New advances in the discovery of thrombin and factor Xa inhibitors

被引：65

作者：

Vacca, JP ^{[1
]}

机构：

[1] Merck Res Labs, West Point, PA 18969 USA

来源：

CURRENT OPINION IN CHEMICAL BIOLOGY | 2000年 / 4卷 / 04期

关键词：

D O I：

10.1016/S1367-5931(00)00112-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The search for the ideal anticoagulant has spanned decades and has resulted in several strategies including the clinical use of heparin, low molecular weight heparins, and the vitamin K antagonist warfarin. Over the past five years, many groups have reported preclinical results with direct-acting thrombin inhibitors and several of these are now moving into clinical trials. In addition, many groups have disclosed the discovery of potent, orally bioavailable factor Xa inhibitors. Several of these compounds are now in early clinical trials and the results are forthcoming.

引用

收藏

页码：394 / 400

页数：7

相关论文

共 39 条

[1] Clinical status of direct thrombin inhibitors [J].

Agnelli, G ;

Sonaglia, F .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 1999, 31 (02) :97-117

[2] Studies towards the identification of potent, selective and bioavailable thrombin inhibitors [J].

Ambler, J ;

Baker, E ;

Bentley, D ;

Brown, L ;

Butler, K ;

Butler, P ;

Farr, D ;

Dunnet, K ;

Le Grand, D ;

Hayler, J ;

Janus, D ;

Jones, D ;

Menear, K ;

Mercer, M ;

Smith, G ;

Talbot, M ;

Tweed, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (05) :737-742

[3] Optimisation of the P2 pharmacophore in a series of thrombin inhibitors:: Ion-dipole interactions with lysine 60G [J].

Ambler, J ;

Brown, L ;

Cockcroft, XL ;

Grütter, M ;

Hayler, J ;

Janus, D ;

Jones, D ;

Kane, P ;

Menear, K ;

Priestle, J ;

Smith, G ;

Talbot, M ;

Walker, CV ;

Wathey, B .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (09) :1317-1322

[4]

Anand S, 1999, HAEMOSTASIS, V29, P76

[5] Design, synthesis, and in vitro biological activity of indole-based factor Xa inhibitors [J].

Arnaiz, DO ;

Zhao, ZS ;

Liang, A ;

Trinh, L ;

Whitlow, M ;

Koovakkat, SK ;

Shaw, KJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (09) :957-961

[6] Secondary structure peptide mimetics:: Design, synthesis, and evaluation of β-strand mimetic thrombin inhibitors [J].

Boatman, PD ;

Ogbu, CO ;

Eguchi, M ;

Kim, HO ;

Nakanishi, H ;

Cao, BL ;

Shea, JP ;

Kahn, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (08) :1367-1375

[7] Combinatorial docking and combinatorial chemistry:: Design of potent non-peptide thrombin inhibitors [J].

Böhm, HJ ;

Banner, DW ;

Weber, L .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1999, 13 (01) :51-56

[8] Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors [J].

Dominguez, C ;

Duffy, DE ;

Han, Q ;

Alexander, RS ;

Galemmo, RA ;

Park, JM ;

Wong, PC ;

Amparo, EC ;

Knabb, RM ;

Luettgen, J ;

Wexler, RR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (07) :925-930

[9]

Ewing William R., 1999, Drugs of the Future, V24, P771, DOI 10.1358/dof.1999.024.07.858624

[10] The de novo design and synthesis of cyclic urea inhibitors of factor Xa: Optimization of the S4 ligand [J].

Galemmo, RA ;

Wells, BL ;

Rossi, KA ;

Alexander, RS ;

Dominguez, C ;

Maduskuie, TP ;

Stouten, PFW ;

Wright, MR ;

Aungst, BJ ;

Wong, PC ;

Knabb, RM ;

Wexler, RR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (03) :301-304

← 1 2 3 4 →