Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes

Mauro Marastoni; Martina Bazzaro; Fabrizio Bortolotti; Severo Salvadori; Roberto Tomatis

doi:10.1016/S0223-5234(00)80034-3

Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes

Mauro Marastoni, Martina Bazzaro, Fabrizio Bortolotti, Severo Salvadori, Roberto Tomatis

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Two series of peptidomimetics containing a novel C₂ pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV- 1 Pt) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC₅₀ = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC₅₀ = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture. (ED₅₀ = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.

Original language	English (US)
Pages (from-to)	651-657
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	34
Issue number	7-8
DOIs	https://doi.org/10.1016/S0223-5234(00)80034-3
State	Published - Jul 1999
Externally published	Yes

Bibliographical note

Funding Information:
Financial support for this work by Ministero dell' Università e della Ricerca Scientifica e Tecnologica (Cofinanziamento Progetto Chimica dei Composti Organici di Interesse Biologico) is gratefully acknowledged. We warmly thank Prof. Y. Kiso of Kyoto Pharmaceutical University (Department of Medicinal Chemistry) for a kind gift of HIV-1 protease inhibitor, KNI-272.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

Aspartyl protease
HIV-1 inhibitors
Peptidomimetic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/S0223-5234(00)80034-3

OpenUrl availability

Full text

Cite this

Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes. / Marastoni, Mauro; Bazzaro, Martina; Bortolotti, Fabrizio et al.
In: European Journal of Medicinal Chemistry, Vol. 34, No. 7-8, 07.1999, p. 651-657.

Research output: Contribution to journal › Article › peer-review

Marastoni, M, Bazzaro, M, Bortolotti, F, Salvadori, S & Tomatis, R 1999, 'Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes', European Journal of Medicinal Chemistry, vol. 34, no. 7-8, pp. 651-657. https://doi.org/10.1016/S0223-5234(00)80034-3

@article{0598ba73d3e34c8fb898a3c09b433b90,

title = "Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes",

abstract = "Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV- 1 Pt) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture. (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.",

keywords = "Aspartyl protease, HIV-1 inhibitors, Peptidomimetic",

author = "Mauro Marastoni and Martina Bazzaro and Fabrizio Bortolotti and Severo Salvadori and Roberto Tomatis",

note = "Funding Information: Financial support for this work by Ministero dell' Universit{\`a} e della Ricerca Scientifica e Tecnologica (Cofinanziamento Progetto Chimica dei Composti Organici di Interesse Biologico) is gratefully acknowledged. We warmly thank Prof. Y. Kiso of Kyoto Pharmaceutical University (Department of Medicinal Chemistry) for a kind gift of HIV-1 protease inhibitor, KNI-272. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "1999",

month = jul,

doi = "10.1016/S0223-5234(00)80034-3",

language = "English (US)",

volume = "34",

pages = "651--657",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson SAS",

number = "7-8",

}

TY - JOUR

T1 - Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes

AU - Marastoni, Mauro

AU - Bazzaro, Martina

AU - Bortolotti, Fabrizio

AU - Salvadori, Severo

AU - Tomatis, Roberto

N1 - Funding Information: Financial support for this work by Ministero dell' Università e della Ricerca Scientifica e Tecnologica (Cofinanziamento Progetto Chimica dei Composti Organici di Interesse Biologico) is gratefully acknowledged. We warmly thank Prof. Y. Kiso of Kyoto Pharmaceutical University (Department of Medicinal Chemistry) for a kind gift of HIV-1 protease inhibitor, KNI-272. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 1999/7

Y1 - 1999/7

N2 - Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV- 1 Pt) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture. (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.

AB - Two series of peptidomimetics containing a novel C2 pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV- 1 Pt) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC50 = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC50 = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture. (ED50 = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.

KW - Aspartyl protease

KW - HIV-1 inhibitors

KW - Peptidomimetic

UR - http://www.scopus.com/inward/record.url?scp=0032710153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032710153&partnerID=8YFLogxK

U2 - 10.1016/S0223-5234(00)80034-3

DO - 10.1016/S0223-5234(00)80034-3

M3 - Article

C2 - 11278050

AN - SCOPUS:0032710153

SN - 0223-5234

VL - 34

SP - 651

EP - 657

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 7-8

ER -

Symmetry-based inhibitors of HIV-1 protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1- hydroxypropanes and 2,4 diamino-1-hydroxybutanes

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this