UA78221C2 - Похідні піримідинів, що інгібують віл - Google Patents
Похідні піримідинів, що інгібують віл Download PDFInfo
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- UA78221C2 UA78221C2 UA2004031903A UA2004031903A UA78221C2 UA 78221 C2 UA78221 C2 UA 78221C2 UA 2004031903 A UA2004031903 A UA 2004031903A UA 2004031903 A UA2004031903 A UA 2004031903A UA 78221 C2 UA78221 C2 UA 78221C2
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- Ukraine
- Prior art keywords
- alkyl
- formula
- group
- substituted
- compound
- Prior art date
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- 230000002401 inhibitory effect Effects 0.000 title description 8
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- -1 pirazinyl Chemical group 0.000 claims abstract description 178
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 150
- 125000001424 substituent group Chemical group 0.000 claims abstract description 93
- 238000002360 preparation method Methods 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 57
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 48
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims abstract description 21
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000003277 amino group Chemical group 0.000 claims abstract 33
- 150000001875 compounds Chemical class 0.000 claims description 492
- 239000002904 solvent Substances 0.000 claims description 200
- 125000000217 alkyl group Chemical group 0.000 claims description 172
- 238000006243 chemical reaction Methods 0.000 claims description 69
- 125000005843 halogen group Chemical group 0.000 claims description 62
- 229920006395 saturated elastomer Polymers 0.000 claims description 55
- 125000002619 bicyclic group Chemical group 0.000 claims description 40
- 125000002950 monocyclic group Chemical group 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 27
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 21
- 150000001412 amines Chemical class 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 239000002585 base Substances 0.000 claims description 19
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 208000031886 HIV Infections Diseases 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 12
- 230000000798 anti-retroviral effect Effects 0.000 claims description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 208000037357 HIV infectious disease Diseases 0.000 claims description 7
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 4
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 claims description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000003607 modifier Substances 0.000 claims description 4
- 230000007958 sleep Effects 0.000 claims description 4
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 claims description 3
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 3
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 229960002656 didanosine Drugs 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229960004556 tenofovir Drugs 0.000 claims description 3
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical group OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims description 3
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 3
- 229960000523 zalcitabine Drugs 0.000 claims description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 3
- KYPOHTVBFVELTG-OWOJBTEDSA-N (e)-but-2-enedinitrile Chemical compound N#C\C=C\C#N KYPOHTVBFVELTG-OWOJBTEDSA-N 0.000 claims description 2
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims description 2
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 claims description 2
- 229960004748 abacavir Drugs 0.000 claims description 2
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
- 229960001627 lamivudine Drugs 0.000 claims description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 238000006485 reductive methylation reaction Methods 0.000 claims description 2
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 claims description 2
- 229910000080 stannane Inorganic materials 0.000 claims description 2
- 229960001203 stavudine Drugs 0.000 claims description 2
- 229960002555 zidovudine Drugs 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims 10
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 4
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 206010010071 Coma Diseases 0.000 claims 1
- 244000257739 Dioscorea bulbifera Species 0.000 claims 1
- 241000087799 Koma Species 0.000 claims 1
- 101100049053 Mus musculus Vash1 gene Proteins 0.000 claims 1
- 238000010306 acid treatment Methods 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 230000010076 replication Effects 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- 125000001475 halogen functional group Chemical group 0.000 abstract description 4
- 125000002098 pyridazinyl group Chemical group 0.000 abstract description 2
- 125000004076 pyridyl group Chemical group 0.000 abstract description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 2
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 2
- 101100240519 Caenorhabditis elegans nhr-13 gene Proteins 0.000 abstract 1
- 150000001204 N-oxides Chemical class 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 239
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
- 238000004440 column chromatography Methods 0.000 description 59
- 239000003480 eluent Substances 0.000 description 58
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- 239000012044 organic layer Substances 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- 239000002244 precipitate Substances 0.000 description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
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- 239000000243 solution Substances 0.000 description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
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- 229910002027 silica gel Inorganic materials 0.000 description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 239000012299 nitrogen atmosphere Substances 0.000 description 22
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
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- 235000019439 ethyl acetate Nutrition 0.000 description 16
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
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- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 12
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- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 6
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- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 5
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- DFHAXXVZCFXGOQ-UHFFFAOYSA-K trisodium phosphonoformate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)P([O-])([O-])=O DFHAXXVZCFXGOQ-UHFFFAOYSA-K 0.000 description 1
- YFNGWGVTFYSJHE-UHFFFAOYSA-K trisodium;phosphonoformate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O YFNGWGVTFYSJHE-UHFFFAOYSA-K 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/12—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Oncology (AREA)
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- Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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EP01203090 | 2001-08-13 | ||
EP02077748 | 2002-06-10 | ||
PCT/EP2002/008953 WO2003016306A1 (en) | 2001-08-13 | 2002-08-09 | Hiv inhibiting pyrimidines derivatives |
Publications (1)
Publication Number | Publication Date |
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UA78221C2 true UA78221C2 (uk) | 2007-03-15 |
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Family Applications (1)
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UA2004031903A UA78221C2 (uk) | 2001-08-13 | 2002-09-08 | Похідні піримідинів, що інгібують віл |
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EP (3) | EP2298761B1 (sl) |
JP (4) | JP2005507380A (sl) |
KR (2) | KR100817453B1 (sl) |
CN (2) | CN100509801C (sl) |
AP (1) | AP1610A (sl) |
AR (1) | AR036387A1 (sl) |
AT (1) | ATE517891T1 (sl) |
AU (1) | AU2002329238C1 (sl) |
BE (3) | BE2012C020I2 (sl) |
BR (3) | BR122015032641B1 (sl) |
CA (1) | CA2452217C (sl) |
CY (4) | CY1112331T1 (sl) |
DE (1) | DE122012000038I1 (sl) |
DK (2) | DK3808743T3 (sl) |
EA (1) | EA006656B1 (sl) |
EG (1) | EG24684A (sl) |
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FR (3) | FR12C0035I2 (sl) |
HK (2) | HK1070066A1 (sl) |
HR (3) | HRP20192051B1 (sl) |
HU (5) | HU231274B1 (sl) |
IL (2) | IL160328A0 (sl) |
JO (1) | JO3429B1 (sl) |
LT (2) | LT3808743T (sl) |
LU (2) | LU92001I2 (sl) |
MX (1) | MXPA04001401A (sl) |
MY (1) | MY189572A (sl) |
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OA (1) | OA12652A (sl) |
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PL (2) | PL216398B1 (sl) |
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UA (1) | UA78221C2 (sl) |
WO (1) | WO2003016306A1 (sl) |
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Families Citing this family (149)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY169670A (en) * | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
US8101629B2 (en) * | 2001-08-13 | 2012-01-24 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
US7638522B2 (en) * | 2001-08-13 | 2009-12-29 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile |
JO3429B1 (ar) | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
EA007272B1 (ru) | 2002-03-13 | 2006-08-25 | Янссен Фармацевтика Н. В. | Новые ингибиторы гистондеацетилазы |
AR039540A1 (es) * | 2002-05-13 | 2005-02-23 | Tibotec Pharm Ltd | Compuestos microbicidas con contenido de pirimidina o triazina |
ATE451104T1 (de) | 2002-07-29 | 2009-12-15 | Rigel Pharmaceuticals Inc | Verfahren zur behandlung oder pruvention von autoimmunkrankheiten mit 2,4-pyrimidindiamin- verbindungen |
JP4822707B2 (ja) * | 2002-08-09 | 2011-11-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 4−[[4−[[4−(2−シアノエテニル)−2,6−ジメチルフェニル]アミノ]−2−ピリミジニル]アミノ]ベンゾニトリルの製造方法 |
EA200500721A1 (ru) * | 2002-11-28 | 2005-12-29 | Шеринг Акциенгезельшафт | Пиримидины, ингибирующие chk, pdk и акт, их получение и применение в качестве лекарственных средств |
US20070021449A1 (en) * | 2003-02-07 | 2007-01-25 | Jan Heeres | Pyrimidine derivatives for the prevention of hiv infection |
WO2004074266A1 (en) | 2003-02-07 | 2004-09-02 | Janssen Pharmaceutica N.V. | Hiv inhibiting 1,2,4-triazines |
CL2004000306A1 (es) | 2003-02-20 | 2005-04-08 | Tibotec Pharm Ltd | Compuestos derivados de pirimidina sustituidas con indano; proceso para su preparacion; composicion farmaceutica que lo comprende; combinacion farmaceutica; y su uso para el tratamiento o profilaxis de una enfermedad infecciosa. |
US20060172010A1 (en) | 2003-07-17 | 2006-08-03 | Gael Lamoureux | Process for preparing particles containing an antiviral |
PL1656372T3 (pl) | 2003-07-30 | 2013-08-30 | Rigel Pharmaceuticals Inc | Związki 2,4-pirymidynodiaminy do stosowania w leczeniu lub zapobieganiu chorobom autoimmunologicznym |
CA2533320A1 (en) * | 2003-08-15 | 2006-02-24 | Novartis Ag | 2, 4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders |
TWI365744B (en) * | 2003-09-03 | 2012-06-11 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
AP2006003517A0 (en) * | 2003-09-25 | 2006-02-28 | Janssen Pharmaceutica Nv | Hiv replication purine derivatives. |
EP1781639B1 (en) | 2004-07-28 | 2012-01-25 | Janssen Pharmaceutica NV | Substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase |
CN101035773B (zh) | 2004-08-10 | 2012-06-06 | 詹森药业有限公司 | 抑制hiv的1,2,4-三嗪-6-酮衍生物 |
ME01512B (me) | 2004-08-25 | 2014-04-20 | Ardea Biosciences Inc | S-triazolil alfa-merkaptoacetanilida kao inhibitori HIV reversne transkriptaze |
WO2007050087A1 (en) | 2004-08-25 | 2007-05-03 | Ardea Biosciences, Inc. | N[S(4-aryl-triazol-3-yl)α -mercaptoacetyl]-p-amino benozoic acids AS HIV REVERSE TRANSCRIPTASE INHIBITORS |
EP1789139B1 (en) * | 2004-09-02 | 2012-03-21 | Janssen Pharmaceutica NV | Fumarate of 4-((4-((4-(2-cyanoethenyl)-2,6-dimethylphenyl amino -2-pyrimidinyl amino benzonitrile |
EA011036B1 (ru) * | 2004-09-02 | 2008-12-30 | Янссен Фармацевтика Н.В. | Фумарат 4-[[4-[[4-(2-цианоэтенил)-2,6-диметилфенил]амино]-2-пиримидинил]амино]бензонитрила |
CN101068597B (zh) * | 2004-09-02 | 2012-04-18 | 詹森药业有限公司 | 4-((4-((4-(2-氰基乙烯基)-2,6-二甲基苯基)氨基)-2-嘧啶基)氨基)苄腈的富马酸盐 |
PL1632232T6 (pl) * | 2004-09-02 | 2022-06-27 | Janssen Pharmaceutica Nv | Sól 4-[[4-[[4-(2-cyjanoetenylo)-2,6-dimetylofenylo]amino]-2-pirymidynylo]amino]benzonitrylu |
EP1632232B3 (en) * | 2004-09-02 | 2022-03-30 | Janssen Pharmaceutica NV | Salt of 4[[4-[[4-(2-Cyanoethenyl)-2,6-dimethylphenyl]amino]-2-Pyrimidinyl]amino]benzonitrile |
AU2005329423A1 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
CN101083982A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 用于治疗硬脂酰CoA去饱和酶介导的疾病的杂环衍生物 |
TW200626155A (en) | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
WO2006034279A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
CN101084207A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 杂环衍生物及其作为硬脂酰CoA去饱和酶抑制剂的用途 |
BRPI0515478A (pt) | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos e seu uso como mediadores de estearoil-coa-desaturase |
TW200626154A (en) | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
TW200626561A (en) * | 2004-09-30 | 2006-08-01 | Tibotec Pharm Ltd | HIV inhibiting 5-substituted pyrimidines |
TW200626574A (en) | 2004-09-30 | 2006-08-01 | Tibotec Pharm Ltd | HIV inhibiting 5-heterocyclyl pyrimidines |
TW200626560A (en) * | 2004-09-30 | 2006-08-01 | Tibotec Pharm Ltd | HIV inhibiting 5-carbo-or heterocyclic substituted pyrimidines |
US7557207B2 (en) | 2004-11-24 | 2009-07-07 | Rigel Pharmaceuticals, Inc. | Spiro 2,4-pyrimidinediamine compounds and their uses |
BRPI0606318B8 (pt) | 2005-01-19 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, composição, e, uso de um composto |
EP1864977B1 (en) | 2005-03-31 | 2015-07-29 | Santen Pharmaceutical Co., Ltd. | Novel cyclic compound having pyrimidinylalkylthio group |
TWI457136B (zh) | 2005-04-04 | 2014-10-21 | Tibotec Pharm Ltd | Hiv-感染之預防 |
WO2006122003A2 (en) | 2005-05-05 | 2006-11-16 | Ardea Biosciences, Inc. | Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of hiv |
PL1888537T3 (pl) * | 2005-05-26 | 2014-02-28 | Janssen Sciences Ireland Uc | Sposób otrzymywania 4-[(1,6-dihydro-6-okso-2-pirymidynylo)amino benzonitrylu |
BRPI0611187A2 (pt) | 2005-06-03 | 2010-08-24 | Xenon Pharmaceuticals Inc | derivados aminotiazàis como inibidores da estearoil-coa desaturase humana |
US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
WO2006133426A2 (en) | 2005-06-08 | 2006-12-14 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
CN101370790B (zh) | 2006-01-19 | 2015-10-21 | 詹森药业有限公司 | 作为组蛋白去乙酰化酶抑制剂的吡啶和嘧啶衍生物 |
DK1981506T6 (da) | 2006-01-20 | 2021-06-14 | Janssen Sciences Ireland Unlimited Co | Langtidsbehandling af hiv-infektion med tcm278 |
EP2004632B1 (en) | 2006-03-30 | 2014-03-12 | Janssen R&D Ireland | Hiv inhibiting 5-amido substituted pyrimidines |
DE602007009508D1 (de) | 2006-03-30 | 2010-11-11 | Little Island Co Cork | Hiv-inhibierende 5-(hydroxymethylen- und aminomethylen) substituierte pyrimidine |
CL2007001847A1 (es) * | 2006-06-23 | 2008-02-08 | Tibotec Pharm Ltd | Composicion farmaceutica intramuscular o subcutanea que comprende tmc278 (rilpivirina); proceso para preparar la composicion; y uso para el tratamiento o prevencion de infeccion por vih. |
AU2016219555B2 (en) * | 2006-06-23 | 2017-08-10 | Janssen Sciences Ireland Uc | Aqueous suspensions of TMC278 |
AU2014200819B2 (en) * | 2006-06-23 | 2016-05-26 | Janssen Sciences Ireland Uc | Aqueous suspensions of TMC278 |
US7595324B2 (en) | 2006-11-09 | 2009-09-29 | Ardea Biosciences, Inc. | Substituted thieno[3,2-D]pyrimidines as HIV inhibitors |
SI2091918T1 (sl) | 2006-12-08 | 2015-01-30 | Irm Llc | Spojine in sestavki kot inhibitorji protein-kinaze |
KR101475091B1 (ko) * | 2006-12-13 | 2014-12-22 | 에프. 호프만-라 로슈 아게 | 비뉴클레오시드 역전사 효소 억제제로서 2-(피페리딘-4-일)-4-페녹시- 또는 페닐아미노-피리미딘 유도체 |
CN101573343B (zh) | 2006-12-29 | 2016-02-24 | 爱尔兰詹森科学公司 | 抑制人免疫缺陷病毒的6-取代的嘧啶 |
CA2923637C (en) | 2006-12-29 | 2018-10-02 | Janssen Sciences Ireland Uc | Hiv inhibiting 5,6-substituted pyrimidines |
NZ578744A (en) * | 2007-01-31 | 2012-02-24 | Vertex Pharma | 2-aminopyridine derivatives useful as kinase inhibitors |
AR065720A1 (es) * | 2007-03-14 | 2009-06-24 | Tibotec Pharm Ltd | Polvos para reconstitucion que comprenden rilpivirina dispersos en ciertos polimeros. uso. proceso. |
CN103951658B (zh) | 2007-04-18 | 2017-10-13 | 辉瑞产品公司 | 用于治疗异常细胞生长的磺酰胺衍生物 |
EA016386B1 (ru) | 2007-05-30 | 2012-04-30 | Ф. Хоффманн-Ля Рош Аг | Ненуклеозидные ингибиторы обратной транскриптазы |
KR101294731B1 (ko) * | 2007-06-04 | 2013-08-16 | 삼성디스플레이 주식회사 | 어레이 기판, 이를 갖는 표시패널 및 이의 제조방법 |
EP2175857B1 (en) * | 2007-07-12 | 2013-09-11 | Janssen R&D Ireland | Crystalline form of (e) 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
CN101407476B (zh) | 2007-10-12 | 2012-07-18 | 中国人民解放军军事医学科学院毒物药物研究所 | 作为非核苷类hiv逆转录酶抑制剂的间二芳烃-多取代苯胺类化合物、其制备方法及用途 |
SI2217577T1 (sl) | 2007-11-27 | 2014-11-28 | Ardea Biosciences, Inc. | Nove spojine in sestavki ter metode uporabe |
ES2389752T3 (es) | 2007-12-14 | 2012-10-31 | Ardea Biosciences, Inc. | Inhibidores de la transcriptasa inversa |
US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
SG10201510696RA (en) | 2008-06-27 | 2016-01-28 | Celgene Avilomics Res Inc | Heteroaryl compounds and uses thereof |
US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
US8569337B2 (en) | 2008-07-23 | 2013-10-29 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
JP5631310B2 (ja) | 2008-07-23 | 2014-11-26 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | 三環式ピラゾロピリジンキナーゼ阻害剤 |
CA2731451A1 (en) | 2008-07-23 | 2010-01-28 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridine kinase inhibitors |
AU2009279611A1 (en) | 2008-08-06 | 2010-02-11 | Vertex Pharmaceuticals Incorporated | Aminopyridine kinase inhibitors |
CN101717364B (zh) * | 2008-10-09 | 2014-08-13 | 中国人民解放军军事医学科学院毒物药物研究所 | 作为hiv逆转录酶抑制剂的吡啶类化合物及其制备方法和用途 |
WO2010040275A1 (zh) * | 2008-10-09 | 2010-04-15 | 中国人民解放军军事医学科学院毒物药物研究所 | 作为非核苷类hiv逆转录酶抑制剂的2-(4-取代苯胺基)多取代吡啶类化合物、其制备方法及用途 |
EP2181991A1 (en) | 2008-10-28 | 2010-05-05 | LEK Pharmaceuticals D.D. | Novel salts of sunitinib |
EP2186809A1 (en) | 2008-11-13 | 2010-05-19 | LEK Pharmaceuticals D.D. | New crystal form of sunitinib malate |
MY160360A (en) | 2008-12-24 | 2017-02-28 | Janssen Sciences Ireland Uc | Implantable devices for treating hiv |
ES2659725T3 (es) | 2009-05-05 | 2018-03-19 | Dana-Farber Cancer Institute, Inc. | Inhibidores de EGFR y procedimiento de tratamiento de trastornos |
AU2010245914A1 (en) | 2009-05-06 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridines |
KR20170078868A (ko) | 2010-01-27 | 2017-07-07 | 비이브 헬쓰케어 컴퍼니 | 항바이러스 치료 |
EP2528917B1 (en) | 2010-01-27 | 2016-10-19 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridines useful for the treatment of autoimmune, inflammatory or (hyper)proliferative diseases |
CA2787079A1 (en) | 2010-01-27 | 2011-08-04 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrazine kinase inhibitors |
CA2787363A1 (en) | 2010-01-27 | 2011-08-04 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrimidine kinase inhibitors |
EP2536696A1 (en) * | 2010-02-18 | 2012-12-26 | Concert Pharmaceuticals Inc. | Pyrimidine derivatives |
US8367315B2 (en) * | 2010-03-05 | 2013-02-05 | Adan Rios | Inactivation of reverse transcriptases by azido-diarylpyrimidines |
CN103096716B (zh) | 2010-08-10 | 2016-03-02 | 西建阿维拉米斯研究公司 | Btk抑制剂的苯磺酸盐 |
WO2012061303A1 (en) | 2010-11-01 | 2012-05-10 | Avila Therapeutics, Inc. | Heteroaryl compounds and uses thereof |
BR112013010564B1 (pt) | 2010-11-01 | 2021-09-21 | Celgene Car Llc | Compostos heterocíclicos e composições compreendendo os mesmos |
WO2012060847A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
WO2012064706A1 (en) | 2010-11-10 | 2012-05-18 | Avila Therapeutics, Inc. | Mutant-selective egfr inhibitors and uses thereof |
ME01980B (me) | 2010-11-19 | 2015-05-20 | Gilead Sciences Inc | Terapeutske kompozicije koje sadrže rilpivirin hcl i tenofovir dizoproksil fumarat |
WO2012125993A1 (en) | 2011-03-17 | 2012-09-20 | Teva Pharmaceutical Industries Ltd. | Solid state forms of rilpivirine base, and rilipivirine salts |
US9126949B2 (en) | 2011-04-25 | 2015-09-08 | Hetero Research Foundation | Process for rilpivirine |
SG2014012926A (en) | 2011-08-30 | 2014-06-27 | Chdi Foundation Inc | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
EP2755959B1 (en) * | 2011-09-16 | 2018-05-16 | Hetero Research Foundation | Rilpivirine hydrochloride |
TW201325593A (zh) | 2011-10-28 | 2013-07-01 | Celgene Avilomics Res Inc | 治療布魯頓(bruton’s)酪胺酸激酶疾病或病症之方法 |
EP2628732A1 (en) | 2012-02-20 | 2013-08-21 | Sandoz AG | Novel crystalline form of rilpivirine hydrochloride |
EP2604593A1 (en) | 2011-12-14 | 2013-06-19 | Sandoz AG | Polymorph of Rilpivirine hydrochloride and its use as antiviral |
WO2013087794A1 (en) | 2011-12-14 | 2013-06-20 | Sandoz Ag | Polymorph of rilpivirine hydrochloride and its use as antiviral |
SG11201405692UA (en) | 2012-03-15 | 2014-10-30 | Celgene Avilomics Res Inc | Salts of an epidermal growth factor receptor kinase inhibitor |
WO2013138495A1 (en) | 2012-03-15 | 2013-09-19 | Celgene Avilomics Research, Inc. | Solid forms of an epidermal growth factor receptor kinase inhibitor |
WO2013153162A1 (en) | 2012-04-11 | 2013-10-17 | Sandoz Ag | Polymorph of rilpivirine hydrochloride |
WO2013153161A2 (en) | 2012-04-11 | 2013-10-17 | Sandoz Ag | Novel polymorph of rilpivirine hydrochloride |
WO2013179105A1 (en) * | 2012-06-01 | 2013-12-05 | Laurus Labs Private Limited | Improved process for preparation of rilpivirine and pharmaceutically acceptable salts thereof |
ES2664094T3 (es) * | 2012-07-12 | 2018-04-18 | Hetero Research Foundation | Procedimiento de preparación de rilpivirina utilizando un intermedio nuevo |
WO2014072419A1 (en) | 2012-11-08 | 2014-05-15 | Universiteit Antwerpen | Novel anti-hiv compounds |
WO2014100748A1 (en) | 2012-12-21 | 2014-06-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
WO2014124230A2 (en) | 2013-02-08 | 2014-08-14 | Celgene Avilomics Research, Inc. | Erk inhibitors and uses thereof |
US9914709B2 (en) | 2013-06-21 | 2018-03-13 | Yale University | Compositions and methods of treating HIV-1 infections using same |
US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
US10258621B2 (en) * | 2014-07-17 | 2019-04-16 | Chdi Foundation, Inc. | Methods and compositions for treating HIV-related disorders |
US10005760B2 (en) | 2014-08-13 | 2018-06-26 | Celgene Car Llc | Forms and compositions of an ERK inhibitor |
JP2017528497A (ja) | 2014-09-26 | 2017-09-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited | 長時間作用型医薬組成物 |
CZ201532A3 (cs) | 2015-01-21 | 2015-02-25 | Zentiva, K.S. | Způsob výroby vysoce čistého Rilpivirinu a jeho solí |
CN104926829A (zh) * | 2015-06-08 | 2015-09-23 | 山东大学 | 一种噻吩并嘧啶类衍生物及其制备方法和应用 |
WO2017004244A1 (en) | 2015-06-30 | 2017-01-05 | Gilead Sciences, Inc. | Pharmaceutical formulations comprising tenofovir and emtricitabine |
CZ2015579A3 (cs) | 2015-08-27 | 2017-03-08 | Zentiva, K.S. | Krystalická forma A Rilpivirin Adipátu a způsob její přípravy |
CN106187916B (zh) * | 2016-07-04 | 2018-08-21 | 宜昌人福药业有限责任公司 | 一种有效去除利匹韦林异构体的方法 |
ES2970870T3 (es) | 2016-10-24 | 2024-05-31 | Janssen Sciences Ireland Unlimited Co | Composiciones dispersables |
CN106749203B (zh) * | 2016-11-28 | 2020-04-10 | 洛阳聚慧医药科技有限公司 | 一种嘧啶类杂环化合物、嘧啶类杂环化合物盐以及制备方法和应用 |
CN106588696B (zh) * | 2016-12-08 | 2018-12-25 | 西北师范大学 | 一种反式α,β-不饱和腈类化合物的制备方法 |
CN106905244B (zh) * | 2017-02-27 | 2019-08-16 | 武汉工程大学 | 二芳基嘧啶-二酮酸类杂合型hiv-1抑制剂及其制备方法 |
EP3853234A1 (en) | 2018-09-18 | 2021-07-28 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
CN109293581B (zh) * | 2018-09-21 | 2020-03-27 | 宜昌人福药业有限责任公司 | 一种制备盐酸利匹韦林异构体z和杂质x的方法及杂质x作为杀虫剂在农业中的应用 |
EP3870568B1 (en) | 2018-10-25 | 2023-06-28 | Minakem | Process for the preparation of rilpivirine |
US20210000823A1 (en) * | 2019-07-03 | 2021-01-07 | Janssen Sciences Ireland Unlimited Company | Methods of treating hiv |
CN110526873B (zh) * | 2019-08-15 | 2022-09-16 | 复旦大学 | 氰乙烯基取代的苯并二芳基嘧啶类化合物及其制备方法和用途 |
WO2021104487A1 (en) | 2019-11-29 | 2021-06-03 | Aptorum Therapeutics Limited | Composition including rilpivirine and use thereof for treating tumors or cancer |
CN111004215B (zh) * | 2019-12-22 | 2022-08-09 | 华北理工大学 | 2,4-取代嘧啶类衍生物及其制备方法和在制备抗肿瘤药物中的应用 |
CN111217833B (zh) * | 2020-02-21 | 2021-03-16 | 山东大学 | 噻吩并[2,3-d]嘧啶类HIV-1非核苷类逆转录酶抑制剂及其制备方法和应用 |
WO2022000019A1 (en) * | 2020-06-30 | 2022-01-06 | University Of South Australia | New therapeutic use of rilpivirine |
CN112028836B (zh) * | 2020-09-09 | 2021-12-07 | 山东大学 | 一种含有六元氮杂环的二芳基嘧啶类衍生物及其制备方法与应用 |
CN112010810B (zh) * | 2020-09-09 | 2024-01-30 | 瑞阳制药股份有限公司 | 一锅法制备高纯度利匹韦林中间体的方法 |
WO2022079739A1 (en) | 2020-10-14 | 2022-04-21 | Cipla Limited | Fixed dose compositions of cabotegravir and rilpivirine |
TW202233192A (zh) | 2020-11-17 | 2022-09-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | Hiv感染之治療或預防 |
CN112546969B (zh) * | 2020-12-07 | 2022-12-23 | 安徽贝克制药股份有限公司 | 催化加氢连续生产装置和利托那韦中间体的制备方法 |
CN112778214A (zh) * | 2021-01-13 | 2021-05-11 | 安徽贝克联合制药有限公司 | 用于合成利匹韦林的中间体、其合成方法和利匹韦林的合成方法 |
CN113105394A (zh) * | 2021-03-08 | 2021-07-13 | 复旦大学 | 一种含芳杂环结构的联苯二芳基嘧啶类衍生物及其制备方法和应用 |
CN113461666A (zh) * | 2021-05-06 | 2021-10-01 | 复旦大学 | 含芳杂环结构的联苯二芳基甲基嘧啶衍生物及其制备方法 |
CN113845515A (zh) * | 2021-09-03 | 2021-12-28 | 复旦大学 | 一种含芳杂环结构的二甲基联苯二芳基嘧啶类衍生物及其制备方法和应用 |
KR20240095514A (ko) | 2021-11-17 | 2024-06-25 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 용해도 평가 |
TW202408580A (zh) | 2022-04-22 | 2024-03-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 冷凍乾燥組成物(二) |
TW202408516A (zh) | 2022-04-22 | 2024-03-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 液體組成物 |
TW202408527A (zh) | 2022-05-17 | 2024-03-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 治療或預防hiv感染(二) |
WO2023222754A1 (en) | 2022-05-17 | 2023-11-23 | Janssen Sciences Ireland Unlimited Company | Rilpivirine for use in the treatment or prevention of hiv infection |
CN115490642A (zh) * | 2022-09-21 | 2022-12-20 | 山东大学 | 一种含醚键的二芳基嘧啶类化合物及其制备方法与应用 |
Family Cites Families (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
US3953398A (en) * | 1970-07-20 | 1976-04-27 | The Goodyear Tire & Rubber Company | Age resistant polymeric compositions |
JPS63159316A (ja) * | 1977-11-28 | 1988-07-02 | アルキユサル インコーポレーテツド ピーテイワイ リミテツド | 中性銅結合体を含む抗炎症組成物 |
JPS5490121A (en) * | 1977-11-28 | 1979-07-17 | Boettcher Barry | Neutral copper bonded body and antiinflaming agent |
JPS5879920A (ja) * | 1981-11-09 | 1983-05-13 | Kanegafuchi Chem Ind Co Ltd | 血小板凝集阻害剤 |
GB9012592D0 (en) | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
US5318780A (en) * | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
US5691364A (en) | 1995-03-10 | 1997-11-25 | Berlex Laboratories, Inc. | Benzamidine derivatives and their use as anti-coagulants |
GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
EP0862463A1 (en) | 1995-11-23 | 1998-09-09 | Janssen Pharmaceutica N.V. | Solid mixtures of cyclodextrins prepared via melt-extrusion |
TW429256B (en) | 1995-12-27 | 2001-04-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-(benzimidazolyl- and imidazopyridinyl)-piperidine derivatives |
GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
US6982091B2 (en) * | 2001-08-29 | 2006-01-03 | Umd, Inc. | Vaginal delivery of chemotherapeutic agents and inhibitors of membrane efflux systems for cancer therapy |
JP3990808B2 (ja) * | 1998-03-26 | 2007-10-17 | Tdk株式会社 | 非水電解質電池用電極の製造方法 |
DE69943247D1 (de) * | 1998-03-27 | 2011-04-14 | Janssen Pharmaceutica Nv | HIV hemmende Pyrimidin Derivate |
KR100699514B1 (ko) | 1998-03-27 | 2007-03-26 | 얀센 파마슈티카 엔.브이. | Hiv를 억제하는 피리미딘 유도체 |
EP0945447A1 (en) * | 1998-03-27 | 1999-09-29 | Janssen Pharmaceutica N.V. | Trisubstituted 1,3,5-triazine derivatives for treatment of HIV infections |
JP2000035628A (ja) * | 1998-07-16 | 2000-02-02 | Konica Corp | ハロゲン化銀写真感光材料 |
AU5438299A (en) * | 1998-08-29 | 2000-03-21 | Astrazeneca Ab | Pyrimidine compounds |
KR100658489B1 (ko) | 1998-11-10 | 2006-12-18 | 얀센 파마슈티카 엔.브이. | Hiv 복제를 억제하는 피리미딘 |
EP1159279B1 (en) | 1999-03-09 | 2002-10-16 | PHARMACIA & UPJOHN COMPANY | 4-oxo-4,7-dihydro-thieno[2,3-b]pyridine-5-carboxamides as antiviral agents |
PT1169038E (pt) | 1999-04-15 | 2012-10-26 | Bristol Myers Squibb Co | Inibidores cíclicos da proteína tirosina cinase |
GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
DE19945982A1 (de) * | 1999-09-24 | 2001-03-29 | Knoll Ag | Geschwindigkeitsbestimmte Partikel |
JP4919566B2 (ja) * | 1999-09-24 | 2012-04-18 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗ウイルス組成物 |
HUP0301117A3 (en) * | 2000-02-17 | 2004-01-28 | Amgen Inc Thousand Oaks | Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them |
GB0004888D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
GB0004887D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
AU783981C (en) | 2000-05-08 | 2007-05-03 | Janssen Pharmaceutica N.V. | HIV replication inhibitors |
EP1282607B1 (en) | 2000-05-08 | 2015-11-11 | Janssen Pharmaceutica NV | Prodrugs of hiv replication inhibiting pyrimidines |
US6596729B2 (en) * | 2000-07-20 | 2003-07-22 | Bristol-Myers Squibb Company | Tricyclic-2-pyridone compounds useful as HIV reverse transcriptase inhibitors |
US6995283B2 (en) * | 2001-03-02 | 2006-02-07 | Smithkline Beecham Corporation | Benzophenones as inhibitors of reverse transcriptase |
JP4160401B2 (ja) * | 2001-03-29 | 2008-10-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | C−junn末端キナーゼ(jnk)および他のタンパク質キナーゼのインヒビター |
MY169670A (en) | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
US8101629B2 (en) * | 2001-08-13 | 2012-01-24 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
JO3429B1 (ar) * | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
US7638522B2 (en) | 2001-08-13 | 2009-12-29 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile |
TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
CN1290893C (zh) * | 2002-05-03 | 2006-12-20 | 詹森药业有限公司 | 聚合物微乳状液 |
JP4822707B2 (ja) | 2002-08-09 | 2011-11-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 4−[[4−[[4−(2−シアノエテニル)−2,6−ジメチルフェニル]アミノ]−2−ピリミジニル]アミノ]ベンゾニトリルの製造方法 |
AU2002350719A1 (en) * | 2002-11-29 | 2004-06-23 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base |
US20070021449A1 (en) | 2003-02-07 | 2007-01-25 | Jan Heeres | Pyrimidine derivatives for the prevention of hiv infection |
US9226970B2 (en) * | 2010-02-22 | 2016-01-05 | Nektar Therapeutics | Oligomer modified diaromatic substituted compounds |
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