2370-56-1Relevant academic research and scientific papers
Synthesis and in vitro opioid activity profiles of DALDA analogues
Schiller, Peter W.,Nguyen, Thi M.-D.,Berezowska, Irena,Dupuis, Sebastien,Weltrowska, Grazyna,Chung, Nga N.,Lemieux, Carole
, p. 895 - 901 (2007/10/03)
The tetrapeptide DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a polar and selective μ agonist showing poor penetration of the placental and blood-brain barriers. In an effort to enhance the potency of DALDA, analogues containing 2',6'-dimethyltyrosine (Dmt), N,2',6'-trimethyltyrosine (Tmt), 2'-methyltyrosine (Mmt) or 2'-hydroxy,6'-methyltyrosine (Hmt) in place of Tyr1, or Orn or α,γ-diaminobutyric acid (A2bu) in place of Lys4, were synthesized. All compounds displayed high it receptor selectivity in the rat and guinea pig brain membrane binding assays and most of them were more potent μ agonists than DALDA in the μ receptor-representative guinea pig ileum assay, with [Dmt1]DALDA showing the highest potency. Because of its extraordinary μ agonist potency, high μ selectivity, polar character (charge of 3 +) and metabolic stability, [Dmt1]DALDA has potential for use in obstetrical or peripheral analgesia. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
Tyrosine analogues as alternative substrates for protein tyrosine kinase Csk: Insights into substrate selectivity and catalytic mechanism
Kim, Kyonghee,Parang, Keykavous,Lau, Ontario D.,Cole, Philip A.
, p. 1263 - 1268 (2007/10/03)
Protein tyrosine kinases are critical enzymes in cell signal transduction but relatively little is known about the molecular recognition of the tyrosine substrate by these enzymes. Details of tyrosine substrate specificity within the context of a short peptide were investigated for protein tyrosine kinase Csk. It was found that aryl ring functional group substitutions the size of methyl group or smaller were generally well tolerated by the protein tyrosine kinase Csk whereas larger groups caused a decline in substrate efficiency. Extension of the phenol from the peptide backbone by a single methylene was acceptable for phosphorylation whereas removal of a methylene nearly abolished reactivity. Only the L-tyrosine derivative was processed. A negative charge ortho to the phenol hydroxyl was incompatible with substrate reactivity, consistent with previous pH rate profiles which indicated the importance of the neutral phenol. Overall, these studies confirmed the interpretation of a previous linear free energy relationship analysis which suggested that the enzyme followed a dissociative transition state mechanism. Copyright (C) 2000 Elsevier Science Ltd.
Pharmaceutically active fluoromethyltyrosine compounds
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, (2008/06/13)
This invention relates to novel monofluoromethyl- and difluoromethyltyrosine compounds which are active as tyrosine hydroxylase inhibitors and are therefore useful in the treatment of conditions caused by high levels of catecholamines such as hypertension
Syntheses ofDL-2-fluoromethy-P-tyrosine andDL-2-difluoromethyl-P-tyrosine as potential inhibitors of tyrosine hydroxylase
McDonald, Ian A.,Nyce, Philip L.,Jung, Michel J.,Sabol, Jeffrey S.
, p. 887 - 890 (2007/10/02)
The syntheses of the title compounds from 3,4-dimethylanisole and ethyl 5-hydroxy-2-methylbenzoate, respectively, are described.
