Diversity-Oriented Synthesis of Functionalized Pyrrolo[3,2-d]pyrimidines with Variation of the Pyrimidine Ring Nitrogen Substituents

Abstract

Nine 2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid benzyl esters 12 were synthesized in four steps from 4-oxo-N-(PhF)proline benzyl ester 7 by a general method in which elements of molecular diversity were readily added onto the pyrimidine nitrogens. Conversion of 4-oxoproline 7 into the corresponding aminopyrrole 8 using benzyl-, allyl-, and isopropylamine followed by treatment with phenyl, allyl, and ethyl isocyanate gave nine different ureas 9. 4-Ureido-1H-pyrrole-2-carboxylic acid benzyl esters 9 were then converted into the respective pyrrolo[3,2-d]pyrimidines 12 using trichloroacetyl chloride in acetonitrile followed by treatment with Cs(2)CO(3). Crystallization from toluene gave the desired deazapurines in 37-55% overall yield from proline 7.

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

“…They bind to dopamine-D 2 -like receptors and modulate protein kinase activity. The pyrrole carboxamide motif is part of many blockbuster drugs like the calcium salt of atorvastatin (a hypolipidemic agent), lisinopril (an inhibitor of angiotensin-converting enzyme), valsartan (angiotensin-II receptor blocker), diltiazem (calcium channel blocker), istamycin and pyrronamycin A & B (used as antibiotics) [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1<em>H</em>-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

“…They bind to dopamine-D 2 -like receptors and modulate protein kinase activity. The pyrrole carboxamide motif is part of many blockbuster drugs like the calcium salt of atorvastatin (a hypolipidemic agent), lisinopril (an inhibitor of angiotensin-converting enzyme), valsartan (angiotensin-II receptor blocker), diltiazem (calcium channel blocker), istamycin and pyrronamycin A & B (used as antibiotics) [12][13][14][15][16][17][18][19][20]. Another structural scaffold that involves hydrazide nitrogens double bonded to carbon atoms (-C=N-NH-), has attracted the attention of many pharmaceutical and academic researchers due to its ability to map a spectrum of biological activity.…”

2-Vinylpyrroles and Pyrrolo[3,2-d]pyrimidines from Direct Addition of Aldehydes to 4-Amino-pyrrole-2-carboxylate Derivatives

“…Such deazapurine derivatives have typically been prepared by pyrrole annulation on properly substituted pyrimidines . Recently, we have presented effective solution- and solid-phase methodology for pyrrolopyrimidine synthesis starting from 4-amino-pyrrole-2-carboxylates. − …”