Title: Ubenimex
CAS Registry Number: 58970-76-6
CAS Name: N-[(2S,3R)-3-Amino-2-hydroxy-1-oxo-4-phenylbutyl]-L-leucine
Manufacturers' Codes: NK-421
Trademarks: Bestatin (Nippon Kayaku)
Molecular Formula: C16H24N2O4
Molecular Weight: 308.37
Percent Composition: C 62.32%, H 7.84%, N 9.08%, O 20.75%
Literature 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).
Properties: Colorless needles, mp 233-236°. [a]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).
Melting point: mp 233-236°
pKa: pKa 8.1, 3.1
Optical Rotation: [a]D20 -15.5° (c = 1.0 in 1N HCl)
Absorption maximum: 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)
Toxicity data: 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)
Therap-Cat: Immunomodulator; antineoplastic.
Keywords: Antineoplastic; Immunomodulators; Immunomodulator. |