Phosphorylase inhibitors

A. Secrist, III, Application of crystallographic and modelling methods in the design of purine nucleoside phosphorylase inhibitors, Proc. Natl. Acad. Sci. USA 88 11540 (1991). 

So S-S. and M. Karplus (1999). A comparative study of ligand-receptor complex binding affinity prediction methods based on glycogen phosphorylase inhibitors. Journal of Computer Aided Molecular Design 13 243-258. 

Gilbertsen RB, Scott ME, Dong MK, Kossarek LM, Bennett MK, Schrier DJ, Sircar JC. Preliminary report on 8-amino-9-(2-thienylmethyl) guanine (PD 119,229), a novel and potent purine nucleoside phosphorylase inhibitor. Agents and Actions 1987 21 272-4. 

A poorly water-soluble glycogen phosphorylase inhibitor with solubility of about 1 mg/mLwas processed into a solid dispersion with 10 wt% drug and 90 wt% HPMCAS using a solvent-based (acetone) spray-drying method. The resulting solid-dispersion particles with a mean diameter of 5-20 microns were shown to be essentially amorphous by a powday diffraction analysis. 

Additionally, computational chemists often use the resulting output alignment of the molecules as input for 3D-QSAR modeling. As already stated, most field-based 3D-QSAR approaches (such as CoMFA) need a pre-aligned set of molecules and the pharmacophore method is certainly one of the best ways to obtain an objective alignment of the compounds. Klabunde et al., for instance, have recently reported the use of a pharmacophore model of human liver glycogen phosphorylase inhibitors together with 3D information from inhibitor-enzyme complexes to derive a predictive CoMFA model [98]. 

The (ft)-4-phenyl-2-oxazolidinonc auxiliary was used in the process development and scale up of Novartis purine nucleoside phosphorylase inhibitor PNP405 (16) (Scheme 23.2).43 Asymmetric alkylation of 17 with bromoacetonitrile provided a 7 1 diastereoisomeric ratio of crude 18. Recrystallization afforded 18 in 80% yield and >99% de. Simple addition of sodium borohydride in tetrahydrofuran (THF)-water at room temperature44 resulted in the desired y-cyano alcohol 19 and recovery of the auxiliary. 

Pyrimidine nucleosides and their analogs as uridine phosphorylase inhibitors and potential chemotherapeutic agents 91CLY171. 

Kawauchi T, Matsumoto H, Yano S (2001) Determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat plasma by reversed-phase ion-pair high-performance liquid chromatography. J Chromatogr Biomed Appl 751(2) 325-330... 

Study of Ligand—Receptor Complex Binding Affinity Prediction Methods Based on Glycogen Phosphorylase Inhibitors. 

So, S.-S. and Karplus, M. (1999). A Comparative Study of Ligand-Receptor Complex Binding Affinity Prediction Methods Based on Glycogen Phosphorylase Inhibitors. J.ComputAid. Molec.Des., 13,243-258. 

So SS, Karplus M. Evaluation of designed ligands by a multiple screening method application to glycogen phosphorylase inhibitors constructed with a variety of approaches. J Comput Aided Mol Des 2001 15(7) 613-647. 

Halazy, S., and Danzin, C., PhosphonoaUcylpurine derivatives as purine nucleoside phosphorylase inhibitors, Merrell Dow Pharmaceuticals, Eur. Patent Appl. EP 338168, 1989 Chem. Abstr., 112, 158267, 1990. 

Yokomatsu, L, Hayakawa, Y, Kihara, T., Soeda, S., Urano, K., and Shibuya, A., Purine derivatives and purine nucleoside phosphorylase inhibitors containing them, Hisamitsu Pharmaceutical, Japanese Patent Appl. JP 2002080486, 2002 Chem. Abstr., 136, 241663, 2002. 

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