18598-74-8Relevant articles and documents
Optimization of N-Phenylpropenoyl- l -amino Acids as Potent and Selective Inducible Nitric Oxide Synthase Inhibitors for Parkinson's Disease
Hu, Xiao-Long,Lv, Xian-Yu,Wang, Rong,Long, Huan,Feng, Jia-Hao,Wang, Bao-Lin,Shen, Wei,Liu, Hao,Xiong, Fei,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
, p. 7760 - 7777 (2021/06/28)
N-Phenylpropenoyl-l-amino acids (NPAs) are inducible nitric oxide synthase (iNOS) inhibitors possessing preventive effects for Parkinson's disease (PD). Here, structural modifications for improving the iNOS inhibitory activity and blood-brain barrier (BBB) permeability of NPAs were conducted, leading to 20 optimized NPA derivatives (1-20). Compound 18, with the most potent activity (IC50 = 74 nM), high BBB permeability (Pe = 19.1 × 10-6 cm/s), and high selectivity over other NOS isoforms, was selected as the lead compound. Further studies demonstrated that 18 directly binds to iNOS. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced acute PD model, the oral administration of 18 (1 and 2 mg/kg) exerted preventive effects by alleviating the loss of dopaminergic (DAergic) neurons. Notably, in the MPTP-/probenecid-induced chronic PD model, the same dose of 18 also displayed a therapeutic effect by repairing the damaged DAergic neurons. Finally, good pharmacokinetic properties and low toxicity made 18 a promising candidate for the treatment of PD.
Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
, p. 1057 - 1072 (2020/08/13)
Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
Ligand-Enabled γ-C(sp3)–H Acetoxylation of Triflyl-Protected Amines
Jia, Wen-Liang,Fernández-Ibá?ez, M. ángeles
supporting information, p. 6088 - 6091 (2018/09/14)
A palladium-catalyzed γ-C(sp3)–H acetoxylation of triflyl-protected amines has been achieved. The use of pyridine or 2-alkoxyquinoline-type ligands is key to the success of this transformation. The reaction is highly diastereoselective and easily scalable, and constitutes a direct approach for the synthesis of γ-hydroxy-α-amino acids and β,γ-dihydroxy amines, which are not readily accessible by other routes.