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Comprehensive exploration of chemical space using trisubstituted carboranes.

ABSTRACT: A total of 42 trisubstituted carboranes categorised into five scaffolds were systematically designed and synthesized by exploiting the different reactivities of the twelve vertices of o-, m-, and p-carboranes to cover all directions in chemical space. Significant inhibitors of hypoxia inducible factor transcriptional activitay were mainly observed among scaffold V compounds (e.g., Vi-m, and Vo), whereas anti-rabies virus activity was observed among scaffold V (Va-h), scaffold II (IIb-g), and scaffold IV (IVb) compounds. The pharmacophore model predicted from compounds with scaffold V, which exhibited significant anti-rabies virus activity, agreed well with compounds IIb-g with scaffold II and compound IVb with scaffold IV. Normalized principal moment of inertia analysis indicated that carboranes with scaffolds I-V cover all regions in the chemical space. Furthermore, the first compounds shown to stimulate the proliferation of the rabies virus were found among scaffold V carboranes.

SUBMITTER: Asawa Y

PROVIDER: S-EPMC8677773 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Comprehensive exploration of chemical space using trisubstituted carboranes.

Asawa Yasunobu Y Hatsuzawa Saki S Yoshimori Atsushi A Yamada Kentaro K Katoh Akira A Kouji Hiroyuki H Nakamura Hiroyuki H

Scientific reports 20211216 1

A total of 42 trisubstituted carboranes categorised into five scaffolds were systematically designed and synthesized by exploiting the different reactivities of the twelve vertices of o-, m-, and p-carboranes to cover all directions in chemical space. Significant inhibitors of hypoxia inducible factor transcriptional activitay were mainly observed among scaffold V compounds (e.g., Vi-m, and Vo), whereas anti-rabies virus activity was observed among scaffold V (Va-h), scaffold II (IIb-g), and sca ...[more]

PMID: 34916538

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Comprehensive exploration of chemical space using trisubstituted carboranes.

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Comprehensive exploration of chemical space using trisubstituted carboranes.

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