Iman A. Al-Masoudi

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

The synthetic routes of 1,2,4-triazole compounds as well as their pharmacological properties have been described. The review focuses intensively on two methods: cycloaddition reaction in the syntheses of various 1,5-dialky-1H-1,2,4-triazole derivatives from the reactive cumulenes with the nitrile precursors as well as the microwave irradiation method.

Amino Acid Derivatives, Part 4: Synthesis and Anti-HIV Activity of New Naphthalene Derivatives

A new series of 2‐(naphthalen‐2‐yloxy)‐N‐[(aryl‐5‐thioxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐yl)methyl] acetamides 5a–f was synthesized from naphthalene‐derived glycine derivative 2 via the hydrazinoacetamide analogs 4a–f. Alternatively, treatment of 4a with H2SO4 afforded 2‐(naphthalen‐2‐yloxy)‐N‐((5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl)methyl) acetamide 6a. Alkylation or sulphonylation of 5a afforded the S‐alkylated derivatives 7 and 8, respectively. Interestingly, treatment of 3 with methoxide ion gave the triazine derivative 9. The synthesized compounds have been screened for their inhibitory activity against HIV‐1 and HIV‐2 in MT‐4 cells. However, 7 was found to be the potent inhibitor in vitro for the replication of HIV‐1 (EC50 = 0.20 μg/mL), suggesting a new lead in the development of an antiviral agent.

SYNTHESIS AND ANTI-HIV ACTIVITY OF NEW HOMO ACYCLIC NUCLEOSIDES, 1-(PENT-4-ENYL)QUINOXALIN-2-ONES AND 2-(PENT-4-ENYLOXY)QUINOXALINES

A series of acyclonucleosides 6,7-disubstituted 1-(pent-4-enyl)quinoxalin-2-one derivatives and the O-analogs were synthesized by a one-step condensation of the corresponding quinoxaline bases with 5-bromo-1-pentene.The acyclonucleosides prepared were assayed against HIV-1 and HIV-2 in MT-4 cells. 6,7-Dimethyl-2-(pent-4-enyloxy)quinoxaline showed inhibition of HIV-1 with EC50 value of 0.22 ± 0.08 µg/ml and a therapeutic index of 13. This means that it was cytotoxic to MT-4 cells at CC50 of 2.6 ± 0.1 µg/ml.

New Acyclic Quinoxaline Nucleosides. Synthesis and Anti-Hiv Activity

A series of acyclonucleosides substituted 1-(4,5-dihydroxypentyl) (13-8) and 2-(4,5-dihydroxypentyloxy)quinoxalines (19-24) were synthesized by the sharpless asymmetric dihydroxylation of the derivatives 1-6 and 7-12, respectively. Treatment of the quinoxaline base 26 with (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl-p-toluenesulfonate (27) in the presence of NaH/DMF furnished 28. Acid hydrolysis of 28 gave 1-(2,3-dihydroxypropyl)-6,7-dimethyl-quinoxaline-2-one (29). Alternatively, 29 was prepared by sharpless dihydroxylation of 30. All the compounds were evaluated for their in vitro anti-HIV-1 and HIV-2 in MT-4 cell and found inactive, except 29, which showed inhibition of HIV-1 with EC50 value of 0.15 ± 0.1 μg/ml and a therapeutic index (SI) of 73.

Synthesis of N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thione-N-nucleosides and S-glycosylated derivatives

Abstract Fusion of the N-substituted 1-amino-2,3-dihydro-1H-imidazole-2-thiones 1-4 with the peracylated ribose 5 in the presence of iodine afforded the N-nucleosides 6-9 in moderate yields. Deblocking with NaOMe/MeOH gave the free nucleosides 10-13. Alternatively, silylation of 4 followed by ribosylation with 5 in the presence of TMSOTf as catalyst afforded 9 in moderate yield. Ribosylation of 4 with the chlorodeoxyribose derivative 15 as well as 5 in the presence of NaH in DMF afforded the thioglycosides 16 and 18, respectively. Deblocking of 16 and 18 with NaOMe/MeOH gave the free S-thioglycosides 17 and 19, respectively. Thermal rearrangement of 19 at high temperature in the presence of iodine furnished 13 in low yield. The new free nucleosides and thioglycosides were inactive against HIV-1 and HIV-2 induced cytopathicity in human MT-4 lymphocyte cells.

Synthesis and Anti-HIV Activity of New 6-Thioarylpyrimidines and Related Compounds

A series of new 5-nitro- and 5-amino-6-arylsulfanyl-1-propyl-1H-pyrimidin-2,4-diones (4–9) were synthesized with the aim to develop new non-nucleoside reverse transcriptase inhibitors (NNRTIs). Similarly, 6-arylsulfanyl-1,3-dimethyl-5-nitro-1H-pyrimidin-2,4-diones (12–15) were prepared from 10. A new 2-amino-2-phenyl-7-phenylsulfanyl-imidazo[1,2-a]pyrimidin-5-one (18) has been synthesized from reaction of 17 with α -bromoacetophenone in the presence of NaH. The newly synthesized compounds were evaluated for their anti HIV-1 and HIV-2 activity in MT-4 cells.

Synthesis and reactions of some new 6,7-dihaloquinolones bearing mercapto groups

Reaction of the 6-chloro-7-fluoroquinoline 7 with methyl 2-mercaptoacetate, methyl 3-mercaptopropionate, or sodium thiophenolate furnished the quinolone derivatives of 3-carbonylsulfanyl-acetic acid methyl ester 8, the propionoate analogue 10, and 3-carbothioic acid S-phenyl ester 11 respectively. Ester 8 was converted into the 3-carbothioic acid S-carbamoyl derivative 9. Analogously, treatment of the 6,7-diflouroquinolone 12 with amino or mercapto precursors led to the formation of 13 and 14 respectively. Reaction of 14 with aqueous NH3 or H2O2/AcOH afforded the acetamide 15 and the sulfoxide 16 analogues, respectively. The 5′-thioalkyl-acyclic quinolone nucleosides 19 and 20 were obtained from reaction of the mesylate derivative 18, prepared from the free nucleoside 17, with the methanthiolate and thiophenolate anions.