Patent ID: 6310078
Filing Date: 2001-10-30
Classification: C07C,C07D

Abstract:
A method for modulating EPO receptor, comprising contacting the EPO receptor with an amount of a compound of Formula I ##STR39##wherein:R.sup.1 is the side chain of a natural or unnatural .alpha.-amino acids, where if said side chain contains a protectable group, that group may be protected with a member of the group consisting of succinyl, glutaryl, 3,3-dimethylglutaryl, C.sub.1-5 alkyl, C.sub.1-5 alkoxycarbonyl, acetyl, N-(9-fluorenylmethoxycarbonyl), trifluoroacetyl, omega-carboxyC.sub.1-5 alkylcarbonyl, t-butoxycarbonyl, benzyl, benzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, phenylsulfonyl, ureido, t-butyl, cinnamoyl, trityl, 4-methyltrityl 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl, tosyl, 4-methoxy-2,3,6-trimethylbenzenesulfonyl, phenylureido, and substituted phenylureido (where the phenyl substituents are phenoxy, halo, C.sub.1-5 alkoxycarbonyl);R.sup.2 and R.sup.3may be taken together to form a six-membered aromatic ring which is fused to the depicted ring, orare independently selected from the group consisting of hydrogen, C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, amino, phenyl, phenoxy, phenylC.sub.1-5 alkyl, phenyl C.sub.1-5 alkoxy,substituted phenyl (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenoxy (where the substituents are selected fromC.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenylC.sub.1-5 alkyl (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenylC.sub.1-5 alkoxy (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino), andsubstituted amino (where the substituents are selected from one or more members of the group consisting of C.sub.1-5 alkyl, halosubstitutedC.sub.1-5 alkyl, C.sub.1-5 alknyl, C.sub.1-5 alkenyl, phenyl, phenylC.sub.1-5 alkyl, C.sub.1-5 alkylcarbonyl, halo substituted C.sub.1-5 alkylcarbonyl, carboxyC.sub.1-5 alkyl, C.sub.1-5 alkoxyC.sub.1-5 alkyl, cinnamoyl, naphthylcarbonyl, furylcarbonyl, pyridylcarbonyl, C.sub.1-5 alkylsulfonyl, phenylcarbonyl, phenylC.sub.1-5 alkylcarbonyl, phenylsulfonyl, phenylC.sub.1-5 alkylsulfonyl substituted phenylcarbonyl, substituted phenylC.sub.1-5 alkylcarbonyl, substituted phenylsulfonyl, substituted phenylC.sub.1-5 alkylsulfonyl, substituted phenyl, and substituted phenylC.sub.1-5 alkyl);R.sup.4 and R.sup.5may be taken together to form a six-membered aromatic ring which is fused to the depicted ring, orare independently selected from the group consisting of hydrogen, C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, amino, phenyl, phenoxy, phenylC.sub.1-5 alkyl, phenyl C.sub.1-5 alkoxy,substituted phenyl (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenoxy (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenylC.sub.1-5 alkyl (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino),substituted phenylC.sub.1-5 alkoxy (where the substituents are selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halo, trifluoromethyl, nitro, cyano, and amino), andsubstituted amino (where the substituents are selected from one or more members of the group consisting of C.sub.1-5 alkyl, halosubstitutedC.sub.1-5 alkyl, C.sub.1-5 alknyl, C.sub.1-5 alkenyl, phenyl, phenylC.sub.1-5 alkyl, C.sub.1-5 alkylcarbonyl, halo substituted C.sub.1-5 alkylcarbonyl, carboxyC.sub.1-5 alkyl, C.sub.1-5 alkoxyC.sub.1-5 alkyl, cinnamoyl, naphthylcarbonyl, furylcarbonyl, pyridylcarbonyl, C.sub.1-5 alkylsulfonyl, phenylcarbonyl, phenylC.sub.1-5 alkylcarbonyl, phenylsulfonyl, phenylC.sub.1-5 alkylsulfonyl substituted phenylcarbonyl, substituted phenylC.sub.1-5 alkylcarbonyl, substituted phenylsulfonyl, substituted phenylC.sub.1-5 alkylsulfonyl, substituted phenyl, and substituted phenylC.sub.1-5 alkyl;W is selected from the group consisting of --CH.dbd.CH--, --S--, and --CH.dbd.N--;Q is selected from the group consisting of --CH.dbd.CH--, --S--, and --CH.dbd.N--;X is selected from the group consisting of carbonyl, C.sub.1-5 alkyl, C.sub.1-5 alkenyl, C.sub.1-5 alkenylcarbonyl, and (CH.sub.2).sub.m --C(O)-- where m is 2-5;Y is selected from the group consisting of carbonyl, C.sub.1-5 alkyl, C.sub.1-5 alkenyl, C.sub.1-5 alkenylcarbonyl, and (CH.sub.2).sub.m --C(O)-- where m is 2-5;n is 1, 2, or 3;Z is selected from the group consisting of hydroxy, C.sub.1-5 alkoxy, phenoxy, phenylC.sub.1-5 alkoxy, amino, C.sub.1-5 alkylamino, diC.sub.1-5 alkylamino, phenylamino, phenylC.sub.1-5 alkylamino, piperidin-1-ylsubstituted piperidin-1-yl (where the substituents are selected from the group consisting of C.sub.1-5 alkyl, C.sub.1-5 alkoxy, halo, aminocarbonyl, C.sub.1-5 alkoxycarbonyl, and oxo;substituted phenylC.sub.1-5 alkylamino (where the aromatic substituents are selected from the group consisting of C.sub.1-5 alkyl, C.sub.1-5 alkoxy, phenylC.sub.1-5 alkenyloxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, and amino),substituted phenoxy (where the aromatic substituents are selected from the group consisting of C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, and amino),substituted phenylC.sub.1-5 alkoxy (where the aromatic substituents are selected from the group consisting of C.sub.1-5 alkyl, C.sub.1-5 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, and amino),--OCH.sub.2 CH.sub.2 (OCH.sub.2 CH.sub.2).sub.s OCH.sub.2 CH.sub.2 O--, --NHCH.sub.2 CH.sub.2 (OCH.sub.2 CH.sub.2).sub.s OCH.sub.2 CH.sub.2 NH--, --NH(CH.sub.2).sub.p O(CH.sub.2).sub.q O(CH.sub.2).sub.p NH--, --NH(CH.sub.2).sub.q NCH.sub.3 (CH.sub.2).sub.s NH--, --NH(CH.sub.2).sub.s NH--, and (NH(CH.sub.2).sub.s).sub.3 N,where s, p, and q are independently selected from 1-7 with the proviso that if n is 2, Z is not hydroxy, C.sub.1-5 alkoxy, amino,C.sub.1-5 alkylamino, diC.sub.1-5 alkylamino, phenylamino, or phenylC.sub.1-5 alkylamino, piperidin-1-ylwith the further proviso that if n is 3, Z is (NH(CH.sub.2).sub.s).sub.3 N,and salts thereof.