BRPI0108485B1 - derivados do antiviral azaindol - Google Patents

Info

Publication number

BRPI0108485B1

BRPI0108485B1 BRPI0108485A BR0108485A BRPI0108485B1 BR PI0108485 B1 BRPI0108485 B1 BR PI0108485B1 BR PI0108485 A BRPI0108485 A BR PI0108485A BR 0108485 A BR0108485 A BR 0108485A BR PI0108485 B1 BRPI0108485 B1 BR PI0108485B1

Authority

BR

Brazil

Prior art keywords

compound

piperazine

azaindol

methyl

benzoyl

Prior art date

2000-02-22

Links

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• Global Dossier
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• 230000000840 anti-viral effect Effects 0.000 title abstract description 12
• 150000001875 compounds Chemical class 0.000 claims description 163
• 229910052739 hydrogen Inorganic materials 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 24
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 abstract description 16
• 230000002401 inhibitory effect Effects 0.000 abstract description 3
• 150000005829 chemical entities Chemical class 0.000 abstract 1
• 238000004949 mass spectrometry Methods 0.000 description 113
• 238000004128 high performance liquid chromatography Methods 0.000 description 106
• 230000014759 maintenance of location Effects 0.000 description 104
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 102
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 208000030507 AIDS Diseases 0.000 description 73
• -1 azaindole piperazine diamide derivatives Chemical class 0.000 description 71
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
• 238000002360 preparation method Methods 0.000 description 61
• 238000000034 method Methods 0.000 description 57
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
• 238000005481 NMR spectroscopy Methods 0.000 description 52
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 48
• 239000000243 solution Substances 0.000 description 46
• 238000012512 characterization method Methods 0.000 description 45
• 208000031886 HIV Infections Diseases 0.000 description 44
• 208000037357 HIV infectious disease Diseases 0.000 description 40
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 40
• 238000006243 chemical reaction Methods 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 235000019439 ethyl acetate Nutrition 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 28
• 239000002904 solvent Substances 0.000 description 28
• 239000000460 chlorine Substances 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• 239000000203 mixture Substances 0.000 description 26
• 230000015572 biosynthetic process Effects 0.000 description 25
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 24
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 23
• 239000002253 acid Substances 0.000 description 23
• 238000003786 synthesis reaction Methods 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
• 125000000304 alkynyl group Chemical group 0.000 description 21
• 229960002555 zidovudine Drugs 0.000 description 21
• 241000725303 Human immunodeficiency virus Species 0.000 description 20
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
• 210000004027 cell Anatomy 0.000 description 20
• 239000003814 drug Substances 0.000 description 19
• 238000002953 preparative HPLC Methods 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
• 239000012043 crude product Substances 0.000 description 16
• 125000000392 cycloalkenyl group Chemical group 0.000 description 16
• 229940079593 drug Drugs 0.000 description 16
• 239000003112 inhibitor Substances 0.000 description 16
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
• 229910001868 water Inorganic materials 0.000 description 16
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 15
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 14
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 14
• 239000007787 solid Substances 0.000 description 14
• 238000011282 treatment Methods 0.000 description 14
• 150000001204 N-oxides Chemical class 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
• 125000000623 heterocyclic group Chemical group 0.000 description 13
• 208000015181 infectious disease Diseases 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
• 239000012044 organic layer Substances 0.000 description 13
• 238000005160 1H NMR spectroscopy Methods 0.000 description 12
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 12
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 11
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• 125000003342 alkenyl group Chemical group 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• XTEOJPUYZWEXFI-UHFFFAOYSA-N butyl n-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate Chemical compound S1C(CC(C)C)=CC(C=2C=CC(CN3C=NC=C3)=CC=2)=C1S(=O)(=O)NC(=O)OCCCC XTEOJPUYZWEXFI-UHFFFAOYSA-N 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 230000005764 inhibitory process Effects 0.000 description 10
• 229910052757 nitrogen Inorganic materials 0.000 description 10
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
• 239000011591 potassium Substances 0.000 description 10
• 229910052700 potassium Inorganic materials 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 150000003112 potassium compounds Chemical class 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
• 208000007766 Kaposi sarcoma Diseases 0.000 description 8
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 8
• 241000700605 Viruses Species 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 150000004820 halides Chemical class 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 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 8
• 229960001936 indinavir Drugs 0.000 description 8
• RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 7
• 108060001084 Luciferase Proteins 0.000 description 7
• 239000005089 Luciferase Substances 0.000 description 7
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 7
• 150000002367 halogens Chemical class 0.000 description 7
• 238000004811 liquid chromatography Methods 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• 239000002777 nucleoside Substances 0.000 description 7
• 229910052708 sodium Inorganic materials 0.000 description 7
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
• 230000010933 acylation Effects 0.000 description 6
• 238000005917 acylation reaction Methods 0.000 description 6
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 6
• 238000005516 engineering process Methods 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 150000002825 nitriles Chemical class 0.000 description 6
• 239000008194 pharmaceutical composition Substances 0.000 description 6
• VUNXBQRNMNVUMV-UHFFFAOYSA-N phenyl(piperazin-1-yl)methanone Chemical class C=1C=CC=CC=1C(=O)N1CCNCC1 VUNXBQRNMNVUMV-UHFFFAOYSA-N 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 238000006722 reduction reaction Methods 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000002560 therapeutic procedure Methods 0.000 description 6
• 230000009466 transformation Effects 0.000 description 6
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 5
• NRSGWEVTVGZDFC-UHFFFAOYSA-N 6-chloro-4-n-[3,5-difluoro-4-[(3-methyl-1h-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl]pyrimidine-2,4-diamine Chemical compound C=12C(C)=CNC2=NC=CC=1OC(C(=C1)F)=C(F)C=C1NC1=CC(Cl)=NC(N)=N1 NRSGWEVTVGZDFC-UHFFFAOYSA-N 0.000 description 5
• 229940127007 Compound 39 Drugs 0.000 description 5
• 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 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
• 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 5
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 5
• XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 5
• 229960003804 efavirenz Drugs 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 150000004702 methyl esters Chemical class 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 5
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 5
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 5
• 150000003833 nucleoside derivatives Chemical class 0.000 description 5
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 5
• 150000004885 piperazines Chemical class 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 4
• SZCBDIVMCGFVPW-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 SZCBDIVMCGFVPW-UHFFFAOYSA-N 0.000 description 4
• WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 4
• SVVZGNAZMPSGMU-UHFFFAOYSA-N 2-chloro-5-fluoro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC(F)=CN=C1Cl SVVZGNAZMPSGMU-UHFFFAOYSA-N 0.000 description 4
• UPDSOLUKSUHRDC-UHFFFAOYSA-N 4-methoxy-1h-pyrrolo[2,3-c]pyridine Chemical compound COC1=CN=CC2=C1C=CN2 UPDSOLUKSUHRDC-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• ZBEYLQBHTDNDDR-UHFFFAOYSA-N 7-chloro-1h-pyrrolo[3,2-b]pyridine Chemical compound ClC1=CC=NC2=C1NC=C2 ZBEYLQBHTDNDDR-UHFFFAOYSA-N 0.000 description 4
• LCTSNWJDFWULAX-UHFFFAOYSA-N 7-chloro-4-fluoro-1h-pyrrolo[2,3-c]pyridine Chemical compound FC1=CN=C(Cl)C2=C1C=CN2 LCTSNWJDFWULAX-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
• 229940122440 HIV protease inhibitor Drugs 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• 229960004748 abacavir Drugs 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 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 4
• 239000003443 antiviral agent Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 229940126212 compound 17a Drugs 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
• 238000006073 displacement reaction Methods 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 210000003714 granulocyte Anatomy 0.000 description 4
• 239000002835 hiv fusion inhibitor Substances 0.000 description 4
• 239000004030 hiv protease inhibitor Substances 0.000 description 4
• 239000002955 immunomodulating agent Substances 0.000 description 4
• 229940121354 immunomodulator Drugs 0.000 description 4
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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