7725. Pregabalin

Nomenclature

CAS number: 148553-50-8
(3S)-3-(Aminomethyl)-5-methylhexanoic acid; (S)-(+)-4-amino-3-(2-methylpropyl)butanoic acid; (S)-(+)-3-isobutyl-γ-aminobutyric acid; CI-1008; PD-144723; Lyrica (Pfizer).
C8H17NO2; mol wt 159.23.
C 60.34%, H 10.76%, N 8.80%, O 20.10%.

Description and references

Structural analog of γ-aminobutyric acid, q.v.; ligand at α2δ subunit of voltage-gated calcium channels. Prepn of racemate: R. Andruszkiewicz, R. B. Silverman, Synthesis 1989, 953. Enantioselective synthesis: P. Yuen et al., Bioorg. Med. Chem. Lett. 4, 823 (1994). Manufacturing process: M. S. Hoekstra et al., Org. Process Res. Dev. 1, 26 (1997). HPLC determn in biological fluids: B. L. Windsor, L. L. Radulovic, J. Chromatogr. B 674, 143 (1995). Clinical trial in post-herpetic neuralgia: R. Sabatowski et al., Pain 109, 26 (2004); in fibromyalgia syndrome: L. J. Crofford et al., Arthritis Rheum. 52, 1264 (2005). Overview of mechanism and pharmacology: S. M. Stahl, J. Clin. Psychiatry 65, 596, 1033 (2004). Review of pharmacology and clinical experience: R. Huckle, Curr. Opin. Investig. Drugs 5, 82-89 (2004); of clinical experience in generalized anxiety disorder: S. A. Montgomery, Expert Opin. Pharmacother. 7, 2139-2154 (2006).

Chemical structure

Properties

White to off-white crystalline solid, mp 186-188°. pKa1 4.2, pKa2 10.6. [α]D23 +10.52° (c = 1.06 in water). Log P (n-octanol/0.05M phosphate buffer): -1.35 (pH 7.4). Freely sol in water and both basic and acidic aqueous solns.

Therapeutic Category

Anticonvulsant; anxiolytic; analgesic in treatment of peripheral neuropathic pain and fibromyalgia syndrome.

Keywords

Anticonvulsant; Anxiolytic; Analgesic; Non-opioids