PMID- 36105337
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220917
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 13
IP  - 9
DP  - 2022 Sep 8
TI  - Turning the Other Cheek: Influence of the cis-Tetrafluorocyclohexyl Motif on 
      Physicochemical and Metabolic Properties.
PG  - 1517-1523
LID - 10.1021/acsmedchemlett.2c00312 [doi]
AB  - The targeted introduction of substituents in order to tailor a molecule's 
      pharmacologic, physicochemical, and metabolic properties has long been of 
      interest to medicinal chemists. The all-cis tetrafluorocyclohexyl motif-dubbed 
      Janus face, due to its electrostatically polarized cyclohexyl ring-represents one 
      such example where chemists might incorporate a metabolically stable, polar, 
      lipocompatible motif. To better understand its potential utility, we have 
      synthesized three series of matched molecular pairs (MMPs) where each MMP differs 
      only in the cyclohexane unit, i.e., with a tetrafluorocyclohexyl or a standard 
      cyclohexyl motif. With the introduction of the facially polarized all-cis 
      tetrafluorocyclohexyl ring, the resulting compounds have significantly modified 
      physicochemical properties (e.g., kinetic solubility, lipophilicity and 
      permeability) and metabolic stabilities. These results further speak to the 
      promise of this substituent as a tactic to improve the drug-like properties of 
      molecules.
CI  - (c) 2022 American Chemical Society.
FAU - Wang, Yong
AU  - Wang Y
AUID- ORCID: 0000-0003-0532-3530
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Lee, Wendy
AU  - Lee W
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Chen, Yi-Chen
AU  - Chen YC
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Zhou, Yuhui
AU  - Zhou Y
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Plise, Emile
AU  - Plise E
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Migliozzi, Madyson
AU  - Migliozzi M
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
FAU - Crawford, James J
AU  - Crawford JJ
AUID- ORCID: 0000-0002-6408-8246
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
LA  - eng
PT  - Journal Article
DEP - 20220814
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC9465827
COIS- The authors declare no competing financial interest.
EDAT- 2022/09/16 06:00
MHDA- 2022/09/16 06:01
PMCR- 2022/08/14
CRDT- 2022/09/15 02:19
PHST- 2022/07/07 00:00 [received]
PHST- 2022/08/04 00:00 [accepted]
PHST- 2022/09/15 02:19 [entrez]
PHST- 2022/09/16 06:00 [pubmed]
PHST- 2022/09/16 06:01 [medline]
PHST- 2022/08/14 00:00 [pmc-release]
AID - 10.1021/acsmedchemlett.2c00312 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2022 Aug 14;13(9):1517-1523. doi: 
      10.1021/acsmedchemlett.2c00312. eCollection 2022 Sep 8.