药物化学apter4.pptVIP

Key Issues of Lead Discovery Means Chapter4 Natural Products Acquisition and extraction Species, parts, location and season Protocol for extraction Screening methods Isolation of active compounds Chromatography, HPLC Structure elucidation NMR, MS, X-ray Further biological assessment Large-scale supplies Other resources, (semi)synthesis, tissue culture, gene engineering Structure-activity relationships Natural products based combichem gene engineering Penicilin morphine purvalanol SemiSynthesis Total synthesis Combinatorial Chemistry (I) It is a synthetic technique to prepare sets of compounds from sets of building blocks in a combinatorial process. Solid phase synthesis Combinatorial Chemistry (II) Advance in solution phase chemistry Combinatorial Chemistry (III) Mix and split Parallel Drug or Non-drug? (I) Rule of Five-bioavailability Molecular less than 500 Number of hydrogen bond donors (OH or NH) equal or less than 5 Number of hydrogen bond acceptors less than 10 Calculated LogP is less than 5 Drug or Non-drug? (II) Functional groups are not likely in a drug Drug or Nondrug? (III) Privileged structures-structure fragment found frequently in bioactive molecules Often used as scaffold in library synthesis