US 7,501,425 B1
Bicyclic pyrimidines and bicyclic 3,4-dihydropyprimidines as inhibitors of cellular proliferation
Ellen Myra Dobrusin, Ann Arbor, Mich. (US); James Marino Hamby, Ann Arbor, Mich. (US); James Bernard Kramer, Sylvania, Ohio (US); Mel Conrad Schroeder, Dexter, Mich. (US); Howard Daniel Hollis Showalter, Ann Arbor, Mich. (US); Peter Toogood, Ann Arbor, Mich. (US); and Susanne A. Trumpp-Kallmeyer, Moeindal (Germany)
Assigned to Warner Lambert Company, New York, N.Y. (US)
Appl. No. 9/623,737
PCT Filed May 10, 1999, PCT No. PCT/US99/10187
§ 371(c)(1), (2), (4) Date Sep. 07, 2000,
PCT Pub. No. WO99/61444, PCT Pub. Date Dec. 02, 1999.
Int. Cl. A61K 31/519 (2006.01); C07D 471/04 (2006.01)
U.S. Cl. 514—262.1  [544/256] 36 Claims
 
1. A compound of formula I

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof,
wherein:
R1 and R2 are independently selected from the group consisting of H, (CH2)nAr, COR4, (CH2)nheteroaryl, (CH2)nheterocyclyl, C1-C10 alkyl, C3-C10 cycloalkyl, C2-C10 alkenyl, and C2-C10 alkynyl, wherein n is 0, 1, 2, or 3, and the (CH2)nAr, (CH2)nheteroaryl, alkyl, cycloalkyl, alkenyl, and alkynyl groups are optionally substituted by up to 5 groups selected from NR4R5, N+(O)R4R5, N+R4R5R6Y−, alkyl, phenyl, substituted phenyl, (CH2)nheteroaryl, hydroxy, alkoxy, phenoxy, thiol, thioalkyl, halo, COR4CO2R4, CONR4R5, SO2NR4R5, SO3R4, PO3R4, aldehyde, nitrile, nitro, heteroaryloxy, T(CH2)mQR4,

OG Complex Work Unit Drawing
C(O)T(CH2)mQR4, NHC(O)T(CH2)mQR4, T(CH2)mC(O)NR4NR5, or T(CH2)mCO2R4 wherein each m is independently 1-6, T is O, S, NR4, N+(O)R4, N+R4R6Y−, or CR4R5, and Q is O, S, NR5, N+(O)R5, or N+R5R6Y−;
R4 and R5 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, substituted alkyl, C2-C6 alkenyl, C2-C6 alkynyl, N(C1-C6alkyl)1 or 2, (CH2)nAr,
C3-C10 cycloalkyl, heterocyclyl, and heteroaryl, or R4 and R5 together with the nitrogen to which they are attached optionally form a ring having 3 to 7 carbon atoms and said ring optionally contains 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, substituted nitrogen, oxygen, and sulfur;
when R4 and R5 together with the nitrogen to which they are attached form a ring, the said ring is optionally substituted by 1 to 3 groups selected from OH, OR4, NR4R5, (CH2)mOR4, CH2)mNR4R5, T—(CH2)mQR4, CO—T—CH2)mQR4, NH(CO)T(CH2)mQR4, T—(CH2)mCO2R4, or T(CH2)mCONR4R5;
R6 is alkyl; and
Y is a halo counter-ion.