Phosphotyrosine peptidomimetics for inhibiting SH2 domain interactions

A compound represented by a general formula:

• ##STR16## wherein R.sub.1 represents hydrogen, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, a carboxyl, an azido, --(CH.sub.2).sub.m --R.sub.7, --(CH.sub.2).sub.m --OH, --(CH.sub.2).sub.m --O-lower alkyl, --(CH.sub.2).sub.m --O-lower alkenyl, --(CH.sub.2).sub.n --O--(CH.sub.2).sub.m --R.sub.7, --(CH.sub.2).sub.m --SH, --(CH.sub.2).sub.m --S-lower alkyl, --(CH.sub.2).sub.m --S-lower alkenyl, --(CH.sub.2).sub.n --S--(CH.sub.2).sub.m --R.sub.7, ##STR17## R.sub.4 and R.sub.5 each independently represent hydrogen, lower alkyl, lower alkenyl, --(CH.sub.2).sub.m --R.sub.7, --C(O)-lower alkyl, --C(O)-lower alkenyl, --C(O)--(CH.sub.2).sub.m --R.sub.7,
• or R.sub.4 and R.sub.5 taken together with the N atom to which they are attached complete a heterocyclic ring having from 4 to 8 atoms in the ring structure;
• R.sub.6 represents hydrogen, a lower alkyl, an lower alkenyl, --(CH.sub.2).sub.m --R.sub.7, or a pharmaceutically acceptable salt forming ion;
• R.sub.7 represents an aryl, a cycloalkyl, a cycloakenyl, or a heterocycle;
• R.sub.8 represents hydrogen, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, a carboxyl, an azido, --(CH.sub.2).sub.m --R.sub.7, --(CH.sub.2).sub.m --OH, --(CH.sub.2).sub.m --O-lower alkyl, --(CH.sub.2).sub.m --O-lower alkenyl, --(CH.sub.2).sub.n --O--(CH.sub.2).sub.m --R.sub.7, --(CH.sub.2).sub.m --SH, --(CH.sub.2).sub.m --S-lower alkyl, --(CH.sub.2).sub.m --S-lower alkenyl, --(CH.sub.2).sub.n --S--(CH.sub.2).sub.m --R.sub.7, ##STR18## R.sub.10 represents an alpha-carbon sidechain of an amino acid residue;
• R.sub.11 represents COOH or a pharmaceutically acceptable salt thereof or a carboxy-terminal blocking group;
• R.sub.12 represents NH--R.sub.17 or a pharmaceutically acceptable salt thereof, or an amino-terminal blocking group;
• R.sub.14 represents a halogen, a lower alkyl, a lower alkoxy, a lower alkylthio, --NO.sub.2, CF.sub.3, --CN, and --OH;
• R.sub.17 represents hydrogen or a C-terminally linked amino acid residue or peptide;
• Y represents a phosphate or phosphate analog;
• X.sub.1 represents O or S;
• X.sub.2 represents hydrogen, a lower alkyl, --(CH.sub.2).sub.m --OH, --(CH.sub.2).sub.m --O-lower alkyl, a carboxyl, an amine, an amide, a nitrosyl, a sulfhydryl, a sulfonyl, or a sulfonamide;
• n is zero or an integer in the range of 1 to 6;
• m is zero or an integer in the range of 1 to 6;
• and p is an integer in the range of 1 to 6.