29602-00-4Relevant academic research and scientific papers
Photochemistry of 2-hydroxy-4-trifluoromethylbenzoic acid, major metabolite of the photosensitizing platelet antiaggregant drug triflusal
Bosca,Cuquerella,Marin,Miranda
, p. 463 - 468 (2001)
Triflusal is a platelet antiaggregant drug with photoallergic side effects. However, it is considered a prodrug since it is metabolized to 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) - the pharmacologically active form. HTB was found to be photolabile under various conditions. Its major photodegradation pathway appears to be the nucleophilic attack at the trifluoromethyl moiety. The involvement of the triplet state in the photodegradation has been unequivocally proved by direct detection of this transient in laser flash photolysis and by quenching experiments with oxygen, cyclohexadiene and naphthalene. Finally, the photobinding of HTB to proteins such as bovine serum albumin has been demonstrated using ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. Nucleophilic groups present in the protein appear to be responsible for the formation of covalent drug photoadducts, which is the first step involved in the photoallergy shown by triflusal.
Novel, Self-Assembling Dimeric Inhibitors of Human β Tryptase
Giardina, Sarah F.,Werner, Douglas S.,Pingle, Maneesh,Feinberg, Philip B.,Foreman, Kenneth W.,Bergstrom, Donald E.,Arnold, Lee D.,Barany, Francis
, p. 3004 - 3027 (2020/04/17)
β-Tryptase, a homotetrameric serine protease, has four identical active sites facing a central pore, presenting an optimized setting for the rational design of bivalent inhibitors that bridge two adjacent sites. Using diol, hydroxymethyl phenols or benzoyl methyl hydroxamates, and boronic acid chemistries to reversibly join two [3-(1-acylpiperidin-4-yl)phenyl]methanamine core ligands, we have successfully produced a series of self-assembling heterodimeric inhibitors. These heterodimeric tryptase inhibitors demonstrate superior activity compared to monomeric modes of inhibition. X-ray crystallography validated the dimeric mechanism of inhibition, and compounds demonstrated high selectivity against related proteases, good target engagement, and tryptase inhibition in HMC1 xenograft models. Screening 3872 possible combinations from 44 boronic acid and 88 diol derivatives revealed several combinations that produced nanomolar inhibition, and seven unique pairs produced greater than 100-fold improvement in potency over monomeric inhibition. These heterodimeric tryptase inhibitors demonstrate the power of target-driven combinatorial chemistry to deliver bivalent drugs in a small molecule form.
AB type hydroxyl-modified polymer of a monomer and its midbody and preparation method
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, (2016/10/08)
The invention discloses monomers and intermediates of an AB type hydroxyl modified high polymer, and preparation methods of the monomers and the intermediates. The intermediates include methyl o-hydroxyl p-carboxyl benzoate (I) and m-hydroxyl p-methoxycarbonyl benzoyl chloride (I'). The monomers of the AB type hydroxyl modified high polymer include a monomer (IV) of AB type hydroxyl modified PPTA (Poly-p-Phenylene Terephthamide) and a monomer (VIII) of AB type hydroxyl modified PBO (Poly-p-phenylenebenzobisthiazole), wherein R1 is H, R2 is OH, or R1 is OH and R2 is OH, and R is CH3 or C2H5. Due to introduction of hydroxyl in the AB type monomer, the light resistance, the composite cohesiveness and the axial pressure resistance of a high polymer prepared from the AB type hydroxyl modified high polymer can be improved, and moreover the preparation methods of the intermediate and the monomer have the characteristics of high yield, high selectivity and industrial production accordance.
COFLUORONS AND METHODS OF MAKING AND USING THEM
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Page/Page column, (2014/06/24)
The present invention is directed to method of using a collection of monomers capable of forming multimers as a fluorescence reporter in different applications such as ligand detection/screening, disease diagnosis, drug discovery or screening, fluorescent labeling and imaging, or other fluorescent methodologies. Each monomer in the collection includes one or more ligand elements useful for binding to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the ligand elements directly or indirectly through a connector. Association of linker elements of different combinations of monomers, with their ligand elements bound to the target molecule to form a multimer, will generate a unique fluorescent signature different from that produced by those monomers either alone or in association with each other in the absence of the target molecule, when subjected to electromagnetic excitement.
MONOMERS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
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Paragraph 0442-0443, (2014/07/22)
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.
Isolation of bright blue fluorescent substances from sonochemical hydroxylation of methyl p-cyanobenzoate
Yamada, Sachiko,Hokari, Hajime,Akasaka, Shinji,Iwamura, Michiko
, p. 197 - 198 (2007/10/03)
Sonochemical hydroxylation of methyl p-cyanobenzoate (1a) in water gave a bright blue fluorescence, which are mainly ascribed to three new fluorescent compounds, 3-hydroxy, 2,3- and 2,5-dihydroxy derivatives of 1a. Other benzenes substituted with electron-withdrawing groups also gave similar fluorescence from their hydroxylated derivatives. Among the fluorescence substances, methyl 2,5-dihydroxybenzoate was supposed to be applicable for a fluorescent chemosensor.
Carboxylic acid derivative
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, (2008/06/13)
Carboxylic acid derivatives having potent retinoid-type pharmacological activities are disclosed. The compounds disclosed are represented by the following formula: STR1 wherein R 1, R 2, and R 3 independently represent a hydrogen atom or an alkyl group wi
Carboxylic acid derivatives having retinoic acid-like activity
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, (2008/06/13)
Carboxylic acid derivatives having potent retinoid-type pharmacological activities are disclosed. The compounds disclosed are represented by the following formula: wherein R1, R2, and R3 independently represent a hydrogen atom or an alkyl group with the e
