Patent ID: 6608061
Filing Date: 2003-08-19
Classification: A61P,C07C,C07D,C07H

Abstract:
A method for inhibiting ribonucleotide reductase comprising administering to a subject in need thereof an effective amount of a compound represented by formula (I), or a physiologically acceptable salt thereof:Ar1â€”Sâ€”R1â€”Sâ€”Ar2â€ƒâ€ƒ(I) wherein R1 represents a nonmetal bridging group selected from â€”C2H4â€”Sâ€”C2H4â€”, â€”C2H4â€”Sâ€”C3H6â€”, â€”C2H4â€”Sâ€”C4H4â€”, â€”C2H4â€”Sâ€”C4H6â€”, â€”C2H4Sâ€”C4H8â€”, â€”C3H6â€”Sâ€”C3H6â€”, â€”C3H6â€”Sâ€”C4H6â€”, â€”C3H6â€”Sâ€”C4H8â€”, â€”C4H8â€”Sâ€”C4H8â€”, â€”CH2COâ€”Sâ€”C2H4â€”, â€”CH2COâ€”Sâ€”C3H6â€”, â€”CH2COâ€”Sâ€”C4H8â€”, â€”CH2COâ€”Sâ€”C4H6â€”, â€”CH2COâ€”Sâ€”C4H4â€”, â€”CH(CH3)COâ€”Sâ€”C2H4â€”, â€”C2H4COâ€”Sâ€”CH2CH(OH)CH2â€”, â€”CH2COâ€”Sâ€”C2H4NHCOCH2â€”, â€”C2H4COâ€”Sâ€”C2H4NHCOC2H4â€”, â€”C2H4Oâ€”C2H4â€”, â€”C2H4â€”Oâ€”C3H6â€”, â€”C2H4â€”Oâ€”C4H4â€”, â€”C2H4â€”Oâ€”C4H6â€”, â€”C2H4â€”Oâ€”C4H8â€”, â€”C3H6â€”Oâ€”C3H6â€”, â€”C3H6â€”Oâ€”C4H6â€”, â€”C3H6â€”Oâ€”C4H8â€”, â€”C4H8â€”Oâ€”C4H8â€”, â€”CH2COâ€”Oâ€”C2H4â€”, â€”CH2COâ€”Oâ€”C3H6â€”, â€”CH2COâ€”Oâ€”C4H8â€”, â€”CH2COâ€”Oâ€”C4H6â€”, â€”CH2COâ€”Oâ€”C4H4â€”, â€”CH(CH3)COâ€”Oâ€”C2H4â€”, â€”C2H4COâ€”Oâ€”CH2CH(OH)CH2â€”, â€”CH2COâ€”Oâ€”C2H4NHCOCH2â€”, â€”C2H4COâ€”Oâ€”C2H4NHCOC2H4â€”; â€”R2â€”N(R4)â€”R3â€”, wherein R2, R3 and R4 are defined as follows: R2R3R4â€”C2H4â€”â€”C2H4â€”â€”Hâ€”â€”C3H6â€”â€”C3H6â€”â€”Hâ€”â€”C4H8â€”â€”C4H8â€”â€”Hâ€”â€”C2H4â€”â€”C2H4â€”â€”OHâ€”â€”C2H4â€”â€”C2H4â€”â€”C(&boxH;NH)NH2â€”C2H4â€”â€”C2H4â€”â€”COC3H7â€”C2H4â€”â€”C2H4â€”â€”COCH2CH2CO2Hâ€”C2H4â€”â€”C2H4â€”â€”COCH2CH2Sâ€”Phâ€”OH-pâ€”C2H4â€”â€”C2H4â€”â€”CHOâ€”C2H4â€”â€”C2H4â€”â€”COCH3â€”C2H4â€”â€”C2H4â€”â€”SO2CH3â€”C3H6â€”â€”C3H6â€”â€”CHOâ€”C2H4â€”â€”C2H4â€”â€”CH2CH2NH2â€”CH2COâ€”â€”C2H4â€”â€”Hâ€”CH2COâ€”â€”C3H6â€”â€”Hâ€”CH2COâ€”â€”C4H8â€”â€”Hâ€”CH2COâ€”â€”C4H6â€”â€”Hâ€”CH2COâ€”â€”C4H4â€”â€”Hâ€”CH2COâ€”â€”C4H4â€”â€”CHOâ€”CH(CH3)COâ€”â€”C2H4â€”â€”Hâ€”CH(CH3)COâ€”â€”C2H4â€”â€”C2H4OHâ€”C2H4COâ€”â€”CH2CH(OH)CH2â€”â€”C2H4OHâ€”CH2COâ€”â€”C2H4NHCOCH2â€”â€”Hâ€”C2H4COâ€”â€”C2H4NHCOC2H4â€”â€”Hâ€”C2H4â€”â€”C2H4â€”â€”C2H5â€”C2H4â€”â€”C2H4â€”â€”C3H7â€”C2H4â€”â€”C2H4â€”â€”CH2â€”Câ‰¡CHâ€”C2H4â€”â€”C2H4â€”â€”CH2â€”CH&boxH;CH2â€”C2H4â€”â€”C2H4â€”â€”CH2-cyclopropylâ€”C2H4â€”â€”C2H4â€”â€”CH2â€”SO2NH2â€”C2H4â€”â€”C2H4â€”â€”CH2â€”CNâ€”C2H4â€”â€”C2H4â€”â€”C2H4â€”COâ€”NH2â€”C2H4â€”â€”C2H4â€”â€”C2H4COâ€”N(CH3)2â€”C2H4â€”â€”C2H4â€”â€”C2H4COâ€”N(C2H5)2â€”C2H4â€”â€”C2H4â€”â€”CH2â€”COâ€”CH3â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”NHâ€”COâ€”NH2â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”NHâ€”COâ€”CH3â€”C2H4â€”â€”C2H4â€”â€”CH2Fâ€”C2H4â€”â€”C2H4â€”â€”CF3â€”C2H4â€”â€”C2H4â€”â€”C2H4-(N-succinimido)â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”Sâ€”CH3â€”C2H4â€”â€”C2H4â€”â€”CH2-ethyleneacetalâ€”C2H4â€”â€”C2H4â€”â€”CH2-(2-thienyl)â€”C2H4â€”â€”C2H4â€”-furfurylâ€”C2H4â€”â€”C2H4â€”â€”CH2-(4-pyridyl)â€”C2H4â€”â€”C2H4â€”-o-hydroxybenzylâ€”C2H4â€”â€”C2H4â€”-m-hydroxybenzylâ€”C2H4â€”â€”C2H4â€”-p-hydroxybenzylâ€”C2H4â€”â€”C2H4â€”â€”(CH2)3â€”OHâ€”C2H4â€”â€”C2H4â€”â€”CH2â€”NHâ€”COâ€”CH3â€”C2H4â€”â€”C2H4â€”â€”CH2â€”COâ€”NH2â€”C2H4â€”â€”C2H4â€”-benzylâ€”C2H4â€”â€”C2H4â€”â€”CH2-(3-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”CH2-(2-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”CH2-(2-quinolinyl)â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”OHâ€”C2H4â€”â€”C2H4â€”â€”(CH2)3â€”OCH3â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”OCH3â€”C2H4â€”â€”C2H4â€”-o-fluorobenzylâ€”C2H4â€”â€”C2H4â€”-p-fluorobenzylâ€”C2H4â€”â€”C2H4â€”â€”C2H4â€”CO-(N-morpholino)â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”CO-(1-piperidyl)â€”C2H4â€”â€”C2H4â€”â€”C2H4â€”N(C2H5)2â€”C2H4â€”â€”C2H4â€”â€”C2H4-(N-morpholino)â€”C2H4â€”â€”C2H4â€”â€”C2H4-(1-piperidyl)â€”C2H4â€”â€”C2H4â€”â€”COâ€”CH3â€”C2H4â€”â€”C2H4â€”â€”COâ€”C2H5â€”C2H4â€”â€”C2H4â€”â€”COâ€”C6H5â€”C2H4â€”â€”C2H4â€”â€”CO-(2-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”CO-(3-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”CO-(4-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”SO2â€”CH3â€”C2H4â€”â€”C2H4â€”â€”SO2â€”C6H5â€”C2H4â€”â€”C2H4â€”â€”COâ€”NH2â€”C2H4â€”â€”C2H4â€”â€”COâ€”NH(CH3)â€”C2H4â€”â€”C2H4â€”â€”COâ€”N(CH3)2â€”C2H4â€”â€”C2H4â€”â€”COâ€”N(C2H5)2â€”C2H4â€”â€”C2H4â€”â€”CO-(N-morpholino)â€”C2H4â€”â€”C2H4â€”â€”CO-(1-piperidyl)â€”C2H4â€”â€”C2H4â€”â€”COâ€”NHâ€”C6H5â€”C2H4â€”â€”C2H4â€”â€”COâ€”NH-(2-pyridyl)â€”C2H4â€”â€”C2H4â€”â€”SO2â€”NH2â€”C2H4â€”â€”C2H4â€”â€”SO2â€”N(C2H5)2â€”C2H4â€”â€”C2H4â€”â€”SO2-(N-morpholino);â€”CH2â€”, â€”C2H4â€”, â€”C3H6â€”, â€”C4H8â€”, â€”C5H10â€”, â€”C6H12â€”, â€”C7H14â€”, â€”C8H16â€”, â€”C9H18â€”, â€”C10H20â€”, â€”C11H22, â€”C2H4â€”SO2â€”C2H4â€”SO2â€”C2H4â€”, â€”CH(CH3), â€”CH(C2H5)â€”, CH(nâ€”C3H7)â€”, â€”CH(C6H5)â€”, â€”C(CH3)2â€”, â€”CH(COOH)â€”, CH(C2H4OH)â€”, â€”CH(CH3)â€”CH2â€”, â€”CH(C2H4OH)â€”CH2â€”, â€”CH(COOH)â€”CH2â€”, â€”CH(C2H5)â€”CH2â€”, â€”CH2â€”CH(OH)â€”CH2â€”, â€”CH2â€”C(CH2B)2â€”CH2, wherein B is p-hydroxyphenylthio, CH2â€”Sâ€”CH2â€”, â€”CH2â€”CH&boxH;CHâ€”CH2â€”, â€”CH2â€”Câ‰¡Câ€”CH2â€”, â€”CH2â€”C6H4â€”CH2â€” wherein â€”C6H4â€”, is an o-phenylene group, â€”C2H4â€”Oâ€”CH2â€”Oâ€”C2H4â€”, â€”C2H4â€”Oâ€”C2H4â€”Oâ€”C2H4â€”, â€”CH2â€”COOâ€”C2H4â€”OCOCH2â€”, â€”CH2â€”COOâ€”C3H6â€”OCOCH2â€”, â€”CH2CH(OH)CH2â€”Oâ€”C2H4â€”Oâ€”CH2CH(OH)CH2â€”, â€”(C2H4O)2â€”COâ€”CH2â€”COâ€”(C2H4O)2, â€”(C2H4O)2â€”COâ€”(trans)CH&boxH;CHâ€”COâ€”(C2H4O)2â€”, â€”CH2â€”COOâ€”(C2H4O)3â€”COâ€”CH2â€”, â€”CH2â€”COOâ€”(C2H4O)4â€”COâ€”CH2â€”, â€”(C2H4O)3â€”C2H4â€”, â€”(C2H4O)4â€”C2H4â€”, â€”(C2H4O)5â€”C2H4â€”, â€”(C2H4O)3â€”COâ€”(C2H4O)3â€”, â€”(C2H4O)2â€”COâ€”C2H4â€”COâ€”(C2H4O)2, â€”CH2â€”COâ€”COâ€”CH2â€”, â€”COâ€”CH2â€”COâ€”, and Ar1 and Ar2 each represents a nonsubstituted 4-hydroxyphenyl group.