JP4762917B2 - 非ヌクレオシド逆転写酵素インヒビター - Google Patents
非ヌクレオシド逆転写酵素インヒビター Download PDFInfo
- Publication number
- JP4762917B2 JP4762917B2 JP2006549182A JP2006549182A JP4762917B2 JP 4762917 B2 JP4762917 B2 JP 4762917B2 JP 2006549182 A JP2006549182 A JP 2006549182A JP 2006549182 A JP2006549182 A JP 2006549182A JP 4762917 B2 JP4762917 B2 JP 4762917B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- compound
- mmol
- cis
- difluoro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 title description 3
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000001424 substituent group Chemical group 0.000 claims abstract description 18
- 239000003443 antiviral agent Substances 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims abstract 5
- -1 C 1 -C 4 -alkyl Chemical group 0.000 claims description 115
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 97
- 239000000203 mixture Substances 0.000 claims description 96
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 47
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 26
- 239000004202 carbamide Substances 0.000 claims description 23
- 229940079593 drug Drugs 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims description 5
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000468 ketone group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 3
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 3
- 229930194542 Keto Natural products 0.000 claims 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 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 229960000311 ritonavir Drugs 0.000 claims description 3
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical group 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 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 5
- 230000002265 prevention Effects 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 11
- 239000000651 prodrug Substances 0.000 abstract description 5
- 229940002612 prodrug Drugs 0.000 abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 229940121357 antivirals Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
- 239000011541 reaction mixture Substances 0.000 description 93
- 238000005160 1H NMR spectroscopy Methods 0.000 description 91
- 239000000243 solution Substances 0.000 description 67
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- 239000000047 product Substances 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- 238000000746 purification Methods 0.000 description 40
- 238000010898 silica gel chromatography Methods 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 37
- 229910002027 silica gel Inorganic materials 0.000 description 37
- 239000012267 brine Substances 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 239000012043 crude product Substances 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 27
- 238000004440 column chromatography Methods 0.000 description 27
- 239000002904 solvent Substances 0.000 description 26
- 239000002253 acid Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 17
- 235000002639 sodium chloride Nutrition 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- XCTLDQQOHIEUCJ-UHFFFAOYSA-N ethyl naphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=CC=CC2=C1 XCTLDQQOHIEUCJ-UHFFFAOYSA-N 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 238000002390 rotary evaporation Methods 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 13
- KECCFSZFXLAGJS-UHFFFAOYSA-N 4-methylsulfonylphenol Chemical compound CS(=O)(=O)C1=CC=C(O)C=C1 KECCFSZFXLAGJS-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
- ZCQSJUGIZGMDDA-UHFFFAOYSA-N 4-(methylsulfinyl)phenol Chemical compound CS(=O)C1=CC=C(O)C=C1 ZCQSJUGIZGMDDA-UHFFFAOYSA-N 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- 239000006227 byproduct Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000010948 rhodium Substances 0.000 description 7
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 7
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 7
- BZENWVMGGHIOMD-UHFFFAOYSA-N 1-(1,1a,2,7b-tetrahydrocyclopropa[c]quinolin-3-yl)ethanone Chemical compound C12=CC=CC=C2N(C(=O)C)CC2C1C2 BZENWVMGGHIOMD-UHFFFAOYSA-N 0.000 description 6
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 6
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 6
- ATXXLNCPVSUCNK-UHFFFAOYSA-N 5-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)C=N1 ATXXLNCPVSUCNK-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- IDJURXRPTLNZPD-BTZDVCGTSA-N (1s,1ar,7bs)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylic acid Chemical compound C1=CC(F)=C2[C@@H]3[C@H](C(=O)O)[C@@H]3COC2=C1F IDJURXRPTLNZPD-BTZDVCGTSA-N 0.000 description 5
- 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 5
- KGWYICAEPBCRBL-UHFFFAOYSA-N 1h-indene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)C=CC2=C1 KGWYICAEPBCRBL-UHFFFAOYSA-N 0.000 description 5
- ZEYLXIHOEHPVAB-UHFFFAOYSA-N 2,6-difluoro-6-prop-1-ynoxycyclohexa-1,3-diene Chemical compound CC#COC1(F)CC=CC(F)=C1 ZEYLXIHOEHPVAB-UHFFFAOYSA-N 0.000 description 5
- QEVFHSARMKZJDY-UHFFFAOYSA-N 5,8-difluoro-2h-chromene Chemical compound C1=CCOC2=C1C(F)=CC=C2F QEVFHSARMKZJDY-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 5
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 4
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
- LVALADFZKPREEF-UHFFFAOYSA-N 5-(4-methylsulfinylphenoxy)pyridin-2-amine Chemical compound C1=CC(S(=O)C)=CC=C1OC1=CC=C(N)N=C1 LVALADFZKPREEF-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- ICSNLGPSRYBMBD-UHFFFAOYSA-N alpha-aminopyridine Natural products NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 4
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- CZYYUYKNPZPCTM-UHFFFAOYSA-N ethyl bicyclo[5.1.0]octa-1(8),2,4,6-tetraene-8-carboxylate Chemical compound C(C)OC(=O)C1=C2C=CC=CC=C21 CZYYUYKNPZPCTM-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 150000002513 isocyanates Chemical class 0.000 description 4
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- YMMQXTBDFCTCJR-HFHMMWAZSA-N (1s,5r,6s)-6-(3,6-difluoro-2-methoxyphenyl)-3-oxabicyclo[3.1.0]hexan-2-one Chemical compound COC1=C(F)C=CC(F)=C1[C@@H]1[C@@H]2C(=O)OC[C@@H]21 YMMQXTBDFCTCJR-HFHMMWAZSA-N 0.000 description 3
- DNWYKNASZCPJOV-UHFFFAOYSA-N 1-(5-fluoro-2h-chromen-8-yl)propan-1-one Chemical compound C1=CCOC2=C1C(F)=CC=C2C(=O)CC DNWYKNASZCPJOV-UHFFFAOYSA-N 0.000 description 3
- LIXUXJLQOIEJKH-UHFFFAOYSA-N 1-bromo-4-fluoro-2-prop-2-ynoxybenzene Chemical compound FC1=CC=C(Br)C(OCC#C)=C1 LIXUXJLQOIEJKH-UHFFFAOYSA-N 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 3
- 150000003930 2-aminopyridines Chemical class 0.000 description 3
- NKDGIXACNXVWNY-UHFFFAOYSA-N 2-bromo-4-fluoro-1-prop-2-ynoxybenzene Chemical compound FC1=CC=C(OCC#C)C(Br)=C1 NKDGIXACNXVWNY-UHFFFAOYSA-N 0.000 description 3
- ONJRTQUWKRDCTA-UHFFFAOYSA-N 2h-thiochromene Chemical compound C1=CC=C2C=CCSC2=C1 ONJRTQUWKRDCTA-UHFFFAOYSA-N 0.000 description 3
- LDHQXNMFGYGNJT-UHFFFAOYSA-N 4,7-difluoro-1h-indene Chemical compound FC1=CC=C(F)C2=C1CC=C2 LDHQXNMFGYGNJT-UHFFFAOYSA-N 0.000 description 3
- KMWBFTTYYGUTNW-UHFFFAOYSA-N 4,7-difluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C(F)C2=C1CCC2=O KMWBFTTYYGUTNW-UHFFFAOYSA-N 0.000 description 3
- VPUZXEGGNFLNNF-UHFFFAOYSA-N 4,7-difluoro-3-methyl-2,3-dihydroinden-1-one Chemical compound FC1=CC=C(F)C2=C1C(C)CC2=O VPUZXEGGNFLNNF-UHFFFAOYSA-N 0.000 description 3
- LYMZQWUSRTUPQW-UHFFFAOYSA-N 4-(6-nitropyridin-3-yl)oxybenzamide Chemical compound C1=CC(C(=O)N)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 LYMZQWUSRTUPQW-UHFFFAOYSA-N 0.000 description 3
- ZQIGXNJXZYUGQI-JWNTYJGQSA-N 4-[6-[[(1s,1as,7bs)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxy-n-cyclopropylbenzamide Chemical compound N([C@@H]1[C@@H]2[C@H]1C=1C(F)=CC=C(C=1OC2)F)C(=O)NC(N=C1)=CC=C1OC(C=C1)=CC=C1C(=O)NC1CC1 ZQIGXNJXZYUGQI-JWNTYJGQSA-N 0.000 description 3
- ADVSYXVAHLSDOY-JKFKMHIGSA-N 4-[6-[[(1s,1as,7bs)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxy-n-morpholin-4-ylbenzamide Chemical compound N([C@@H]1[C@@H]2[C@H]1C=1C(F)=CC=C(C=1OC2)F)C(=O)NC(N=C1)=CC=C1OC(C=C1)=CC=C1C(=O)NN1CCOCC1 ADVSYXVAHLSDOY-JKFKMHIGSA-N 0.000 description 3
- OMSOZMDPJCEEDR-UHFFFAOYSA-N 5,8-difluoro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=C1C(F)=CC=C2F OMSOZMDPJCEEDR-UHFFFAOYSA-N 0.000 description 3
- UYKLYBZOLIDIJN-UHFFFAOYSA-N 5-(4-methylsulfinylphenoxy)-2-nitropyridine Chemical compound C1=CC(S(=O)C)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 UYKLYBZOLIDIJN-UHFFFAOYSA-N 0.000 description 3
- BIRDZFUEYJFWNV-UHFFFAOYSA-N 6-bromo-1h-indene Chemical compound BrC1=CC=C2C=CCC2=C1 BIRDZFUEYJFWNV-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 150000005215 alkyl ethers Chemical class 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- VDMVKJJFBDTKBO-UHFFFAOYSA-N bicyclo[5.1.0]octa-1(8),2,4,6-tetraene-8-carboxylic acid Chemical compound C1(=C2C=CC=CC=C21)C(=O)O VDMVKJJFBDTKBO-UHFFFAOYSA-N 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- XDYQDLVZJKAJBM-UHFFFAOYSA-N ethyl 1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound C1=CC=C2C3C(C(=O)OCC)C3CCC2=C1 XDYQDLVZJKAJBM-UHFFFAOYSA-N 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- ORANYXMBYVUFGD-UHFFFAOYSA-N tert-butyl n-[(4-hydroxybenzoyl)amino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)C1=CC=C(O)C=C1 ORANYXMBYVUFGD-UHFFFAOYSA-N 0.000 description 3
- VXUMQTIYRXHDCM-UHFFFAOYSA-N tert-butyl n-[(4-phenylmethoxybenzoyl)amino]carbamate Chemical compound C1=CC(C(=O)NNC(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC=C1 VXUMQTIYRXHDCM-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- MPBBYVVHPSVLBY-UHFFFAOYSA-N (4-formyl-3-hydroxyphenyl) trifluoromethanesulfonate Chemical compound OC1=CC(OS(=O)(=O)C(F)(F)F)=CC=C1C=O MPBBYVVHPSVLBY-UHFFFAOYSA-N 0.000 description 2
- KJPUDCIRLXJKDX-IHWYPQMZSA-N (z)-3-(3,6-difluoro-2-methoxyphenyl)prop-2-en-1-ol Chemical compound COC1=C(F)C=CC(F)=C1\C=C/CO KJPUDCIRLXJKDX-IHWYPQMZSA-N 0.000 description 2
- ZOFTWFDLBJRYJI-UHFFFAOYSA-N 1,3-difluoro-5-prop-2-ynoxybenzene Chemical compound FC1=CC(F)=CC(OCC#C)=C1 ZOFTWFDLBJRYJI-UHFFFAOYSA-N 0.000 description 2
- JOXFVWGHNMYWMK-UHFFFAOYSA-N 1-(2-hydroxy-4-prop-2-ynoxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(OCC#C)C=C1O JOXFVWGHNMYWMK-UHFFFAOYSA-N 0.000 description 2
- VGEPKKUTRKZFEW-UHFFFAOYSA-N 1-(2h-quinolin-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CC=CC2=C1 VGEPKKUTRKZFEW-UHFFFAOYSA-N 0.000 description 2
- RGIUTOWSKBMSNP-UHFFFAOYSA-N 1-(4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl)-3-[5-(4-methylsulfinylphenoxy)pyridin-2-yl]urea Chemical compound C1=CC(S(=O)C)=CC=C1OC(C=N1)=CC=C1NC(=O)NC1C2C3=C(F)C=CC(F)=C3OCC21 RGIUTOWSKBMSNP-UHFFFAOYSA-N 0.000 description 2
- CPGYSXCJYFRARD-UHFFFAOYSA-N 1-(4-fluoro-2-prop-2-ynoxyphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(F)C=C1OCC#C CPGYSXCJYFRARD-UHFFFAOYSA-N 0.000 description 2
- QCELVCNDJKBEOC-UHFFFAOYSA-N 1-(5-hydroxy-2h-chromen-6-yl)ethanone Chemical compound O1CC=CC2=C(O)C(C(=O)C)=CC=C21 QCELVCNDJKBEOC-UHFFFAOYSA-N 0.000 description 2
- FLHOJYDOUKXBNH-UHFFFAOYSA-N 1-(5-hydroxy-2h-chromen-6-yl)propan-1-one Chemical compound O1CC=CC2=C(O)C(C(=O)CC)=CC=C21 FLHOJYDOUKXBNH-UHFFFAOYSA-N 0.000 description 2
- PFADTYFSNRIQSI-LXGCGDOSSA-N 1-[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-(4-aminophenoxy)pyridin-2-yl]urea Chemical compound C1=CC(N)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 PFADTYFSNRIQSI-LXGCGDOSSA-N 0.000 description 2
- SZNGTXICNFZNPI-BSLALVQMSA-N 1-[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-[4-(1,2,4-triazol-1-yl)phenoxy]pyridin-2-yl]urea Chemical compound N([C@@H]1[C@H]2[C@@H]1C=1C(F)=CC=C(C=1OC2)F)C(=O)NC(N=C1)=CC=C1OC(C=C1)=CC=C1N1C=NC=N1 SZNGTXICNFZNPI-BSLALVQMSA-N 0.000 description 2
- WRPPTQFLZZPOAY-BSLALVQMSA-N 1-[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-[4-(2-hydroxyethyl)phenoxy]pyridin-2-yl]urea Chemical compound C1=CC(CCO)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 WRPPTQFLZZPOAY-BSLALVQMSA-N 0.000 description 2
- RAGDKTDYPRMXMT-RZPHLTDDSA-N 1-[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-[4-[2-(2-methoxyethoxy)ethoxy]phenoxy]pyridin-2-yl]urea Chemical compound C1=CC(OCCOCCOC)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 RAGDKTDYPRMXMT-RZPHLTDDSA-N 0.000 description 2
- ZTEAVGODJINUKJ-ADLFWFRXSA-N 1-[(1s,1as,7bs)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-[4-(hydrazinecarbonyl)phenoxy]pyridin-2-yl]urea Chemical compound C1=CC(C(=O)NN)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@@H]2C3=C(F)C=CC(F)=C3OC[C@@H]21 ZTEAVGODJINUKJ-ADLFWFRXSA-N 0.000 description 2
- LKOKECONINHMQQ-UHFFFAOYSA-N 1-chloro-4-fluoro-2-prop-2-ynoxybenzene Chemical compound FC1=CC=C(Cl)C(OCC#C)=C1 LKOKECONINHMQQ-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- KZUMNNCSWYNQBY-UHFFFAOYSA-N 1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylic acid Chemical compound C1=CC=C2C3C(C(=O)O)C3CCC2=C1 KZUMNNCSWYNQBY-UHFFFAOYSA-N 0.000 description 2
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical compound OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 description 2
- WZUODJNEIXSNEU-UHFFFAOYSA-N 2-Hydroxy-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(O)=C1 WZUODJNEIXSNEU-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- OZRRJOKSPDLXJL-UHFFFAOYSA-N 2-[4-(6-aminopyridin-3-yl)oxyphenyl]ethanol Chemical compound C1=NC(N)=CC=C1OC1=CC=C(CCO)C=C1 OZRRJOKSPDLXJL-UHFFFAOYSA-N 0.000 description 2
- OSAUDWJMOWVVHZ-UHFFFAOYSA-N 2-[4-(6-nitropyridin-3-yl)oxyphenyl]ethanol Chemical compound C1=CC(CCO)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 OSAUDWJMOWVVHZ-UHFFFAOYSA-N 0.000 description 2
- SCBFBAWJWLXVHS-ZCFIWIBFSA-N 2-amino-9-[(2r)-4-hydroxy-2-(hydroxymethyl)butyl]-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N(C[C@H](CO)CCO)C=N2 SCBFBAWJWLXVHS-ZCFIWIBFSA-N 0.000 description 2
- RZPFVRFSYMUDJO-UHFFFAOYSA-N 2h-naphthalen-1-one Chemical compound C1=CC=C2C(=O)CC=CC2=C1 RZPFVRFSYMUDJO-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- VLNCFEDGTSGRLG-UHFFFAOYSA-N 4,7-difluoro-3-methyl-2,3-dihydro-1h-inden-1-ol Chemical compound FC1=CC=C(F)C2=C1C(C)CC2O VLNCFEDGTSGRLG-UHFFFAOYSA-N 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- RHZKUSUOPWINRE-UHFFFAOYSA-N 5,7-difluoro-2h-chromene Chemical compound C1=CCOC2=CC(F)=CC(F)=C21 RHZKUSUOPWINRE-UHFFFAOYSA-N 0.000 description 2
- RFUKKMRICUCHSX-UHFFFAOYSA-N 5-(6-nitropyridin-3-yl)oxypyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 RFUKKMRICUCHSX-UHFFFAOYSA-N 0.000 description 2
- OSRAVPSVVPUFCE-UHFFFAOYSA-N 5-[4-[2-(2-methoxyethoxy)ethoxy]phenoxy]-2-nitropyridine Chemical compound C1=CC(OCCOCCOC)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 OSRAVPSVVPUFCE-UHFFFAOYSA-N 0.000 description 2
- RZRFEASMYRJEMO-UHFFFAOYSA-N 5-[4-[2-(2-methoxyethoxy)ethoxy]phenoxy]pyridin-2-amine Chemical compound C1=CC(OCCOCCOC)=CC=C1OC1=CC=C(N)N=C1 RZRFEASMYRJEMO-UHFFFAOYSA-N 0.000 description 2
- MIDRBTSEQWIFIX-CFSSXQINSA-N 5-[6-[[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxy-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 MIDRBTSEQWIFIX-CFSSXQINSA-N 0.000 description 2
- KJMLESCAVJARPJ-QHLBDZCJSA-N 5-[6-[[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxypyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 KJMLESCAVJARPJ-QHLBDZCJSA-N 0.000 description 2
- OXYMXKWYYJNHHK-UHFFFAOYSA-N 5-fluoro-8-methoxy-2h-chromene Chemical compound C1=CCOC2=C1C(F)=CC=C2OC OXYMXKWYYJNHHK-UHFFFAOYSA-N 0.000 description 2
- ZHKPHJFAXZCKDQ-UHFFFAOYSA-N 6-fluoro-2-hydroxy-3-methoxybenzaldehyde Chemical compound COC1=CC=C(F)C(C=O)=C1O ZHKPHJFAXZCKDQ-UHFFFAOYSA-N 0.000 description 2
- JZVYKRTWKMZJMX-UHFFFAOYSA-N 6-fluoro-2h-chromene Chemical compound O1CC=CC2=CC(F)=CC=C21 JZVYKRTWKMZJMX-UHFFFAOYSA-N 0.000 description 2
- SUSHJFGCRWJSAQ-UHFFFAOYSA-N 6-methoxy-1,2-dihydronaphthalene Chemical compound C1CC=CC2=CC(OC)=CC=C21 SUSHJFGCRWJSAQ-UHFFFAOYSA-N 0.000 description 2
- GABLTKRIYDNDIN-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1CCC(=O)C2=CC(OC)=CC=C21 GABLTKRIYDNDIN-UHFFFAOYSA-N 0.000 description 2
- QMKXIHSGSUGVEE-UHFFFAOYSA-N 8-bromo-5-fluoro-2h-chromene Chemical compound O1CC=CC2=C1C(Br)=CC=C2F QMKXIHSGSUGVEE-UHFFFAOYSA-N 0.000 description 2
- WTMSWLPATMMPQX-UHFFFAOYSA-N 8-bromo-6-fluoro-2h-chromene Chemical compound O1CC=CC2=CC(F)=CC(Br)=C21 WTMSWLPATMMPQX-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- ACBSZTQIFTYFGH-IAPPQJPRSA-N [(2r)-4-[(2s)-2-amino-3-methylbutanoyl]oxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]butyl] octadecanoate Chemical compound N1C(N)=NC(=O)C2=C1N(C[C@@H](CCOC(=O)[C@@H](N)C(C)C)COC(=O)CCCCCCCCCCCCCCCCC)C=N2 ACBSZTQIFTYFGH-IAPPQJPRSA-N 0.000 description 2
- VPFQYWIBPWCYTN-IHWYPQMZSA-N [(Z)-3-(3,6-difluoro-2-methoxyphenyl)prop-2-enyl] 2-diazoacetate Chemical compound COC1=C(F)C=CC(F)=C1\C=C/COC(=O)C=[N+]=[N-] VPFQYWIBPWCYTN-IHWYPQMZSA-N 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- 150000003927 aminopyridines Chemical class 0.000 description 2
- 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 2
- 229960001830 amprenavir Drugs 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
- 229960003804 efavirenz Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- DFHYDTUCGWQFGL-UHFFFAOYSA-N ethyl 1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound C1=CC=CC2=C3C(C(=O)OCC)C3=CC=C21 DFHYDTUCGWQFGL-UHFFFAOYSA-N 0.000 description 2
- ZLKONRQQCWIOLW-UHFFFAOYSA-N ethyl 7-fluoro-4-propanoyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylate Chemical compound C1=CC(F)=C2C3C(C(=O)OCC)C3COC2=C1C(=O)CC ZLKONRQQCWIOLW-UHFFFAOYSA-N 0.000 description 2
- GAEKPEKOJKCEMS-UHFFFAOYSA-N gamma-valerolactone Chemical compound CC1CCC(=O)O1 GAEKPEKOJKCEMS-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000011984 grubbs catalyst Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- OCZZRYINBHHVCN-UHFFFAOYSA-N n-[4-(6-aminopyridin-3-yl)oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1=CC=C(N)N=C1 OCZZRYINBHHVCN-UHFFFAOYSA-N 0.000 description 2
- PETUEFUDRXSEEO-UHFFFAOYSA-N n-[4-(6-nitropyridin-3-yl)oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 PETUEFUDRXSEEO-UHFFFAOYSA-N 0.000 description 2
- TUDFUCVXINCDDH-XUEUYAKLSA-N n-[4-[6-[[(1s,1as,7bs)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@@H]2C3=C(F)C=CC(F)=C3OC[C@@H]21 TUDFUCVXINCDDH-XUEUYAKLSA-N 0.000 description 2
- NITSQFHCAVBSDW-UHFFFAOYSA-N n-methyl-5-(6-nitropyridin-3-yl)oxypyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 NITSQFHCAVBSDW-UHFFFAOYSA-N 0.000 description 2
- HSWHVRIIEDGZOH-UHFFFAOYSA-N n-morpholin-4-yl-4-phenylmethoxybenzamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)NN1CCOCC1 HSWHVRIIEDGZOH-UHFFFAOYSA-N 0.000 description 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 description 2
- 235000011151 potassium sulphates Nutrition 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000002976 reverse transcriptase assay Methods 0.000 description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 2
- 238000002821 scintillation proximity assay Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 150000003751 zinc Chemical class 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- JIMSXLUBRRQALI-VXGBXAGGSA-N (1r,2r)-2-phenylmethoxycyclopentan-1-amine Chemical compound N[C@@H]1CCC[C@H]1OCC1=CC=CC=C1 JIMSXLUBRRQALI-VXGBXAGGSA-N 0.000 description 1
- TTWWBBZHMQTZRR-ITWGVGNSSA-N (1s,5r,6s)-6-(3,6-difluoro-2-methoxyphenyl)-2-methoxy-3-oxabicyclo[3.1.0]hexane Chemical compound C1([C@@H]2[C@H]3[C@@H]2COC3OC)=C(F)C=CC(F)=C1OC TTWWBBZHMQTZRR-ITWGVGNSSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- HINZVVDZPLARRP-YSVIXOAZSA-N (4r,5s,6s,7r)-1,3-bis[(3-aminophenyl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.NC1=CC=CC(CN2C(N(CC=3C=C(N)C=CC=3)[C@H](CC=3C=CC=CC=3)[C@H](O)[C@@H](O)[C@H]2CC=2C=CC=CC=2)=O)=C1 HINZVVDZPLARRP-YSVIXOAZSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- GWKIPRVERALPRD-ZDUSSCGKSA-N (s)-4-isopropoxycarbonyl-6-methoxy-3-methylthiomethyl-3,4-dihydroquinoxalin-2(1h)-thione Chemical compound N1C(=S)[C@H](CSC)N(C(=O)OC(C)C)C2=CC(OC)=CC=C21 GWKIPRVERALPRD-ZDUSSCGKSA-N 0.000 description 1
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 1
- PSJHPMXPGDTSDP-UHFFFAOYSA-N 1,1a,2,3a-tetrahydrocyclopropa[c]chromene-1-carboxylic acid Chemical compound C1=CC=CC2=C3C(C(=O)O)C3COC21 PSJHPMXPGDTSDP-UHFFFAOYSA-N 0.000 description 1
- ITLYQJSISCHVRH-UHFFFAOYSA-N 1,1a,2,7b-tetrahydrocyclopropa[c]thiochromene-1-carboxylic acid Chemical compound C1=CC=C2C3C(C(=O)O)C3CSC2=C1 ITLYQJSISCHVRH-UHFFFAOYSA-N 0.000 description 1
- MRQQKEOKFDVEEL-UHFFFAOYSA-N 1,1a,6,6a-tetrahydrocyclopropa[a]inden-1-amine Chemical compound C1=CC=C2C3C(N)C3CC2=C1 MRQQKEOKFDVEEL-UHFFFAOYSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HUDMAQLYMUKZOZ-UHFFFAOYSA-N 1,4-difluoro-2-methoxybenzene Chemical compound COC1=CC(F)=CC=C1F HUDMAQLYMUKZOZ-UHFFFAOYSA-N 0.000 description 1
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 1
- HYUVYQNOTXGHLX-UHFFFAOYSA-N 1-(2-hydroxy-4-prop-2-ynoxyphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(OCC#C)C=C1O HYUVYQNOTXGHLX-UHFFFAOYSA-N 0.000 description 1
- GFYDYQHYABTTSZ-UHFFFAOYSA-N 1-(4-fluoro-2-hydroxyphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(F)C=C1O GFYDYQHYABTTSZ-UHFFFAOYSA-N 0.000 description 1
- HOCFDYZWQYGULA-UHFFFAOYSA-N 1-(5-bromopyridin-2-yl)-3-(2-pyridin-2-ylethyl)thiourea Chemical compound N1=CC(Br)=CC=C1NC(=S)NCCC1=CC=CC=N1 HOCFDYZWQYGULA-UHFFFAOYSA-N 0.000 description 1
- NKPHEWJJTGPRSL-OCCSQVGLSA-N 1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea Chemical compound CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O NKPHEWJJTGPRSL-OCCSQVGLSA-N 0.000 description 1
- GWYNIMFXFXQTPO-QFIXIFRTSA-N 1-[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]-3-[5-[4-(methanesulfonamido)phenoxy]pyridin-2-yl]urea Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 GWYNIMFXFXQTPO-QFIXIFRTSA-N 0.000 description 1
- MHDWTUSVABUGMH-UHFFFAOYSA-N 1-iodo-2-methoxy-3-oxabicyclo[3.1.0]hexane Chemical compound COC1OCC2CC12I MHDWTUSVABUGMH-UHFFFAOYSA-N 0.000 description 1
- CJWIVHXPQDARHX-UHFFFAOYSA-N 1-iodo-3-oxabicyclo[3.1.0]hexan-2-one Chemical compound C1OC(=O)C2(I)C1C2 CJWIVHXPQDARHX-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-M 1-naphthoate Chemical compound C1=CC=C2C(C(=O)[O-])=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-M 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- WFEGNTSZTMKNFT-UHFFFAOYSA-N 1a,6b-dihydro-1h-cyclopropa[b][1]benzothiole-1-carboxylic acid Chemical compound C1=CC=C2C3C(C(=O)O)C3SC2=C1 WFEGNTSZTMKNFT-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 1
- CVQSWZMJOGOPAV-UHFFFAOYSA-N 2,3-dihydrothiochromen-4-one Chemical compound C1=CC=C2C(=O)CCSC2=C1 CVQSWZMJOGOPAV-UHFFFAOYSA-N 0.000 description 1
- INXKVYFOWNAVMU-UHFFFAOYSA-N 2,5-difluorophenol Chemical compound OC1=CC(F)=CC=C1F INXKVYFOWNAVMU-UHFFFAOYSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- BMNPHDAEFAIIRI-UHFFFAOYSA-N 2-[4-(5-bromopyridin-2-yl)oxyphenyl]ethanol Chemical class C1=CC(CCO)=CC=C1OC1=CC=C(Br)C=N1 BMNPHDAEFAIIRI-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MEYRABVEYCFHHB-UHFFFAOYSA-N 2-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Br MEYRABVEYCFHHB-UHFFFAOYSA-N 0.000 description 1
- HUVAOAVBKOVPBZ-UHFFFAOYSA-N 2-bromo-5-fluorophenol Chemical compound OC1=CC(F)=CC=C1Br HUVAOAVBKOVPBZ-UHFFFAOYSA-N 0.000 description 1
- CMQOZIKIOASEIN-UHFFFAOYSA-N 2-chloro-5-fluorophenol Chemical compound OC1=CC(F)=CC=C1Cl CMQOZIKIOASEIN-UHFFFAOYSA-N 0.000 description 1
- BTHLKLUTMYTDFM-UHFFFAOYSA-N 2-ethoxyoxane Chemical class CCOC1CCCCO1 BTHLKLUTMYTDFM-UHFFFAOYSA-N 0.000 description 1
- WSJYDTGMIVULJI-UHFFFAOYSA-N 2-fluoro-2h-chromene Chemical compound C1=CC=C2C=CC(F)OC2=C1 WSJYDTGMIVULJI-UHFFFAOYSA-N 0.000 description 1
- LCIMJULVQOQTEZ-UHFFFAOYSA-N 2-hydroxyacetyl chloride Chemical compound OCC(Cl)=O LCIMJULVQOQTEZ-UHFFFAOYSA-N 0.000 description 1
- WFJPRCMYUOOTNS-UHFFFAOYSA-N 2-isothiocyanatopyridine Chemical compound S=C=NC1=CC=CC=N1 WFJPRCMYUOOTNS-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- TXFPXOOSYYKSKL-UHFFFAOYSA-N 2h-chromen-7-yl trifluoromethanesulfonate Chemical compound C1=CCOC2=CC(OS(=O)(=O)C(F)(F)F)=CC=C21 TXFPXOOSYYKSKL-UHFFFAOYSA-N 0.000 description 1
- FWVSZXYNCFXKRT-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromen-4-ol Chemical compound C1=CC=C2C(O)CCSC2=C1 FWVSZXYNCFXKRT-UHFFFAOYSA-N 0.000 description 1
- HJSSBIMVTMYKPD-UHFFFAOYSA-N 3,5-difluorophenol Chemical compound OC1=CC(F)=CC(F)=C1 HJSSBIMVTMYKPD-UHFFFAOYSA-N 0.000 description 1
- DURXQDAFKSWAES-UHFFFAOYSA-N 3-(2,5-difluorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC(F)=CC=C1F DURXQDAFKSWAES-UHFFFAOYSA-N 0.000 description 1
- VAPDTIYXQSYKLV-UHFFFAOYSA-N 3-(2,5-difluorophenyl)propanoyl chloride Chemical compound FC1=CC=C(F)C(CCC(Cl)=O)=C1 VAPDTIYXQSYKLV-UHFFFAOYSA-N 0.000 description 1
- WFNISJZUJCKTLT-UHFFFAOYSA-N 3-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=NC=CC=C1Br WFNISJZUJCKTLT-UHFFFAOYSA-N 0.000 description 1
- ZURMHOLLXQZTHT-UHFFFAOYSA-N 3-cyclohexyl-3-iodo-2-methoxyoxane Chemical compound COC1OCCCC1(I)C1CCCCC1 ZURMHOLLXQZTHT-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- LLCFJJCXVUDYNK-UHFFFAOYSA-N 4,7-difluoro-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylic acid Chemical compound C1=CC(F)=C2C3C(C(=O)O)C3CCC2=C1F LLCFJJCXVUDYNK-UHFFFAOYSA-N 0.000 description 1
- ZOPIBCDDKMAEII-UHFFFAOYSA-N 4-(1,2,4-triazol-1-yl)phenol Chemical compound C1=CC(O)=CC=C1N1N=CN=C1 ZOPIBCDDKMAEII-UHFFFAOYSA-N 0.000 description 1
- UVMHDCHUQLBHGS-UHFFFAOYSA-N 4-(6-aminopyridin-3-yl)oxy-n-cyclopropylbenzamide Chemical compound C1=NC(N)=CC=C1OC1=CC=C(C(=O)NC2CC2)C=C1 UVMHDCHUQLBHGS-UHFFFAOYSA-N 0.000 description 1
- QASBCTGZKABPKX-UHFFFAOYSA-N 4-(methylsulfanyl)phenol Chemical compound CSC1=CC=C(O)C=C1 QASBCTGZKABPKX-UHFFFAOYSA-N 0.000 description 1
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 1
- YOZSDUPFXGVCCI-UHFFFAOYSA-N 4-[2-(2-methoxyethoxy)ethoxy]phenol Chemical compound COCCOCCOC1=CC=C(O)C=C1 YOZSDUPFXGVCCI-UHFFFAOYSA-N 0.000 description 1
- ILAYIAGXTHKHNT-UHFFFAOYSA-N 4-[4-(2,4,6-trimethyl-phenylamino)-pyrimidin-2-ylamino]-benzonitrile Chemical compound CC1=CC(C)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 ILAYIAGXTHKHNT-UHFFFAOYSA-N 0.000 description 1
- HYEXHFRZMQGPEJ-UHFFFAOYSA-N 4-chloro-1-fluoro-2-prop-2-ynoxybenzene Chemical compound FC1=CC=C(Cl)C=C1OCC#C HYEXHFRZMQGPEJ-UHFFFAOYSA-N 0.000 description 1
- YSHYFXQIAJFBMV-UHFFFAOYSA-N 4-chloro-1-fluorocyclohexa-2,4-dien-1-ol Chemical compound OC1(F)CC=C(Cl)C=C1 YSHYFXQIAJFBMV-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- VKDNYQKDAXLFIL-UHFFFAOYSA-N 4-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(O)C=C1 VKDNYQKDAXLFIL-UHFFFAOYSA-N 0.000 description 1
- HPJYZURCOVYQOG-UHFFFAOYSA-N 4-hydroxy-n-morpholin-4-ylbenzamide Chemical compound C1=CC(O)=CC=C1C(=O)NN1CCOCC1 HPJYZURCOVYQOG-UHFFFAOYSA-N 0.000 description 1
- AQSCHALQLXXKKC-UHFFFAOYSA-N 4-phenylmethoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC=C1 AQSCHALQLXXKKC-UHFFFAOYSA-N 0.000 description 1
- JWSWGVMVRLVNAA-UHFFFAOYSA-N 4h-thiochromene Chemical compound C1=CC=C2CC=CSC2=C1 JWSWGVMVRLVNAA-UHFFFAOYSA-N 0.000 description 1
- LYIVLMSQQXPGPR-UHFFFAOYSA-N 5,8-dichloro-2h-chromene Chemical compound C1=CCOC2=C1C(Cl)=CC=C2Cl LYIVLMSQQXPGPR-UHFFFAOYSA-N 0.000 description 1
- QHDRSZZWBSPTNM-UHFFFAOYSA-N 5,8-difluoro-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1=CC(F)=C2C(O)CCCC2=C1F QHDRSZZWBSPTNM-UHFFFAOYSA-N 0.000 description 1
- BUKJVHZRDGJFDO-UHFFFAOYSA-N 5,8-difluoro-1-methyl-1,2-dihydronaphthalene Chemical compound C1=CC(F)=C2C(C)CC=CC2=C1F BUKJVHZRDGJFDO-UHFFFAOYSA-N 0.000 description 1
- NMCXLPZZVMUXCS-UHFFFAOYSA-N 5,8-difluoro-4-methyl-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1=CC(F)=C2C(C)CCC(O)C2=C1F NMCXLPZZVMUXCS-UHFFFAOYSA-N 0.000 description 1
- FNNYVLPUTIYSSV-UHFFFAOYSA-N 5-(3-fluorophenyl)pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1=CC=CC(F)=C1 FNNYVLPUTIYSSV-UHFFFAOYSA-N 0.000 description 1
- KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 1
- QZVSSBLBKKLOMH-UHFFFAOYSA-N 5-bromo-2-[4-[2-(2-methoxyethoxy)ethoxy]phenoxy]pyridine Chemical compound C1=CC(OCCOCCOC)=CC=C1OC1=CC=C(Br)C=N1 QZVSSBLBKKLOMH-UHFFFAOYSA-N 0.000 description 1
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
- BILNDQPIZRBLPW-UHFFFAOYSA-N 5-methoxy-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylic acid Chemical compound C1CC2=CC(OC)=CC=C2C2C(C(O)=O)C12 BILNDQPIZRBLPW-UHFFFAOYSA-N 0.000 description 1
- IZFJPQFHAVXLRF-UHFFFAOYSA-N 6-acetyl-7-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylic acid Chemical compound O1CC2C(C(O)=O)C2C2=C(O)C(C(=O)C)=CC=C21 IZFJPQFHAVXLRF-UHFFFAOYSA-N 0.000 description 1
- GDOQJEBNBOJBQX-UHFFFAOYSA-N 6-fluoro-2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=C(F)C(C=O)=C1OC GDOQJEBNBOJBQX-UHFFFAOYSA-N 0.000 description 1
- AJGKGZIQURARTL-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-2h-chromen-4-ol Chemical compound C1=C(F)C=C2C(O)CCOC2=C1 AJGKGZIQURARTL-UHFFFAOYSA-N 0.000 description 1
- IVSJZMUJOFGIOR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound OC1CCCC2=CC(OC)=CC=C21 IVSJZMUJOFGIOR-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- HMPWBLCKJLKFJN-UHFFFAOYSA-N 7,8-dihydronaphthalen-2-yl trifluoromethanesulfonate Chemical compound C1=CCCC2=CC(OS(=O)(=O)C(F)(F)F)=CC=C21 HMPWBLCKJLKFJN-UHFFFAOYSA-N 0.000 description 1
- NKFNEIYWSQIOLY-UHFFFAOYSA-N 7-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1CCC(O)C2=CC(OC)=CC=C21 NKFNEIYWSQIOLY-UHFFFAOYSA-N 0.000 description 1
- OAWCMXCTQPOKQN-UHFFFAOYSA-N 7-methoxy-1,2-dihydronaphthalene Chemical compound C1=CCCC2=CC(OC)=CC=C21 OAWCMXCTQPOKQN-UHFFFAOYSA-N 0.000 description 1
- VXMCTKXUCTZEFB-UHFFFAOYSA-N 8-chloro-2-fluoro-2H-chromene Chemical compound FC1OC2=C(C=C1)C=CC=C2Cl VXMCTKXUCTZEFB-UHFFFAOYSA-N 0.000 description 1
- PPAWWLWTYSTUDY-UHFFFAOYSA-N 8-chloro-5-fluoro-2h-chromene Chemical compound O1CC=CC2=C1C(Cl)=CC=C2F PPAWWLWTYSTUDY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- UXCAQJAQSWSNPQ-XLPZGREQSA-N Alovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](F)C1 UXCAQJAQSWSNPQ-XLPZGREQSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- QQGNBBUUTQKEPW-UHFFFAOYSA-N C(C)OC(=O)C1C2C1C(C=1C=CC=CC21)C Chemical compound C(C)OC(=O)C1C2C1C(C=1C=CC=CC21)C QQGNBBUUTQKEPW-UHFFFAOYSA-N 0.000 description 1
- HKOKRRDXAQWVTG-UHFFFAOYSA-L C([O-])([O-])=O.[Cs+].[N+](=O)([O-])C1=NC=C(C=C1)OC1=CC=C(C=C1)N1N=CN=C1.[Cs+] Chemical compound C([O-])([O-])=O.[Cs+].[N+](=O)([O-])C1=NC=C(C=C1)OC1=CC=C(C=C1)N1N=CN=C1.[Cs+] HKOKRRDXAQWVTG-UHFFFAOYSA-L 0.000 description 1
- IDXFKLZTLHSFPV-UHFFFAOYSA-N C1=C(C=CC=2C=CCCC12)O.FC(S(=O)(=O)OC1=CC=2CCC=CC2C=C1)(F)F Chemical compound C1=C(C=CC=2C=CCCC12)O.FC(S(=O)(=O)OC1=CC=2CCC=CC2C=C1)(F)F IDXFKLZTLHSFPV-UHFFFAOYSA-N 0.000 description 1
- AUVNJUMJAHNFPS-UHFFFAOYSA-N C1C2OC2c2ccccc2SC1 Chemical compound C1C2OC2c2ccccc2SC1 AUVNJUMJAHNFPS-UHFFFAOYSA-N 0.000 description 1
- NYQIKJPNUJZBFQ-UHFFFAOYSA-N C1C=CC2=CC=CC=C12.C(C)OC(=O)C1C2C1CC=1C=CC=CC21 Chemical compound C1C=CC2=CC=CC=C12.C(C)OC(=O)C1C2C1CC=1C=CC=CC21 NYQIKJPNUJZBFQ-UHFFFAOYSA-N 0.000 description 1
- VIDHILKLKOQXEB-UHFFFAOYSA-N C1Sc2ccccc2SC1 Chemical compound C1Sc2ccccc2SC1 VIDHILKLKOQXEB-UHFFFAOYSA-N 0.000 description 1
- XZQMHNHSRHKNKN-KTFPLMLQSA-N CC12C(OC)OC[C@@H]1[C@@H]2c(c(F)ccc1F)c1OC Chemical compound CC12C(OC)OC[C@@H]1[C@@H]2c(c(F)ccc1F)c1OC XZQMHNHSRHKNKN-KTFPLMLQSA-N 0.000 description 1
- HJIWXAOXEUPBBS-IONNQARKSA-N CCC(c(c(O)c1[C@H]2C)ccc1OC[C@H]2C(O)=O)=O Chemical compound CCC(c(c(O)c1[C@H]2C)ccc1OC[C@H]2C(O)=O)=O HJIWXAOXEUPBBS-IONNQARKSA-N 0.000 description 1
- RLRWTZMZWGRXCQ-RMTLLUHYSA-N CCC(c(c(OC[C@H]12)c3C1[C@@H]2C(O)=O)ccc3F)=O Chemical compound CCC(c(c(OC[C@H]12)c3C1[C@@H]2C(O)=O)ccc3F)=O RLRWTZMZWGRXCQ-RMTLLUHYSA-N 0.000 description 1
- QMEILCBMVGGUHN-SUFHQJMPSA-N CCOC(C(C)(COC1)[C@@H]1[C@](C)([C@H](C)C(F)=C)F)=O Chemical compound CCOC(C(C)(COC1)[C@@H]1[C@](C)([C@H](C)C(F)=C)F)=O QMEILCBMVGGUHN-SUFHQJMPSA-N 0.000 description 1
- LVVQBRQSNFYPPO-WHFVKQHSSA-N CCOC([C@H]1[C@H]2c(c(Cl)ccc3F)c3OC[C@@H]12)=O Chemical compound CCOC([C@H]1[C@H]2c(c(Cl)ccc3F)c3OC[C@@H]12)=O LVVQBRQSNFYPPO-WHFVKQHSSA-N 0.000 description 1
- DFDNEXRGYNQWHQ-UHFFFAOYSA-N COC1=CC=C2CCCC(C2=C1)O.COC1=CC=C2CCCC(C2=C1)O Chemical compound COC1=CC=C2CCCC(C2=C1)O.COC1=CC=C2CCCC(C2=C1)O DFDNEXRGYNQWHQ-UHFFFAOYSA-N 0.000 description 1
- YVFYFYAEIPDXQM-UHFFFAOYSA-N COC=1C=C2C=CCCC2=CC1.COC=1C=C2C=CCCC2=CC1 Chemical compound COC=1C=C2C=CCCC2=CC1.COC=1C=C2C=CCCC2=CC1 YVFYFYAEIPDXQM-UHFFFAOYSA-N 0.000 description 1
- KJUFDNWWVJTNBB-UHFFFAOYSA-N COC=1C=C2CCCC(C2=CC1)=O.COC=1C=C2CCCC(C2=CC1)O Chemical compound COC=1C=C2CCCC(C2=CC1)=O.COC=1C=C2CCCC(C2=CC1)O KJUFDNWWVJTNBB-UHFFFAOYSA-N 0.000 description 1
- VUWZLHQWWWJJCK-UHFFFAOYSA-N COc1ccc(CC(CC23)C2C(O)=O)c3c1 Chemical compound COc1ccc(CC(CC23)C2C(O)=O)c3c1 VUWZLHQWWWJJCK-UHFFFAOYSA-N 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- RGIUTOWSKBMSNP-GDDKPDEQSA-N CS(c(cc1)ccc1Oc1ccc(NC(NC([C@@H]2COc3c(cc4)F)[C@H]2c3c4F)=O)nc1)=O Chemical compound CS(c(cc1)ccc1Oc1ccc(NC(NC([C@@H]2COc3c(cc4)F)[C@H]2c3c4F)=O)nc1)=O RGIUTOWSKBMSNP-GDDKPDEQSA-N 0.000 description 1
- YGQJQLHKCZWUAW-FSIIMWSLSA-N C[C@@H]1[C@@H]2[C@@H](O)OC[C@H]12 Chemical compound C[C@@H]1[C@@H]2[C@@H](O)OC[C@H]12 YGQJQLHKCZWUAW-FSIIMWSLSA-N 0.000 description 1
- AEAMWWNTHKZRTR-VZFHVOOUSA-N C[C@@H]1[C@@H]2[C@@H](OC)OC[C@H]12 Chemical compound C[C@@H]1[C@@H]2[C@@H](OC)OC[C@H]12 AEAMWWNTHKZRTR-VZFHVOOUSA-N 0.000 description 1
- VHEYEWLYFNZQKL-IIYZAJTGSA-N C[C@H]([C@@H]1c(c(O)c(cc2)F)c2F)[C@H]1NC(Nc(nc1)ccc1Oc(cc1)ccc1-[n]1ncnc1)=O Chemical compound C[C@H]([C@@H]1c(c(O)c(cc2)F)c2F)[C@H]1NC(Nc(nc1)ccc1Oc(cc1)ccc1-[n]1ncnc1)=O VHEYEWLYFNZQKL-IIYZAJTGSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- WFQGUDBFZDFZQF-UHFFFAOYSA-N Cc(cc(cn1)Oc(cc2)ccc2OCCOCCOC)c1[N+]([O-])=O Chemical compound Cc(cc(cn1)Oc(cc2)ccc2OCCOCCOC)c1[N+]([O-])=O WFQGUDBFZDFZQF-UHFFFAOYSA-N 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
- XIPJOTAQXUQLHZ-UHFFFAOYSA-N ClC1(C2COC=3C(=CC=CC3C21)F)C(=O)OCC Chemical compound ClC1(C2COC=3C(=CC=CC3C21)F)C(=O)OCC XIPJOTAQXUQLHZ-UHFFFAOYSA-N 0.000 description 1
- YKMAZWIQAOKVHS-UHFFFAOYSA-N ClC1=C(C=C(C=C1)Cl)O.ClC1=C(C=C(C=C1)Cl)OCC#C Chemical compound ClC1=C(C=C(C=C1)Cl)O.ClC1=C(C=C(C=C1)Cl)OCC#C YKMAZWIQAOKVHS-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 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 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- FDVCXLXYCVQRTR-UHFFFAOYSA-N FC1=C2C(CC(C2=C(C=C1)F)O)C.FC1=C2C(CC(C2=C(C=C1)F)O)C Chemical compound FC1=C2C(CC(C2=C(C=C1)F)O)C.FC1=C2C(CC(C2=C(C=C1)F)O)C FDVCXLXYCVQRTR-UHFFFAOYSA-N 0.000 description 1
- OONSVGURFLSEGU-UHFFFAOYSA-N FC1=CC(=C(C=C1)CCC)OCC#C Chemical compound FC1=CC(=C(C=C1)CCC)OCC#C OONSVGURFLSEGU-UHFFFAOYSA-N 0.000 description 1
- VDWCNUXINPDNDD-UHFFFAOYSA-N FC1=CC=C(C(=C1C=O)O)OC.FC1=C2C=CCOC2=C(C=C1)OC Chemical compound FC1=CC=C(C(=C1C=O)O)OC.FC1=C2C=CCOC2=C(C=C1)OC VDWCNUXINPDNDD-UHFFFAOYSA-N 0.000 description 1
- PPHQBVIGLNLSIA-UHFFFAOYSA-N FC1=CC=C(C=C1)F.FC1=C2C(CCC(C2=C(C=C1)F)=O)C Chemical compound FC1=CC=C(C=C1)F.FC1=C2C(CCC(C2=C(C=C1)F)=O)C PPHQBVIGLNLSIA-UHFFFAOYSA-N 0.000 description 1
- YVVWHBKFYSDCOE-UHFFFAOYSA-N FC=1C=C2C(CCOC2=CC1)=O.FC=1C=C2C(CCOC2=CC1)O Chemical compound FC=1C=C2C(CCOC2=CC1)=O.FC=1C=C2C(CCOC2=CC1)O YVVWHBKFYSDCOE-UHFFFAOYSA-N 0.000 description 1
- ODPPHJXKNIXNRX-UHFFFAOYSA-N FC=1C=C2C(CCOC2=CC1)O.FC=1C=C2C=CCOC2=CC1 Chemical compound FC=1C=C2C(CCOC2=CC1)O.FC=1C=C2C=CCOC2=CC1 ODPPHJXKNIXNRX-UHFFFAOYSA-N 0.000 description 1
- NGOHKHNRBOLITK-UHFFFAOYSA-N Fc(c1c2C=CCC1)ccc2F Chemical compound Fc(c1c2C=CCC1)ccc2F NGOHKHNRBOLITK-UHFFFAOYSA-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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- UQEVVJBHSYWCAN-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C12.C(C)(=O)N1CC=CC2=CC=CC=C12 Chemical compound N1=CC=CC2=CC=CC=C12.C(C)(=O)N1CC=CC2=CC=CC=C12 UQEVVJBHSYWCAN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- XJIXNZGMQJTQKG-OAGPBXRQSA-N OC([C@@](C1)(CO[C@H]23)[C@H]1C2C(F)=CC=C3F)=O Chemical compound OC([C@@](C1)(CO[C@H]23)[C@H]1C2C(F)=CC=C3F)=O XJIXNZGMQJTQKG-OAGPBXRQSA-N 0.000 description 1
- VAAYPVVZZQNUFZ-UHFFFAOYSA-N OC1=C(C=CC(=C1)OCC#C)CCC Chemical compound OC1=C(C=CC(=C1)OCC#C)CCC VAAYPVVZZQNUFZ-UHFFFAOYSA-N 0.000 description 1
- WDPMDWMRJXVUNX-UHFFFAOYSA-N OC1=C2C=CCOC2=CC=C1C(C)=O.OC1=C2C=CCOC2=CC=C1C(C)=O Chemical compound OC1=C2C=CCOC2=CC=C1C(C)=O.OC1=C2C=CCOC2=CC=C1C(C)=O WDPMDWMRJXVUNX-UHFFFAOYSA-N 0.000 description 1
- RMILMILAEMNRHN-CBAPKCEASA-N OC=1C=2[C@@H]3[C@H](COC2C=CC1C(CC)=O)C3 Chemical compound OC=1C=2[C@@H]3[C@H](COC2C=CC1C(CC)=O)C3 RMILMILAEMNRHN-CBAPKCEASA-N 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
- JKIJEFPNVSHHEI-UHFFFAOYSA-N Phenol, 2,4-bis(1,1-dimethylethyl)-, phosphite (3:1) Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC=C1OP(OC=1C(=CC(=CC=1)C(C)(C)C)C(C)(C)C)OC1=CC=C(C(C)(C)C)C=C1C(C)(C)C JKIJEFPNVSHHEI-UHFFFAOYSA-N 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 239000012327 Ruthenium complex Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- RLAHNGKRJJEIJL-RFZPGFLSSA-N [(2r,4r)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1CO[C@@H](CO)O1 RLAHNGKRJJEIJL-RFZPGFLSSA-N 0.000 description 1
- BINXAIIXOUQUKC-UIPNDDLNSA-N [(3as,4r,6ar)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] n-[(2s,3r)-3-hydroxy-4-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(CC(C)C)C[C@@H](O)[C@@H](NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)CC1=CC=CC=C1 BINXAIIXOUQUKC-UIPNDDLNSA-N 0.000 description 1
- GHKJXEICAPOWQS-UHFFFAOYSA-K [Au+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O Chemical class [Au+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O GHKJXEICAPOWQS-UHFFFAOYSA-K 0.000 description 1
- 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 1
- 229960004748 abacavir Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960001997 adefovir Drugs 0.000 description 1
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229950004424 alovudine Drugs 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 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
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 229930188620 butyrolactone Natural products 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- YQXCVAGCMNFUMQ-UHFFFAOYSA-N capravirine Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC1=C(C(C)C)N=C(COC(N)=O)N1CC1=CC=NC=C1 YQXCVAGCMNFUMQ-UHFFFAOYSA-N 0.000 description 1
- 229950008230 capravirine Drugs 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012679 convergent method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910000336 copper(I) sulfate Inorganic materials 0.000 description 1
- WIVXEZIMDUGYRW-UHFFFAOYSA-L copper(i) sulfate Chemical compound [Cu+].[Cu+].[O-]S([O-])(=O)=O WIVXEZIMDUGYRW-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products 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 1
- 230000001419 dependent effect Effects 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 125000002720 diazolyl group Chemical group 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229960000366 emtricitabine Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- VRAYVWUMBAJVGH-UHFFFAOYSA-M ethenyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=C)C1=CC=CC=C1 VRAYVWUMBAJVGH-UHFFFAOYSA-M 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- UJTJVQIYRQALIK-ARJAWSKDSA-N ethyl (z)-3-bromoprop-2-enoate Chemical compound CCOC(=O)\C=C/Br UJTJVQIYRQALIK-ARJAWSKDSA-N 0.000 description 1
- LEYDLBCEHUAAPZ-UHFFFAOYSA-N ethyl 1,1a,2,7b-tetrahydrocyclopropa[c]thiochromene-1-carboxylate Chemical compound C1=CC=C2C3C(C(=O)OCC)C3CSC2=C1 LEYDLBCEHUAAPZ-UHFFFAOYSA-N 0.000 description 1
- BRDRYHSDPGWGOA-UHFFFAOYSA-N ethyl 1a,6b-dihydro-1h-cyclopropa[b][1]benzothiole-1-carboxylate Chemical compound C1=CC=C2C3C(C(=O)OCC)C3SC2=C1 BRDRYHSDPGWGOA-UHFFFAOYSA-N 0.000 description 1
- JESFDMBNMJDIKG-UHFFFAOYSA-N ethyl 1h-indene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)C=CC2=C1 JESFDMBNMJDIKG-UHFFFAOYSA-N 0.000 description 1
- HVWZHUYSGHKPNF-UHFFFAOYSA-N ethyl 4,7-difluoro-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound C1=CC(F)=C2C3C(C(=O)OCC)C3CCC2=C1F HVWZHUYSGHKPNF-UHFFFAOYSA-N 0.000 description 1
- BOPIUPIQZCPCDB-UHFFFAOYSA-N ethyl 4,7-difluoro-3-methyl-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound C1=CC(F)=C2C3C(C(=O)OCC)C3CC(C)C2=C1F BOPIUPIQZCPCDB-UHFFFAOYSA-N 0.000 description 1
- MDSLTRFIWIIXAK-UHFFFAOYSA-N ethyl 5-(2-trimethylsilylethynyl)-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound C[Si](C)(C)C#CC1=CC=C2C3C(C(=O)OCC)C3CCC2=C1 MDSLTRFIWIIXAK-UHFFFAOYSA-N 0.000 description 1
- MZUUSGBFCAVPNX-UHFFFAOYSA-N ethyl 5-(trifluoromethylsulfonyloxy)-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C2C3C(C(=O)OCC)C3CCC2=C1 MZUUSGBFCAVPNX-UHFFFAOYSA-N 0.000 description 1
- MOUWAYIUIGHADT-UHFFFAOYSA-N ethyl 5-cyano-1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalene-1-carboxylate Chemical compound N#CC1=CC=C2C3C(C(=O)OCC)C3CCC2=C1 MOUWAYIUIGHADT-UHFFFAOYSA-N 0.000 description 1
- MTHORIMGWXYCSU-UHFFFAOYSA-N ethyl 6-acetyl-7-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylate Chemical compound C1=C(C(C)=O)C(O)=C2C3C(C(=O)OCC)C3COC2=C1 MTHORIMGWXYCSU-UHFFFAOYSA-N 0.000 description 1
- HOAQEFUDHVGJSE-UHFFFAOYSA-N ethyl 7-hydroxy-6-propanoyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylate Chemical compound C1=C(C(=O)CC)C(O)=C2C3C(C(=O)OCC)C3COC2=C1 HOAQEFUDHVGJSE-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-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
- 239000013604 expression vector Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960005102 foscarnet Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 1
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 1
- 229960001936 indinavir Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- VLODBNNWEWTQJX-UHFFFAOYSA-N iodocyclopropane Chemical compound IC1CC1 VLODBNNWEWTQJX-UHFFFAOYSA-N 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 229940112586 kaletra Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229960000829 kaolin Drugs 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229950004697 lasinavir Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000020094 liqueur Nutrition 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- CJPLEFFCVDQQFZ-UHFFFAOYSA-N loviride Chemical compound CC(=O)C1=CC=C(C)C=C1NC(C(N)=O)C1=C(Cl)C=CC=C1Cl CJPLEFFCVDQQFZ-UHFFFAOYSA-N 0.000 description 1
- 229950006243 loviride Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 235000005398 marita Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 235000020938 metabolic status Nutrition 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000005217 methyl ethers Chemical class 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- YJASRJZSSUOGKB-UHFFFAOYSA-N n-(4-hydroxyphenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=C(O)C=C1 YJASRJZSSUOGKB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PJZGKFIQQGYRGI-UHFFFAOYSA-N n-cyclopropyl-4-hydroxybenzamide Chemical compound C1=CC(O)=CC=C1C(=O)NC1CC1 PJZGKFIQQGYRGI-UHFFFAOYSA-N 0.000 description 1
- APWKCUUEJQXCJJ-UHFFFAOYSA-N n-cyclopropyl-4-phenylmethoxybenzamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)NC1CC1 APWKCUUEJQXCJJ-UHFFFAOYSA-N 0.000 description 1
- SVEUVITYHIHZQE-UHFFFAOYSA-N n-methylpyridin-2-amine Chemical compound CNC1=CC=CC=N1 SVEUVITYHIHZQE-UHFFFAOYSA-N 0.000 description 1
- KTPCYITVXBEZPT-UHFFFAOYSA-N n-morpholin-4-yl-4-(6-nitropyridin-3-yl)oxybenzamide Chemical compound C1=NC([N+](=O)[O-])=CC=C1OC1=CC=C(C(=O)NN2CCOCC2)C=C1 KTPCYITVXBEZPT-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960000689 nevirapine Drugs 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229950002238 omaciclovir Drugs 0.000 description 1
- AWRICOJVWDPBQF-BTJKTKAUSA-N org-gc-94 Chemical compound OC(=O)\C=C/C(O)=O.O1C2=CC=C(C)C=C2N2CCN(C)CC2C2=CC=CC=C21 AWRICOJVWDPBQF-BTJKTKAUSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940023569 palmate Drugs 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- QXSAKPUBHTZHKW-UHFFFAOYSA-N para-hydroxybenzamide Natural products NC(=O)C1=CC=C(O)C=C1 QXSAKPUBHTZHKW-UHFFFAOYSA-N 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 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
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- CPGRMGOILBSUQC-UHFFFAOYSA-N phosphoryl azide Chemical compound [N-]=[N+]=NP(=O)(N=[N+]=[N-])N=[N+]=[N-] CPGRMGOILBSUQC-UHFFFAOYSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 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 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical group 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000005872 self-metathesis reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000005737 synergistic response Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- JFVZFKDSXNQEJW-CQSZACIVSA-N tenofovir disoproxil Chemical compound N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N JFVZFKDSXNQEJW-CQSZACIVSA-N 0.000 description 1
- BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 description 1
- TYGVVVHFKIIJKQ-UHFFFAOYSA-N tert-butyl n-[4-(6-nitropyridin-3-yl)oxyphenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 TYGVVVHFKIIJKQ-UHFFFAOYSA-N 0.000 description 1
- BXORLIVVCQAFGE-ODOSVJCGSA-N tert-butyl n-[4-[6-[[(1s,1ar,7br)-4,7-difluoro-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-1-yl]carbamoylamino]pyridin-3-yl]oxyphenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1OC(C=N1)=CC=C1NC(=O)N[C@H]1[C@H]2C3=C(F)C=CC(F)=C3OC[C@H]21 BXORLIVVCQAFGE-ODOSVJCGSA-N 0.000 description 1
- FSQVVXZNQZWLHV-UHFFFAOYSA-N tert-butyl n-[[4-(6-nitropyridin-3-yl)oxybenzoyl]amino]carbamate Chemical compound C1=CC(C(=O)NNC(=O)OC(C)(C)C)=CC=C1OC1=CC=C([N+]([O-])=O)N=C1 FSQVVXZNQZWLHV-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229950000977 trovirdine Drugs 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0400021A SE0400021D0 (sv) | 2004-01-08 | 2004-01-08 | Non-nucleoside reverse transcriptase inhibitors |
| SE0400021-2 | 2004-01-08 | ||
| SE0400585-6 | 2004-03-09 | ||
| SE0400585A SE0400585D0 (sv) | 2004-03-09 | 2004-03-09 | NNRTI Antivirals |
| PCT/SE2004/002034 WO2005066131A1 (en) | 2004-01-08 | 2004-12-30 | Non-nucleotide reverse transcriptase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007519640A JP2007519640A (ja) | 2007-07-19 |
| JP2007519640A5 JP2007519640A5 (enExample) | 2008-01-24 |
| JP4762917B2 true JP4762917B2 (ja) | 2011-08-31 |
Family
ID=34752289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006549182A Expired - Fee Related JP4762917B2 (ja) | 2004-01-08 | 2004-12-30 | 非ヌクレオシド逆転写酵素インヒビター |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7915295B2 (enExample) |
| EP (1) | EP1701942B1 (enExample) |
| JP (1) | JP4762917B2 (enExample) |
| AT (1) | ATE451357T1 (enExample) |
| AU (1) | AU2004312284B2 (enExample) |
| BR (1) | BRPI0418306B8 (enExample) |
| CA (1) | CA2550187C (enExample) |
| DE (1) | DE602004024584D1 (enExample) |
| DK (1) | DK1701942T3 (enExample) |
| EA (1) | EA009700B1 (enExample) |
| ES (1) | ES2337794T3 (enExample) |
| IL (1) | IL176740A (enExample) |
| NZ (1) | NZ548367A (enExample) |
| SG (1) | SG149070A1 (enExample) |
| WO (1) | WO2005066131A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE413174T1 (de) * | 2002-09-05 | 2008-11-15 | Medivir Ab | Nicht-nucleoside revers-transcriptase inhibitoren |
| US7388008B2 (en) | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
| EP1877091B1 (en) * | 2005-04-27 | 2015-03-25 | TaiMed Biologics, Inc. | Method for improving pharmacokinetics of protease inhibitors and protease inhibitor precursors |
| EP1971615B1 (en) | 2005-11-30 | 2014-01-01 | TaiMed Biologics, Inc. | Lysme-based prodrugs of aspartyl protease inhibitors and processes for their preparation |
| GB0608876D0 (en) * | 2006-05-05 | 2006-06-14 | Medivir Ab | Combination therapy |
| WO2007136573A2 (en) * | 2006-05-15 | 2007-11-29 | Merck & Co., Inc. | Antidiabetic bicyclic compounds |
| EP2064177B1 (en) | 2006-09-21 | 2017-04-05 | TaiMed Biologics, Inc. | Protease inhibitors |
| EP3250552B1 (en) * | 2015-01-30 | 2019-03-27 | Genentech, Inc. | Therapeutic compounds and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002536435A (ja) * | 1999-02-12 | 2002-10-29 | メディヴィル・アクチボラグ | 非ヌクレオシド逆転写酵素インヒビター |
| WO2003020705A1 (en) * | 2001-08-28 | 2003-03-13 | Medivir Ab | Urea and thiourea derivatives as non-nucleoside reverse transcriptase inhibitors |
| JP2004529112A (ja) * | 2001-03-05 | 2004-09-24 | メディヴィル・アクチボラグ | 非ヌクレオシド逆転写酵素インヒビターとしてのシクロプロパヘテロ環 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1054867T3 (da) * | 1998-01-16 | 2004-08-09 | Medivir Ab | Antivirale midler |
| ATE413174T1 (de) * | 2002-09-05 | 2008-11-15 | Medivir Ab | Nicht-nucleoside revers-transcriptase inhibitoren |
-
2004
- 2004-12-30 US US10/584,933 patent/US7915295B2/en not_active Expired - Fee Related
- 2004-12-30 EP EP04809207A patent/EP1701942B1/en not_active Expired - Lifetime
- 2004-12-30 AT AT04809207T patent/ATE451357T1/de not_active IP Right Cessation
- 2004-12-30 SG SG200809639-8A patent/SG149070A1/en unknown
- 2004-12-30 NZ NZ548367A patent/NZ548367A/en not_active IP Right Cessation
- 2004-12-30 BR BRPI0418306A patent/BRPI0418306B8/pt not_active IP Right Cessation
- 2004-12-30 AU AU2004312284A patent/AU2004312284B2/en not_active Ceased
- 2004-12-30 WO PCT/SE2004/002034 patent/WO2005066131A1/en not_active Ceased
- 2004-12-30 DK DK04809207.6T patent/DK1701942T3/da active
- 2004-12-30 JP JP2006549182A patent/JP4762917B2/ja not_active Expired - Fee Related
- 2004-12-30 ES ES04809207T patent/ES2337794T3/es not_active Expired - Lifetime
- 2004-12-30 DE DE602004024584T patent/DE602004024584D1/de not_active Expired - Lifetime
- 2004-12-30 CA CA2550187A patent/CA2550187C/en not_active Expired - Fee Related
- 2004-12-30 EA EA200601289A patent/EA009700B1/ru not_active IP Right Cessation
-
2006
- 2006-07-06 IL IL176740A patent/IL176740A/en not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002536435A (ja) * | 1999-02-12 | 2002-10-29 | メディヴィル・アクチボラグ | 非ヌクレオシド逆転写酵素インヒビター |
| JP2004529112A (ja) * | 2001-03-05 | 2004-09-24 | メディヴィル・アクチボラグ | 非ヌクレオシド逆転写酵素インヒビターとしてのシクロプロパヘテロ環 |
| WO2003020705A1 (en) * | 2001-08-28 | 2003-03-13 | Medivir Ab | Urea and thiourea derivatives as non-nucleoside reverse transcriptase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005066131A1 (en) | 2005-07-21 |
| ES2337794T3 (es) | 2010-04-29 |
| DE602004024584D1 (de) | 2010-01-21 |
| AU2004312284B2 (en) | 2010-08-05 |
| US7915295B2 (en) | 2011-03-29 |
| ATE451357T1 (de) | 2009-12-15 |
| CA2550187C (en) | 2012-08-07 |
| HK1101400A1 (en) | 2007-10-18 |
| EA200601289A1 (ru) | 2006-12-29 |
| IL176740A (en) | 2011-09-27 |
| US20080070951A1 (en) | 2008-03-20 |
| BRPI0418306B1 (pt) | 2018-09-18 |
| EP1701942B1 (en) | 2009-12-09 |
| SG149070A1 (en) | 2009-01-29 |
| IL176740A0 (en) | 2006-10-31 |
| BRPI0418306B8 (pt) | 2021-05-25 |
| AU2004312284A1 (en) | 2005-07-21 |
| NZ548367A (en) | 2010-06-25 |
| EP1701942A1 (en) | 2006-09-20 |
| AU2004312284A2 (en) | 2005-07-21 |
| CA2550187A1 (en) | 2005-07-21 |
| DK1701942T3 (da) | 2010-04-06 |
| BRPI0418306A (pt) | 2007-05-02 |
| JP2007519640A (ja) | 2007-07-19 |
| EA009700B1 (ru) | 2008-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009102436A (ja) | 非ヌクレオシド逆転写酵素インヒビターとしてのシクロプロパヘテロ環 | |
| JP4762917B2 (ja) | 非ヌクレオシド逆転写酵素インヒビター | |
| JP2005538155A (ja) | 非ヌクレオシド逆転写酵素インヒビター | |
| AU2002308231A1 (en) | Cyclopropaheterocycles as non-nucleoside reverse transcriptase inhibitors | |
| MXPA02009618A (es) | Sulfonatos arilicos y heteroarilicos. | |
| US6610714B2 (en) | Non-nucleoside reverse transcriptase inhibitors | |
| CN1926108B (zh) | 非核苷酸逆转录酶抑制剂 | |
| MXPA06007726A (en) | Non-nucleotide reverse transcriptase inhibitors | |
| HK1101400B (en) | Non-nucleotide reverse transcriptase inhibitors | |
| AU2002311031A1 (en) | Urea and thiourea derivatives as non-nucleoside reverse transcriptase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071127 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071127 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090917 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101207 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110222 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110322 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110412 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110510 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110608 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140617 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |