Synthesis of a small library of non-symmetric cyclic sulfamide HIV-1 protease inhibitors

被引：15

作者：

Ax, Anna ^{[1
]}

Joshi, Advait A. ^{[1
]}

Orrling, Kristina M. ^{[1
]}

Vrang, Lotta ^{[2
]}

Samuelsson, Bertil ^{[2
]}

Hallberg, Anders ^{[1
]}

Karlen, Anders ^{[1
]}

Larhed, Mats ^{[1
]}

机构：

[1] Uppsala Univ, BMC, Dept Med Chem, SE-75123 Uppsala, Sweden

[2] Medivir AB, SE-14144 Huddinge, Sweden

来源：

TETRAHEDRON | 2010年 / 66卷 / 23期

基金：

瑞典研究理事会;

关键词：

HIV-1; Protease inhibitor; Microwave; Palladium catalysis; Benzylation; CATALYZED COUPLING REACTIONS; DRUG DISCOVERY; MICROWAVE;

D O I：

10.1016/j.tet.2010.04.023

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A set of 11 non-symmetric cyclic sulfamide HIV-1 protease inhibitors were synthesized and evaluated. The use of a key microwave-assisted silver(I) oxide mediated selective mono N-benzylation reaction enabled fast and straightforward synthesis. The K(i) values of the new inhibitors ranged between 0.28 mu M and >20 mu M. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4049 / 4056

页数：8

共 19 条

[1] Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2′ to P1/P1′ [J].

Ax, A ;

Schaal, W ;

Vrang, L ;

Samuelsson, B ;

Hallberg, A ;

Karlén, A .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (03) :755-764

[2] Highly selective silver(I) oxide mediated monoprotection of symmetrical diols [J].

Bouzide, A ;

Sauve, G .

TETRAHEDRON LETTERS, 1997, 38 (34) :5945-5948

[3]

Bremberg U, 2000, SYNTHESIS-STUTTGART, P1004

[4] Fast and selective synthesis of novel cyclic sulfamide HIV-1 protease inhibitors under controlled microwave heating [J].

Gold, H ;

Ax, A ;

Vrang, L ;

Samuelsson, B ;

Karlén, A ;

Hallberga, A ;

Larhed, M .

TETRAHEDRON, 2006, 62 (19) :4671-4675

[5] Cyclic HIV-1 protease inhibitors derived from mannitol: Synthesis, inhibitory potencies, and computational predictions of binding affinities [J].

Hulten, J ;

Bonham, NM ;

Nillroth, U ;

Hansson, T ;

Zuccarello, G ;

Bouzide, A ;

Aqvist, J ;

Classon, B ;

Danielson, UH ;

Karlen, A ;

Kvarnstrom, I ;

Samuelsson, B ;

Hallberg, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (06) :885-897

[6] The impact of microwave synthesis on drug discovery [J].

Kappe, CO ;

Dallinger, D .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (01) :51-63

[7] Transition metal complexes in organic synthesis.: Part 65:: Iron-mediated synthesis of carazostatin, a free radical scavenger from Streptomyces chromofuscus, and O-methylcarazostatin [J].

Knölker, HJ ;

Hopfmann, T .

TETRAHEDRON, 2002, 58 (44) :8937-8945

[8] RATIONAL DESIGN OF POTENT, BIOAVAILABLE, NONPEPTIDE CYCLIC UREAS AS HIV PROTEASE INHIBITORS [J].

LAM, PYS ;

JADHAV, PK ;

EYERMANN, CJ ;

HODGE, CN ;

RU, Y ;

BACHELER, LT ;

MEEK, JL ;

OTTO, MJ ;

RAYNER, MM ;

WONG, YN ;

CHANG, CH ;

WEBER, PC ;

JACKSON, DA ;

SHARPE, TR ;

ERICKSONVIITANEN, S .

SCIENCE, 1994, 263 (5145) :380-384

[9] Microwave-assisted high-speed chemistry: a new technique in drug discovery [J].

Larhed, M ;

Hallberg, A .

DRUG DISCOVERY TODAY, 2001, 6 (08) :406-416

[10] Microwave-promoted palladium-catalyzed coupling reactions [J].

Larhed, M ;

Hallberg, A .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (26) :9582-9584

← 1 2 →