INHIBITORS OF COLLAGEN PROLYL 4-HYDROXYLASE

摘要

Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula:;;and salts thereof where:

X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms;

R1 and R2 independently are —OR7, or —NHSO2R8, where R7 is selected from:

hydrogen, alkyl, alkenyl, alkoxyalkyl, —R′—CO—R″, —R′—CO—O—R″, —CO—R″, —R′—O—CO—R″, —R′—CO—NR″, —CO—NR″, or —R′—O—CO—NR″, and R8 is selected from hydrogen, alkyl, aryl, arylalkyl;

R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; —R′— is a divalent straight chain or branched alkylene, and —R″ is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.

主权项

1. A compound of formula: or salts thereof where: X is S, O, NH, or NR,
where R is an alkyl group having 1-3 carbon atoms; R1 and R2 independently are —OR7, or —NHSO2R8,
where R7 is selected from:hydrogen, alkyl, alkoxyalkyl, —R′—CO—R″, —R′—CO—O—R″, —CO—R″, —R′—O—CO—R″, —R′—CO—NR″, —CO—NR″, —R′—O—CO—NR″, andR8 is selected from hydrogen, alkyl, aryl or arylalkyl; R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyoxy; R5 is hydrogen, an alkyl having 1-3 carbon atoms or an alkoxy having 1-3 carbon atoms; —R′— is a divalent straight chain or branched alkylene, and —R″ is an alkyl, aryl or arylalkyl.