Patent TW-I225060-B (TW)
Title: 6,9-disubstituted 2-[trans-(4-aminocyclohexyl)amino]purines
Inventor: DUMONT JENNIFER A
IPC: C07D473/00
Filed: 1999-02-24
Granted: 2004-12-11
Abstract: The present invention provides novel compounds of the formula (I), wherein R is selected from the group consisting of R2, R2NH-, or R3R4N-R5- wherein R2 is selected from the group consisting of C9-C12 alkyl, wherein each R6 is independently selected from the group consisting of hydrogen, C3-C8 cycloalkyl, C1-C4 alkyl, and (CH2)m-phenyl, wherein m is an integer 0-8; x is an integer 1-8; n is an integer 0-8; Z is selected from the group consisting of phenyl, heterocycle, cycloalkyl, and naphthanlene; and M is selected from the group consisting of hydrogen, C1-C4 alkyl, wherein each R6' is independently selected from the group consisting of hydrogen, C3-C8 cycloalkyl, C1-C4 alkyl, and (CH2)m'-phenyl, wherein m' is an integer 0-8; n' is an integer 0-8; x' is an integer 1-8; Q is hydrogen or C1-C4 alkyl; and Z' is selected from the group consisting of phenyl, heterocycle, cycloalkyl, and napthalene; and wherein each C9-C12 alkyl or Z is optionally substituted with 1 to 3 substituents, which may be the same or different and which are selected from the group consisting of D, E, wherein each D is independently selected from the group consisting of trifluoromethyl, trifluoromethoxy, and C1-C4 alkoxy; each E is independently selected from the group consisting of Hal, OH, and C1-C8 alkyl; b is an integer 0-2; Z"" is selected from the group consisting of phenyl, heterocycle, cycloalkyl, and naphthalene; each R6"" is independently selected from the group consisting of hydrogen, C3-C8 cycloalkyl, C1-C4 alkyl, and (CH2)m""-phenyl, wherein m"" is an integer 0-8; n"" is an integer 0-8; x"" is an integer 1-8; and M' is selected from the group consisting of hydrogen, C1-C4 alkyl, wherein each R6""' is independently selected from the group consisting of hydrogen, C3-C8 cycloalkyl, C1-C4 alkyl, and (CH2)m""'-phenyl, wherein m""' is an integer 0-8; n""' is an integer 0-8; x""' is an integer 1-8; Q' is hydrogen or C1-C4 alkyl; and Z""' is selected from the group consisting of phenyl, heterocycle, cycloalkyl, and napthalene, wherein the groups M' and Z"" may be optionally substituted with the groups D', E' or wherein each R6"""" is independently selected from the group consisting of hydrogen, C3-C8 cycloalkyl, C1-C4 alkyl, and (CH2)m""""-phenyl, wherein m"""" is an integer 0-8; x"""" is an integer 0-8; Q"" is hydrogen, phenyl or C1-C4 alkyl; each D' is independently selected from the group consisting of trifluoromethyl, trifluoromethoxy, and C1-C4 alkoxy; each E' is independently selected from the group consisting of Hal, OH, and C1-C8 alkyl; R3 and R4 are selected from the group consisting of hydrogen, C1-C4 alkyl and (CH2)y-phenyl, wherein y is an integer 0-8, with the proviso that R3 and R4 not both be hydrogen; R5 is C1-C8 alkylene; and R1 is selected from the group consisting of cyclopentyl, cyclopentenyl and isopropyl, and the pharmaceutically acceptable salts, optical isomers, and hydrates thereof, with the proviso that when R2 is the group wherein n is 1 or greater; R1 is isopropyl or cyclopentyl; R6 is hydrogen, C1-C4 alkyl, or (CH2)m-phenyl; and Z is phenyl, heterocycle, or cycloalkyl, that Z is substituted with 1 to 3 substituents, which may be the same or different, and which are selected from the group consisting of wherein D, b, R6"", x"", n"", M', and Z"" are as previously defined. In addition, the present invention provides a method of inhibiting cell cycle progression. More specifically, the present invention provides a method of inhibiting cyclin dependent kinases, particularly cdk-2. The present invention also provides a method of preventing apoptosis in neuronal cells and a method of inhibiting the development of neoplasms. In addition, the present invention provides a composition comprising an assayable amount of a compound of formula (I) in admixture or otherwise in association with an inert carrier. The present invention also provides a pharmaceutical composition comprising an effective inhibitory amount of a compound of formula (I) in admixture or otherwise in association with one or more pharmaceutically acceptable carriers or excipients.