Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors

• Georg Schitter,
• Elisabeth Scheucher,
• Andreas J. Steiner,
• Arnold E. Stütz,
• Martin Thonhofer,
• Chris A. Tarling,
• Stephen G. Withers,
• Jacqueline Wicki,
• Katrin Fantur,
• Eduard Paschke,
• Don J. Mahuran,
• Brigitte A. Rigat,
• Michael Tropak and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2010, 6, No. 21, doi:10.3762/bjoc.6.21

• pharmacological chaperone therapy, PCT) are able to cross the blood brain barrier. This gives the opportunity also to treat types of lysosomal storage diseases involving the central nervous system. Furthermore, CMT is a cost-efficient alternative to ERT. In this context, N-alkylated derivatives of 1

• -β-valienamine (10) (Figure 3), a competitive inhibitor of lysosomal β-galactosidase, when orally administered to GM1-gangliosidosis model mice, is able to enter the brain through the blood-brain barrier and thereby enhancing β-galactosidase activity, reduce substrate storage, and clinically improve

Synthesis and enzymatic evaluation of 2- and 4-aminothiazole- based inhibitors of neuronal nitric oxide synthase

• Graham R. Lawton,
• Haitao Ji,
• Pavel Martásek,
• Linda J. Roman and
• Richard B. Silverman

Beilstein J. Org. Chem. 2009, 5, No. 28, doi:10.3762/bjoc.5.28

• will be less protonated at physiological pH than the aminopyridine ring, and so the molecule will carry a lower net charge. This could lead to an increased ability to cross the blood-brain barrier thereby increasing the in vivo potency of these compounds. The 2-aminothiazole-based compound was less

• the isoforms [6]. In addition, the active site of nNOS is polar with multiple acidic groups, and so most inhibitors that bind with high potency are polar with multiple basic groups. In general, highly charged, hydrophilic molecules do not diffuse passively across the blood-brain barrier (BBB), thus

Flexible synthesis of poison- frog alkaloids of the 5,8-disubstituted indolizidine- class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

• Soushi Kobayashi,
• Naoki Toyooka,
• Dejun Zhou,
• Hiroshi Tsuneki,
• Tsutomu Wada,
• Toshiyasu Sasaoka,
• Hideki Sakai,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 30, doi:10.1186/1860-5397-3-30

• ligand of α7 nicotinic receptors has been available so far. Radiolabeled α-Bgt could not be used for in vivo mapping because of the large molecular weight, high toxicity and poor blood-brain barrier permeability. [19] Indolizidines are low molecular weight, lipophilic compounds that should penetrate well