CA2678949A1 - Biaryl and biheteroaryl compounds useful in treating iron disorders - Google Patents

Info

Publication number

CA2678949A1

CA2678949A1 CA002678949A CA2678949A CA2678949A1 CA 2678949 A1 CA2678949 A1 CA 2678949A1 CA 002678949 A CA002678949 A CA 002678949A CA 2678949 A CA2678949 A CA 2678949A CA 2678949 A1 CA2678949 A1 CA 2678949A1

Authority

CA

Canada

Prior art keywords

alkyl

optionally substituted

independently

hydrogen

haloalkyl

Prior art date

2007-03-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 455
• 208000016286 Iron metabolism disease Diseases 0.000 title claims abstract description 62
• 125000005841 biaryl group Chemical group 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 79
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 57
• 239000000203 mixture Substances 0.000 claims abstract description 56
• 239000000651 prodrug Substances 0.000 claims abstract description 44
• 229940002612 prodrug Drugs 0.000 claims abstract description 44
• 150000003839 salts Chemical class 0.000 claims abstract description 44
• 239000012453 solvate Substances 0.000 claims abstract description 32
• 125000000217 alkyl group Chemical group 0.000 claims description 600
• 239000001257 hydrogen Substances 0.000 claims description 510
• 229910052739 hydrogen Inorganic materials 0.000 claims description 510
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 312
• 125000001188 haloalkyl group Chemical group 0.000 claims description 299
• 125000001072 heteroaryl group Chemical group 0.000 claims description 148
• 125000000623 heterocyclic group Chemical group 0.000 claims description 147
• -1 2-[2-({[amino(imino)methyl]thio}methyl)-4-fluorophenoxy]-5-nitrobenzyl Chemical group 0.000 claims description 144
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 134
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 130
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 118
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 118
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 117
• 125000002947 alkylene group Chemical group 0.000 claims description 116
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 94
• 125000003342 alkenyl group Chemical group 0.000 claims description 89
• 125000003107 substituted aryl group Chemical group 0.000 claims description 82
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 80
• 125000000304 alkynyl group Chemical group 0.000 claims description 76
• 125000003118 aryl group Chemical group 0.000 claims description 70
• 241000124008 Mammalia Species 0.000 claims description 68
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 54
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
• 201000010099 disease Diseases 0.000 claims description 32
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 25
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 10
• HSUFRFVNRNOTOR-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=CC=C1CSC(N)=N HSUFRFVNRNOTOR-UHFFFAOYSA-N 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• WTXHVCTVIQDVOV-UHFFFAOYSA-N 1-[2-[2-(1-carbamimidoylsulfanylethyl)phenoxy]phenyl]ethyl carbamimidothioate Chemical compound NC(=N)SC(C)C1=CC=CC=C1OC1=CC=CC=C1C(C)SC(N)=N WTXHVCTVIQDVOV-UHFFFAOYSA-N 0.000 claims description 2
• VOXZLVJQBLMVEQ-UHFFFAOYSA-N 2-[2-[2-(2-amino-2-cyanoiminoethyl)phenyl]sulfanylphenyl]-n'-cyanoethanimidamide Chemical compound N#CNC(=N)CC1=CC=CC=C1SC1=CC=CC=C1CC(=N)NC#N VOXZLVJQBLMVEQ-UHFFFAOYSA-N 0.000 claims description 2
• UTOCRXVKMBCTAZ-UHFFFAOYSA-N 2-[2-[2-(2-amino-2-iminoethyl)phenyl]sulfanylphenyl]ethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1SC1=CC=CC=C1CC(N)=N UTOCRXVKMBCTAZ-UHFFFAOYSA-N 0.000 claims description 2
• BDPMFFFSDGZBMI-UHFFFAOYSA-N 2-[2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-5-chlorophenyl]ethyl carbamimidothioate Chemical compound NC(=N)SCCC1=CC(Cl)=CC=C1SC1=CC=C(F)C=C1CSC(N)=N BDPMFFFSDGZBMI-UHFFFAOYSA-N 0.000 claims description 2
• VHJARNXKQOJTGO-UHFFFAOYSA-N 2-[2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-5-fluorophenyl]ethyl carbamimidothioate Chemical compound NC(=N)SCCC1=CC(F)=CC=C1SC1=CC=C(F)C=C1CSC(N)=N VHJARNXKQOJTGO-UHFFFAOYSA-N 0.000 claims description 2
• DJHSJLAXWTUNSX-UHFFFAOYSA-N 2-[2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfanylphenyl]ethyl carbamimidothioate Chemical compound NC(=N)SCCC1=CC=CC=C1SC1=CC=CC=C1CSC(N)=N DJHSJLAXWTUNSX-UHFFFAOYSA-N 0.000 claims description 2
• KEBXKALGJXAQTF-UHFFFAOYSA-N 2-[[2-[2-[(diaminomethylideneamino)methyl]phenyl]sulfanylphenyl]methyl]guanidine Chemical compound NC(=N)NCC1=CC=CC=C1SC1=CC=CC=C1CNC(N)=N KEBXKALGJXAQTF-UHFFFAOYSA-N 0.000 claims description 2
• XHJYKDXELPKWGD-UHFFFAOYSA-N 3-[2-[2-(3-amino-3-cyanoiminopropyl)phenyl]sulfanylphenyl]-n'-cyanopropanimidamide Chemical compound N#CNC(=N)CCC1=CC=CC=C1SC1=CC=CC=C1CCC(=N)NC#N XHJYKDXELPKWGD-UHFFFAOYSA-N 0.000 claims description 2
• BACAWUYBWXPUMW-UHFFFAOYSA-N 3-[2-[2-(3-amino-3-iminopropyl)phenyl]sulfanylphenyl]propanimidamide Chemical compound NC(=N)CCC1=CC=CC=C1SC1=CC=CC=C1CCC(N)=N BACAWUYBWXPUMW-UHFFFAOYSA-N 0.000 claims description 2
• KHOXIIURHMWVFQ-UHFFFAOYSA-N 4-[2-[2-(4-amino-4-cyanoiminobutyl)phenyl]sulfanylphenyl]-n'-cyanobutanimidamide Chemical compound N#CNC(=N)CCCC1=CC=CC=C1SC1=CC=CC=C1CCCC(=N)NC#N KHOXIIURHMWVFQ-UHFFFAOYSA-N 0.000 claims description 2
• FTJUUHYWNYVKEX-UHFFFAOYSA-N 4-[2-[2-(4-amino-4-iminobutyl)phenyl]sulfanylphenyl]butanimidamide Chemical compound NC(=N)CCCC1=CC=CC=C1SC1=CC=CC=C1CCCC(N)=N FTJUUHYWNYVKEX-UHFFFAOYSA-N 0.000 claims description 2
• BDDPRJLXXZPCPO-UHFFFAOYSA-N [2-[1-(carbamimidoylsulfanylmethyl)naphthalen-2-yl]sulfanyl-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1SC1=CC=C(C=CC=C2)C2=C1CSC(N)=N BDDPRJLXXZPCPO-UHFFFAOYSA-N 0.000 claims description 2
• OAGRFSWUPPEWOG-UHFFFAOYSA-N [2-[1-(carbamimidoylsulfanylmethyl)naphthalen-2-yl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=C(C=CC=C2)C2=C1CSC(N)=N OAGRFSWUPPEWOG-UHFFFAOYSA-N 0.000 claims description 2
• YDJXWMJZIDNNJW-UHFFFAOYSA-N [2-[2,6-bis(carbamimidoylsulfanylmethyl)phenyl]-3-(carbamimidoylsulfanylmethyl)phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC(CSC(N)=N)=C1C1=C(CSC(N)=N)C=CC=C1CSC(N)=N YDJXWMJZIDNNJW-UHFFFAOYSA-N 0.000 claims description 2
• CKOPRHWLMDTTQR-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-3-chlorophenoxy]-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1OC1=CC=CC(Cl)=C1CSC(N)=N CKOPRHWLMDTTQR-UHFFFAOYSA-N 0.000 claims description 2
• CMMRFQALGJBNQE-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4,5-difluorophenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC(F)=C(F)C=C1CSC(N)=N CMMRFQALGJBNQE-UHFFFAOYSA-N 0.000 claims description 2
• VHLNBLUSPLVOGG-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-(ethylamino)phenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(NCC)=CC=C1SC1=CC=CC=C1CSC(N)=N VHLNBLUSPLVOGG-UHFFFAOYSA-N 0.000 claims description 2
• PBSCISQPVBETEK-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-(trifluoromethyl)phenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=C(C(F)(F)F)C=C1CSC(N)=N PBSCISQPVBETEK-UHFFFAOYSA-N 0.000 claims description 2
• MJOORKVVDZCKMJ-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-chlorobenzoyl]phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1CSC(N)=N MJOORKVVDZCKMJ-UHFFFAOYSA-N 0.000 claims description 2
• DXAKSZOTWNBXRP-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-chlorophenoxy]-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1OC1=CC=C(Cl)C=C1CSC(N)=N DXAKSZOTWNBXRP-UHFFFAOYSA-N 0.000 claims description 2
• OOTAEMOWZJVODF-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-chlorophenyl]sulfanyl-5-chlorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(Cl)=CC=C1SC1=CC=C(Cl)C=C1CSC(N)=N OOTAEMOWZJVODF-UHFFFAOYSA-N 0.000 claims description 2
• PPUCUOCGNCIUNC-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-chlorophenyl]sulfanyl-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1SC1=CC=C(Cl)C=C1CSC(N)=N PPUCUOCGNCIUNC-UHFFFAOYSA-N 0.000 claims description 2
• LUTKZCHGIBGYGY-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-chlorophenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=C(Cl)C=C1CSC(N)=N LUTKZCHGIBGYGY-UHFFFAOYSA-N 0.000 claims description 2
• OXJUBBYOLNTDQU-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorobenzoyl]phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C(=O)C1=CC=C(F)C=C1CSC(N)=N OXJUBBYOLNTDQU-UHFFFAOYSA-N 0.000 claims description 2
• NAGNVZUDILOUCT-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenoxy]-4-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=C(F)C=C1OC1=CC=C(F)C=C1CSC(N)=N NAGNVZUDILOUCT-UHFFFAOYSA-N 0.000 claims description 2
• OXAGDHOUNYGFBJ-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenoxy]-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1OC1=CC=C(F)C=C1CSC(N)=N OXAGDHOUNYGFBJ-UHFFFAOYSA-N 0.000 claims description 2
• FNXDTKKOGLILRY-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-4,5-difluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1SC1=CC(F)=C(F)C=C1CSC(N)=N FNXDTKKOGLILRY-UHFFFAOYSA-N 0.000 claims description 2
• UNJZGYJZWXJEEN-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-4-chlorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=C(Cl)C=C1SC1=CC=C(F)C=C1CSC(N)=N UNJZGYJZWXJEEN-UHFFFAOYSA-N 0.000 claims description 2
• IFGQXQWCEDKROS-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-5-(trifluoromethyl)phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1SC1=CC=C(C(F)(F)F)C=C1CSC(N)=N IFGQXQWCEDKROS-UHFFFAOYSA-N 0.000 claims description 2
• UTMWAIBVJNMOFA-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1SC1=CC=C(F)C=C1CSC(N)=N UTMWAIBVJNMOFA-UHFFFAOYSA-N 0.000 claims description 2
• MZGWPZUKSRDPSD-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-5-methoxyphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(OC)=CC=C1SC1=CC=C(F)C=C1CSC(N)=N MZGWPZUKSRDPSD-UHFFFAOYSA-N 0.000 claims description 2
• PVODIKFSJIQMMH-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=C(F)C=C1CSC(N)=N PVODIKFSJIQMMH-UHFFFAOYSA-N 0.000 claims description 2
• ZENFKCUWAZNEQE-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfonyl-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(F)=CC=C1S(=O)(=O)C1=CC=C(F)C=C1CSC(N)=N ZENFKCUWAZNEQE-UHFFFAOYSA-N 0.000 claims description 2
• CXRHXJYNKBOVOY-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-methoxyphenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(OC)=CC=C1SC1=CC=CC=C1CSC(N)=N CXRHXJYNKBOVOY-UHFFFAOYSA-N 0.000 claims description 2
• BHQRWNYLGUZQNK-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-methylphenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(C)=CC=C1SC1=CC=CC=C1CSC(N)=N BHQRWNYLGUZQNK-UHFFFAOYSA-N 0.000 claims description 2
• HEDAXPWHUOOTSL-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-methylsulfonylphenyl]sulfanyl-5-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC(S(=O)(=O)C)=CC=C1SC1=CC=C(F)C=C1CSC(N)=N HEDAXPWHUOOTSL-UHFFFAOYSA-N 0.000 claims description 2
• HINMYCWYDKUMAI-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-6-methylphenyl]-3-methylphenyl]methyl carbamimidothioate;dihydrobromide Chemical compound Br.Br.CC1=CC=CC(CSC(N)=N)=C1C1=C(C)C=CC=C1CSC(N)=N HINMYCWYDKUMAI-UHFFFAOYSA-N 0.000 claims description 2
• WOJXWAUYLHOFCS-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-6-methylphenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound CC1=CC=CC(CSC(N)=N)=C1SC1=CC=CC=C1CSC(N)=N WOJXWAUYLHOFCS-UHFFFAOYSA-N 0.000 claims description 2
• OKNAEBOMLWDZOB-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)benzoyl]-4-chlorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C(=O)C1=CC(Cl)=CC=C1CSC(N)=N OKNAEBOMLWDZOB-UHFFFAOYSA-N 0.000 claims description 2
• PCGCPEDEXIPNAO-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)benzoyl]-4-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C(=O)C1=CC(F)=CC=C1CSC(N)=N PCGCPEDEXIPNAO-UHFFFAOYSA-N 0.000 claims description 2
• NONDOVCWISGVGK-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)benzoyl]phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C(=O)C1=CC=CC=C1CSC(N)=N NONDOVCWISGVGK-UHFFFAOYSA-N 0.000 claims description 2
• OFWJXPLLFCTWLR-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1C1=CC=CC=C1CSC(N)=N OFWJXPLLFCTWLR-UHFFFAOYSA-N 0.000 claims description 2
• WFIYATQCWXRHSR-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfanyl-4-chlorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC(Cl)=CC=C1CSC(N)=N WFIYATQCWXRHSR-UHFFFAOYSA-N 0.000 claims description 2
• FCADQHISGWXHMC-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfanyl-4-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC(F)=CC=C1CSC(N)=N FCADQHISGWXHMC-UHFFFAOYSA-N 0.000 claims description 2
• GMONPOQPZDXTSE-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfanyl-4-methylphenyl]methyl carbamimidothioate Chemical compound CC1=CC=C(CSC(N)=N)C(SC=2C(=CC=CC=2)CSC(N)=N)=C1 GMONPOQPZDXTSE-UHFFFAOYSA-N 0.000 claims description 2
• QGIIHEYHAPPAGG-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenyl]sulfonylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1CSC(N)=N QGIIHEYHAPPAGG-UHFFFAOYSA-N 0.000 claims description 2
• BSEAMVNQHQCMRY-UHFFFAOYSA-N [2-[2-[[(z)-c-aminocarbonohydrazonoyl]sulfanylmethyl]phenyl]sulfanylphenyl]methyl n'-aminocarbamimidothioate Chemical compound NNC(=N)SCC1=CC=CC=C1SC1=CC=CC=C1CSC(=N)NN BSEAMVNQHQCMRY-UHFFFAOYSA-N 0.000 claims description 2
• QHFIEZHJPCSFSO-UHFFFAOYSA-N [2-[4-amino-2-(carbamimidoylsulfanylmethyl)phenyl]sulfanylphenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1SC1=CC=C(N)C=C1CSC(N)=N QHFIEZHJPCSFSO-UHFFFAOYSA-N 0.000 claims description 2
• RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 2
• 239000012965 benzophenone Substances 0.000 claims description 2
• BVVJMILMFLTNNC-UHFFFAOYSA-N methyl 3-(carbamimidoylsulfanylmethyl)-2-[2-(carbamimidoylsulfanylmethyl)-6-methoxycarbonylphenyl]benzoate Chemical compound COC(=O)C1=CC=CC(CSC(N)=N)=C1C1=C(CSC(N)=N)C=CC=C1C(=O)OC BVVJMILMFLTNNC-UHFFFAOYSA-N 0.000 claims description 2
• NHPWICWOYKASEE-UHFFFAOYSA-N n-(diaminomethylidene)-2-[2-(diaminomethylidenecarbamoyl)phenyl]sulfanylbenzamide Chemical compound NC(N)=NC(=O)C1=CC=CC=C1SC1=CC=CC=C1C(=O)N=C(N)N NHPWICWOYKASEE-UHFFFAOYSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 92
• NVOIGUVRBGFWQZ-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-4-fluorophenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=C(F)C=C1SC1=CC=C(F)C=C1CSC(N)=N NVOIGUVRBGFWQZ-UHFFFAOYSA-N 0.000 claims 1
• LIXZFBJVABMLMV-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)-4-fluorophenyl]sulfanyl-4-methylphenyl]methyl carbamimidothioate Chemical compound CC1=CC=C(CSC(N)=N)C(SC=2C(=CC(F)=CC=2)CSC(N)=N)=C1 LIXZFBJVABMLMV-UHFFFAOYSA-N 0.000 claims 1
• NVPQZZSXWUTRKL-UHFFFAOYSA-N [2-[2-(carbamimidoylsulfanylmethyl)phenoxy]phenyl]methyl carbamimidothioate Chemical compound NC(=N)SCC1=CC=CC=C1OC1=CC=CC=C1CSC(N)=N NVPQZZSXWUTRKL-UHFFFAOYSA-N 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 22
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 222
• 150000002431 hydrogen Chemical group 0.000 description 170
• 229910052742 iron Inorganic materials 0.000 description 110
• 125000005843 halogen group Chemical group 0.000 description 100
• 125000004093 cyano group Chemical group *C#N 0.000 description 97
• 102100021867 Natural resistance-associated macrophage protein 2 Human genes 0.000 description 67
• 101710171645 Natural resistance-associated macrophage protein 2 Proteins 0.000 description 66
• 238000006243 chemical reaction Methods 0.000 description 48
• 206010065973 Iron Overload Diseases 0.000 description 38
• 150000003254 radicals Chemical class 0.000 description 36
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 36
• 230000000694 effects Effects 0.000 description 31
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 28
• 125000001246 bromo group Chemical group Br* 0.000 description 25
• 208000035475 disorder Diseases 0.000 description 24
• 125000004450 alkenylene group Chemical group 0.000 description 21
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 239000003814 drug Substances 0.000 description 20
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 18
• 208000033981 Hereditary haemochromatosis Diseases 0.000 description 17
• 238000006887 Ullmann reaction Methods 0.000 description 17
• 239000002253 acid Substances 0.000 description 16
• 210000002966 serum Anatomy 0.000 description 16
• 210000001519 tissue Anatomy 0.000 description 16
• 125000004419 alkynylene group Chemical group 0.000 description 15
• 229910052799 carbon Inorganic materials 0.000 description 15
• 239000007788 liquid Substances 0.000 description 15
• 229910052757 nitrogen Inorganic materials 0.000 description 15
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
• 238000006073 displacement reaction Methods 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 239000007858 starting material Substances 0.000 description 14
• 241001465754 Metazoa Species 0.000 description 12
• 230000009102 absorption Effects 0.000 description 12
• 238000010521 absorption reaction Methods 0.000 description 12
• 125000001309 chloro group Chemical group Cl* 0.000 description 12
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