Mycophenolic Acid
Title: Mycophenolic Acid
CAS Registry Number: 24280-93-1
CAS Name: (4E)-6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid
Additional Names: 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid
Molecular Formula: C17H20O6
Molecular Weight: 320.34
Percent Composition: C 63.74%, H 6.29%, O 29.97%
Literature References: Antibiotic produced by Penicillium brevi-compactum, P. stoloniferum and related spp. Selectively inhibits lymphocyte proliferation by blocking inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of purine nucleotides. Isoln: C. L. Alsberg, O. F. Black, USDA Bur. Plant Ind. Bull. 270, 7 (1912), C.A. 7, 3992 (1913); P. W. Clutterbuck et al., Biochem. J. 26, 1441 (1932); and antimicrobial activity: H. W. Florey et al., Lancet 1, 46 (1946). Structure: J. H. Birkinshaw et al., Biochem. J. 50, 630 (1952); W. R. Logan, G. T. Newbold, J. Chem. Soc. 1957, 1946. Total synthesis: A. J. Birch, J. J. Wright, Aust. J. Chem. 22, 2635 (1969). Biosynthesis: L. Canonica et al., J. Chem. Soc. Perkin Trans. 1 1972, 2639. Fermentation, isoln and biological properties: R. H. Williams et al., Antimicrob. Agents Chemother. 1968, 229. Immunosuppressive effect: A. Mitsui, S. Suzuki, J. Antibiot. 22, 358 (1969). Mechanism of action: A. C. Allison, E. M. Eugui, Transplant. Proc. 26, 3205 (1994); J. T. Ransom, Ther. Drug Monit. 17, 681 (1995). HPLC determn in plasma: J. Shen et al., J. Chromatogr. B 817, 207 (2005); D. Indjova et al., ibid. 327.
Properties: Needles from hot water, mp 141°. pKa 4.5. Partition coefficient (n-octanol/water): 570 (pH 2); 1.6 (pH 7.4). Almost insol in cold water. Sol in alcohol. LD50 in mice (mg/kg): >1250 orally; 972.9±77 i.p. (Williams).
Melting point: mp 141°
pKa: pKa 4.5
Log P: Partition coefficient (n-octanol/water): 570 (pH 2); 1.6 (pH 7.4)
Toxicity data: LD50 in mice (mg/kg): >1250 orally; 972.9±77 i.p. (Williams)
 
Derivative Type: 2-(4-Morpholinyl)ethyl ester
CAS Registry Number: 128794-94-5
Additional Names: Mycophenolate mofetil
Manufacturers' Codes: RS-61443
Trademarks: CellCept (Roche)
Molecular Formula: C23H31NO7
Molecular Weight: 433.49
Percent Composition: C 63.73%, H 7.21%, N 3.23%, O 25.84%
Literature References: Prepn: P. H. Nelson et al., US 4753935 (1988 to Syntex); and bioavailability: W. A. Lee et al., Pharm. Res. 7, 161 (1990). Pharmacokinetics: R. E. S. Bullingham et al., Transplant. Proc. 28, 925 (1996). Clinical trial in renal transplantation: P. A. Keown et al., Transplantation 61, 1029 (1996). Reviews: D. O. Taylor et al., J. Heart Lung Transplant. 13, 571-582 (1994); J. J. Lipsky, Lancet 348, 1357-1359 (1996). Review of clinical experience in inflammatory bowel disease: A. C. Ford et al., Aliment. Pharmacol. Ther. 17, 1365-1369 (2003).
Properties: White to off-white crystalline powder, mp 93-94°. pKa 5.6. Partition coefficient (n-octanol/water): 0.0085 (pH 2); 238 (pH 7.4). Sol in acetone, methanol. Slightly sol in water; sparingly sol in ethanol.
Melting point: mp 93-94°
pKa: pKa 5.6
Log P: Partition coefficient (n-octanol/water): 0.0085 (pH 2); 238 (pH 7.4)
 
Derivative Type: Sodium salt
CAS Registry Number: 37415-62-6
Additional Names: Mycophenolate sodium
Trademarks: Myfortic (Novartis)
Molecular Formula: C17H19NaO6
Molecular Weight: 342.32
Percent Composition: C 59.65%, H 5.59%, Na 6.72%, O 28.04%
Literature References: Clinical trial in renal transplantation: M. Salvadori et al., Am. J. Transplant. 4, 231 (2003); K. Budde et al., ibid. 237. Review of pharmacology and clinical development of enteric-coated formulation: idem et al., Expert Opin. Pharmacother. 5, 1333-1345 (2004).
Properties: LD50 in mice (mg/kg): 1176±151 orally; 568±53 i.p. (Williams).
Toxicity data: LD50 in mice (mg/kg): 1176±151 orally; 568±53 i.p. (Williams)
 
Therap-Cat: Immunosuppressant.
Keywords: IMPDH Inhibitor; Immunosuppressant.

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