SUBSTITUTED TETRA- AND PENTAPEPTIDE INHIBITORS OF PROTEIN:FARNESYL TRANSFERASE

摘要

Accordingly, the present invention is a substituted tetra- or pentapeptide compound of Formula I, wherein n is independently 1 or 2; A is Cbz or BnNHCO; R is independently H or Me; Y is independently H or Me; Z is independently H or Me; R4 is, wherein R4 is H or Me; R5 is wherein R5' is H, OH, -O-C1-6alkyl, -C1-6alkyl, CO-aryl, -(CH2)m-aryl, -O-(CH2)m- C3-10cycloalkyl, -O(CH2)m-aryl, -O(CH2)m-heteroaryl, wherein the definition of aryl is an aromatic ring which is a phenyl, 5-fluorenyl, 1-naphthyl or 2-naphthyl group, -I, -CF3, -NO2, -NH2, -NHCH3, -N(CH3)2, -NHCO-alkyl, -(CH2)mCO2H, -(CH2)m-CO2-alkyl,-(CH2)mSO3H, -(CH2)mPO3H2, -(CH2)mPO3(alkyl)2, -(CH2)mSO2NH2, and -(CH2)mSO2NH-alkyl wherein alkyl is C1-6-alkyl, m is 0, 1, 2, or 3 and wherein the definition of heteroaryl is a heteroaromatic ring which is a 2- or 3-thienyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 3-, 4-, 5-, 6- or 7-indolyl group, substituted or unsubstituted by 1 or 2 substituents from the group of substituents described above for aryl, -OPO3(R5")2, -CH2PO3(R5'')2, -CF2PO3(R5'')2, or -CFHPO3(R5'')2, wherein R5' is located at either the ortho, meta, or para position and R5'' is H, C1-6alkyl-aryl wherein the definition of aryl is an aromatic ring which is as defined above or cyclohexyl, and m is independently 0, 1, 2 or 3, -COOR7, wherein R7 is H, Me, t-butyl, or benzyl; -SR8, wherein R8 is H or trityl; R6 is -OR6' wherein R6' is H, benzyl, -PO3R5''2, wherein R5'' is as described above; -CH2-R9, wherein R9 is -PO3R5''2, wherein R5'' is as described above; -SR6'', wherein R6'' is H, benzyl, or trityl, C is Gly, Ala, Val, Leu, Ile, Phe, Tyr, Tyr(OMe), Pgl, homoPhe, Trp, Trp(Me), or Trp(CHO); D is Gly, Ala, or absent; E is -OH, -NH2, -NHNH2, -NHR10, or -OR10 wherein R10 is H, C1-6alkyl, -(CH2)m-C3-10cycloalkyl, -(CH2)m-aryl, or -(CH2)m-heteroaryl, wherein aryl and heteroaryl and m is as described above; an isomer or a pharmaceutically acceptable salt thereof.