Adnan M.M. Mjalli

Imidazole libraries on solid support

The method of synthesis of highly substituted imidazole libraries on solid support using an aldehyde, an amine and a 1,2-dione in the presence of NH4OAc is described. The synthesis was accomplished by attaching the aldehyde or amine component to Wang resin via ester or ether linkages. A class of unsymmetrical bis-imidazoles has also been prepared without any need for selective protection of the synthetic intermediates.

Synthesis of tetrasubstituted imidazoles via α-(N-acyl-N-alkylamino)-β-ketoamides on Wang resin

The first example of a four component condensation of arylglyoxals, 1° amines, carboxylic acids and isocyanides on Wang resin is described. These products can be cyclized in the presence of NH4OAcAcOH to yield tetrasubstituted imidazoles.

Solid phase synthesis of pyrroles derived from a four component condensation

Abstract The first synthesis of tetra- and penta-substituted pyrroles via a 1,3-dipolar cycloaddition of alkynes to polymer bound munchnones is reported. These munchnones are generated in a single step from a four component condensation product of an aldehyde, an amine, a carboxylic acid and an isocyanide. The process produces pyrroles in good overall yield and high purity.

A solid-phase combinatorial method for the synthesis of novel 5- and 6-membered ring lactams

The synthesis of small-ring lactams via the condensation of ω-ketoacids, isocyanides and amines is reported. This process is shown to proceed well in a combinatorial fashion, by immobilization of the isocyanide component on Wang resin. The product is then released from the support on treatment with 10% TFA/CH2Cl2

2,4,5-trisubstituted imidazoles : Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 1

Solution-phase combinatorial chemistry was applied to the optimization and development of clinical candidate OC144-093 (22), a novel and nontoxic modulator of P-glycoprotein mediated multidrug resistance.

Phenylalkyl ketones as potent reversible inhibitors of interleukin-1β converting enzyme

Abstract Phenylalkyl ketones are potent reversible inhibitors of interleukin-1β converting enzyme (ICE). The extended alkyl chain ketones AcTyrValAlaAspCO(CH2)nPh display increased potency over the simple aryl ketone. In particular, the tetrapeptide AcTyrValAlaAspCOPh has a Ki of 10μM while AcTyrValAlaAspCO(CH2)5Ph has a Ki of 18.5nM.

Synthesis of Nh-acyl-α-aminoamides on rink resin: Inhibitors of the hematopoietic protein tyrosine phosphatase (HePTP)

Abstract Cinnamic acid derivatives were prepared on Rink resin using tert -butyl-4-carboxycinnamate in a four-component Ugi condensation. Inhibition of the hematopoietic protein tyrosine phosphatase (HePTP) by these small molecules is reported. An IC 50 value of 3.9 μM was determined for the most potent inhibitor discovered.

The synthesis of hydantoin 4-imides on solid support

Abstract Solid phase synthesis of hydantoin 4-imides via the ‘Ugi’ 4-component condensation reaction is reported. This process is then shown to proceed well in a combinatorial fashion, by immobilization of the isocyanide component on Wang resin. The desired product is then released from the support upon treatment with 20% trifluoroacetic acid-CH 2 Cl 2 .

A combinatorial method for the solid phase synthesis of α-amino phosphonates and phosphonic acids

Abstract Lewis acids or ultrasound catalyze the condensation of imines with Wang resin bound H-phosphonates to give high yields of the corresponding α-amino phosphonates or phosphonic acids.

Combinatorial method for the synthesis of α-hydroxy phosphonates on Wang resin

Abstract An efficient synthesis of α-hydroxy phosphonates has been achieved via the reaction of polymer supported H-phosphonate ester·DBU salts with aldehydes.