) -2- (7 -methylquinolin- 6 - yl) acetic acid derivatives for treating aids |
| US9284323B2 (en) | 2012-01-04 | 2016-03-15 | Gilead Sciences, Inc. | Naphthalene acetic acid derivatives against HIV infection |
| ES2571479T3 (es) | 2012-04-20 | 2016-05-25 | Gilead Sciences Inc | Derivados del ácido benzotiazol-6-il acético y su uso para tratar una infección por VIH |
| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| JP2016516692A (ja) * | 2013-03-13 | 2016-06-09 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ヒト免疫不全ウイルス複製の阻害剤 |
| JP6268656B2 (ja) * | 2013-03-14 | 2018-01-31 | ビーブ・ヘルスケア・ユーケイ・（ナンバー５）・リミテッドＶｉｉＶ Ｈｅａｌｔｈｃａｒｅ ＵＫ （Ｎｏ．５） Ｌｉｍｉｔｅｄ | ヒト免疫不全ウイルス複製の阻害剤 |
| EP3152211A1 (en) | 2014-02-12 | 2017-04-12 | ViiV Healthcare UK (No.5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015123230A1 (en) | 2014-02-12 | 2015-08-20 | Bristol-Myers Squibb Company | Benzothiazole macrocycles as inhibitors of human immunodeficiency virus replication |
| US9834566B2 (en) * | 2014-02-18 | 2017-12-05 | VIIV Healthcare UK (No.5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9932353B2 (en) * | 2014-02-18 | 2018-04-03 | Viiv Healthcare Uk (No. 5) Limited | Imidazopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9409922B2 (en) * | 2014-02-18 | 2016-08-09 | Bristol-Myers Squibb Company | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9273067B2 (en) | 2014-02-19 | 2016-03-01 | Bristol-Myers Squibb Company | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| PT3107917T (pt) * | 2014-02-19 | 2018-11-13 | Viiv Healthcare Uk No 5 Ltd | Macrociclos de pirazolopirimidina como inibidores da replicação do vírus da imunodeficiência humana |
| ES2687322T3 (es) | 2014-02-19 | 2018-10-24 | VIIV Healthcare UK (No.5) Limited | Inhibidores de la replicación del virus de inmunodeficiencia humana |
| PT3116880T (pt) | 2014-02-20 | 2018-05-10 | Viiv Healthcare Uk No 5 Ltd | Macrociclos de ácido piridin-3-il acético como inibidores da replicação do vírus da imunodeficiência humana |
| EP3144311A4 (en) * | 2014-05-16 | 2018-01-03 | Shionogi & Co., Ltd. | Tricyclic heterocyclic derivative having hiv replication-inhibiting effect |
| MX2017015256A (es) | 2015-05-29 | 2018-02-19 | Shionogi & Co | Derivados triciclicos que contienen nitrogeno que tienen actividad inhibidora de la replicacion del virus de inmunodeficiencia adquirida (vih). |
| AU2016305338A1 (en) * | 2015-08-10 | 2018-03-01 | VIIV Healthcare UK (No.5) Limited | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| JP7164542B2 (ja) | 2017-04-06 | 2022-11-01 | インベンティバ | 新規な化合物であるｙａｐ／ｔａｚ－ｔｅａｄ相互作用阻害剤、および悪性中皮腫の治療でのその使用 |
| EP3632908A1 (en) | 2018-10-02 | 2020-04-08 | Inventiva | Inhibitors of the yap/taz-tead interaction and their use in the treatment of cancer |
| WO2020197991A1 (en) | 2019-03-22 | 2020-10-01 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and their pharmaceutical use |
| IL295677B1 (en) | 2020-02-24 | 2026-04-01 | Gilead Sciences Inc | Tetracyclic compounds for the treatment of HIV infection |
| CA3192145A1 (en) | 2020-09-30 | 2022-04-07 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| FI4196479T3 (fi) | 2021-01-19 | 2024-01-17 | Gilead Sciences Inc | Substituoituja pyridotriatsiiniyhdisteitä ja niiden käyttöjä |
| TWI856796B (zh) | 2022-04-06 | 2024-09-21 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB427857A (en) | 1934-08-02 | 1935-05-01 | Newsum Sons & Company Ltd H | A new or improved system of construction for skeleton structures, particularly vehicle body frames and door frames |
| US7939545B2 (en) | 2006-05-16 | 2011-05-10 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| AU2008323561B2 (en) * | 2007-11-15 | 2013-07-18 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| CA2705318C (en) | 2007-11-15 | 2013-12-31 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| MX2010005334A (es) | 2007-11-16 | 2010-05-27 | Boehringer Ingelheim Int | Inhibidores de la replicacion del virus de la inmunodeficiencia humana. |
| JP5269087B2 (ja) | 2007-11-16 | 2013-08-21 | ギリアード サイエンシス インコーポレーテッド | ヒト免疫不全ウイルス複製のインヒビター |
| EP2215298B1 (en) | 2007-11-23 | 2014-03-26 | Koninklijke Philips N.V. | Compartment |
| TW200942243A (en) * | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
| US8129398B2 (en) * | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| GB0813980D0 (en) | 2008-07-31 | 2008-09-10 | Univ St Andrews | Control of relaxation oscillations in intracavity optical parametric oscillato rs |
| JP5331404B2 (ja) | 2008-08-01 | 2013-10-30 | 国立大学法人 東京医科歯科大学 | 先天性異常症の染色体欠失の検出方法 |
| US8338441B2 (en) * | 2009-05-15 | 2012-12-25 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
| EP2491033A4 (en) * | 2009-10-20 | 2013-03-13 | Eiger Biopharmaceuticals Inc | AZAINDAZOLES FOR THE TREATMENT OF FLAVIVIRIDAE VIRUS INFECTION |
| SG10201408512RA (en) | 2009-12-23 | 2015-02-27 | Univ Leuven Kath | Novel antiviral compounds |
| RU2567385C2 (ru) * | 2010-04-02 | 2015-11-10 | ЯНССЕН Ар ЭНД Ди АЙРЛЭНД | Макроциклические ингибиторы интегразы |
| AP2013006706A0 (en) | 2010-07-02 | 2013-02-28 | Gilead Sciences Inc | Napht-2-ylacetic acid derivatives to treat AIDS |
| KR20130124291A (ko) | 2010-07-02 | 2013-11-13 | 길리애드 사이언시즈, 인코포레이티드 | Ｈｉｖ 항바이러스 화합물로서의 2-퀴놀리닐-아세트산 유도체 |
| US8633200B2 (en) | 2010-09-08 | 2014-01-21 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| WO2012066442A1 (en) | 2010-11-15 | 2012-05-24 | Pfizer Limited | Inhibitors of hiv replication |
| JP2013542243A (ja) | 2010-11-15 | 2013-11-21 | カトリーケ ウニヴェルシテイト ルーヴェン | 新規な抗ウイルス性化合物 |
| US8791108B2 (en) | 2011-08-18 | 2014-07-29 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US8629276B2 (en) | 2012-02-15 | 2014-01-14 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US9034882B2 (en) | 2012-03-05 | 2015-05-19 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US9006235B2 (en) | 2012-03-06 | 2015-04-14 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
-
2013
- 2013-08-05 US US13/959,268 patent/US8906929B2/en not_active Expired - Fee Related
- 2013-08-12 CA CA2882077A patent/CA2882077A1/en active Pending
- 2013-08-12 KR KR20157006290A patent/KR20150042830A/ko not_active Withdrawn
- 2013-08-12 MX MX2015001899A patent/MX2015001899A/es unknown
- 2013-08-12 EP EP13750479.1A patent/EP2888266B1/en not_active Not-in-force
- 2013-08-12 BR BR112015003175A patent/BR112015003175A2/pt active Search and Examination
- 2013-08-12 CN CN201380043596.7A patent/CN104583214B/zh not_active Expired - Fee Related
- 2013-08-12 SG SG11201500887QA patent/SG11201500887QA/en unknown
- 2013-08-12 AU AU2013302873A patent/AU2013302873B2/en not_active Ceased
- 2013-08-12 WO PCT/US2013/054532 patent/WO2014028384A1/en not_active Ceased
- 2013-08-12 ES ES13750479.1T patent/ES2619960T3/es active Active
- 2013-08-12 JP JP2015527515A patent/JP6214657B2/ja not_active Expired - Fee Related
- 2013-08-12 EA EA201590358A patent/EA201590358A1/ru unknown
- 2013-08-15 TW TW102129364A patent/TW201412750A/zh unknown
-
2015
- 2015-02-09 IL IL237154A patent/IL237154A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014028384A1 (en) | 2014-02-20 |
| TW201412750A (zh) | 2014-04-01 |
| EA201590358A1 (ru) | 2015-05-29 |
| JP2015524841A (ja) | 2015-08-27 |
| EP2888266B1 (en) | 2017-01-11 |
| MX2015001899A (es) | 2015-05-07 |
| AU2013302873A1 (en) | 2015-04-02 |
| US8906929B2 (en) | 2014-12-09 |
| ES2619960T3 (es) | 2017-06-27 |
| CN104583214A (zh) | 2015-04-29 |
| IL237154A0 (en) | 2015-04-30 |
| EP2888266A1 (en) | 2015-07-01 |
| BR112015003175A2 (pt) | 2017-08-08 |
| CA2882077A1 (en) | 2014-02-20 |
| AU2013302873B2 (en) | 2017-02-02 |
| JP6214657B2 (ja) | 2017-10-18 |
| IL237154A (en) | 2017-03-30 |
| CN104583214B (zh) | 2017-06-09 |
| SG11201500887QA (en) | 2015-03-30 |
| US20140051692A1 (en) | 2014-02-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20150042830A (ko) | 인간 면역결핍 바이러스 복제의 억제제 | |
| CN105189503B (zh) | 人免疫缺陷病毒复制的抑制剂 | |
| CN105189511B (zh) | 人免疫缺陷病毒复制的抑制剂 | |
| AU2013213474B2 (en) | New indolizine derivatives, method for preparing same and pharmaceutical compositions containing same | |
| CA3141748A1 (en) | Prmt5 inhibitors | |
| CN105189510B (zh) | 人免疫缺陷病毒复制的抑制剂 | |
| EP2953456B1 (en) | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c | |
| EP2953462B1 (en) | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c | |
| WO2016168641A1 (en) | Tricyclic modulators of tnf signaling | |
| KR20170045308A (ko) | 인간 면역결핍 바이러스 복제의 억제제로서 이미다조[1,2-a]피리딘 유도체 | |
| KR20180035916A (ko) | 인간 면역결핍 바이러스 복제의 억제제로서 5-(n-융합된 트리사이클릭 아릴 테트라하이드로이소퀴놀린-6-일) 피리딘-3-일 아세트산 유도체 | |
| KR20180032649A (ko) | 인간 면역결핍 바이러스 복제의 억제제로서 5-(n-벤질 테트라하이드로이소퀴놀린-6-일)피리딘-3-일 아세트산 유도체 | |
| WO2024031089A1 (en) | Sars-cov2 main protease inhibitors | |
| US20130184273A1 (en) | Bicyclic pyrimidines | |
| EP2953461B1 (en) | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c | |
| KR20180038047A (ko) | 인간 면역결핍 바이러스 복제의 억제제로서 피리딘-3-일 아세트산 유도체 | |
| JP2018519348A (ja) | ヒト免疫不全ウイルス複製の阻害剤としてのピリジン−３−イル酢酸誘導体 | |
| WO2025240835A2 (en) | Jak2 inhibitors and their use as pharmaceuticals | |
| KR20180035908A (ko) | 인간 면역결핍 바이러스 복제의 억제제로서의 이미다조피리딘 매크로사이클 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20150311 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20171220 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |