77153-05-0Relevant articles and documents
Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators
Keune, Willem-Jan,Potjewyd, Frances,Heidebrecht, Tatjana,Salgado-Polo, Fernando,Macdonald, Simon J. F.,Chelvarajan, Lakshman,Abdel Latif, Ahmed,Soman, Sony,Morris, Andrew J.,Watson, Allan J. B.,Jamieson, Craig,Perrakis, Anastassis
, p. 2006 - 2017 (2017/03/17)
Autotaxin produces the bioactive lipid lysophosphatidic acid (LPA) and is a drug target of considerable interest for numerous pathologies. We report the expedient, structure-guided evolution of weak physiological allosteric inhibitors (bile salts) into potent competitive Autotaxin inhibitors that do not interact with the catalytic site. Functional data confirms that our lead compound attenuates LPA mediated signaling in cells and reduces LPA synthesis in vivo, providing a promising natural product derived scaffold for drug discovery.
HYDRAZINYL-PYRROLO COMPOUNDS AND METHODS FOR PRODUCING A CONJUGATE
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Paragraph 00710; 00711, (2015/06/11)
The present disclosure provides conjugate structures and hydrazinyl-pyrrolo compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same. Aspects of the present disclosure include a pharmaceutical composition. The pharmaceutical composition includes a conjugate as described herein and a pharmaceutically acceptable excipient. Aspects of the present disclosure include a method of delivering a conjugate to a subject. The method includes administering to the subject an effective amount of a conjugate as described herein. Aspects of the present disclosure include a method of treating a condition in a subject.
Solid phase synthesis of peptide hydroxamic acids on poly(ethylene glycol)-based support
Cal, Marta,Jaremko, Mariusz,Jaremko, Lukasz,Stefanowicz, Piotr
, p. 9 - 15 (2013/02/25)
A novel resin designed for solid-phase synthesis of peptide hydroxamic acids (PHA) combining the trityl linker with poly(ethylene glycol)-based support, ChemMatrix type, is described. The synthesis of PHA can be performed according to a standard protocol,
Parallel synthesis of an oligomeric imidazole-4, 5-dicarboxamide library
Xu, Zhigang,DiCesare, John C.,Baures, Paul W.
supporting information; experimental part, p. 248 - 254 (2010/08/19)
A library of oligomeric compounds was synthesized based on the imidazole-4, 5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.
Efficient, solventless N-Boc protection of amines carried out at room temperature using sulfamic acid as recyclable catalyst
Upadhyaya, Dharita J.,Barge, Alessandro,Stefania, Rachele,Cravotto, Giancarlo
, p. 8318 - 8322 (2008/04/13)
A simple, rapid, and efficient protocol for the chemoselective N-Boc protection of amines using sulfamic acid as catalyst is described. N-Boc protection of various structurally diverse aliphatic, aromatic, alicyclic, and heterocyclic amines (1°, 2°, 3°) was carried out with (Boc)2O using sulfamic acid as catalyst (5 mol %) at room temperature under solventless conditions. The advantages of this method are simplicity, shorter reaction times (1-15 min), a cost-effective catalyst, and excellent isolated yields (90-100%); it is also environmentally benign. Moreover, the combined use of ultrasound and sulfamic acid achieves a synergic effect that is especially marked in the N-Boc protection of deactivated (sterically hindered and electron-deficient) amines. The catalyst possesses distinct advantages: ease of handling, cleaner reactions, high activity, and excellent chemoselectivity.
Design and synthesis of peptides passing through the blood-brain barrier
Wakamiya, Tateaki,Kamata, Makoto,Kusumoto, Shoichi,Kobayashi, Hiroyuki,Sai, Yoshimichi,Tamai, Ikumi,Tsuji, Akira
, p. 699 - 709 (2007/10/03)
The blood-brain barrier (BBB) is a highly selective membranous barrier regulating the transport of substances in blood into the brain parenchyma. At present, delivery of biologically active peptides or peptide drugs into the brain is quite an important subject from the standpoint of chemotherapy for brain diseases H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH2 termed 001-C8 was first synthesized to elucidate the structural specificity of peptides for passing through the BBB. The Na-methylamino acid and D-amino acid residues were appropriately situated in this peptide to protect against the digestion by peptidase. Furthermore, a number of basic peptides were prepared as 001-C8 analogs for studying the relationship between structure and BBB permeability of peptides.
Mild, efficient cleavage of arenesulfonamides by magnesium reduction
Nyasse, Barthelemy,Grehn, Leif,Ragnarsson, Ulf
, p. 1017 - 1018 (2007/10/03)
The cleavage of arenesulfonamides via N-arenesulfonylcarbamates is achieved within a few minutes under ultrasonic conditions by reaction with magnesium in anhydrous methanol.
Acylation of Dibasic Compounds Containing Amino Amidine and Aminoguanidine Functions
Barker, Peter L.,Gendler, Paul L.,Rapoport, Henry
, p. 2455 - 2465 (2007/10/02)
The site of acylation in difunctional compounds containing an amine and either an amidine or guanidine can be determined from the ultraviolet absorption spectrum of the acylated product.If the amidine or guanidine has been acylated, the product possesses a chromophore that is pH dependent, whereas if an amide was formed, the chromophore is independent of pH.
