Patent ID: 6288037
Filing Date: 2001-09-11
Classification: A61K,A61P,C07K

Abstract:
An Ich-1 inhibitor compound of Formula I:X-Asp-A.sub.3 --A.sub.2 --Z Iwherein:X is R.sub.1 --(W).sub.n --A.sub.5, whereinA.sub.5 is Val;W is any .alpha.-amino acid;n is an integer from 0 to 5;R.sub.1 is hydrogen or R.sub.6 ;R.sub.6 is an N-terminal acyl group selected from the group consisting of Aha-, Biotinyl-, Biotinyl-Aha-, R.sub.3 CO--, R.sub.3 CH.sub.2 CO--, R.sub.3 NHCO--, (R.sub.4).sub.2 NCO--, and R.sub.3 OCO-- whereinR.sub.3 is selected from the group consisting of t-butyl, i-butyl, n-butyl, n-propyl, i-propyl, c-propyl, ethyl, methyl, c-hexyl, c-hexyl-CH.sub.2 --, c-hexyl-(CH.sub.2).sub.2 --, phenyl, phenyl-CH.sub.2 --, phenyl-(CH.sub.2).sub.2 --, 4-hydroxyphenyl, 4-hydroxyphenyl-CH.sub.2 --, and 4-hydroxyphenyl(CH.sub.2).sub.2 --; andR.sub.4 is methyl or ethyl;Asp is aspartic acid;A.sub.3 is an .alpha.-amino acid selected from the group consisting of Val, Glu, Thr, Ser,Gln, Ile, Abu, (2-n-Pr)Gly, (2-c-Pr)Gly, (2-t-Bu)Gly and (2-Et)Gly;A.sub.2 is an .alpha.-amino acid selected from the group consisting of Ala, Ser, Lys, Val,Met, Gln, Leu, Ile, Abu, His, Orn, Gly, (2-n-Pr)Gly, (2-c-Pr)Gly, (2-t-Bu)Gly and(2-Et)Gly; andZ is A.sub.1, wherein:A.sub.1 is a C-terminally-modified residue selected from the group consisting of Asp[CHO], Asp[CN], Asp[COCHN.sub.2 ], Asp [COCH.sub.2 Cl], Asp[COCH.sub.2 Br], Asp[COCH.sub.2 F], Asp[COCH.sub.2 OCO-Aryl], Asp[COCH.sub.2 OCO-Heteroaryl], Asp[COCH.sub.2 O(CH.sub.2).sub.a -Aryl], Asp[COCH.sub.2 O(CH.sub.2).sub.a -Heteroaryl], Asp[COCH.sub.2 S(CH.sub.2).sub.a -Aryl], Asp[COCH.sub.2 S(CH.sub.2).sub.a -Heteroaryl], Asp[CO(CH.sub.2).sub.b -Aryl], Asp[CO(CH.sub.2).sub.b -Heteroaryl], Asp[CH.sub.2 S--R.sub.5 ], Glu[CHO], Glu[CN], Glu[COCHN.sub.2 ], Glu[COCH.sub.2 Cl], Glu[COCH.sub.2 Br], Glu[COCH.sub.2 F], Glu[COCH.sub.2 OCO-Aryl], Glu[COCH.sub.2 OCO-Heteroaryl], Glu[COCH.sub.2 O(CH.sub.2).sub.a -Aryl], Glu[COCH.sub.2 O(CH.sub.2).sub.a -Heteroaryl], Glu[COCH.sub.2 S(CH.sub.2).sub.a -Aryl], Glu[COCH.sub.2 S(CH.sub.2).sub.a -Heteroaryl], Glu[CO(CH.sub.2).sub.b -Aryl], Glu[CO(CH.sub.2).sub.b -Heteroaryl], and Glu[CH.sub.2 SR.sub.5 ] whereina is an integer from 0 to 5;b is an integer from 1 to 7; andR.sub.5 is selected from the group consisting of --S-alkyl, --S-cycloalkyl, --S-(cycloalkyl)alkyl, --S-aryl, --S-arylalkyl, --S-heterocycle, --S-(heterocycle)alkyl, --S-heteroaryl, --S-heteroarylalkyl, X-Asp-A.sub.3 --A.sub.2 -Asp(CH.sub.2 S)--, and X-Asp-A.sub.3 --A.sub.2 -Glu(CH.sub.2 S)--.