Delivery and Release of Small-Molecule Probes in Mitochondria Using Traceless Linkers
Mitochondria-penetrating peptides (MPPs) are specific targeting vectors for the localization of small molecules to the mitochondrial matrix. Mitochondrial targeting of small molecules has enabled the development of a number of potential therapeutics and c
Pharmacophore-fusing design of pyrimidine sulfonylacetanilides as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase
Twenty-seven derivatives (40–66) were generated by pharmacophore fusing of sulfonylacetanilide-diarylpyrimidine (1) with rilpivirine or biphenyl-diarylpyrimidines. They displayed up to single-digit nanomolar activity against wild-type (WT) virus and vario
There is described herein compound comprising a mitochondrial targeting portion, a cargo portion including a drug unit, and a linker conjugating the mitochondrial targeting portion and the cargo portion, the linker portion cleavable in a mitochondrion of
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Paragraph 0072
(2019/01/15)
Chiral Mercaptoacetamides Display Enantioselective Inhibition of Histone Deacetylase6 and Exhibit Neuroprotection in Cortical Neuron Models of Oxidative Stress
Mercaptoacetamide-based ligands have been designed as a new class of histone deacetylase (HDAC) inhibitors for possible use in the treatment of neurodegenerative diseases. The thiol group of these compounds provides a key binding element for interaction with the catalytic zinc ion, and thus differs from the more typically employed hydroxamic acid based zinc binding groups. Herein we disclose the chemistry and biology of some substituted mercaptoacetamides with the intention of increasing HDAC6 isoform selectivity while maintaining potency similar to their hydroxamic acid analogues. The introduction of a stereocenter α to the thiol group was found to have a considerable impact on HDAC inhibitor potency. These new compounds were also profiled for their therapeutic potential in an invitro model of stress-induced neuronal injury and were found to act as nontoxic neuroprotective agents.
Kalin, Jay H.,Zhang, Hankun,Gaudrel-Grosay, Sophie,Vistoli, Giulio,Kozikowski, Alan P.
experimental part
p. 425 - 439
(2012/06/04)
DERIVATIVES OF SUCCINIC AND GLUTARIC ACIDS AND ANALOGS THEREOF USEFUL AS INHIBITORS OF PHEX
The present invention relates to derivatives of succinic and glutaric acids and analogues thereof, having the following general formula (I), useful as inhibitors of PHEX. These derivatives are useful for promoting generation of bone mass and treating or preventing diseases or conditions associated with a phosphate metabolism defect. Methods for preparation and intermediates are also disclosed.
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Page 41
(2010/02/07)
Heterocyclic compounds, method of developing new drug leads and combinatorial libraries used in such method
The present invention provides according to a first of its aspects, new compounds that have a flexible scaffold with various degrees of conformational restriction and accordingly are useful as drug candidates. These compounds may be used to produce new combinatorial libraries that will permit to screen for and select drug candidates for a variety of uses in human medicine, veterinary medicine and in agriculture.
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(2008/06/13)
Peptidic Cyclols. Synthesis, and Crystal and Molecular Structure of a Tricyclic Thia-cyclol
By following a three-step procedure, the linear peptide -L-phenylalanyl-L-proline (6) has been converted into the cyclic derivative (9).On the basis of spectroscopic data and X-ray crystallographic analysis, compound (9) is shown to be a thia-cyclol whose tricyclic system is related to the peptidic portion of the ergot alkaloids.Properties of the new compound are compared to those of previously studied peptidic aza- and oxa-cyclols.The thiazolidinone ring of (9) adopts in the crystal an approximate envelope conformation, whereas the pyrrolidine ring assumes a half-chair conformation.The benzylic side chain of the phenylalanine residue adopts in the crystal a folded conformation which seems to be preferred even in chloroform solution.
Lucente, Gino,Pinnen, Francesco,Zanotti, Giancarlo,Cerrini, Silvio,Fedeli, Walter,Mazza, Fernando
p. 1499 - 1506
(2007/10/02)
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