Publications by authors named "Brian Bestvater"

Article Synopsis
  • Researchers discovered a strong and selective antagonist for the lysophosphatidic acid receptor 1 (LPAR1), which has antifibrotic properties, initially validated through a specific assay involving MRTF-A.* -
  • Structural modifications improved the compound's stability and pharmacokinetics, leading to a promising candidate for oral dosing that effectively blocked LPA-induced histamine release and showed efficacy against lung fibrosis in preclinical tests.* -
  • Despite its potential, the development of the LPAR1 antagonist was discontinued due to observed CNS toxicity in dog models, raising safety concerns for clinical use in idiopathic pulmonary fibrosis (IPF).*
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Aldimines and ketimines containing electron-donating and electron-withdrawing groups can be hydrosilylated with borenium catalysts at as low as 1 mol% catalyst loading at room temperature, providing the corresponding secondary amines in excellent yields. Reactions with 2-phenylquinoline gave the 1,4-hydrosilylquinoline product selectively which can be further functionalized in a one-pot synthesis to give unique γ-amino alcohol derivatives. Control experiments suggest that the borenium ion catalyzes both the hydrosilylation and subsequent addition to the aldehyde.

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The carbene derived from (1R,3S)-camphoric acid was used to prepare the borane adduct with Piers' borane 7. Subsequent hydride abstraction gave the borenium cation 8. Adducts with 9-BBN and the corresponding (1R,3S)-camphoric acid-derived carbene bearing increasingly sterically demanding N-substituents (R = Me 9, Et 10, i-Pr 11) and the corresponding borenium cations 12-14 were also prepared.

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Article Synopsis
  • Researchers developed a simple one-pot method to create mesoionic carbene boranes from 1,2,3-triazolium salts, a base, and borane.
  • The process generates borenium ions, which are important intermediates formed by removing a hydride.
  • These borenium ions act as catalysts for effective hydrogenation reactions of imines and unsaturated N-heterocycles under mild conditions, like room temperature and normal pressure.
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Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2.

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Aims: fibroblast growth factor-2 (FGF-2), implicated in paracrine induction of cardiac hypertrophy, is translated as high molecular weight (Hi-FGF-2) and low molecular weight (Lo-FGF-2) isoforms. Paracrine activities are assigned to Lo-FGF-2, whereas Hi-FGF-2 is presumed to have nuclear functions. In this work, we re-examined the latter presumption by asking whether: cardiac non-myocytes (CNMs) accumulate and export Hi-FGF-2 in response to pro-hypertrophic [angiotensin II (Ang II)] stimuli; an unconventional secretory pathway requiring activated caspase-1 affects Hi-FGF2 export; and secreted Hi-FGF-2 is pro-hypertrophic.

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