US 6,982,260 B1
Quinazolines and their use for inhibiting cyclin-dependent kinase enzymes
Mark Robert Barvian, Ann Arbor, Mich. (US); Ellen Myra Dobrusin, Ann Arbor, Mich. (US); James Stanley Kaltenbronn, Ann Arbor, Mich. (US); Peter L. Toogood, Ann Arbor, Mich. (US); Roy Thomas Winters, Pinckney, Mich. (US); Inderjit S. Sidhu, Edmonton (Canada); Rajeshwar Singh, Edmonton (Canada); Yadagiri Bathini, Alberta (Canada); and Ronald George Micetich, Sherwood Park (Canada)
Assigned to Warner-Lambert Company, Morris Plains, N.J. (US)
Appl. No. 10/130,843
PCT Filed Nov. 03, 2000, PCT No. PCT/US00/30376
§ 371(c)(1), (2), (4) Date May 21, 2002,
PCT Pub. No. WO01/38315, PCT Pub. Date May 31, 2001.
Claims priority of provisional application 60/166840, filed on Nov. 22, 1999.
Int. Cl. C07D 239/84 (2006.01); C07D 239/78 (2006.01); C07D 239/80 (2006.01); C07D 403/12 (2006.01); A61K 31/517 (2006.01)
U.S. Cl. 514—218 66 Claims
 
1. A compound of Formula I:
OG Complex Work Unit Drawing
wherein,
R1 is hydrogen, alkyl, alkyl substituted with at least one of amine, halogen, hydroxy, or alkoxy, cycloalkyl, or 4–10 membered heterocyclyl having 1–3 heteroatoms selected from O, S or N;
R2 is OH, alkyloxy, aryloxy, or NR3R4;
A is N, or CW3;
R3 and R4 are independently hydrogen, alkyl, alkenyl, alkynyl, (CH2)nAr, cycloalkyl, 4–10 membered heterocyclyl having 1–3 heteroatoms selected from O, S, or N, or a 4–9 membered heteroaryl having 1–4 heteroatoms selected from O, S or N, or R3 and R4 together with the nitrogen to which they are attached optionally may 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 including S(O) and S(O)2, said ring also may be additionally substituted with up to 3 groups selected from alkyl, haloalkyl, NR8C(O)R9, C(O)OR8, C(O)R8, C(O)NR8R9, NR8R9, NR8SO2R9, OR8, SO2NR3R4, or SR8;
W1 and W2 are independently selected from NR3R4, N(O)R3R4, NR3R4X, OR3, SR3, hydrogen, halogen, haloalkyl, COR3, CO2R3, CONR3R4, S(O)R3, SO2R3, SO2NR3R4, SO3R3, P(O)(OR3)2, CHO, CN, nitro, alkyl, T(CH2)mQR8, C(O)T(CH2)mQR8, or T(CH2)mCO2R8 where m is 1–6, T is O, S, NR3, N(O)R3, NR3R4X, or CR3R4, and Q is O, S, NR9, N(O)R9 or NR9R10X, or NR9C(O)T(CH2)mQR9;
R5 is hydrogen, or alkyl;
R6 is hydrogen, alkyl, halogen, haloalkyl, alkynyl, alkenyl, COR3, CO2R3, CONR3R4, SO2NR3R4, SO2R3, SO3R3, P(O)(OR3)2, aldehyde, nitrile, nitro, OR3, or NR3R4
W3 is hydrogen, NR3R4, N(O)R3R4, NR3R4R8X, OH, OR3, SH, SR3, halogen, COR3, CO2R3, CONR3R4, S(O)R3, SO2R3, SO2NR3R4, SO3R3, (CH2)nP(O)(OR3)2, NR3SO2R4, aldehyde, nitrile, nitro, alkyl, T(CH2)mQR8, C(O)T(CH2)mQR8, NR8C(O)T(CH2)mQR11, or T(CH2)mCO2R3 where m and n are independently 1–6, T is O, S, NR3, N(O)R3, or CR3R4, and Q is O, S, NR9, N(O)R9 or NR9R10X;
R8, R9, R10 and R11 are hydrogen, alkyl, or aryl;
X is a halogen;
or a pharmaceutically acceptable salt thereof.