875574-10-0Relevant articles and documents
TYROSINE AMIDE DERIVATIVES AS RHO- KINASE INHIBITORS
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Page/Page column 43-44, (2020/02/14)
The invention relates to compounds of formula I inhibiting Rho Kinase that are bicyclic dihydropyrimidine-carboxamide derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof Particularly the compounds of the invention may be useful in the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
Mono-, di-, tri-, and tetra-substituted fluorotyrosines: New probes for enzymes that use tyrosyl radicals in catalysis
Seyedsayamdost, Mohammad R.,Reece, Steven Y.,Nocera, Daniel G.,Stubbe, JoAnne
, p. 1569 - 1579 (2007/10/03)
A set of N-acylated, carboxyamide fluorotyrosine (FnY) analogues [Ac-S-FY-NH2, Ac-3,5-F2Y-NH2, Ac-2,3-F 2Y-NH2, Ac-2,3,5-F3Y-NH2, Ac-2,3,6-F3Y-NH2 and Ac-2,3,5,6-F4Y-NH 2] have been synthesized from their corresponding amino acids to interrogate the detailed reaction mechanism(s) accessible to F nY?s in small molecules and in proteins. These Ac-F nY-NH2 derivatives span a pKa range from 5.6 to 8.4 and a reduction potential range of 320 mV in the pH region accessible to most proteins (6-9). DFT electronic-structure calculations capture the observed trends for both the reduction potentials and pKaS. Dipeptides of the methyl ester of 4-benzoyl-L-phenylalanyl-FnYs at pH 4 were examined with a nanosecond laser pulse and transient absorption spectroscopy to provide absorption spectra of FnY?s. The EPR spectrum of each F nY? has also been determined by UV photolysis of solutions at pH 11 and 77 K. The ability to vary systematically both pKa and radical reduction potential, together with the facility to monitor radical formation with distinct absorption and EPR features, establishes that FnYs will be useful in the study of biological charge-transport mechanisms involving tyrosine. To demonstrate the efficacy of the fluorotyrosine method in unraveling charge transport in complex biological systems, we report the global substitution of tyrosine by 3-fluorotyrosine (3-FY) in the R2 subunit of ribonucleotide reductase (RNR) and present the EPR spectrum along with its simulation of 3-FY122?. In the companion paper, we demonstrate the utility of FnYs in providing insight into the mechanism of tyrosine oxidation in biological systems by incorporating them site-specifically at position 356 in the R2 subunit of Escherichia coli RNR.
