Drugs for Metabolic Syndrome---Structural Optimization of Hypoglycemic nstpbp 168 Derivatives and HSU-STD Lead Compounds

Based on the consults opinion of the righteousness committee member of findings and achievement meeting at 98 year and the recently research data, we revises partial plan contents of 99 year. In this year, we will be focus on the development of medicine for metabolism syndrome - diabetes, antilipeiliz drug as a goal, developing lead compound for preclinical trials, this work include: (1) Lead compound optimization: This plans focus optimize lead compound as nstpbp168, nstpbp169 and nstpbp169-G derivatives, and backup compound HSU-STD derivatives, finding the most ideal compound achievement as a hypoglycemic or anti-lipidemia new drug candidate for preclinical trial. (2) The total synthesis of target compound and its derivative: chemical modification of the active compound, optimize the structure, pharmacological mechanism, pharmacokinetic, toxicology, safety and the most suitable dosage-form and supply material for clinical. Including: 1. The syntheses of nspbp168 derivative and check its SAR. 2. Syntheses of compound 7 and nstpp169. 3. Chemical modification of active HSU-STD compound. (3) Animal experimentation, to examine pharmacological mechanism and its toxicology. (4) Preparation for preclinical try. Following works and dicussion: 1. the nstpbp168 total synthesis has completed and will be try to scale up. The related experiences of synthesis method and procedures establishment from nstpbp168 total synthesis can apply in nstpbp169 and 169-G. 2. The modification of OH or =CO functional group on C-2, C-3, and substituted polar group to increase bioactive is helpful for optimize lead compound 3. Backup compound HSU-STD are effective for hypoglycemic (HSU-STD 001, 003, 004, 015, 023, 037, 040, 043) or for anti-lipidemia ingredient (HSU-STD 012).