10221. Voclosporin

Nomenclature

CAS number: 515814-01-4
6-[(2S,3R,4R,6E)-3-Hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]cyclosporin A; cyclo[l-alanyl-d-alanyl-N-methyl-l-leucyl-N-methyl-l-leucyl-N-methyl-l-valyl-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)nona-6,8-dienoyl]-(2S)-2-aminobutanoyl-N-methylglycyl-N-methyl-l-leucyl-l-valyl-N-methyl-l-leucyl]; ISA-247; ISAtx-247.
C63H111N11O12; mol wt 1214.62.
C 62.30%, H 9.21%, N 12.68%, O 15.81%.

Description and references

Cyclic peptide calcineurin inhibitor; semi-synthetic analog of cyclosporin A, q.v., containing a modified MeBmt side chain. Prepn: S. Naicker et al., WO 9918120; eidem, US 6605593 (1999, 2003 both to Isotecknika). Stereoselective syntheses: S. Naiker et al. WO 03033526 (2003 to Isotechnika; Roche); B. Molino et al., WO 06014872 (2006 to AMR Technology). Pharmacology: W. P. Maksymowych et al., J. Rheumatol. 29, 1646 (2002) PubMed. Pharmacokinetics: M. Stalder et al., J. Heart Lung Transplant. 22, 1343 (2003) DOI PubMed. Efficacy in primate renal transplants: C. R. Gregory et al., Transplantation 78, 681 (2004) DOI PubMed. Review of preclinical studies and therapeutic potential: L. Aspeslet et al., Transplant. Proc. 33, 1048-1051 (2001) DOI PubMed; F. J. Dumont, Curr. Opin. Investig. Drugs 5, 542-550 (2004) PubMed. Clinical trial in plaque psoriasis: R. Bissonnette et al., J. Am. Acad. Dermatol. 54, 472 (2006) DOI PubMed.

Chemical structure

Properties

White solid.

Therapeutic Category

Immunosuppressant; antipsoriatic.

Keywords

Immunosuppressant; Antipsoriatic; Calcineurin Inhibitor