Fondaparinux

Fondaparinux

Clinical data
Trade names	Arixtra
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN US DailyMed: Fondaparinux
Subcutaneous
ATC code	B01AX05 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only EU: Rx-only
JSmol)		Interactive image
SMILES [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S(=O)(=O)N[C@@H]5[C@@H](O)[C@H](O)[C@@H](COS([O-])(=O)=O)O[C@@H]5O[C@H]1[C@H](O)[C@@H](O)[C@@H](O[C@@H]1C([O-])=O)O[C@@H]4[C@@H](COS([O-])(=O)=O)O[C@H](O[C@H]3[C@H](O)[C@@H](OS([O-])(=O)=O)[C@H](O[C@H]2[C@H](O)[C@@H](NS([O-])(=O)=O)[C@@H](OC)O[C@@H]2COS([O-])(=O)=O)O[C@H]3C([O-])=O)[C@H](NS([O-])(=O)=O)[C@H]4OS([O-])(=O)=O
InChI InChI=1S/C31H53N3O49S8.10Na/c1-69-27-9(33-85(48,49)50)13(37)17(6(74-27)3-71-88(57,58)59)76-31-22(83-91(66,67)68)16(40)21(24(81-31)26(43)44)79-29-10(34-86(51,52)53)19(82-90(63,64)65)18(7(75-29)4-72-89(60,61)62)77-30-15(39)14(38)20(23(80-30)25(41)42)78-28-8(32-84(45,46)47)12(36)11(35)5(73-28)2-70-87(54,55)56;;;;;;;;;;/h5-24,27-40H,2-4H2,1H3,(H,41,42)(H,43,44)(H,45,46,47)(H,48,49,50)(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62)(H,63,64,65)(H,66,67,68);;;;;;;;;;/q;10*+1/p-10/t5-,6-,7-,8-,9-,10-,11-,12-,13-,14-,15-,16+,17-,18-,19-,20+,21+,22-,23+,24-,27+,28-,29-,30-,31-;;;;;;;;;;/m1........../s1 Y Key:XEKSTYNIJLDDAZ-JASSWCPGSA-D Y
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Fondaparinux (trade name Arixtra) is an

Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery^[2] as well as for the treatment of deep vein thrombosis and pulmonary embolism.^[3]

Fondaparinux is similar to

It has been investigated for use in conjunction with streptokinase.^[5]

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anti-coagulate patients with established HIT as it has no affinity for PF4. However, its renal excretion precludes its use in patients with renal dysfunction.

Unlike

Fondaparinux is a synthetic pentasaccharide

Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycans heparin and heparan sulfate (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor antithrombin (AT). Binding of heparin or HS to AT has been shown to increase the anti-coagulant activity of antithrombin 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Chemistry

Abbreviations

• GlcNS6S = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside
• GlcA = β-D-glucopyranuronoside
• GlcNS3,6S = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl
• IdoA2S = 2-O-sulfo-α-L-idopyranuronoside
• GlcNS6SOMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside

Fondaparinux is only accessible by chemical synthesis. Recently, Supriya Dey et al. reported an effective and scalable one-pot synthesis of Fondaparinux.^[7]

The sequence of monosaccharides is D-GlcNS6S-α-(1,4)-D-GlcA-β-(1,4)-D-GlcNS3,6S-α-(1,4)-L-IdoA2S-α-(1,4)-D-GlcNS6S-OMe, as shown in the following structure:

References