Modulators of proteins with phosphotyrosine recognition units

A compound with the structure depicted in Formula (A8):

• ##STR200## wherein R, is selected from --COR.sub.16, --COOR.sub.17, --CONR.sub.18 R.sub.19 wherein R.sub.16 thru R.sub.19 are independently selected from hydrogen, C.sub.1 -C.sub.11 alkyl, substituted C.sub.1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC.sub.0 C.sub.11 alkyl where the aryl substituents are as defined below, or R.sub.18 and R.sub.19 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl substituent, and wherein R.sub.2 has the general structure depicted in Formula (B)
• X--C(R').dbd.C(R")COOR"' (B)
• wherein
• (i) R' and R" are independently selected from the group consisting of
• hydrogen, halo, cyano, nitro, trihalomethyl, C.sub.1-11 alkyl, optionally substituted arylC.sub.1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C.sub.1-11 alkyl, arylC.sub.1-11 alkyl, C.sub.0-11 alkyloxyC.sub.0-11 alkyl, arylC.sub.0-11 alkyloxyC.sub.0-11 alkyl, C.sub.0-11 alkylthioC.sub.0-11 alkyl, arylC.sub.0-11 alkylthioC.sub.0-11 alkyl, C.sub.0-11 alkylaminoC.sub.0-11 alkyl, arylC.sub.0-11 alkylaminoC.sub.0-11 alkyl, di(arylC.sub.1-11 alkyl)aminoC.sub.0-11 alkyl, C.sub.1-11 alkylcarbonylC.sub.0-11 alkyl, arylC.sub.1-11 alkyl, C.sub.1-11 alkylcarboxyC.sub.0-11 alkyl, arylC.sub.1-11 alkylcarboxyC.sub.0-11 alkyl, C.sub.1-11 alkylcarbonylaminoC.sub.0-11 alkyl, arylC.sub.1-11 alkylcarbonylaminoC.sub.0-11 alkyl, --C.sub.0-11 alkylCOOR.sub.4, --C.sub.0-11 alkylCONR.sub.5 R.sub.6 wherein R.sub.4, R.sub.5 and R.sub.6 are independently selected from hydrogen, C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl, or R.sub.5 and R.sub.6 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl substituent.
• (ii) R"' is selected from the group consisting of
• (a) hydrogen,
• (b) C.sub.1-11 alkyl, substituted C.sub.1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C.sub.0-11 alkyloxy, arylC.sub.0-11 alkyloxy, C.sub.0-11 alkylthio, arylC.sub.0-11 alkylthio, C.sub.0-11 alkylamino, arylC.sub.0-11 alkylamino, di(arylC.sub.0-11 alkyl)amino, C.sub.1-11 alkylcarbonyl, arylC.sub.1-11 alkylcarbonyl, C.sub.1-11 alkylcarboxy, arylC.sub.1-11 alkylcarboxy, C.sub.1-11 alkylcarbonylamino, aryl C.sub.1-11 alkylcarbonylamino, --C.sub.0-11 alkylCOOR.sub.7, --C.sub.0-11 alkylCONR.sub.8 R.sub.9 wherein R.sub.7, R.sub.8 and R.sub.9 are independently selected from hydrogen, C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl, or R.sub.8 and R.sub.9 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl substituent,
• (c) mono-, di- and tri-substituted arylC.sub.0 -C.sub.11 alkyl wherein the aryl substituents are defined as above for R' and R",
• (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R' and R", and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzothienyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,
• and wherein R.sub.2 is selected from the group consisting of:
• (i) hydrogen;
• (ii) C.sub.1-11 alkyl, substituted C.sub.1-11 alkyl wherein the alkyl substituents are defined as above, (iii) arylC.sub.0-11 alkyl, (iv) mono-, di- and tri-substituted arylC.sub.0 -C.sub.11 alkyl wherein the aryl substituents are defined as above,
• and wherein m is an integer between 0 and 4 and each R.sub.3 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C.sub.1-11 alkyl, C.sub.0-11 alkyloxyC.sub.0-11 alkyl, arylC.sub.0-11 alkyloxyC.sub.0-11 alkyl, C.sub.0-11 alkylthioC.sub.0-11 alkyl, arylC.sub.0-11 alkylthioC.sub.0-11 alkyl, C.sub.0-11 alkylaminoC.sub.0-11 alkyl, arylC.sub.0-11 alkylaminoC.sub.0-11 alkyl, di(arylC,.sub.1-11 alkyl)aminoC.sub.0-11 alkyl, C.sub.1-11 alkylcarbonylC.sub.0-11 alkyl, C.sub.1-11 alkylcarboxyC.sub.0-11 alkyl, C.sub.1-11 alkylcarbonylaminoC.sub.0-11 alkyl, arylC.sub.1-11 alkylcarbonylC.sub.0-11 alkyl, arylC.sub.1-11 alkylcarboxyC.sub.0-11 alkyl, arylC.sub.1-11 alkylcarbonylaminoC.sub.0-11 alkyl, --CH.dbd.CHCOOR.sub.10, --CH.dbd.CHCONR.sub.11 R.sub.12, --C.sub.0-11 alkylCOOR.sub.13, --C.sub.0-11 alkylCONR.sub.14 R.sub.15 wherein R.sub.10 thru R.sub.15 are independently selected from hydrogen, C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl, or R.sub.11 and R.sub.12 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl substituent, or R.sub.14 and R.sub.15 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C.sub.1 -C.sub.11 alkyl, arylC.sub.0 -C.sub.11 alkyl substituent,
• or its pharmaceutically acceptable salts, or esters, thereof.