216086-64-5Relevant academic research and scientific papers
Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase
Augeri, David J.,Janowick, Dave,Kalvin, Douglas,Sullivan, Gerry,Larsen, John,Dickman, Daniel,Ding, Hong,Cohen, Jerry,Lee, Jang,Warner, Robert,Kovar, Peter,Cherian, Sajeev,Saeed, Badr,Zhang, Haichao,Tahir, Steve,Ng, Shi-Chung,Sham, Hing,Rosenberg, Saul H.
, p. 1069 - 1074 (1999)
Potent and orally bioavailable nonthiol-containing inhibitors of protein farnesyltransferase are described. Oral bioavailability was achieved by replacement of the pyridyl ether moiety of 1 with a 2-substituted furan ether to give 4. Potency was regained with 2,5-disubstituted furan ethers while maintaining the bioavailability inherent in 4. p-Chlorophenylfuran ether 24 is 0.7 nM in vitro (FTase) and is 32% bioavailable in the mouse, 30% bioavailable in rats, and 21% bioavailable in dogs.
Inhibitors of protein isoprenyl transferases
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, (2008/06/13)
Compounds having the formula STR1or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 --, and (i) heterocyclic-L 2 --; R 2 is selected from STR2(b) --C(O)NH--CH(R 14)--C(O)OR 15, STR3(d) --C(O)NH--CH(R 14)--C(O)NHSO 2 R 16, (e) --C(O)NH--CH(R 14)-tetrazolyl, (f) --C(O)NH-heterocyclic, and (g) --C(O)NH--CH(R 14)--C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) --L 4 --N(R 5)--L 5 --, (b) --L 4 --O--L 5 --, (c) --L 4 --S(O) n --L 5 -- (d) --L 4 --L 6 --C(W)--N(R 5)--L 5 --, (e) --L 4 --L 6 --S(O)m--N(R 5)--L 5 --, (f) --L 4 --N(R 5)--C(W)--L 7 --L 5 --, (g) --L 4 --N(R 5)--S(O) p --L 7 --L 5 --, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
