222986-83-6

Upstream product

• 65-49-6 4-Aminosalicylic acid 
• 1666-28-0 4-bromosalicylic acid 
• 93830-58-1 diethyl (pyridin-4-yl)borane 

Relevant academic research and scientific papers

Bi-aryl analogues of salicylic acids: Design, synthesis and sar study to ameliorate endoplasmic reticulum stress

Introduction: Endoplasmic reticulum (ER) stress condition is characterized as the accu-mulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphtha-lene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods: Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results: Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion: Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases.

NOVEL ETHYLENEDIAMINE DERIVATIVES

A compound represented by the following formula (1):Q-Q-T-N(R)-Q-N(R)-T-Q [wherein, R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may have a substituent, or the like; Q2 is a single bond or the like; Q3 represents the following group: -C(R3a)(R4a)-{C(R3b)(R4b)}m1-{C(R3c)(R4c)}m2-{C(R3d)(R4d)}m3-{C(R3e)(R4e)}m4-C(R3f)(R4f)- (in which, R3a to R4e represent hydrogen or the like); T0 represents a carbonyl group or the like; and T1 represents -COCONR- or the like]; or salt thereof, solvate thereof, or N-oxide thereof. The compound is useful as a preventive and/or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites

Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1 mg/kg of compound 75b.

Sulfonyl derivatives

Sulfonyl derivatives represented by general formula (I), salts of the same, and solvates of both: and application of them as drugs: [wherein R1is hydrogen, hydroxyl, nitro or the like; R2and R3are each independently hydrogen, halogeno or the like; R4and R5are each dependently hydrogen, halogeno or the like; Q1is an optionally substituted saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group or the like; Q2is a single bond, oxygen or the like; Q3is, e.g., a group represented by formula (a): T1is carbonyl or the like; and X1and X2are each independently methylidyne or nitrogen]. These compounds exhibit potent Fxa inhibiting activities and serve as excellent anticoagulants which speedily exert satisfactory and persistent anti-thrombotic effects through oral administration and little cause adverse effects.

NOVEL SULFONYL DERIVATIVES

Sulfonyl derivatives represented by the following general formula (I): Q1-Q2-T1-Q3-SO2-QA and drugs containing the same (wherein Q1 is an optionally substituted, saturated or unsaturated, five- or six-membered cyclic hydrocarbon group, a five- or six-membered heterocyclic group, or the like; Q2 is a single band, oxygen, sulfur, C1-C6 alkylene or the like; QA is optionally substituted arylalkenyl, heteroarylalkenyl or the like; and T1 is carbonyl or the like). These compounds have potent FXa-inhibitory effects and promptly exert satisfactory and persistent antithrombotic effects through oral administration, thus being useful as anticoagulant agents little accompanied with side effects.