2498-50-2Relevant articles and documents
Design, Synthesis, and Testing of Potent, Selective Hepsin Inhibitors via Application of an Automated Closed-Loop Optimization Platform
Pant, Shishir M.,Mukonoweshuro, Amanda,Desai, Bimbisar,Ramjee, Manoj K.,Selway, Christopher N.,Tarver, Gary J.,Wright, Adrian G.,Birchall, Kristian,Chapman, Timothy M.,Tervonen, Topi A.,Klefstr?m, Juha
supporting information, p. 4335 - 4347 (2018/05/14)
Hepsin is a membrane-anchored serine protease whose role in hepatocyte growth factor (HGF) signaling and epithelial integrity makes it a target of therapeutic interest in carcinogenesis and metastasis. Using an integrated design, synthesis, and screening platform, we were able to rapidly develop potent and selective inhibitors of hepsin. In progressing from the initial hit 7 to compound 53, the IC50 value against hepsin was improved from ~1 μM to 22 nM, and the selectivity over urokinase-type plasminogen activator (uPA) was increased from 30-fold to >6000-fold. Subsequent in vitro ADMET profiling and cellular studies confirmed that the leading compounds are useful tools for interrogating the role of hepsin in breast tumorigenesis.
A to prepare to aminobenzoic amidine hydrochloride method
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Paragraph 0056; 0057, (2017/02/02)
The invention relates to the technical field of pharmaceutical chemistry and provides a method for preparing p-amino-benzamidine hydrochloride. The method comprises the following steps: (1) p-nitrobenzonitfile II undergoes an amidining reaction in an amidining reagent I to obtain an intermediate p-nitrobenzene methylenimine III; (2) the intermediate p-nitrobenzene methylenimine III undergoes an amidining reaction in an amidining reagent II to obtain p-nitrobenzamidine IV; and (3) under an acidic condition, p-nitrobenzamidine IV undergoes a reduction reaction in a reaction solvent II by the use of a reducing agent to obtain p-amino-benzamidine hydrochloride. In the step (1), the amidining reagent I is thionyl chloride, phosphorus trichloride or phosphorus pentachloride; in the step (2), the amidining reagent II is ammonium carbonate, ammonium bicarbonate or ammonium chloride; and in the step (3), the reaction solvent II is a mixed solvent of water and alcohols. The synthetic method provided by the invention is safe and simple and has advantages of high yield and good product quality. The preparation method of p-amino-benzamidine hydrochloride is suitable for industrial production.
PROCESS FOR THE MANUFACTURE OF 4-AMINOBENZOAMIDINE DIHYDROCHLORIDE
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, (2014/05/24)
The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I), preferably the salts thereof with hydrochloric or hydrobromic acid, particularly preferred the dichloride salt.