申请人:University of Pittsburgh
公开号:US20020193596A1
公开(公告)日:2002-12-19
Compounds having the formula
1
or 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
(a)
2
(b) —C(O)NH—CH(R
14
)—C(O)OR
15
, (c)
3
(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.
具有以下公式的化合物或其药学上可接受的盐,其中R1为(a)氢,(b)较低的烷基,(c)烯基,(d)烷氧基,(e)硫代烷氧基,(f)卤素,(g)卤代烷基,(h)芳基-L2—,以及(i)杂环-L2—;R2从(a)中选择,(b) -C(O)NH-CH(R14)-C(O)OR15,(c)中选择,(d) -C(O)NH-CH(R14)-C(O)NHSO2R16,(e) -C(O)NH-CH(R14)-四唑基,(f) -C(O)NH-杂环,以及(g) -C(O)NH-CH(R14)-C(O)NR17R18;R3为杂环,芳基,取代或未取代的环烷基;R4为氢,较低烷基,卤代烷基,卤素,芳基,芳基烷基,杂环基,或(杂环)烷基;L1为空缺或从(a) -L4-N(R5)-L5-,(b) -L4-O-L5-,(c) -L4-S(O)n-L5-,(d) -L4-L6-C(W)-N(R5)-L5-,(e) -L4-L6-S(O)m-N(R5)-L5-,(f) -L4-N(R5)-C(W)-L7-L5-,(g) -L4-N(R5)-S(O)p-L7-L5-,(h)可选择取代的烷基,(i)可选择取代的烯基,以及(j)可选择取代的炔基是蛋白异戊二烯转移酶的抑制剂。还公开了蛋白异戊二烯转移酶抑制组合物和抑制蛋白异戊二烯转移酶的方法。