Guanidine analogues

A phenyl guanidine analogue is readily prepared by first I i acting 2-imino-]i-methylpyrrolidine with phenyl isothiocyanate III give synthon 21, This is next -methylated with methyl io-illcle to give 16 which itself, on reaction with pyrrolidine, is... 

A general method for the guanidine analogue of the Biginelli reaction has been developed using the two reagents 25 and 26, which overcome some of the limitations of the direct... 

In 1979, Ross et al 22i" measured the ODMR of tyrosine in glucagon and the derivative [12-homoarginine]glucagon to examine the effect of chemical modification of a lysine residue adjacent to Tyr-10 and Tyr-13. The guanidinated analogue had lower potency than glucagon in a fat cell hormone receptor assay. Since the tyrosine ODMR and other spectral properties of the polypeptide, including circular dichroism, were essentially identical, it was... 

Thus, for example, guanidine analogues guanoxyf n (79) and guanochlor (82) also possess antihypertensive activity. Guanoxyfen is synthesized by base-catalyzed condensation of phenol with chloroaceto-nitrile, followed by hydride reduction to amine 78. 

NA in the latter two cases. However, the guanidine analogue of GS4071 had only modestly improved inhibition (compare 166 with 147). The origins of this differential improvement are unclear, but suggest that the nature of the alkyl ether component affects the hydrogen-bonding network in S2. 

Abacavir is a guanidine analogue that inhibits HIV reverse transcriptase. In vitro, its potency is similar to that of zidovudine, protease inhibitors, and dual nucleoside combinations. There is evidence that abacavir is effective in reducing viral load and increasing the CD4 count in HIV-infected patients. Viral resistance is not rapidly selected for, but cross-resistance has been shown to other analogues of cytosine and guanidine (didanosine, lamivudine, and zalcitabine). 

The guanidine analogues, in general, are not found to be active unless and imtil they get cyclized metabolically to a dihydro-s-triazine analogue having a close resemblance either to the pteridine moiety of folic acid or pyrimethamine as shown below ... 

In fact, under homogenous reaction conditions it was found that the SET mechanism prevailed, affording phenylsulfonyl-derivative 108 as the major product. Similar reactivity patterns were observed in guanidine analogues, with sulfonylation of the 2-NH2 group occurring as the most common side product. 

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