CA2657651A1 - Antiviral agents - Google Patents
Antiviral agents Download PDFInfo
- Publication number
- CA2657651A1 CA2657651A1 CA002657651A CA2657651A CA2657651A1 CA 2657651 A1 CA2657651 A1 CA 2657651A1 CA 002657651 A CA002657651 A CA 002657651A CA 2657651 A CA2657651 A CA 2657651A CA 2657651 A1 CA2657651 A1 CA 2657651A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- carbonylmethyl
- methyl
- amino
- compound
- 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
- 239000003443 antiviral agent Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 231
- 239000000203 mixture Substances 0.000 claims abstract description 65
- 230000009385 viral infection Effects 0.000 claims abstract description 11
- 241000710781 Flaviviridae Species 0.000 claims abstract description 10
- -1 amino, substituted amino Chemical group 0.000 claims description 688
- 125000000623 heterocyclic group Chemical group 0.000 claims description 168
- 125000001072 heteroaryl group Chemical group 0.000 claims description 120
- 125000000217 alkyl group Chemical group 0.000 claims description 86
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 65
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 65
- 125000003118 aryl group Chemical group 0.000 claims description 58
- 241000711549 Hepacivirus C Species 0.000 claims description 55
- 125000003107 substituted aryl group Chemical group 0.000 claims description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 36
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 19
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 18
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 18
- 241000700605 Viruses Species 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- 125000004442 acylamino group Chemical group 0.000 claims description 14
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 208000036142 Viral infection Diseases 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000005518 carboxamido group Chemical group 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 108060004795 Methyltransferase Proteins 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000000732 arylene group Chemical group 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000005549 heteroarylene group Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000004463 2,4-dimethyl-thiazol-5-yl group Chemical group CC=1SC(=C(N1)C)* 0.000 claims description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- 102000016600 Inosine-5'-monophosphate dehydrogenases Human genes 0.000 claims description 4
- 108050006182 Inosine-5'-monophosphate dehydrogenases Proteins 0.000 claims description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 4
- 108091005804 Peptidases Proteins 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000004365 Protease Substances 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 3
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 3
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 3
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 3
- MZYXHLMULHPGKX-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)ethanamine Chemical compound NCCC1=NN=NN1 MZYXHLMULHPGKX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical compound NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- HQCVEGNPQFRFPC-UHFFFAOYSA-N carboxy acetate Chemical compound CC(=O)OC(O)=O HQCVEGNPQFRFPC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 101800001019 Non-structural protein 4B Proteins 0.000 claims description 2
- 101800001014 Non-structural protein 5A Proteins 0.000 claims description 2
- 102000035195 Peptidases Human genes 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000036961 partial effect Effects 0.000 claims description 2
- 125000001116 prolino group Chemical group [H]OC(=O)C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 82
- 238000006243 chemical reaction Methods 0.000 description 70
- IULABJQOVJBYGK-UHFFFAOYSA-N 4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound N1C=CC2=C1C=C(C(=O)O)S2 IULABJQOVJBYGK-UHFFFAOYSA-N 0.000 description 63
- 239000002253 acid Substances 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- 150000002431 hydrogen Chemical class 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
- 125000001424 substituent group Chemical group 0.000 description 28
- 239000007787 solid Substances 0.000 description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 229960000329 ribavirin Drugs 0.000 description 20
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 20
- 108010047761 Interferon-alpha Proteins 0.000 description 19
- 102000006992 Interferon-alpha Human genes 0.000 description 19
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 125000004104 aryloxy group Chemical group 0.000 description 19
- 239000000843 powder Substances 0.000 description 19
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 229910052736 halogen Inorganic materials 0.000 description 13
- 150000002367 halogens Chemical class 0.000 description 13
- 150000004702 methyl esters Chemical class 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 208000015181 infectious disease Diseases 0.000 description 10
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 125000004423 acyloxy group Chemical group 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 8
- 229950006081 taribavirin Drugs 0.000 description 8
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 description 7
- 102000014150 Interferons Human genes 0.000 description 7
- 108010050904 Interferons Proteins 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 230000000840 anti-viral effect Effects 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 229940079322 interferon Drugs 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- NCNOPYBJCBOGQU-UHFFFAOYSA-N 6-(cyclohexen-1-yl)-5-[2-(2,4-dimethyl-1,3-thiazol-5-yl)quinolin-6-yl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound S1C(C)=NC(C)=C1C1=CC=C(C=C(C=C2)C=3N(C=4C=C(SC=4C=3C=3CCCCC=3)C(O)=O)CC(=O)N3CCOCC3)C2=N1 NCNOPYBJCBOGQU-UHFFFAOYSA-N 0.000 description 6
- SLMBJCZHIWFVHE-UHFFFAOYSA-N 6-(cyclohexen-1-yl)-5-[2-(2-fluorophenyl)quinolin-6-yl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C2N=C(C=3C(=CC=CC=3)F)C=CC2=CC=1C1=C(C=2CCCCC=2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 SLMBJCZHIWFVHE-UHFFFAOYSA-N 0.000 description 6
- MVEOHWRUBFWKJY-UHFFFAOYSA-N 7-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(O)=CC=C21 MVEOHWRUBFWKJY-UHFFFAOYSA-N 0.000 description 6
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83104006P | 2006-07-14 | 2006-07-14 | |
| US60/831,040 | 2006-07-14 | ||
| PCT/US2007/073391 WO2008008912A1 (en) | 2006-07-14 | 2007-07-12 | Antiviral agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2657651A1 true CA2657651A1 (en) | 2008-01-17 |
Family
ID=38742551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002657651A Abandoned CA2657651A1 (en) | 2006-07-14 | 2007-07-12 | Antiviral agents |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP2044083A1 (pt) |
| JP (1) | JP2009543807A (pt) |
| KR (1) | KR20090033881A (pt) |
| CN (1) | CN101490058A (pt) |
| AR (1) | AR062258A1 (pt) |
| AU (1) | AU2007272441A1 (pt) |
| BR (1) | BRPI0714346A2 (pt) |
| CA (1) | CA2657651A1 (pt) |
| MX (1) | MX2009000513A (pt) |
| PE (1) | PE20080427A1 (pt) |
| RU (1) | RU2009105196A (pt) |
| TW (1) | TW200813070A (pt) |
| WO (2) | WO2008008912A1 (pt) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
| WO2008137126A2 (en) | 2007-05-04 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of hcv infection |
| MY159958A (en) | 2009-12-18 | 2017-02-15 | Idenix Pharmaceuticals Inc | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
| EP2655362A1 (en) * | 2010-12-22 | 2013-10-30 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| US20120252721A1 (en) * | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| FR3008975A1 (fr) | 2013-07-23 | 2015-01-30 | Servier Lab | Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| RU2546006C1 (ru) | 2014-03-07 | 2015-04-10 | Римма Ильинична Ашкинази | Противовирусное средство |
| EP3248596B1 (en) | 2015-01-20 | 2023-12-06 | Tets, Viktor Veniaminovich | Hemostatic agent |
| US10167293B2 (en) * | 2016-05-26 | 2019-01-01 | Bayer Pharma Aktiengesellschaft | [8-(phenylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanones |
| WO2018217743A1 (en) | 2017-05-24 | 2018-11-29 | Viktor Veniaminovich Tets | Fractionated antimicrobial compositions and use thereof |
| IL307203A (en) * | 2021-04-16 | 2023-11-01 | Gilead Sciences Inc | THIENOPYRROLE COMPOUNDS |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE438637T1 (de) * | 2001-06-11 | 2009-08-15 | Virochem Pharma Inc | Thiophenderivate als antivirale mittel gegen flavivirus-infektion |
| KR20060015742A (ko) * | 2003-06-04 | 2006-02-20 | 제네랩스 테크놀로지스, 인코포레이티드 | Ｈｃｖ 감염의 치료를 위한 질소 함유 헤테로아릴 유도체 |
-
2007
- 2007-07-12 WO PCT/US2007/073391 patent/WO2008008912A1/en active Application Filing
- 2007-07-12 MX MX2009000513A patent/MX2009000513A/es not_active Application Discontinuation
- 2007-07-12 BR BRPI0714346-0A patent/BRPI0714346A2/pt not_active Application Discontinuation
- 2007-07-12 CN CNA2007800266569A patent/CN101490058A/zh active Pending
- 2007-07-12 EP EP07799544A patent/EP2044083A1/en not_active Withdrawn
- 2007-07-12 RU RU2009105196/04A patent/RU2009105196A/ru not_active Application Discontinuation
- 2007-07-12 WO PCT/US2007/073386 patent/WO2008008907A2/en active Application Filing
- 2007-07-12 CA CA002657651A patent/CA2657651A1/en not_active Abandoned
- 2007-07-12 AU AU2007272441A patent/AU2007272441A1/en not_active Abandoned
- 2007-07-12 JP JP2009519699A patent/JP2009543807A/ja active Pending
- 2007-07-12 KR KR1020097001707A patent/KR20090033881A/ko not_active Application Discontinuation
- 2007-07-13 TW TW096125693A patent/TW200813070A/zh unknown
- 2007-07-13 PE PE2007000902A patent/PE20080427A1/es not_active Application Discontinuation
- 2007-07-13 AR ARP070103144A patent/AR062258A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009543807A (ja) | 2009-12-10 |
| CN101490058A (zh) | 2009-07-22 |
| EP2044083A1 (en) | 2009-04-08 |
| WO2008008912A1 (en) | 2008-01-17 |
| TW200813070A (en) | 2008-03-16 |
| AU2007272441A2 (en) | 2009-03-19 |
| BRPI0714346A2 (pt) | 2013-03-19 |
| PE20080427A1 (es) | 2008-06-11 |
| WO2008008907A3 (en) | 2008-03-20 |
| AU2007272441A1 (en) | 2008-01-17 |
| MX2009000513A (es) | 2009-03-09 |
| RU2009105196A (ru) | 2010-08-27 |
| WO2008008907A2 (en) | 2008-01-17 |
| AR062258A1 (es) | 2008-10-29 |
| KR20090033881A (ko) | 2009-04-06 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |