Ashot Martirosyan

1-Substituted derivatives of 2-phenylpyrrolidine-2-carboxamide.

The structures of two potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTI), namely 1-(2-chlorobenzoyl)-2-phenylpyrrolidine-2-carboxamide, C(18)H(17)ClN(2)O(2), and 1-(2-furoyl)-2-phenylpyrrolidine-2-carboxamide, C(16)H(16)N(2)O(3), have been investigated by X-ray diffraction and the butterfly-like conformation established in each case. The pyrrolidine ring has the same half-chair conformation in both structures.

1-Substituted derivatives of 2-aryl-5-oxopyrrolidine-2-carboxylic acid

The structures of two potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTI), namely 1-benzyl-5-oxo-2-phenylpyrrolidine-2-carboxamide, C(18)H(18)N(2)O(2), (III), and 2-(4-isopropoxyphenyl)-5-oxo-1-(4-tolyl)pyrrolidine-2-carbonitrile, C(21)H(22)N(2)O(2), (IV), have been investigated by X-ray diffraction, confirming the butterfly-like conformation of both compounds. The pyrrolidine ring is in an envelope conformation in (III) and a half-chair conformation in (IV). Two intermolecular N[bond]H...O hydrogen bonds are present in the crystal structure of (III), with N...O distances of 2.995 (2) and 2.927 (2) A.

Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs

A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values <20 µM. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g–j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.

Synthesis of new derivatives of 5-(3,4-dihydro-2Н-pyrrol-5-yl)-pyrimidine

By one-stage condensation of 6-(arylamino)pyrimidine-2,4(1Н,3Н)-diones with pyrrolidin-2-one new potential antiviral compounds were obtained, analogs of pyrrolinylpyrimidine containing structural fragments of known drugs AZT and HEPT used in treating HIV-infections.

1-Benzyl-6-phenyl­imino-5-(pyrrol-2-yl­idene)hexa­hydro­pyrimidine-2,4-dione

In the title compound, C21H20N4O2, a potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor, the pyrrolidine ring adopts an envelope conformation, while the hydrogenated pyrimidine ring adopts a weakly expressed twist conformation. The molecules are connected into infinite chains via N—H⋯O hydrogen bonds.

1-(4-Bromo­benzo­yl)-2-phenyl­pyrrolidine-2-carboxamide

In the title compound, C18H17BrN2O2, which is a potential human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor, the pyrrolidine ring exhibits an envelope conformation. In the crystal structure, intermolecular N—H⋯O hydrogen bonds [N⋯O = 2.861 (3) Å] link the molecules into centrosymmetric dimers.

N-substituted 2-(6-amino-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-oxoacetamides

In reaction of 6-aminouracyles with ethyl oxochloroacetate ethyl 2-(6-amino-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-oxoacetates were obtained, which by further reaction with various amines afforded oxo(pyrimidinyl)acetamides. According to the data of biological tests, the synthesized compounds showed low antibacterial and antitumor activity.

Synthesis of 10-(R-benzoyl)-2,4-dimethyl-6-(R-phenyl)-8,9-dihydropyrimido[5,4-e]pyrrolo[1,2-c]pyrimidine-1,3(2H,4H)-diones and 2,4-dimethyl-9,10-dihydro-6λ4-pyrimido[5,4-d]pyrrolo- [1,2-b][1,2,6]thiadiazine-1,3,6(2H,4H,8H)-trione

Abstract6-Imino-1,3-dimethyl-5-(pyrrolidin-2-ylidene)-5,6-dihydropyrimidine-2,4(1H,3H)-dione reacted with substituted benzoyl chlorides in the presence of triethylamine to give the corresponding 10-(R-benzoyl)-2,4-dimethyl-6-(R-phenyl)-8,9-dihydropyrimido[5,4-e]pyrrolo[1,2-c]pyrimidine-1,3(2H,4H)-diones. Analogous reaction with thionyl chloride afforded 2,4-dimethyl-9,10-dihydro-6λ4-pyrimido[5,4-d]pyrrolo[1,2-b][1,2,6]-thiadiazine-1,3,6(2H,4H,8H)-trione.

Synthesis and X-ray analysis of 2-aryl-4-chloropyrrolidine-2-carbonitrile derivatives

A procedure has been developed for the synthesis of ethyl 1-benzoyl-4-chloro-2-phenylpyrrolidine-2-carboxylate and 4-chloro-5-oxo-1,2-diphenyl-, 1-benzoyl-2-(2-benzyloxy-5-chlorophenyl)-4-chloro-, and 1-benzoyl-2-(4-benzyloxyphenyl)-4-chloropyrrolidine-2-carbonitriles in high yields via intramolecular cyclization of the corresponding 2,3-dichloropropionamides under conditions of phase-transfer catalysis.

7-Chloro-11a-phenyl-2,3,5,10,11,11a-hexa­hydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

The title compound, C18H15ClN2O2, is a potential human immunodeficiency virus type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitor. The pyrrolidine ring adopts an envelope and the diazepine ring a boat conformation. In the crystal structure, two isomers (R and S) form centrosymmetric dimers via N—H⋯O hydrogen bonds.