CA2118324A1 - Substituted indolizino¬1,2-b|quinolinones - Google Patents
Substituted indolizino¬1,2-b|quinolinonesInfo
- Publication number
- CA2118324A1 CA2118324A1 CA002118324A CA2118324A CA2118324A1 CA 2118324 A1 CA2118324 A1 CA 2118324A1 CA 002118324 A CA002118324 A CA 002118324A CA 2118324 A CA2118324 A CA 2118324A CA 2118324 A1 CA2118324 A1 CA 2118324A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- quinolin
- oxy
- propyl
- methyl
- 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.)
- Abandoned
Links
- 229930185107 quinolinone Natural products 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 100
- 230000009385 viral infection Effects 0.000 claims abstract description 14
- 208000036142 Viral infection Diseases 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 246
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 44
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 241000700605 Viruses Species 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- YJSPDKPPDSKBQZ-UHFFFAOYSA-N 11h-indolizino[1,2-b]quinolin-9-one Chemical compound C1=CC=C2C=C(CN3C(=O)C=CC=C33)C3=NC2=C1 YJSPDKPPDSKBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 241000701022 Cytomegalovirus Species 0.000 claims description 4
- 241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 4
- 241000700584 Simplexvirus Species 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 3
- 241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 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
- 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- NZNUDBVXWDYNEN-UHFFFAOYSA-N 1-(12-cyano-8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-aminoacetate Chemical compound C1=CC=C2C(C#N)=C(CN3C4=CC(=C(C3=O)C)C(OC(=O)CN)CC)C4=NC2=C1 NZNUDBVXWDYNEN-UHFFFAOYSA-N 0.000 claims 2
- RVWPSIYNXOHDGG-UHFFFAOYSA-N 1-(2-cyano-8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-aminoacetate Chemical compound C1=C(C#N)C=C2C=C(CN3C4=CC(=C(C3=O)C)C(OC(=O)CN)CC)C4=NC2=C1 RVWPSIYNXOHDGG-UHFFFAOYSA-N 0.000 claims 2
- ATFRQBIQAUCQOY-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-amino-2-methylpropanoate Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(OC(=O)C(C)(C)N)CC)C4=NC2=C1 ATFRQBIQAUCQOY-UHFFFAOYSA-N 0.000 claims 2
- CYLKLPDYCVLODG-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-aminoacetate Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(OC(=O)CN)CC)C4=NC2=C1 CYLKLPDYCVLODG-UHFFFAOYSA-N 0.000 claims 2
- LEVQPAPUQREIEZ-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-morpholin-4-ylacetate Chemical compound C1=C2C3=NC4=CC=CC=C4C=C3CN2C(=O)C(C)=C1C(CC)OC(=O)CN1CCOCC1 LEVQPAPUQREIEZ-UHFFFAOYSA-N 0.000 claims 2
- YUBLCKWWYTZJDS-UHFFFAOYSA-M 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-pyridin-1-ium-1-ylacetate;iodide Chemical compound [I-].C1=C2C3=NC4=CC=CC=C4C=C3CN2C(=O)C(C)=C1C(CC)OC(=O)C[N+]1=CC=CC=C1 YUBLCKWWYTZJDS-UHFFFAOYSA-M 0.000 claims 2
- PABQHVNMQAWSRO-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 3-aminopropanoate Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(OC(=O)CCN)CC)C4=NC2=C1 PABQHVNMQAWSRO-UHFFFAOYSA-N 0.000 claims 2
- GASBXNGOHVGADU-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl dihydrogen phosphate Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(OP(O)(O)=O)CC)C4=NC2=C1 GASBXNGOHVGADU-UHFFFAOYSA-N 0.000 claims 2
- CATJSCBBZPENJL-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl pyrrolidine-2-carboxylate Chemical compound C1=C2C3=NC4=CC=CC=C4C=C3CN2C(=O)C(C)=C1C(CC)OC(=O)C1CCCN1 CATJSCBBZPENJL-UHFFFAOYSA-N 0.000 claims 2
- ASMQRBZYXVVTQS-UHFFFAOYSA-N aminomethyl-[1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propoxy]phosphinic acid Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(OP(O)(=O)CN)CC)C4=NC2=C1 ASMQRBZYXVVTQS-UHFFFAOYSA-N 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- ZGSVCOICEJUBMP-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 2-(pyrrolidine-2-carbonylamino)acetate Chemical compound C1=C2C3=NC4=CC=CC=C4C=C3CN2C(=O)C(C)=C1C(CC)OC(=O)CNC(=O)C1CCCN1 ZGSVCOICEJUBMP-UHFFFAOYSA-N 0.000 claims 1
- OZXUAXMPTKVOSJ-UHFFFAOYSA-N 1-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propyl 4-[(dimethylamino)methyl]benzoate Chemical compound C1=C2C3=NC4=CC=CC=C4C=C3CN2C(=O)C(C)=C1C(CC)OC(=O)C1=CC=C(CN(C)C)C=C1 OZXUAXMPTKVOSJ-UHFFFAOYSA-N 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 6
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 abstract description 2
- IJKXJZJLJSCTHE-UHFFFAOYSA-N indolizin-1-ol Chemical class C1=CC=CC2=C(O)C=CN21 IJKXJZJLJSCTHE-UHFFFAOYSA-N 0.000 abstract 1
- 229910001868 water Inorganic materials 0.000 description 80
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- -1 molpholine Natural products 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- 239000002904 solvent Substances 0.000 description 23
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 150000008648 triflates Chemical class 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- 229940127093 camptothecin Drugs 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 125000000468 ketone group Chemical group 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 102000003915 DNA Topoisomerases Human genes 0.000 description 5
- 108090000323 DNA Topoisomerases Proteins 0.000 description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 150000004678 hydrides Chemical class 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000007333 cyanation reaction Methods 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
- 150000002596 lactones Chemical group 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- SEBNUFCVXMXPAE-UHFFFAOYSA-N 2h-indolizino[1,2-b]quinolin-1-one Chemical class C1=CC=CC2=C3N=C4C=CCC(=O)C4=CC3=CN21 SEBNUFCVXMXPAE-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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 229930194542 Keto Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 125000002346 iodo group Chemical group I* 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 description 2
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HAWSQZCWOQZXHI-UHFFFAOYSA-N CPT-OH Natural products C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- 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 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical class C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
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- 229940099990 ogen Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229940116254 phosphonic acid Drugs 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- RTWCHRMHGXBETA-UHFFFAOYSA-N prop-1-yn-1-amine Chemical class CC#CN RTWCHRMHGXBETA-UHFFFAOYSA-N 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 210000004767 rumen Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 238000006886 vinylation reaction Methods 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229940107931 zovirax Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87064992A | 1992-04-17 | 1992-04-17 | |
| US07/870,649 | 1992-04-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2118324A1 true CA2118324A1 (en) | 1993-10-28 |
Family
ID=25355849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002118324A Abandoned CA2118324A1 (en) | 1992-04-17 | 1993-04-15 | Substituted indolizino¬1,2-b|quinolinones |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0637960A4 (enrdf_load_stackoverflow) |
| JP (1) | JPH07506099A (enrdf_load_stackoverflow) |
| KR (1) | KR950701219A (enrdf_load_stackoverflow) |
| CN (1) | CN1083064A (enrdf_load_stackoverflow) |
| AU (1) | AU4288893A (enrdf_load_stackoverflow) |
| CA (1) | CA2118324A1 (enrdf_load_stackoverflow) |
| TW (1) | TW264471B (enrdf_load_stackoverflow) |
| ZA (1) | ZA932721B (enrdf_load_stackoverflow) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093358B (zh) * | 2011-02-21 | 2012-09-05 | 中山大学 | 溴代中氮茚并喹啉二酮类衍生物及其在制备抗菌药物中的应用 |
| CN104398514B (zh) * | 2014-10-28 | 2017-04-19 | 中山大学 | 氯喹在制备抗疱疹病毒药物中的应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5422344A (en) * | 1990-05-08 | 1995-06-06 | The United States Of America As Represented By The Secretary Of The Department Of Health & Human Services | Method of treating retroviral infections in mammals |
| US5155225A (en) * | 1990-09-28 | 1992-10-13 | Smithkline Beecham Corporation | Method for making certain pyrano[3',4':6,7]indolizino-[1,2-B]quinolinones |
| WO1992007856A1 (en) * | 1990-10-31 | 1992-05-14 | Smithkline Beecham Corporation | SUBSTITUTED INDOLIZINO[1,2-b]QUINOLINONES |
-
1993
- 1993-04-15 JP JP5518629A patent/JPH07506099A/ja active Pending
- 1993-04-15 CA CA002118324A patent/CA2118324A1/en not_active Abandoned
- 1993-04-15 AU AU42888/93A patent/AU4288893A/en not_active Abandoned
- 1993-04-15 KR KR1019940703719A patent/KR950701219A/ko not_active Withdrawn
- 1993-04-15 EP EP93912281A patent/EP0637960A4/en not_active Withdrawn
- 1993-04-17 CN CN93105930A patent/CN1083064A/zh active Pending
- 1993-04-19 ZA ZA932721A patent/ZA932721B/xx unknown
- 1993-05-29 TW TW082104275A patent/TW264471B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| EP0637960A4 (en) | 1995-06-07 |
| AU4288893A (en) | 1993-11-18 |
| EP0637960A1 (en) | 1995-02-15 |
| ZA932721B (en) | 1993-11-29 |
| KR950701219A (ko) | 1995-03-23 |
| TW264471B (enrdf_load_stackoverflow) | 1995-12-01 |
| CN1083064A (zh) | 1994-03-02 |
| JPH07506099A (ja) | 1995-07-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |