Synthesis of di- and tripeptide analogues containing α-ketoamide as a new core structure for inhibition of HIV-1 protease

Sheha, Mahmoud; Mahfouz, Nadia M.; Hassan, Hoda Y.; Youssef, Adel F.; Mimoto, Tsutomu; Kiso, Yoshiaki

doi:10.1016/s0223-5234(00)00187-2

Cited by 63 publications

(21 citation statements)

References 28 publications

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“…All other chemicals and solvents were of analytical grade. The starting compound, KNI-279, was prepared in a pure crystalline form according to the reported method [9].…”

Section: Methodsmentioning

confidence: 99%

“…KNI-279 (1) was prepared by a solution method for peptide synthesis using Boc-derivatives of thioproline (Thz), allophenylnorstatine (Apns), and valine (Val) and the ter- minal isoquinolineoxyacetic acid (iQoa) [9]. Quaternization of the isoquinoline residue of 1 was performed by treating 1 with alkyl halide (methyl iodide, ethyl bromide, ethyl bromoacetate, or bromoacetic acid) at ambient temperature, and afforded the derivatives 2-5 as shown in Scheme1.…”

Section: Synthesis Of the Dihydroisoquinoline Derivative Of Kni-279mentioning

confidence: 99%

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Brain Delivery of HIV Protease Inhibitors

Sheha

El-Koussi

Farag

2003

Archiv der Pharmazie

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To overcome the problems of peptidomimetic drug delivery to the specific organs, the use of dihydropyridine <--> pyridinium chemical delivery systems to deliver peptides to the brain is considered in this work. An HIV protease inhibitor lead compound; KNI 279 was selected for the study. The N-alkylated dihydroisoquinoline derivatives of KNI-279 were synthesized and tested for their ability to be oxidized by brain homogenate and showed good results with reasonable half-life times specially for the N-alkoxycarbonyl-methyl derivative 8. The in-vivo distribution of compound 8 proved the brain delivery and locked in property of HIV PR inhibitors in the brain. All the prepared compounds (both quaternary and dihydro derivatives) showed between 51 and 86 % HIV PR inhibitory activity compared to the parent compound.

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“…All other chemicals and solvents were of analytical grade. The starting compound, KNI-279, was prepared in a pure crystalline form according to the reported method [9].…”

Section: Methodsmentioning

confidence: 99%

Section: Synthesis Of the Dihydroisoquinoline Derivative Of Kni-279mentioning

confidence: 99%

Brain Delivery of HIV Protease Inhibitors

Sheha

El-Koussi

Farag

2003

Archiv der Pharmazie

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“…2,6-dimethyl-4-hydroxy phenol was discovered to be a good replacement for aminoindanol [107]. A different strategy for HIV-1 protease inhibitors is the synthesis of α-keto amide peptides [108]. A solid-phase peptide synthetic methodology was used for this purpose.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

Recent Advances in Combinatorial Chemistry Applied to Development of Anti-HIV Drugs

Pettersson¹,

Clotet‐Codina

Ballana

et al. 2006

MRMC

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“…[1][2][3][4][5][6] The activities of transition state inhibitory immunosuppressive drugs like tacrolimus and sirolimus can be attributed to the presence of this moiety. α-Ketoamide based compounds have also been reported to act as anticancer agents, HIV inhibitor, FIV protease inhibitors and histone deacetylase inhibitors.…”

Section: Introductionmentioning

confidence: 99%