CA2448058C - Pyrazole derivatives as hiv reverse transcriptase inhibitors - Google Patents
Pyrazole derivatives as hiv reverse transcriptase inhibitors Download PDFInfo
- Publication number
- CA2448058C CA2448058C CA002448058A CA2448058A CA2448058C CA 2448058 C CA2448058 C CA 2448058C CA 002448058 A CA002448058 A CA 002448058A CA 2448058 A CA2448058 A CA 2448058A CA 2448058 C CA2448058 C CA 2448058C
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- Canada
- Prior art keywords
- methyl
- alkyl
- substituted
- isopropyl
- pyridyl
- 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.)
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- 150000003217 pyrazoles Chemical class 0.000 title abstract description 23
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 title abstract description 5
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 238000000034 method Methods 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 241000725303 Human immunodeficiency virus Species 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 9
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 hydroxy, amino Chemical group 0.000 claims description 192
- 125000001424 substituent group Chemical group 0.000 claims description 91
- 239000000203 mixture Substances 0.000 claims description 57
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 239000000460 chlorine Substances 0.000 claims description 31
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 30
- 229910052794 bromium Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 235000019000 fluorine Nutrition 0.000 claims description 23
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000005002 aryl methyl group Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 9
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- DGHNSWWBAOTIDW-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanamine Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CN)C=1CC1=CC=NC=C1 DGHNSWWBAOTIDW-UHFFFAOYSA-N 0.000 claims description 5
- HAUURQXLCOVNLL-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1 HAUURQXLCOVNLL-UHFFFAOYSA-N 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- MSXAJIBSJLYBOY-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethoxymethyl)pyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1COCC1=CC=NC=C1 MSXAJIBSJLYBOY-UHFFFAOYSA-N 0.000 claims description 3
- LLVOEMQIEYNQGW-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methylurea Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CNC(N)=O)C=1CC1=CC=NC=C1 LLVOEMQIEYNQGW-UHFFFAOYSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- RVAHELGGEXONEH-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethoxymethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1COCC1=CC=NC=C1 RVAHELGGEXONEH-UHFFFAOYSA-N 0.000 claims description 2
- AQSLEAXCHMHJJH-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1CC1=CC=NC=C1 AQSLEAXCHMHJJH-UHFFFAOYSA-N 0.000 claims description 2
- QQVBJSXOXZZXDV-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl n-methylcarbamate Chemical compound C=1C=NC=CC=1CC=1C(COC(=O)NC)=NN(C(C)C)C=1SC1=CC(Cl)=CC(Cl)=C1 QQVBJSXOXZZXDV-UHFFFAOYSA-N 0.000 claims description 2
- ZICBEMJXOXYDGZ-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-3-(hydroxymethyl)-1-propan-2-ylpyrazol-4-yl]methanol Chemical compound CC(C)N1N=C(CO)C(CO)=C1SC1=CC(Cl)=CC(Cl)=C1 ZICBEMJXOXYDGZ-UHFFFAOYSA-N 0.000 claims description 2
- YNHGRUGOAQSFTE-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-ethyl-1-propan-2-ylpyrazol-3-yl]methyl carbamate Chemical compound NC(=O)OCC1=NN(C(C)C)C(SC=2C=C(Cl)C=C(Cl)C=2)=C1CC YNHGRUGOAQSFTE-UHFFFAOYSA-N 0.000 claims description 2
- DGMGBAZYKZEBCN-UHFFFAOYSA-N [cyano(hydroxy)amino] thiohypofluorite Chemical compound ON(SF)C#N DGMGBAZYKZEBCN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 2
- XFBBYLMAVHMFEV-UHFFFAOYSA-N methyl n-[[5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl]carbamate Chemical compound C=1C=NC=CC=1CC=1C(CNC(=O)OC)=NN(C(C)C)C=1SC1=CC(Cl)=CC(Cl)=C1 XFBBYLMAVHMFEV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- JLRAHNOJEOLANY-UHFFFAOYSA-N 3-[[5-(3,5-dichlorophenyl)sulfanyl-3-(hydroxymethyl)-1-propan-2-ylpyrazol-4-yl]methoxymethyl]benzonitrile Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1COCC1=CC=CC(C#N)=C1 JLRAHNOJEOLANY-UHFFFAOYSA-N 0.000 claims 1
- LHSOBQYZSOZNEM-UHFFFAOYSA-N 3-chloro-5-[5-(hydroxymethyl)-2-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]sulfanylbenzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1 LHSOBQYZSOZNEM-UHFFFAOYSA-N 0.000 claims 1
- DBXFPTRWZRLIST-UHFFFAOYSA-N [4-[(5-bromo-2-methylpyrimidin-4-yl)methyl]-5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-ylpyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=NC(C)=NC=C1Br DBXFPTRWZRLIST-UHFFFAOYSA-N 0.000 claims 1
- HPKVLNVUKUBTGU-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-ethyl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(CC)N=C(CO)C=1CC1=CC=NC=C1 HPKVLNVUKUBTGU-UHFFFAOYSA-N 0.000 claims 1
- CYEICROBFYOXPI-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(thiophen-2-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=CS1 CYEICROBFYOXPI-UHFFFAOYSA-N 0.000 claims 1
- IKEBYYWKPKJSSM-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(thiophen-2-ylmethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1CC1=CC=CS1 IKEBYYWKPKJSSM-UHFFFAOYSA-N 0.000 claims 1
- BFBJQRZHUFYATF-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-(hydroxymethyl)-1-propan-2-ylpyrazol-3-yl]methyl carbamate Chemical compound CC(C)N1N=C(COC(N)=O)C(CO)=C1SC1=CC(Cl)=CC(Cl)=C1 BFBJQRZHUFYATF-UHFFFAOYSA-N 0.000 claims 1
- HLAIHUXWSCAYHM-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-[(3,4-difluorophenyl)methyl]-1-propan-2-ylpyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=C(F)C(F)=C1 HLAIHUXWSCAYHM-UHFFFAOYSA-N 0.000 claims 1
- QYYLPSKHIXPRHU-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-[(3-fluoropyridin-4-yl)methyl]-1-propan-2-ylpyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1F QYYLPSKHIXPRHU-UHFFFAOYSA-N 0.000 claims 1
- ZZVUSIQKMJZFSY-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-[(3-methoxyphenyl)methyl]-1-propan-2-ylpyrazol-3-yl]methanol Chemical compound COC1=CC=CC(CC2=C(N(C(C)C)N=C2CO)SC=2C=C(Cl)C=C(Cl)C=2)=C1 ZZVUSIQKMJZFSY-UHFFFAOYSA-N 0.000 claims 1
- PUVXZYAQSZGOLL-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-[(3-methoxyphenyl)methyl]-1-propan-2-ylpyrazol-3-yl]methyl carbamate Chemical compound COC1=CC=CC(CC2=C(N(C(C)C)N=C2COC(N)=O)SC=2C=C(Cl)C=C(Cl)C=2)=C1 PUVXZYAQSZGOLL-UHFFFAOYSA-N 0.000 claims 1
- IFSIFGYRPVEASN-UHFFFAOYSA-N [5-(3,5-dichlorophenyl)sulfanyl-4-ethyl-1-propan-2-ylpyrazol-3-yl]methanol Chemical compound OCC1=NN(C(C)C)C(SC=2C=C(Cl)C=C(Cl)C=2)=C1CC IFSIFGYRPVEASN-UHFFFAOYSA-N 0.000 claims 1
- XBAUZMKFMSCWMY-UHFFFAOYSA-N [5-(3,5-dicyanophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(C#N)=CC(C#N)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1CC1=CC=NC=C1 XBAUZMKFMSCWMY-UHFFFAOYSA-N 0.000 claims 1
- XKMLQNVIELJJRO-UHFFFAOYSA-N [5-(3,5-difluorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C(F)=CC(F)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1 XKMLQNVIELJJRO-UHFFFAOYSA-N 0.000 claims 1
- UHBCWADUEMCPRL-UHFFFAOYSA-N [5-(3,5-difluorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(F)=CC(F)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1CC1=CC=NC=C1 UHBCWADUEMCPRL-UHFFFAOYSA-N 0.000 claims 1
- QREAIDRGKWQLHY-UHFFFAOYSA-N [5-(3-bromo-5-chlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C(Cl)=CC(Br)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1 QREAIDRGKWQLHY-UHFFFAOYSA-N 0.000 claims 1
- DLSOGHRQXUNPBH-UHFFFAOYSA-N [5-(3-chloro-5-cyanophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl carbamate Chemical compound C=1C(Cl)=CC(C#N)=CC=1SC=1N(C(C)C)N=C(COC(N)=O)C=1CC1=CC=NC=C1 DLSOGHRQXUNPBH-UHFFFAOYSA-N 0.000 claims 1
- FBAOEMZTRYDRBM-UHFFFAOYSA-N [5-(3-chlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methanol Chemical compound C=1C=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CO)C=1CC1=CC=NC=C1 FBAOEMZTRYDRBM-UHFFFAOYSA-N 0.000 claims 1
- XWZBFWRTWAQXAZ-UHFFFAOYSA-N n-[[5-(3,5-dichlorophenyl)sulfanyl-1-propan-2-yl-4-(pyridin-4-ylmethyl)pyrazol-3-yl]methyl]methanesulfonamide Chemical compound C=1C(Cl)=CC(Cl)=CC=1SC=1N(C(C)C)N=C(CNS(C)(=O)=O)C=1CC1=CC=NC=C1 XWZBFWRTWAQXAZ-UHFFFAOYSA-N 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 abstract description 17
- 239000003112 inhibitor Substances 0.000 abstract description 9
- 230000029812 viral genome replication Effects 0.000 abstract description 3
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 146
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 230000007246 mechanism Effects 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 238000001819 mass spectrum Methods 0.000 description 21
- 125000000217 alkyl group Chemical group 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000010828 elution Methods 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 150000002430 hydrocarbons Chemical group 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000003638 chemical reducing agent Substances 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
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- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
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- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
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- 239000012730 sustained-release form Substances 0.000 description 1
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- 230000009897 systematic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- PUAKAEDMCXRDPR-UHFFFAOYSA-N tert-butyl n-(propan-2-ylamino)carbamate Chemical compound CC(C)NNC(=O)OC(C)(C)C PUAKAEDMCXRDPR-UHFFFAOYSA-N 0.000 description 1
- XCMYPTLLFDFJAE-UHFFFAOYSA-N tert-butyl n-(propan-2-ylideneamino)carbamate Chemical compound CC(C)=NNC(=O)OC(C)(C)C XCMYPTLLFDFJAE-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- ZHOVAWFVVBWEGQ-UHFFFAOYSA-N tripropylsilane Chemical compound CCC[SiH](CCC)CCC ZHOVAWFVVBWEGQ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0113524.3 | 2001-06-04 | ||
| GBGB0113524.3A GB0113524D0 (en) | 2001-06-04 | 2001-06-04 | Pyrazole derivatives |
| PCT/EP2002/005898 WO2002100853A1 (en) | 2001-06-04 | 2002-05-29 | Pyrazole derivatives as hiv reverse transcriptase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2448058A1 CA2448058A1 (en) | 2002-12-19 |
| CA2448058C true CA2448058C (en) | 2008-12-23 |
Family
ID=9915841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002448058A Expired - Fee Related CA2448058C (en) | 2001-06-04 | 2002-05-29 | Pyrazole derivatives as hiv reverse transcriptase inhibitors |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US6538015B1 (enExample) |
| EP (1) | EP1401826B1 (enExample) |
| JP (1) | JP4088249B2 (enExample) |
| KR (1) | KR100627532B1 (enExample) |
| CN (1) | CN1249052C (enExample) |
| AT (1) | ATE357439T1 (enExample) |
| AU (1) | AU2002325221B2 (enExample) |
| BR (1) | BR0210158A (enExample) |
| CA (1) | CA2448058C (enExample) |
| DE (1) | DE60219009T2 (enExample) |
| DK (1) | DK1401826T3 (enExample) |
| ES (1) | ES2282446T3 (enExample) |
| GB (1) | GB0113524D0 (enExample) |
| MX (1) | MXPA03011199A (enExample) |
| PT (1) | PT1401826E (enExample) |
| WO (1) | WO2002100853A1 (enExample) |
| ZA (1) | ZA200308781B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200423930A (en) * | 2003-02-18 | 2004-11-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitors |
| JP4993407B2 (ja) | 2004-08-04 | 2012-08-08 | 大正製薬株式会社 | トリアゾール誘導体 |
| WO2006072833A1 (en) * | 2005-01-06 | 2006-07-13 | Pfizer Limited | Imidazole derivatives as enzyme reverse transcriptase modulators |
| EP1988083B1 (en) | 2006-02-03 | 2014-04-02 | Taisho Pharmaceutical Co., Ltd. | Triazole derivative |
| RU2395499C2 (ru) * | 2006-02-06 | 2010-07-27 | Тайсо Фармасьютикал Ко., Лтд. | Ингибитор связывания сфингозин-1-фосфата |
| PL2057125T3 (pl) | 2006-08-16 | 2011-09-30 | Hoffmann La Roche | Nienukleozydowe inhibitory odwrotnej transkryptazy |
| BRPI0813404A2 (pt) | 2007-06-22 | 2014-12-30 | Hoffmann La Roche | Derivados de uréia e carbamato como inibidores de transcriptase reversa de não-nucleosídeo |
| SI2177512T1 (sl) | 2007-08-01 | 2012-06-29 | Taisho Pharmaceutical Co Ltd | Inhibitor vezave S1P1 |
| RU2495878C2 (ru) | 2007-12-21 | 2013-10-20 | Ф.Хоффманн-Ля Рош Аг | Гетероциклические антивирусные соединения |
| DE102008015032A1 (de) | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte Pyrazolamide und ihre Verwendung |
| DE102008015033A1 (de) * | 2008-03-17 | 2009-09-24 | Aicuris Gmbh & Co. Kg | Substituierte (Pyrazolyl-carbonyl)imidazolidinone und ihre Verwendung |
| DE102008062878A1 (de) | 2008-12-17 | 2010-06-24 | Aicuris Gmbh & Co. Kg | Substituierte Furancarboxamide und ihre Verwendung |
| DE102008062863A1 (de) | 2008-12-17 | 2010-06-24 | Aicuris Gmbh & Co. Kg | Substituierte (Thiophenyl-carbonyl)imidazolidinone und ihre Verwendung |
| EP2295038B1 (en) * | 2009-09-11 | 2013-05-29 | AiCuris GmbH & Co. KG | Solid dispersion comprising an anti-HIV agent |
| ES2528646T3 (es) * | 2010-05-20 | 2015-02-11 | Bayer Intellectual Property Gmbh | Procedimiento para la fabricación de 1-alquil-3-difluorometil-5-hidroxipirazoles |
| JP5722891B2 (ja) | 2010-07-15 | 2015-05-27 | 大日本住友製薬株式会社 | ピラゾール化合物 |
| WO2014074628A1 (en) * | 2012-11-08 | 2014-05-15 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Compounds for treating hiv and methods for using the compounds |
| US9925190B2 (en) | 2015-02-16 | 2018-03-27 | University of Pittsburgh—of the Commonwealth System of Higher Education | Small molecules targeting HIV-1 Nef |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0627423A4 (en) | 1992-01-22 | 1995-02-15 | Nissan Chemical Ind Ltd | SUBSTITUTED PYRAZOLE DERIVATIVES AND BACTERICIDES FOR AGRICULTURE AND GARDENING. |
| US6005109A (en) | 1997-10-30 | 1999-12-21 | Pflizer Inc. | Pyrazoles and pyrazolopyrimidines having CRF antagonistic activity |
| DK0786455T3 (da) | 1994-09-26 | 2004-03-29 | Shionogi & Co | Imidazolderivater |
| US5698495A (en) | 1995-11-15 | 1997-12-16 | Zeneca Limited | Herbicidal substituted pyrazole compounds |
| GB0016787D0 (en) | 2000-07-07 | 2000-08-30 | Pfizer Ltd | Compounds useful in therapy |
| GB0024795D0 (en) | 2000-10-10 | 2000-11-22 | Hoffmann La Roche | Pyrazole derivatives for the treatment of viral diseases |
-
2001
- 2001-06-04 GB GBGB0113524.3A patent/GB0113524D0/en not_active Ceased
-
2002
- 2002-05-24 US US10/154,585 patent/US6538015B1/en not_active Expired - Fee Related
- 2002-05-29 JP JP2003503620A patent/JP4088249B2/ja not_active Expired - Fee Related
- 2002-05-29 WO PCT/EP2002/005898 patent/WO2002100853A1/en not_active Ceased
- 2002-05-29 PT PT02758207T patent/PT1401826E/pt unknown
- 2002-05-29 AT AT02758207T patent/ATE357439T1/de not_active IP Right Cessation
- 2002-05-29 KR KR1020037015833A patent/KR100627532B1/ko not_active Expired - Fee Related
- 2002-05-29 BR BR0210158-0A patent/BR0210158A/pt not_active IP Right Cessation
- 2002-05-29 CA CA002448058A patent/CA2448058C/en not_active Expired - Fee Related
- 2002-05-29 CN CNB028111974A patent/CN1249052C/zh not_active Expired - Fee Related
- 2002-05-29 AU AU2002325221A patent/AU2002325221B2/en not_active Ceased
- 2002-05-29 EP EP02758207A patent/EP1401826B1/en not_active Expired - Lifetime
- 2002-05-29 MX MXPA03011199A patent/MXPA03011199A/es active IP Right Grant
- 2002-05-29 DK DK02758207T patent/DK1401826T3/da active
- 2002-05-29 DE DE60219009T patent/DE60219009T2/de not_active Expired - Fee Related
- 2002-05-29 ES ES02758207T patent/ES2282446T3/es not_active Expired - Lifetime
-
2003
- 2003-11-11 ZA ZA200308781A patent/ZA200308781B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT1401826E (pt) | 2007-06-19 |
| AU2002325221B2 (en) | 2008-07-31 |
| JP4088249B2 (ja) | 2008-05-21 |
| CN1527829A (zh) | 2004-09-08 |
| WO2002100853A1 (en) | 2002-12-19 |
| CN1249052C (zh) | 2006-04-05 |
| MXPA03011199A (es) | 2004-02-26 |
| US6538015B1 (en) | 2003-03-25 |
| DE60219009T2 (de) | 2007-12-13 |
| EP1401826A1 (en) | 2004-03-31 |
| ATE357439T1 (de) | 2007-04-15 |
| JP2004532276A (ja) | 2004-10-21 |
| ZA200308781B (en) | 2005-02-11 |
| GB0113524D0 (en) | 2001-07-25 |
| CA2448058A1 (en) | 2002-12-19 |
| DK1401826T3 (da) | 2007-07-30 |
| EP1401826B1 (en) | 2007-03-21 |
| BR0210158A (pt) | 2004-06-08 |
| DE60219009D1 (de) | 2007-05-03 |
| KR20040003050A (ko) | 2004-01-07 |
| KR100627532B1 (ko) | 2006-09-21 |
| ES2282446T3 (es) | 2007-10-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |