BG107677A - Аза - и полиаза - нафталенил карбоксамиди, приложими като инхибитори на hiv интеграза - Google Patents

Info

Publication number

BG107677A

BG107677A BG107677A BG10767703A BG107677A BG 107677 A BG107677 A BG 107677A BG 107677 A BG107677 A BG 107677A BG 10767703 A BG10767703 A BG 10767703A BG 107677 A BG107677 A BG 107677A

Authority

BG

Bulgaria

Prior art keywords

alkyl

fluoroalkyl

substituted

phenyl

hydroxy

Prior art date

2000-10-12

Links

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• Global Dossier
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• 229940099797 HIV integrase inhibitor Drugs 0.000 title description 2
• 239000003084 hiv integrase inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 98
• 150000003839 salts Chemical class 0.000 claims abstract description 27
• 108010002459 HIV Integrase Proteins 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 159
• -1 1,2-Thiazinan-2-yl Chemical group 0.000 claims description 86
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 66
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
• 125000001424 substituent group Chemical group 0.000 claims description 54
• 229910052757 nitrogen Inorganic materials 0.000 claims description 46
• 150000002367 halogens Chemical class 0.000 claims description 45
• 229910052736 halogen Inorganic materials 0.000 claims description 44
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 238000002360 preparation method Methods 0.000 claims description 31
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 27
• 125000005842 heteroatom Chemical group 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 208000031886 HIV Infections Diseases 0.000 claims description 17
• 208000037357 HIV infectious disease Diseases 0.000 claims description 17
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 229920006395 saturated elastomer Polymers 0.000 claims description 16
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 12
• 239000011593 sulfur Substances 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 125000001624 naphthyl group Chemical group 0.000 claims description 10
• 239000001301 oxygen Substances 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 125000001246 bromo group Chemical group Br* 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 3
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• LLHVPPRDIBQMKN-UHFFFAOYSA-N 5-(1,1-dioxothiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound O=S1(N(CCCC1)C1=C2C=CC=NC2=C(C(=N1)C(=O)N)O)=O LLHVPPRDIBQMKN-UHFFFAOYSA-N 0.000 claims 1
• 108010044467 Isoenzymes Proteins 0.000 claims 1
• 150000001721 carbon Chemical group 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 34
• 239000003112 inhibitor Substances 0.000 abstract description 14
• 239000003443 antiviral agent Substances 0.000 abstract description 10
• 230000010076 replication Effects 0.000 abstract description 9
• 208000030507 AIDS Diseases 0.000 abstract description 5
• 239000004615 ingredient Substances 0.000 abstract description 5
• JKNBCQYLFYHBHU-UHFFFAOYSA-N 1,8-naphthyridine-2-carboxamide Chemical class C1=CC=NC2=NC(C(=O)N)=CC=C21 JKNBCQYLFYHBHU-UHFFFAOYSA-N 0.000 abstract description 3
• 239000002955 immunomodulating agent Substances 0.000 abstract description 3
• 229940121354 immunomodulator Drugs 0.000 abstract description 3
• 230000002265 prevention Effects 0.000 abstract description 3
• 229960005486 vaccine Drugs 0.000 abstract description 3
• 229940053202 antiepileptics carboxamide derivative Drugs 0.000 abstract description 2
• 208000015181 infectious disease Diseases 0.000 abstract 2
• 239000003242 anti bacterial agent Substances 0.000 abstract 1
• 229940088710 antibiotic agent Drugs 0.000 abstract 1
• 229940042443 other antivirals in atc Drugs 0.000 abstract 1
• ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
• 239000000243 solution Substances 0.000 description 38
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• 239000000203 mixture Substances 0.000 description 35
• 239000007787 solid Substances 0.000 description 35
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
• 238000005481 NMR spectroscopy Methods 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
• 241000725303 Human immunodeficiency virus Species 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 22
• 239000011541 reaction mixture Substances 0.000 description 22
• 239000002904 solvent Substances 0.000 description 19
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
• 239000000047 product Substances 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 15
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 14
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• 238000010265 fast atom bombardment Methods 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 229910052739 hydrogen Inorganic materials 0.000 description 11
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 102100034343 Integrase Human genes 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
• 239000012074 organic phase Substances 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• 108010061833 Integrases Proteins 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 125000004122 cyclic group Chemical group 0.000 description 8
• 239000002777 nucleoside Substances 0.000 description 8
• 150000003833 nucleoside derivatives Chemical class 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• PQIYSSSTRHVOBW-UHFFFAOYSA-N 3-bromopropan-1-amine;hydron;bromide Chemical compound Br.NCCCBr PQIYSSSTRHVOBW-UHFFFAOYSA-N 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 238000010829 isocratic elution Methods 0.000 description 7
• 230000014759 maintenance of location Effects 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• YKEGCGXXZWOYCF-UHFFFAOYSA-N 1,6-naphthyridine-7-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)N)=CC2=N1 YKEGCGXXZWOYCF-UHFFFAOYSA-N 0.000 description 6
• 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 6
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 238000012546 transfer Methods 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• HHEOXNRPYVCORL-UHFFFAOYSA-N methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C1=CC=NC2=C(O)C(C(=O)OC)=NC(Br)=C21 HHEOXNRPYVCORL-UHFFFAOYSA-N 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 238000000634 powder X-ray diffraction Methods 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 159000000000 sodium salts Chemical group 0.000 description 5
• 229940124530 sulfonamide Drugs 0.000 description 5
• 150000003456 sulfonamides Chemical class 0.000 description 5
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical class N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• ACOKNWXGEPFMGV-UHFFFAOYSA-N 4-fluoro-2-methylsulfonylbenzonitrile Chemical compound CS(=O)(=O)C1=CC(F)=CC=C1C#N ACOKNWXGEPFMGV-UHFFFAOYSA-N 0.000 description 4
• DIDKWCOCQJWMDJ-UHFFFAOYSA-N 5-(1,1-dioxothiazinan-2-yl)-n-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide Chemical compound C12=CC=CN=C2C(O)=C(C(=O)NCC=2C=CC(F)=CC=2)N=C1N1CCCCS1(=O)=O DIDKWCOCQJWMDJ-UHFFFAOYSA-N 0.000 description 4
• 108020004414 DNA Proteins 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 239000012300 argon atmosphere Substances 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 150000003857 carboxamides Chemical class 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 239000004030 hiv protease inhibitor Substances 0.000 description 4
• 230000010354 integration Effects 0.000 description 4
• 125000000842 isoxazolyl group Chemical group 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
• 239000000825 pharmaceutical preparation Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 125000001544 thienyl group Chemical group 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 230000002924 anti-infective effect Effects 0.000 description 3
• 230000000840 anti-viral effect Effects 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• 239000010949 copper Substances 0.000 description 3
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• 238000010168 coupling process Methods 0.000 description 3
• LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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• 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 3
• 229960003804 efavirenz Drugs 0.000 description 3
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
• 238000004108 freeze drying Methods 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
• VRDCTKAFGYAUBU-UHFFFAOYSA-N methyl 5-(1,1-dioxothiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C=12C=CC=NC2=C(O)C(C(=O)OC)=NC=1N1CCCCS1(=O)=O VRDCTKAFGYAUBU-UHFFFAOYSA-N 0.000 description 3
• YXGQKWXSHVOXAQ-UHFFFAOYSA-N methyl 5-bromo-8-(4-methylphenyl)sulfonyloxy-1,6-naphthyridine-7-carboxylate Chemical compound COC(=O)C1=NC(Br)=C2C=CC=NC2=C1OS(=O)(=O)C1=CC=C(C)C=C1 YXGQKWXSHVOXAQ-UHFFFAOYSA-N 0.000 description 3
• WDCSXBRXJCGXNG-UHFFFAOYSA-N methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate Chemical compound C1=CC=NC2=C(O)C(C(=O)OC)=NC=C21 WDCSXBRXJCGXNG-UHFFFAOYSA-N 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• 150000005054 naphthyridines Chemical class 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 125000004043 oxo group Chemical group O=* 0.000 description 3
• 230000001566 pro-viral effect Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 125000003373 pyrazinyl group Chemical group 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
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