[Design Strategy of Biologically Active Compounds Using Various Elements].

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Organometallic Chemistry

Background:

• Conventional drug discovery relies on hydrocarbon frameworks and common elements (N, O, S, halogens).
• The success of bortezomib (a boronic acid drug) has spurred interest in incorporating non-native elements.
• Boron-containing pharmaceuticals are increasingly marketed, indicating a trend towards elemental diversity.

Purpose of the Study:

• To review 'elements chemistry' approaches for developing novel biologically active compounds.
• To focus on silicon and phosphorus incorporation strategies.
• To explore unique substructures beyond simple isosteric exchange.

Main Methods:

• Investigating silicon-carbon (Si/C) isosteric exchange and its physicochemical effects.
• Exploring applications of silyl functionalities.
• Analyzing phosphorus-boron (P-B) substructures as isosteres for C-C or Si-C bonds.
• Introducing unique boron and organometallic compounds (carboranes, boron clusters, ferrocene).

Main Results:

• Detailed physicochemical impacts of Si/C-exchange were elucidated.
• Novel applications of silyl functionalities beyond simple exchange were proposed.
• P-B substructures demonstrated potential as isosteres.
• Biologically active compounds with carboranes, boron clusters, and ferrocene were introduced.

Conclusions:

• Elemental diversity, particularly using silicon and phosphorus, offers promising strategies for novel drug development.
• Isosteric exchange and unique substructures expand the chemical space for medicinal chemistry.
• These approaches provide new avenues for designing distinctive drug candidates.