ZA200104376B - Alpha-methybenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine groups. - Google Patents

Alpha-methybenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine groups. Download PDF

Info

Publication number: ZA200104376B
Authority: ZA; South Africa
Prior art keywords: phenyl; carbon atoms; thioureido; ethyl; fluoro
Prior art date: 1998-12-09

Application number

ZA200104376A

Other languages

English (en)

Inventor

Jonathan David Bloom

Martin Joseph Digrandi

Stanley Albert Lang

Adma Antonia Ross

Kevin Joseph Curran

Russel George Dushin

Emily Boucher Norton

Bryan Mark O'hara

Original Assignee

Wyeth Corp

Priority date (The priority date 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 date listed.)

1998-12-09

Filing date

2001-05-28

Publication date

2002-08-28

2001-05-28 Application filed by Wyeth Corp filed Critical Wyeth Corp

2002-08-28 Publication of ZA200104376B publication Critical patent/ZA200104376B/en

Links

241001529453 unidentified herpesvirus Species 0.000 title claims description 13
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title description 3
239000003112 inhibitor Substances 0.000 title description 3
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical group NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 title description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 113
238000000034 method Methods 0.000 claims description 60
125000000217 alkyl group Chemical group 0.000 claims description 48
150000001875 compounds Chemical class 0.000 claims description 35
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 30
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 26
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 25
125000000753 cycloalkyl group Chemical group 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 22
125000001072 heteroaryl group Chemical group 0.000 claims description 21
-1 { 1-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl } amino Chemical group 0.000 claims description 21
239000000203 mixture Substances 0.000 claims description 19
125000003342 alkenyl group Chemical group 0.000 claims description 15
150000002431 hydrogen Chemical class 0.000 claims description 15
229910052736 halogen Inorganic materials 0.000 claims description 14
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
238000011282 treatment Methods 0.000 claims description 11
241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
230000003287 optical effect Effects 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000004001 thioalkyl group Chemical group 0.000 claims description 5
NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 claims description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
241000700584 Simplexvirus Species 0.000 claims description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
KGGHWIKBOIQEAJ-UHFFFAOYSA-N 2-fluorobenzamide Chemical compound NC(=O)C1=CC=CC=C1F KGGHWIKBOIQEAJ-UHFFFAOYSA-N 0.000 claims description 3
241000701024 Human betaherpesvirus 5 Species 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
ZSSFBXCDEYYUQO-UHFFFAOYSA-N 2-cyano-n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]benzamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C#N ZSSFBXCDEYYUQO-UHFFFAOYSA-N 0.000 claims description 2
JBAVFKKQNLPAOH-MRXNPFEDSA-N 2-fluoro-n-[4-[[(1r)-1-(4-methylphenyl)ethyl]carbamothioylamino]phenyl]benzamide Chemical compound N([C@H](C)C=1C=CC(C)=CC=1)C(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F JBAVFKKQNLPAOH-MRXNPFEDSA-N 0.000 claims description 2
ZRVIPJPXTSLRJK-UHFFFAOYSA-N 2-fluoro-n-[4-[[4-methoxy-3-(trifluoromethyl)phenyl]carbamothioylamino]phenyl]benzamide Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F ZRVIPJPXTSLRJK-UHFFFAOYSA-N 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
KYENQJICITXEGJ-UHFFFAOYSA-N 3-cyano-n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]benzamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC(C#N)=C1 KYENQJICITXEGJ-UHFFFAOYSA-N 0.000 claims description 2
VUEQUHWFLBWRLA-UHFFFAOYSA-N 4-cyano-n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]benzamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=C(C#N)C=C1 VUEQUHWFLBWRLA-UHFFFAOYSA-N 0.000 claims description 2
AQYKJMOSYVEXMK-UHFFFAOYSA-N n-[4-[(2-amino-5-fluorophenyl)carbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound NC1=CC=C(F)C=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F AQYKJMOSYVEXMK-UHFFFAOYSA-N 0.000 claims description 2
GXXXPEKVXGHZLD-UHFFFAOYSA-N n-[4-[(5-chloro-2-hydroxyphenyl)carbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound OC1=CC=C(Cl)C=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F GXXXPEKVXGHZLD-UHFFFAOYSA-N 0.000 claims description 2
ILOGWDZBCSHQBB-UHFFFAOYSA-N n-[4-[1-(1-benzofuran-2-yl)ethylcarbamothioylamino]phenyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(NC(=S)NC=3C=CC(NC(=O)C=4OC5=CC=CC=C5C=4)=CC=3)C)=CC2=C1 ILOGWDZBCSHQBB-UHFFFAOYSA-N 0.000 claims description 2
YKLVRCZOSNIPDI-UHFFFAOYSA-N n-[4-[1-(1-benzofuran-2-yl)ethylcarbamothioylamino]phenyl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2OC(C(NC(=S)NC=3C=CC(NC(=O)C=4N=CC5=CC=CC=C5C=4)=CC=3)C)=CC2=C1 YKLVRCZOSNIPDI-UHFFFAOYSA-N 0.000 claims description 2
RRAFDJZKBPJYFX-UHFFFAOYSA-N n-[4-[1-(3-chloro-4-methoxyphenyl)ethylcarbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F RRAFDJZKBPJYFX-UHFFFAOYSA-N 0.000 claims description 2
GKCCRVKZRMVSOM-UHFFFAOYSA-N n-[4-[1-(4-bromophenyl)ethylcarbamothioylamino]phenyl]-1-benzofuran-2-carboxamide Chemical compound C=1C=C(NC(=O)C=2OC3=CC=CC=C3C=2)C=CC=1NC(=S)NC(C)C1=CC=C(Br)C=C1 GKCCRVKZRMVSOM-UHFFFAOYSA-N 0.000 claims description 2
WOGPBVDSRUSUCE-UHFFFAOYSA-N n-[4-[1-(4-cyanophenyl)ethylcarbamothioylamino]phenyl]-1-benzofuran-2-carboxamide Chemical compound C=1C=C(NC(=O)C=2OC3=CC=CC=C3C=2)C=CC=1NC(=S)NC(C)C1=CC=C(C#N)C=C1 WOGPBVDSRUSUCE-UHFFFAOYSA-N 0.000 claims description 2
RYTSOXCTIOKYJF-UHFFFAOYSA-N n-[4-[1-(4-cyanophenyl)ethylcarbamothioylamino]phenyl]isoquinoline-1-carboxamide Chemical compound C=1C=C(NC(=O)C=2C3=CC=CC=C3C=CN=2)C=CC=1NC(=S)NC(C)C1=CC=C(C#N)C=C1 RYTSOXCTIOKYJF-UHFFFAOYSA-N 0.000 claims description 2
FBOCPBSEVJRVHE-UHFFFAOYSA-N n-[4-[2-(1-benzofuran-2-yl)ethylcarbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound FC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC(=S)NCCC1=CC2=CC=CC=C2O1 FBOCPBSEVJRVHE-UHFFFAOYSA-N 0.000 claims description 2
PNZKYPKDRLHMCZ-INIZCTEOSA-N n-[4-[[(1s)-1-(4-bromophenyl)ethyl]carbamothioylamino]phenyl]isoquinoline-3-carboxamide Chemical compound C1([C@@H](NC(=S)NC=2C=CC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=CC=2)C)=CC=C(Br)C=C1 PNZKYPKDRLHMCZ-INIZCTEOSA-N 0.000 claims description 2
QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 claims description 2
230000010076 replication Effects 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
239000000126 substance Substances 0.000 claims 9
125000004429 atom Chemical group 0.000 claims 3
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 claims 2
VQMSRUREDGBWKT-UHFFFAOYSA-N quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=NC2=C1 VQMSRUREDGBWKT-UHFFFAOYSA-N 0.000 claims 2
BKJWSTYYRNWKAC-UHFFFAOYSA-N 2-fluoro-n-[4-[(3-fluoro-4-methylphenyl)carbamothioylamino]phenyl]benzamide Chemical compound C1=C(F)C(C)=CC=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F BKJWSTYYRNWKAC-UHFFFAOYSA-N 0.000 claims 1
CJHCDXCWGMOBKJ-OAHLLOKOSA-N 2-fluoro-n-[4-[[(1r)-1-phenylethyl]carbamothioylamino]phenyl]benzamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F CJHCDXCWGMOBKJ-OAHLLOKOSA-N 0.000 claims 1
QDZIRMLZFBIPAY-UHFFFAOYSA-N 2-fluoro-n-[4-[[2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl]carbamothioylamino]phenyl]benzamide Chemical compound COC1=CC(OCC(F)(F)F)=CC=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F QDZIRMLZFBIPAY-UHFFFAOYSA-N 0.000 claims 1
208000029433 Herpesviridae infectious disease Diseases 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
BQLWTSBATVZGNT-UHFFFAOYSA-N n-[4-[1-(1-benzofuran-2-yl)ethylcarbamothioylamino]phenyl]isoquinoline-1-carboxamide Chemical compound C1=CC=C2OC(C(NC(=S)NC=3C=CC(NC(=O)C=4C5=CC=CC=C5C=CN=4)=CC=3)C)=CC2=C1 BQLWTSBATVZGNT-UHFFFAOYSA-N 0.000 claims 1
IOABVAYQZBFYFU-UHFFFAOYSA-N n-[4-[1-(4-bromophenyl)ethylcarbamothioylamino]phenyl]-2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC(=S)NC(C)C1=CC=C(Br)C=C1 IOABVAYQZBFYFU-UHFFFAOYSA-N 0.000 claims 1
MZNGRRVYCARXOA-UHFFFAOYSA-N n-[4-[1-(4-bromophenyl)ethylcarbamothioylamino]phenyl]isoquinoline-1-carboxamide Chemical compound C=1C=C(NC(=O)C=2C3=CC=CC=C3C=CN=2)C=CC=1NC(=S)NC(C)C1=CC=C(Br)C=C1 MZNGRRVYCARXOA-UHFFFAOYSA-N 0.000 claims 1
TVATXXIZGDVIGL-UHFFFAOYSA-N n-[4-[1-(4-cyanophenyl)ethylcarbamothioylamino]phenyl]-2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC(=S)NC(C)C1=CC=C(C#N)C=C1 TVATXXIZGDVIGL-UHFFFAOYSA-N 0.000 claims 1
OZTAEVMWXGURMY-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]-2-(trifluoromethyl)benzamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C(F)(F)F OZTAEVMWXGURMY-UHFFFAOYSA-N 0.000 claims 1
KASXRKXITVNVKR-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]isoquinoline-1-carboxamide Chemical compound C=1C=C(NC(=O)C=2C3=CC=CC=C3C=CN=2)C=CC=1NC(=S)NC(C)C1=CC=C(F)C=C1 KASXRKXITVNVKR-UHFFFAOYSA-N 0.000 claims 1
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GWYPRXPVHZUXGJ-AWEZNQCLSA-N n-[4-[[(1s)-1-(4-bromophenyl)ethyl]carbamothioylamino]phenyl]-4-fluorobenzamide Chemical compound N([C@@H](C)C=1C=CC(Br)=CC=1)C(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=C(F)C=C1 GWYPRXPVHZUXGJ-AWEZNQCLSA-N 0.000 claims 1
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PPZKIYGBNYLPOA-UHFFFAOYSA-N n-[4-[[3-chloro-4-(2-methylpropoxy)phenyl]carbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound C1=C(Cl)C(OCC(C)C)=CC=C1NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F PPZKIYGBNYLPOA-UHFFFAOYSA-N 0.000 claims 1
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HNWMYUNXUZWIFV-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]-4-(trifluoromethyl)benzamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=C(C(F)(F)F)C=C1 HNWMYUNXUZWIFV-UHFFFAOYSA-N 0.000 description 1
UKTPEFAEFIQITA-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]quinoline-3-carboxamide Chemical compound C=1C=C(NC(=O)C=2C=C3C=CC=CC3=NC=2)C=CC=1NC(=S)NC(C)C1=CC=C(F)C=C1 UKTPEFAEFIQITA-UHFFFAOYSA-N 0.000 description 1
AXSHDVBYRZOMLM-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]quinoline-4-carboxamide Chemical compound C=1C=C(NC(=O)C=2C3=CC=CC=C3N=CC=2)C=CC=1NC(=S)NC(C)C1=CC=C(F)C=C1 AXSHDVBYRZOMLM-UHFFFAOYSA-N 0.000 description 1
UBESZTWLNINWSH-UHFFFAOYSA-N n-[4-[1-(4-fluorophenyl)ethylcarbamothioylamino]phenyl]quinoline-6-carboxamide Chemical compound C=1C=C(NC(=O)C=2C=C3C=CC=NC3=CC=2)C=CC=1NC(=S)NC(C)C1=CC=C(F)C=C1 UBESZTWLNINWSH-UHFFFAOYSA-N 0.000 description 1
KOOVZLLETLDOIE-UHFFFAOYSA-N n-[4-[1-[4-(dimethylsulfamoyl)phenyl]ethylcarbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound C=1C=C(S(=O)(=O)N(C)C)C=CC=1C(C)NC(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F KOOVZLLETLDOIE-UHFFFAOYSA-N 0.000 description 1
IOABVAYQZBFYFU-OAHLLOKOSA-N n-[4-[[(1r)-1-(4-bromophenyl)ethyl]carbamothioylamino]phenyl]-2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC(=S)N[C@H](C)C1=CC=C(Br)C=C1 IOABVAYQZBFYFU-OAHLLOKOSA-N 0.000 description 1
SUWGJAQKGMMPAP-CQSZACIVSA-N n-[4-[[(1r)-1-(4-chlorophenyl)ethyl]carbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound N([C@H](C)C=1C=CC(Cl)=CC=1)C(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F SUWGJAQKGMMPAP-CQSZACIVSA-N 0.000 description 1
MZNGRRVYCARXOA-INIZCTEOSA-N n-[4-[[(1s)-1-(4-bromophenyl)ethyl]carbamothioylamino]phenyl]isoquinoline-1-carboxamide Chemical compound C1([C@@H](NC(=S)NC=2C=CC(NC(=O)C=3C4=CC=CC=C4C=CN=3)=CC=2)C)=CC=C(Br)C=C1 MZNGRRVYCARXOA-INIZCTEOSA-N 0.000 description 1
SUWGJAQKGMMPAP-AWEZNQCLSA-N n-[4-[[(1s)-1-(4-chlorophenyl)ethyl]carbamothioylamino]phenyl]-2-fluorobenzamide Chemical compound N([C@@H](C)C=1C=CC(Cl)=CC=1)C(=S)NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1F SUWGJAQKGMMPAP-AWEZNQCLSA-N 0.000 description 1
VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical class [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
230000002276 neurotropic effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
244000039328 opportunistic pathogen Species 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000007918 pathogenicity Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
201000000317 pneumocystosis Diseases 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
230000010322 reactivation of latent virus Effects 0.000 description 1
210000003296 saliva Anatomy 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
206010040872 skin infection Diseases 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
229940055764 triaz Drugs 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C335/20—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biotechnology (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Quinoline Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Furan Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)

ZA200104376A 1998-12-09 2001-05-28 Alpha-methybenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine groups. ZA200104376B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US20890298A	1998-12-09	1998-12-09

Publications (1)

Publication Number	Publication Date
ZA200104376B true ZA200104376B (en)	2002-08-28

Family

ID=22776519

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200104376A ZA200104376B (en)	1998-12-09	2001-05-28	Alpha-methybenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine groups.

Country Status (21)

Country	Link
EP (1)	EP1137645B1 (de)
JP (1)	JP2002531555A (de)
KR (1)	KR20010089551A (de)
CN (1)	CN1165531C (de)
AR (1)	AR035308A1 (de)
AT (1)	ATE267824T1 (de)
AU (1)	AU1934600A (de)
BR (1)	BR9916084A (de)
CA (1)	CA2350833A1 (de)
CZ (1)	CZ20012067A3 (de)
DE (1)	DE69917673T2 (de)
DK (1)	DK1137645T3 (de)
EA (1)	EA004205B1 (de)
ES (1)	ES2221470T3 (de)
HU (1)	HUP0104492A3 (de)
IL (1)	IL143183A0 (de)
NO (1)	NO20012833L (de)
NZ (1)	NZ512135A (de)
PT (1)	PT1137645E (de)
WO (1)	WO2000034260A2 (de)
ZA (1)	ZA200104376B (de)

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Publication number	Priority date	Publication date	Assignee	Title
US6844367B1 (en)	1999-09-17	2005-01-18	Millennium Pharmaceuticals, Inc.	Benzamides and related inhibitors of factor Xa
WO2001064642A2 (en)	2000-02-29	2001-09-07	Cor Therapeutics, Inc.	Benzamides and related inhibitors of factor xa
CA2417507A1 (en) *	2000-08-21	2002-02-28	Pacific Corporation	Novel thiourea derivatives and the pharmaceutical compositions containing the same
JP4360885B2 (ja)	2003-11-28	2009-11-11	富士フイルム株式会社	アルキルチオ基を有する芳香族アミン化合物の製造方法
WO2007024754A1 (en) *	2005-08-22	2007-03-01	Amgen Inc.	Bis-aryl urea compounds for the treatment of protein kinase-mediated diseaes
CN101595092B (zh)	2006-11-02	2012-02-01	米伦纽姆医药公司	合成因子xa抑制剂的医药盐的方法
CN112807294B (zh) *	2019-11-18	2023-09-05	武汉大学	一种酰基硫脲类化合物在制备治疗或预防单纯疱疹病毒i型感染药物中的应用
CN115433093A (zh) *	2022-09-26	2022-12-06	无锡双启科技有限公司	一种3-氯-4-三氟甲基苯胺的制备方法

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU210683B (en) *	1990-06-18	1995-06-28	Sandoz Ag	Process for producing n-benzyl-n1-(phenyl-alkyl)-thiourea derivatives and pharmaceutical compositions containing the same
JPH11503110A (ja) *	1995-02-17	1999-03-23	スミスクライン・ビーチャム・コーポレイション	Ｉｌ−８受容体拮抗剤
GB9519270D0 (en) *	1995-09-21	1995-11-22	Sandoz Pharma Uk	Organic compounds
HUP0004421A3 (en) *	1996-04-23	2002-10-28	Vertex Pharmaceuticals Inc Cam	Urea derivatives and pharmaceutical compositions containing them, use thereof for the treatment of deseases mediated by impdh enzyme

1999
- 1999-12-06 PT PT99963022T patent/PT1137645E/pt unknown
- 1999-12-06 AT AT99963022T patent/ATE267824T1/de not_active IP Right Cessation
- 1999-12-06 ES ES99963022T patent/ES2221470T3/es not_active Expired - Lifetime
- 1999-12-06 AU AU19346/00A patent/AU1934600A/en not_active Abandoned
- 1999-12-06 KR KR1020017007053A patent/KR20010089551A/ko not_active Withdrawn
- 1999-12-06 CZ CZ20012067A patent/CZ20012067A3/cs unknown
- 1999-12-06 EP EP99963022A patent/EP1137645B1/de not_active Expired - Lifetime
- 1999-12-06 NZ NZ512135A patent/NZ512135A/en unknown
- 1999-12-06 BR BR9916084-6A patent/BR9916084A/pt not_active IP Right Cessation
- 1999-12-06 DE DE69917673T patent/DE69917673T2/de not_active Expired - Fee Related
- 1999-12-06 CA CA002350833A patent/CA2350833A1/en not_active Abandoned
- 1999-12-06 JP JP2000586707A patent/JP2002531555A/ja active Pending
- 1999-12-06 IL IL14318399A patent/IL143183A0/xx unknown
- 1999-12-06 DK DK99963022T patent/DK1137645T3/da active
- 1999-12-06 WO PCT/US1999/028839 patent/WO2000034260A2/en not_active Ceased
- 1999-12-06 CN CNB998142778A patent/CN1165531C/zh not_active Expired - Fee Related
- 1999-12-06 EA EA200100638A patent/EA004205B1/ru not_active IP Right Cessation
- 1999-12-06 HU HU0104492A patent/HUP0104492A3/hu unknown
- 1999-12-07 AR ARP990106228A patent/AR035308A1/es not_active Application Discontinuation
2001
- 2001-05-28 ZA ZA200104376A patent/ZA200104376B/en unknown
- 2001-06-08 NO NO20012833A patent/NO20012833L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
HUP0104492A3 (en)	2002-12-28
AU1934600A (en)	2000-06-26
BR9916084A (pt)	2001-09-04
CN1329608A (zh)	2002-01-02
NZ512135A (en)	2003-12-19
DK1137645T3 (da)	2004-08-09
CA2350833A1 (en)	2000-06-15
DE69917673T2 (de)	2005-06-09
JP2002531555A (ja)	2002-09-24
CZ20012067A3 (cs)	2001-10-17
WO2000034260A2 (en)	2000-06-15
EP1137645A2 (de)	2001-10-04
ES2221470T3 (es)	2004-12-16
DE69917673D1 (de)	2004-07-01
NO20012833L (no)	2001-08-02
CN1165531C (zh)	2004-09-08
EA004205B1 (ru)	2004-02-26
NO20012833D0 (no)	2001-06-08
EA200100638A1 (ru)	2001-12-24
HUP0104492A2 (hu)	2002-04-29
ATE267824T1 (de)	2004-06-15
PT1137645E (pt)	2004-09-30
AR035308A1 (es)	2004-05-12
KR20010089551A (ko)	2001-10-06
WO2000034260A3 (en)	2000-09-08
EP1137645B1 (de)	2004-05-26
IL143183A0 (en)	2002-04-21

Publication	Publication Date	Title
DK168323B1 (da)	1994-03-14	Anvendelse af visse pyrimidinnucleosider til fremstilling af et lægemiddel mod VZV-infektioner; hidtil ukendte pyrimidinnucleosider, sådanne forbindelser til anvendelse i human terapi samt fremgangsmåde til fremstilling af forbindelserne
ZA200104142B (en)	2002-10-25	Acetamide and substituted acetamide-containing thiourea inhibitors of herpes viruses.
AU603012B2 (en)	1990-11-01	N-substituted derivatives of 1-desoxynojirimycin 1- desoxymannojirimycin, processes for their preparation and their use in medicaments
RU2642463C2 (ru)	2018-01-25	Циклопропанкарбоксилатные эфиры пуриновых аналогов
PL179417B1 (en)	2000-09-29	Pharmacologically active derivatives of pyridine and methods of obtaining them
DK159683B (da)	1990-11-19	9-(4-hydroxybutyl)-guaninderivat, farmaceutisk praeparat indeholdende en saadan forbindelse og anvendelse af den til fremstilling af et laegemiddel
ZA200104322B (en)	2002-10-25	Heterocyclic carboxamide-containing thiourea inhibitors of herpes viruses containing a substituted phenylenediamine group.
ZA200104376B (en)	2002-08-28	Alpha-methybenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine groups.
EP3932910A1 (de)	2022-01-05	Anilin-wdr5-protein-protein-interaktionsinhibitor, verfahren zu seiner herstellung und seine verwendung
EP3597184A2 (de)	2020-01-22	Indanonderivate, pharmazeutisch zulässige salze oder optische isomere davon, herstellungsverfahren dafür und pharmazeutische zusammensetzungen damit als wirkstoff zur verhinderung oder behandlung von virenerkrankungen
EP3594205A1 (de)	2020-01-15	Phenyl-n-aryl-derivate zur behandlung einer rna-virusinfektion
US20210040109A1 (en)	2021-02-11	Biphenyl-containing diarylpyrimido compounds, pharmaceutically-acceptable salts thereof, composition and preparation thereof
DE69919023T2 (de)	2005-07-28	Thioharnstoff-inhibitoren von herpes-virus
ZA200104373B (en)	2002-09-18	Thiourea inhibitors of herpes viruses.
ZA200104318B (en)	2002-08-26	Thiourea inhibitors of herpes viruses.
TWI385172B (zh)	2013-02-11	新穎化合物
SK7682001A3 (en)	2002-07-02	Heterocyclic carboxamide-containing thiourea inhibitors of herpes viruses containing phenylenediamine group
EP0168003B1 (de)	1991-04-03	Oxindolverbindungen, diese enthaltende Zusammensetzungen sowie Verfahren zur Herstellung derselben
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