Forward synthetic synthon generation and its useto identify molecules similar in 3 dimensional shape to pharmaceutical lead compounds

• US 20080172216A1
• Filed: 03/26/2007
• Published: 07/17/2008
• Est. Priority Date: 03/24/2006
• Status: Active Grant

• Current Assignee: Richard D. Cramer, Robert Jilek
• Original Assignee: Richard D. Cramer, Robert Jilek
• Inventors: Cramer, Richard D., Jilek, Robert
• Granted Patent: US 7,860,657 B2
• Time in Patent Office: Days
• US Class Current: 703/12
• CPC Class Codes: G16C 20/10 Analysis or design of chemical reactions, syntheses or processes
• CPC Class Codes: G16C 20/40 Searching chemical structures or physicochemical data
• CPC Class Codes: G16C 20/50 Molecular design, e.g. of drugs

Abstract

A forward synthetic method is described that utilizes recursive application of established organic chemical reactions to derive more complex synthons from available reagents than are available from the reagent synthons themselves. The product of each reaction serves as the starting point for further reactions thereby permitting the generation of multiple complex molecular structures. This synthon generation procedure typically yields 20 ? 30 new structures within the limits of easily accessible syntheses based upon each starting reagent. More complex syntheses yield even more structures. The generated synthons are characterized with a molecular structural descriptor possessing a neighborhood property and can be further characterized with features. The synthons are searched for three dimensional shape and feature similarity to molecular fragments derived from query molecules, typically pharmacological molecules of interest. Identified synthons can be assembled into molecules possessing the same three dimensional shape and likely activity as the molecule of interest.

Claims

1. a computer implemented method of generating the structures of new synthons using available starting materials and known chemical reactions comprising the steps of:

a. inputting definitions of available starting materials;

b. defining reactions;

c. applying a recursive forward synthesis synthon generator;

d. outputting the results.