131105-91-4Relevant academic research and scientific papers
Antioxidant and antimicrobial assessment of synthesized and spectrally characterized new nitrophenothiazines and their sulfone analogues
Gautam, Naveen,Garg, Ankita,Bishnoi, Ajay Kumar,Agarwal, Shikha,Gautam, Dinesh Chand
, p. 528 - 536 (2015)
A series of new nitrophenothiazines and their sulfones were synthesized and their in vitro antimicrobial assessment was carried out against a representative panel of gram positive and gram negative bacterial strains and selected fungi species. The synthes
Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-1 ,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position
Yanagisawa,Fujimoto,Shimoji,Kanazaki,Mizutari,Nishino,Shiga,Koike
, p. 2055 - 2061 (2007/10/02)
In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hyperte
Novel, potent aldose reductase inhibitors: 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1- phthalazineacetic acid (zopolrestat) and congeners
Mylari,Larson,Beyer,Zembrowski,Aldinger,Dee,Siegel,Singleton
, p. 108 - 122 (2007/10/02)
A new working hypothesis that there is a hitherto unrecognized binding site on the aldose reductase (AR) enzyme with strong affinity for benzothiazoles was pursued for the design of novel, potent aldose reductase inhibitors (ARIs). The first application of this hypothesis led to a novel series of 3,4-dihydro-4-oxo-3-(benzothiazolylmethyl)-1-phthalazineacetic acids. The parent of this series (207) was a potent inhibitor of AR from human placenta (IC50 = 1.9 x 10-8 M) and was orally active in preventing sorbitol accumulation in rat sciatic nerve, in an acute test of diabetic complications (ED50 = 18.5 mg/kg). Optimization of this lead through medicinal chemical rationale, including analogy from other drug series, led to more potent congeners of 207 and culminated in the design of 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1- phthalazineacetic acid (216, CP-73,850, zopolrestat). Zopolrestat was found to be more potent than 207, both in vitro and in vivo. Its IC50 against AR and ED50 in the acute test were 3.1 x 10-9 M and 3.6 mg/kg, respectively. Its ED50s in reversing already elevated sorbitol accumulation in rat sciatic nerve, retina, and lens in a chronic test were 1.9, 17.6, and 18.4 mg/kg, respectively. It was well absorbed in diabetic patients, resulting in high blood level, showed a highly favorable plasma half-life (27.5 h), and is undergoing further clinical evaluation. An assortment of synthetic methods used for the construction of benzothiazoles, including an efficient synthesis of zopolrestat, is described. Structure-activity relationships in the new series are discussed.
