Homepage of SYNOPSIS

A platform for the Design of Synthetically Accessible Molecules with Desirable Properties in Medicine and Material Sciences

The Synopsis Platform

Synopsis is a de novo design platform that generates synthetically accessible molecules with desirable properties.
The properties are calculated by a scoring function that is independent from the molecule generation. The scoring function can be based upon any proprietary or commercially available software. As such, Synopsis can be deployed in structure-based and ligand-based drug design, or in any area of material science where the properties of the molecules of interest can be reliably predicted.
The designed compounds are generated by applying a set of well-documented organic chemistry reactions to a database of available starting materials. The outcome of a Synopsis run is a list of good-scoring compounds together with their proposed synthesis route from these reactions and available starting materials.

An Illustrative Example: Capsaicin look-alikes

To illustrate the working of Synopsis, we have used the program to generate molecules that resemble capsaicin, known as the molecule that gives chili peppers their spiciness by binding to the Vanilloid TRPV1 receptor:

Capsaicin: 2D structure and surface
capsaicin, 2D capsaicin, surface

Antagonists of this receptor are being investigated as novel agents for pain management. Syopsis was run with as scoring function the SEAL score (Steric and Electronic Alignment, S.K. Kearsley and G.M. Smith, Tetrahedron Comput. Method., 3, 1990, 615-633) between the generated molecules and capsaicin. Below, the structure and electrostatically colored surface of the best scoring molecule generated in one particular Synopsis run is shown, together with its synthesis in two reaction steps from commercially available compounds:

Syn009603: 2D structure and surface
Syn009693, 2D Syn009693, surface
FD Computing: Synopsis
Synthesis of Syn009693 in 2 steps:
step 1: reaction = SUZUKI
MFCD00002533 picture of MFCD00002533 MFCD01009694 picture of MFCD01009694
product: Int015717 picture of Int015717
step 2: reaction = AMIDEFROMACID
Int015717 picture of Int015717 MFCD00144934 picture of MFCD00144934
product: Syn009693 picture of Syn009693

Two other molecules, generated by different Synopsis runs are shown below. To view their synthesis routes, click on the 2D structures:

Syn003739: 2D structure and surface
Syn003739, 2D Syn003739, surface
FD Computing: Synopsis
Synthesis of Syn003739 in 1 step:
step 1: reaction = UREA
MFCD00002030 picture of MFCD00002030 MFCD00040765 picture of MFCD00040765
product: Syn003739 picture of Syn003739
Syn009902: 2D structure and surface
Syn009902, 2D Syn009902, surface
FD Computing: Synopsis
Synthesis of Syn009902 in 3 steps:
step 1: reaction = ESTER
MFCD00626845 picture of MFCD00626845 MFCD00082203 picture of MFCD00082203
product: Int018588 picture of Int018588
step 2: reaction = BUCHWALDHARTWIG
Int018588 picture of Int018588 MFCD00239388 picture of MFCD00239388
product: Int018589 picture of Int018589
step 3: reaction = REDALDOKETO
Int018589 picture of Int018589
product: Syn009902 picture of Syn009902

For comparison we show the structure and molecular surface of 3 known synthetic capsaicin antagonists that are either clinical candidates or lead compounds:

BCTC: 2D structure and surface
bctc, 2D bctc, surface
ABT-102: 2D structure and surface
abt102, 2D abt102, surface
MK2295: 2D structure and surface
mk2295, 2D mk2295, surface

It may be appreciated that even with a very simple scoring function the overall shape and electrostatics of both capsaicin and its synthetic analogs are reflected in the molecules generated by Synopsis. In an actual de novo design effort the scoring function will be a more elaborate and carefully validated computational protocol derived from structural and biological data on the target system. Additionaly, ADME-Tox or other desirable properties can be included in the scoring function. For computational efficiency Synopsis can be run in parallel on a multiple cpu machine.