9842. Ubenimex

Nomenclature

CAS number: 58970-76-6
N-[(2S,3R)-3-Amino-2-hydroxy-1-oxo-4-phenylbutyl]-l-leucine; NK-421; Bestatin (Nippon Kayaku).
C16H24N2O4; mol wt 308.37.
C 62.32%, H 7.84%, N 9.08%, O 20.75%.

Description and references

Dipeptide antitumor antibiotic produced by Streptomyces olivoreticuli with immunostimulant activity; inhibits leucine aminopeptidase and aminopeptidases B and N. Prepn from fermentation broth: H. Umezawa et al., DE 2528984; eidem, US 4052449 (1976, 1977 both to Microbiochem. Res. Found., Japan); eidem, J. Antibiot. 29, 97 (1976). Structure: H. Suda et al., ibid. 100. Synthesis of stereoisomers and structure-activity study: R. Nishizawa et al., J. Med. Chem. 20, 510 (1977). Stereocontrolled synthesis: S. Kobayashi et al., Tetrahedron Lett. 25, 5079 (1984). Crystal structure: J. S. Ricci, Jr. et al., J. Org. Chem. 47, 3063 (1982). Cell surface binding studies: H. Umezawa et al., J. Antibiot. 29, 857 (1976); W. E. Müller et al., Int. J. Immunopharmacol. 4, 393 (1982). Acute toxicity: T. Sakakibara et al., Jpn. J. Antibiot. 36, 2971 (1983). Review of pharmacology: G. Mathé, Biomed. Pharmacother. 45, 49-54 (1991); of clinical studies: K. Ota, ibid. 55-60. Clinical trial in squamous-cell lung carcinoma: Y. Ichinose et al., J. Natl. Cancer Inst. 95, 605 (2003).

Chemical structure

Properties

Colorless needles, mp 233-236°. [α]D20 15.5° (c = 1.0 in 1N HCl). pKa 8.1, 3.1. uv max: 241.5, 248, 253, 258, 264.5, 268 nm (E1%1cm 3.8, 4.0, 5.0, 6.0, 4.6, 2.7). Sol in acetic acid, DMSO, methanol. Less sol in water. Insol in ethyl acetate, benzene, hexane, chloroform. LD50 in male, female mice, male, female rats (g/kg): 1.3, 1.9, 1.9, 2.1 s.c.; 0.19, 0.19, 0.90, 0.78 i.p.; >4.0, >4.0, >2.0, >2.0 orally (Sakakibara).

Therapeutic Category

Immunomodulator; antineoplastic.

Keywords

Antineoplastic; Immunomodulators; Immunomodulator