Silicon-Containing Building Blocks for Drug Design
Silicon-containing compounds have been largely ignored in drug design until recently. Silicon can be considered a bioisostere of carbon and hence offers an innovative avenue in drug discovery. For example, C/Si exchange in drug-like scaffolds provides an exciting approach in medicinal chemistry to improve ADME/Tox profile and to enhance potency of the biologically active compounds. Herein we have designed and synthesized a library of silicon-containing building blocks for drug design.
Advantages of “Silicon Switch”:
- Larger C−Si bond length (C–C = 1.54 T91;, C–Si = 1.87 T91;) → changes in the interactions with specific proteins.
- Increase in lipophilicity → improved cell penetration and selectivity.
- Difference in bonding preferences: Si prefers higher coordination numbers → access to compounds for which corresponding carbon analogs are not available.
Over 15 unique silicon-containing building blocks on a 1-30 g scale from stock. We also have designed a library of silicon-containing building blocks for drug discovery programs. These molecules can be synthesized upon request within 4-6 weeks.
Compounds from Stock:
- Aliphatic Trifluoroborates (-BF3) for C-C couplings
- Functionalized Vinyl Boronates for C-C couplings
- Unique 3D-shaped Spirocycles
- Water-soluble non-classical benzene mimics
- gem-Difluorinated Amines for Drug Design
- Fluorosulfates and Sulfamoyl Fluorides
- Alkyne-containing Linkers
- Structurally optimized tetrazines for rapid biological labeling
- Building blocks and linkers for PROTAC synthesis
- Heterocyclic Sulfonyl Fluorides
- Silicon-Containing Building Blocks
- Epoxides for Drug Design
- Analogues of CF3-Pyridine for Drug Design
- Piperazine Bioisosteres for Drug Design
- Sugar-like Building Blocks for Drug Design
- Cyclic Sulfonamides for Drug Design
- Morpholine Bioisosteres for Drug Design
- P(O)Me2-containing Building Blocks
- Saturated Bioisosteres of ortho-/meta-substituted Benzenes
- Saturated bioisosteres of para-substituted benzenes
- Sulfonyl fluorides (-SO2F)
- Oxetane-containing Building Blocks
- SF5-Building Blocks
- Stannanes for coupling reactions
- Sulfoximines for Drug Design
- Heterocyclic scaffolds
- Azide-linkers for Drug Design
- Unnatural Amino Acids
- Cubane-containing building blocks
- Benzoxaboroles for Drug Design