Patent ID: 6596687
Filing Date: 2003-07-22
Classification: A61K,A61P,C07K,Y10S

Abstract:
A cell adhesion inhibitory compound of formula (I),Zâ€”(Y1)â€”(Y2)â€”(Y3)nâˆ’Xâ€ƒâ€ƒ(I) wherein:Z is selected from the group consisting of aliphatic acyl substituted with N-alkyl- or N-arylamido, heterocycloyl, alkylsulfonyl, substituted aralkylcarbonyl, heterocycloalkylcarbonyl, cycloalkylcarbonyl fused with aryl, heterocycloalkoxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl optionally substituted with bis-(alkylsulfonyl)amino, alkoxycarbonylamino or alkenyl, and aralkylaminocarbonyl optionally substituted with bis-(alkylsulfonyl)amino, alkoxycarbonylamino or alkenyl; Y1 is â€”N(R1)â€”C(R2)(A1)â€”C(O)â€”; Y2 is â€”N(R1)â€”C(R2)(A2)â€”C(O)â€”; each Y3is independently represented by the formula â€”N(R1)â€”C(R2)(A3)â€”C(O)â€”; A1 is independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, mercaptoalkyl, (alkylthio)alkyl, arylalkyl, (hydroxyaryl)alkyl, aminocarbonylalkyl, hydroxycarbonylalkyl, ureaalkyl, amidoalkyl, alkylcarbonylalkyl, alkoxyarylalkyl, and alkyl substituted with acylamino, amino-substituted acylamino, alkoxycarbonylamino, cycloalkyl, carboxy, alkoxy, aralkyloxy, alkoxycarbonyl, aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (alkyl)(aralkyl)aminocarbonyl, aralkylaminocarbonyl, diaralkylaminocarbonyl, carboxyaminocarbonyl, hydroxylaminocarbonyl, thioalkoxy or heterocycle; each of which can be in its protected form; A2 is selected from the group consisting of acidic functional groups and alkyl optionally substituted with an acidic functional group, protected acidic functional group or aryl; each A3 is independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, mercaptoalkyl, (alkylthio)alkyl, arylalkyl, (hydroxyaryl)alkyl, aminocarbonylalkyl, hydroxycarbonylalkyl, ureaalkyl, amidoalkyl, alkylcarbonylalkyl, alkoxyarylalkyl, aryl, and alkyl substituted with acylamino, amino-substituted acylamino, cycloalkyl, carboxy, alkoxy, aralkyloxy, alkoxycarbonyl, aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (alkyl)(aralkyl) aminocarbonyl, aralkylaminocarbonyl, diaralkylaminocarbonyl, carboxyalkylaminocarbonyl, hydroxylaminocarbonyl, thioalkoxy or heterocycle; each of which can be in its protected form; provided that R1 and any of A1, A2, and A3 can be taken together with the atoms to which they are each attached to form a 3- to 6-membered ring heterocycle; each R2 is independently selected from the group consisting of hydrogen and alkyl; n is an integer from 0 to 8; and X is selected from the group consisting of alkoxy, aryloxy, aralkyloxy, hydroxyl, amino, dialkylamino, cycloalkylamino, dicycloalkylamino, cycloalkylalkylamino, (alkyl)(aryl)amino, (mono- or bis-carboxylic acid)-substituted alkylamine, alkylamino optionally substituted with hydroxy, aminocarbonyl, N-alkylaminocarbonyl, carboxy or alkoxycarbonyl, aralkylamino optionally substituted with carboxy, diaralkylamino, arylamino, heterocycle; further provided that the compound of formula I is expressly not Nâ€²-carboxymethyl-N-(phenylacetyl-L-leucyl-L-aspartyl-L-phenylalanyl-L-prolyl)piperazine (i.e., when Z=phenylacetyl, Y1=L, Y2=D, Y3=F/P, n=2, and x=4-caraboxymethylpiperazinyl) and expressly not phenylacetyl-L-leucyl-L-aspartyl-L-phenylalanyl-D-proline amide (i.e., when Z=phenylacetyl, Y1=L, Y2=D, Y3=F/p, n=2, and x=NH2).