Patent ID: 6660758
Filing Date: 2003-12-09
Classification: C07D

Abstract:
A method for treating a mammal having a proliferative disease, the method comprising the step of administering to said mammal a therapeutically effective dose for inhibiting said proliferative disease of a compound, said compound being represented by the following structure (formula (I)): wherein n is 1 to 5;either R* is â€”OR1 and R** is hydrogen, or R* and R** together form a further bond so that a double bond is present between the two carbon atoms carrying R* and R**; R1 is a radical selected from the group consisting of hydrogen or methyl, or a protecting group; R2 is a radical selected from the group consisting of hydrogen, methylene and methyl; R3 is a radical selected from the group consisting of hydrogen, methylene and methyl; R4 is a radical selected from the group consisting of hydrogen or methyl, or is a protecting group; R5 is a radical selected from the group consisting of hydrogen, methyl, â€”CHO, â€”COOH, â€”CO2Me, â€”CO2(tert-butyl), â€”CO2(iso-propyl), â€”CO2(phenyl), â€”CO2(benzyl), â€”CONH(furfuryl), â€”CO2(N-benzoyl-(2R,3S)-3-phenyliso-serine), â€”CON(methyl)2, â€”CON(ethyl)2, â€”CONH(benzyl), â€”CH&boxH;CH2, HCCâ€” and â€”CH2R11; R11 is a radical selected from the group consisting of â€”OH, â€”O-Trityl, â€”Oâ€”(C1-C6 alkyl), â€”(C1-C6 alkyl), â€”O-benzyl, â€”O-allyl, â€”Oâ€”COCH3, â€”Oâ€”COCH2Cl, â€”Oâ€”COCH2CH3, â€”Oâ€”COCF3; â€”Oâ€”COCH(CH3)2, â€”Oâ€”COâ€”C(CH3)3, â€”Oâ€”CO(cyclopropane), â€”OCO(cyclohexane), â€”Oâ€”COCH&boxH;CH2, â€”Oâ€”CO-Phenyl, â€”O-(2-furoyl), â€”O-(N-benzoyl-(2R,3S)-3-phenyliso-serine), â€”O-cinnamoyl, â€”O-(acetyl-phenyl), â€”O-(2-thiophenesulfonyl), â€”S-(C1-C6 alkyl), â€”SH, â€”S-Phenyl, â€”S-Benzyl, â€”S-furfuryl, â€”NH2, â€”N3, â€”NHCOCH3, â€”NHCOCH2Cl, â€”NHCOCH2CH3, â€”NHCOCF3, â€”NHCOCH(CH3)2, â€”NHCOâ€”C(CH3)3, â€”NHCO(cyclopropane), â€”NHCO(cyclohexane), â€”NHCOCH&boxH;CH2, â€”NHCO-Phenyl, â€”NH(2-furoyl), â€”NH-(N-benzoyl-(2R,3S)-3-phenylisoserine), â€”NH-(cinnamoyl), â€”NH-(acetyl-phenyl), â€”NH-(2-thiophenesulfonyl), â€”F, â€”Cl, â€”CH2CO2H and methyl; R6 is absent, methylene, or oxygen; R8 is a radical selected from the group represented by the formulas: â€ƒwherein R9 is a radical selected from the group consisting of hydrogen and methyl; R10 is a radical represented by the formula: or a salt thereof where a salt-forming group is present;where, in the above structures, â€œaâ€  can be either absent or a single bond; â€œbâ€  can be either a single or double bond; â€œcâ€  can be either absent or a single bond; â€œdâ€  can be either absent or a single bond, and â€ƒthe following provisos pertain: a. if R2 is methylene, then R3 is methylene; b. if R2 and R3 are both methylene, then â€œaâ€  is a single bond; c. if R2 and R3 are selected from the group consisting of hydrogen and methyl, then the single bond â€œaâ€  is absent; d. if R6 is oxygen, then â€œcâ€  and â€œdâ€  are both a single bond and â€œbâ€  is a single bond; e. if R6 is absent, then â€œcâ€  and â€œdâ€  are absent and â€œbâ€  is a double bond; and f. if â€œbâ€  is a double bond then R6, â€œcâ€ , and â€œdâ€  are absent.