DE69626915T2 - 8-Arylalkyl- und 8-Arylheteroalkyl-5, 11-dihydro-6H-dipyrido-(3,2-b:2', 3'-e)(1,4)diazepine und ihre Verwendung zur Vorbeugung oder Behandlung von HIV-Infektion - Google Patents
8-Arylalkyl- und 8-Arylheteroalkyl-5, 11-dihydro-6H-dipyrido-(3,2-b:2', 3'-e)(1,4)diazepine und ihre Verwendung zur Vorbeugung oder Behandlung von HIV-InfektionInfo
- Publication number
- DE69626915T2 DE69626915T2 DE69626915T DE69626915T DE69626915T2 DE 69626915 T2 DE69626915 T2 DE 69626915T2 DE 69626915 T DE69626915 T DE 69626915T DE 69626915 T DE69626915 T DE 69626915T DE 69626915 T2 DE69626915 T2 DE 69626915T2
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- ethyl
- carbon atoms
- dihydro
- dipyrido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 12
- 208000031886 HIV Infections Diseases 0.000 title claims abstract description 9
- 230000002265 prevention Effects 0.000 title claims abstract description 7
- 208000037357 HIV infectious disease Diseases 0.000 title abstract 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 title abstract 2
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical class N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 253
- 125000004432 carbon atom Chemical group C* 0.000 claims description 149
- -1 ethylamino, acetamido, acetyl Chemical group 0.000 claims description 120
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000004429 atom Chemical group 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 125000004414 alkyl thio group Chemical group 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical group 0.000 claims description 18
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 18
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 18
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 229910052801 chlorine Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 8
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- JISVFSBNJCUDHU-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(2-pyridin-4-ylethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1CCC1=CC=NC=C1 JISVFSBNJCUDHU-UHFFFAOYSA-N 0.000 claims description 7
- 150000001336 alkenes Chemical class 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- ULVUURBFDYVMPY-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(2-pyridin-4-ylethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1CCC1=CC=NC=C1 ULVUURBFDYVMPY-UHFFFAOYSA-N 0.000 claims description 4
- VCLGTWSYOLHYCH-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(2-pyridin-4-yloxyethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1CCOC1=CC=NC=C1 VCLGTWSYOLHYCH-UHFFFAOYSA-N 0.000 claims description 4
- TYPYIAOCHCKFIA-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(phenylsulfanylmethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1CSC1=CC=CC=C1 TYPYIAOCHCKFIA-UHFFFAOYSA-N 0.000 claims description 4
- MGZRDDUEGVRPHN-UHFFFAOYSA-N 2-chloro-11-ethyl-8-(2-hydroxy-2-pyridin-4-ylethyl)-5-methyldipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1CC(O)C1=CC=NC=C1 MGZRDDUEGVRPHN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000466 oxiranyl group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 4
- RCZBRRIUHGFFMJ-UHFFFAOYSA-N 11-ethyl-2-fluoro-8-(2-hydroxy-2-pyridin-4-ylethyl)-5-methyldipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1CC(O)C1=CC=NC=C1 RCZBRRIUHGFFMJ-UHFFFAOYSA-N 0.000 claims description 3
- AHAQASQWEHMCHG-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(pyridin-4-ylsulfanylmethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1CSC1=CC=NC=C1 AHAQASQWEHMCHG-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- YUHUGAAISLIFCE-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(2-pyridin-4-yloxyethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1CCOC1=CC=NC=C1 YUHUGAAISLIFCE-UHFFFAOYSA-N 0.000 claims description 2
- SPXQUPQCZUOOCQ-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(phenylsulfanylmethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1CSC1=CC=CC=C1 SPXQUPQCZUOOCQ-UHFFFAOYSA-N 0.000 claims description 2
- YKGOEDBDALKHFV-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(pyridin-4-ylmethoxymethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1COCC1=CC=NC=C1 YKGOEDBDALKHFV-UHFFFAOYSA-N 0.000 claims description 2
- BMCALDMFEXQQRY-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(pyridin-4-yloxymethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1COC1=CC=NC=C1 BMCALDMFEXQQRY-UHFFFAOYSA-N 0.000 claims description 2
- MHYFAWNAKSZSLJ-UHFFFAOYSA-N 11-ethyl-2-fluoro-5-methyl-8-(pyridin-4-ylsulfanylmethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1CSC1=CC=NC=C1 MHYFAWNAKSZSLJ-UHFFFAOYSA-N 0.000 claims description 2
- SSBKOEBEWJHUQR-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(pyridin-4-yloxymethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1COC1=CC=NC=C1 SSBKOEBEWJHUQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- DHUJHUFQRGWMTJ-UHFFFAOYSA-N 8-[(3-aminophenoxy)methyl]-11-ethyl-2-fluoro-5-methyldipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(F)=CC=C3N(C)C(=O)C2=CC=1COC1=CC=CC(N)=C1 DHUJHUFQRGWMTJ-UHFFFAOYSA-N 0.000 claims description 2
- GGICVMHKERQRRS-UHFFFAOYSA-N 8-[(3-aminophenoxy)methyl]-2-chloro-11-ethyl-5-methyldipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1COC1=CC=CC(N)=C1 GGICVMHKERQRRS-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000005002 aryl methyl group Chemical group 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- OJNIFBJDBPQXIY-UHFFFAOYSA-N 2-chloro-11-ethyl-5-methyl-8-(pyridin-4-ylmethoxymethyl)dipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound C=1N=C2N(CC)C3=NC(Cl)=CC=C3N(C)C(=O)C2=CC=1COCC1=CC=NC=C1 OJNIFBJDBPQXIY-UHFFFAOYSA-N 0.000 claims 1
- 238000013329 compounding Methods 0.000 claims 1
- 150000004908 diazepines Chemical class 0.000 claims 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 336
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 139
- 238000000034 method Methods 0.000 description 133
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 73
- 239000011541 reaction mixture Substances 0.000 description 73
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- 239000000047 product Substances 0.000 description 67
- 239000000243 solution Substances 0.000 description 66
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- 238000003818 flash chromatography Methods 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
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- 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 34
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- 102100034343 Integrase Human genes 0.000 description 32
- 229920006395 saturated elastomer Polymers 0.000 description 31
- 239000002904 solvent Substances 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- 238000001953 recrystallisation Methods 0.000 description 29
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 239000013078 crystal Substances 0.000 description 26
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- NSXKHLFKMRRCOE-UHFFFAOYSA-N 2-chloro-8-(chloromethyl)-11-ethyl-5-methyldipyrido[2,4-d:2',3'-h][1,4]diazepin-6-one Chemical compound CN1C(=O)C2=CC(CCl)=CN=C2N(CC)C2=NC(Cl)=CC=C21 NSXKHLFKMRRCOE-UHFFFAOYSA-N 0.000 description 22
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- 238000003556 assay Methods 0.000 description 19
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 19
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
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- 229910000104 sodium hydride Inorganic materials 0.000 description 13
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- 238000005984 hydrogenation reaction Methods 0.000 description 12
- MYJWRKKBBZLUSJ-UHFFFAOYSA-N 11-ethyl-8-iodo-5-methyldipyrido[2,3-d:2',3'-h][1,4]diazepin-6-one Chemical compound CN1C(=O)C2=CC(I)=CN=C2N(CC)C2=NC=CC=C21 MYJWRKKBBZLUSJ-UHFFFAOYSA-N 0.000 description 11
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- 238000012546 transfer Methods 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- C07D471/12—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 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (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 |
|---|---|---|---|
| US480695P | 1995-10-06 | 1995-10-06 | |
| US869595P | 1995-12-15 | 1995-12-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69626915D1 DE69626915D1 (de) | 2003-04-30 |
| DE69626915T2 true DE69626915T2 (de) | 2003-11-13 |
Family
ID=26673503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69626915T Expired - Fee Related DE69626915T2 (de) | 1995-10-06 | 1996-10-04 | 8-Arylalkyl- und 8-Arylheteroalkyl-5, 11-dihydro-6H-dipyrido-(3,2-b:2', 3'-e)(1,4)diazepine und ihre Verwendung zur Vorbeugung oder Behandlung von HIV-Infektion |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5705499A (enExample) |
| EP (1) | EP0767172B1 (enExample) |
| JP (1) | JPH09188680A (enExample) |
| AT (1) | ATE235495T1 (enExample) |
| DE (1) | DE69626915T2 (enExample) |
| DK (1) | DK0767172T3 (enExample) |
| ES (1) | ES2191075T3 (enExample) |
| PT (1) | PT767172E (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5747488A (en) * | 1996-01-30 | 1998-05-05 | Boehringer Ingelheim Pharmaceuticals, Inc. | 2-aryl-5,11-dihydro-6H-dipyrido 3,2-B:2',3'-E! 1, 4!diazepines and their use in the treatment of HIV infection |
| GB9715584D0 (en) * | 1997-07-23 | 1997-10-01 | Eisai Co Ltd | Compounds |
| UA71971C2 (en) | 1999-06-04 | 2005-01-17 | Agoron Pharmaceuticals Inc | Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases |
| US6455554B1 (en) | 1999-06-07 | 2002-09-24 | Targacept, Inc. | Oxopyridinyl pharmaceutical compositions and methods for use |
| US7141581B2 (en) * | 1999-07-02 | 2006-11-28 | Agouron Pharmaceuticals, Inc. | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
| TWI262914B (en) * | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| HN2001000008A (es) * | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| BR0110302A (pt) | 2000-04-18 | 2003-01-14 | Agouron Pharma | Compostos de pirazol para inibição de proteìnas cinase, sal e pró-droga farmaceuticamente aceitável, metabólito farmaceuticamente ativo ou sal farmaceuticamente aceitável de metabólito, composição farmacêutica, método de tratamento de condição doentia em mamìferos mediada pela atividade de proteìna cinase, método de modulação ou inibição da atividade de um receptor de proteìna cinase |
| TWI270547B (en) * | 2000-06-16 | 2007-01-11 | Boehringer Ingelheim Ca Ltd | Non-nucleoside reverse transcriptase inhibitors |
| SI1294720T1 (sl) * | 2000-06-16 | 2006-08-31 | Boehringer Ingelheim Ca Ltd | Nenukleozidni inhibitorji reverzne transkriptaze |
| US6716836B2 (en) | 2001-03-22 | 2004-04-06 | Boehringer Ingelheim (Canada) Ltd. | Non-nucleoside reverse transcriptase inhibitors |
| US6673791B2 (en) * | 2001-07-30 | 2004-01-06 | Boehringer Ingelheim (Canada) Ltd. | Non-nucleoside reverse transcriptase inhibitors |
| US6706706B2 (en) | 2002-03-27 | 2004-03-16 | Boehringer Ingelheim International Gmbh | Non-nucleoside reverse transcriptase inhibitors |
| US6806265B2 (en) * | 2002-05-16 | 2004-10-19 | Boehringer Ingelheim International Gmbh | Non-nucleoside reverse transcriptase inhibitors |
| DE60306539T2 (de) * | 2002-09-19 | 2007-07-19 | Boehringer Ingelheim (Canada) Ltd., Laval | Nicht-nukleosidische inhibitoren der reverse transkriptase |
| WO2004026875A1 (en) * | 2002-09-19 | 2004-04-01 | Boehringer Ingelheim (Canada) Ltd. | Non-nucleoside reverse transcriptase inhibitors |
| US7384937B2 (en) | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| EP1610782A1 (en) * | 2003-03-27 | 2006-01-04 | Boehringer Ingelheim International GmbH | Antiviral combination of a dipyridodiazepinone and a further antiretroviral compound |
| EP1737852A2 (en) * | 2004-04-13 | 2007-01-03 | Icagen, Inc. | Polycyclic pyridines as potassium ion channel modulators |
| EP1781300A1 (en) | 2004-07-16 | 2007-05-09 | ProteoSys AG | Muscarinic antagonists with parp and sir modulatng activity as agents for inflammatory diseases |
| EP2387405A2 (en) | 2009-01-13 | 2011-11-23 | ProteoSys AG | Pirenzepine as an agent in cancer treatment |
| CA2968464A1 (en) | 2014-11-25 | 2016-06-02 | Bayer Pharma Aktiengesellschaft | Substituted pyridobenzodiazepinone-derivatives and use thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5366972A (en) * | 1989-04-20 | 1994-11-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | 5,11-dihydro-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepines and their use in the prevention or treatment of HIV infection |
| CA2183571A1 (en) * | 1994-02-18 | 1995-08-24 | Karl D. Hargrave | 2-heteroaryl-5,11-dihydro-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepines and their use in the prevention or treatment of hiv infection |
-
1996
- 1996-09-25 US US08/710,996 patent/US5705499A/en not_active Expired - Lifetime
- 1996-10-04 ES ES96115901T patent/ES2191075T3/es not_active Expired - Lifetime
- 1996-10-04 EP EP96115901A patent/EP0767172B1/en not_active Expired - Lifetime
- 1996-10-04 PT PT96115901T patent/PT767172E/pt unknown
- 1996-10-04 AT AT96115901T patent/ATE235495T1/de not_active IP Right Cessation
- 1996-10-04 JP JP8264860A patent/JPH09188680A/ja active Pending
- 1996-10-04 DE DE69626915T patent/DE69626915T2/de not_active Expired - Fee Related
- 1996-10-04 DK DK96115901T patent/DK0767172T3/da active
Also Published As
| Publication number | Publication date |
|---|---|
| DE69626915D1 (de) | 2003-04-30 |
| EP0767172A1 (en) | 1997-04-09 |
| EP0767172B1 (en) | 2003-03-26 |
| US5705499A (en) | 1998-01-06 |
| ATE235495T1 (de) | 2003-04-15 |
| PT767172E (pt) | 2003-08-29 |
| JPH09188680A (ja) | 1997-07-22 |
| ES2191075T3 (es) | 2003-09-01 |
| DK0767172T3 (da) | 2003-07-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |