Effects of substitution on 9-(3-bromo-4-fluorophenyl)-5,9-dihydro-3H,4H-2,6-dioxa-4- azacyclopenta[b]naphthalene-1,8-dione, a dihydropyridine ATP-sensitive potassium channel opener. | LitMetric
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6123, USA.
Published: November 2006
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Article Abstract
Structure-activity relationships were investigated on the tricyclic dihydropyridine (DHP) KATP openers 9-(3-bromo-4-fluorophenyl)-5,9-dihydro-3H,4H-2,6-dioxa-4-azacyclopenta[b]naphthalene-1,8-dione (6) and 10-(3-bromo-4-fluorophenyl)-9,10-dihydro-1H,8H-2,7-dioxa-9-azaanthracene-4,5-dione (65). Substitution off the core of the DHP, absolute stereochemistry, and aromatic substitution were evaluated for KATP channel activity using Ltk- cells stably transfected with the Kir6.2/SUR2B exon 17- splice variant and in an electrically stimulated pig bladder strip assay. A select group of compounds was evaluated for in vitro inhibition of spontaneous bladder contractions. Several compounds were found to have the unique characteristic of partial efficacy in both the cell-based and electrically stimulated bladder strip assays but full efficacy in inhibiting spontaneous bladder strip contractions. For compound 23b, this profile was mirrored in vivo where it was fully efficacious in inhibiting spontaneous myogenic bladder contractions but only partially able to reduce neurogenically mediated reflex bladder contractions.
Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia in Katowice, 9 Bankowa St., 40-007 Katowice, Poland.
The (bladderworts) species are carnivorous plants that prey mainly on invertebrates using traps (bladders) of leaf origin. On the outer surfaces of the trap, there are dome-shaped glands (capitate trichomes). Each such trichome consists of a basal cell, a pedestal cell, and a terminal cell.
Javed E, Thangavel C, Frara N, et al. Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2. The FASEB Journal.
Objectives: This study aimed to identify the level of spirituality, faith and meaning, and quality of life (QOL) among Muslim advanced cancer patients undergoing active treatment and to enhance the understanding of the relationships among clinical and socio-demographic factors, spirituality, and QOL of patients in the Gaza Strip.
Methods: A secondary analysis was conducted on a convenience sample of 298 advanced cancer patients. The Arabic versions of the Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Functional Assessment of Cancer Therapy-General (FACT-G) were used for data collection.
Inhibition of inflammation is crucial for treating interstitial cystitis (IC), and NK1R antagonists, like fosaprepitant (FOS), show promise in managing inflammatory diseases.
In a study, mice with cystitis induced by cyclophosphamide (CP) were treated with FOS, resulting in improved bladder function and reduced inflammatory markers.
FOS significantly decreased myeloperoxidase (MPO) activity and TLR4 expression in the bladder, suggesting its role in reducing inflammation and promoting recovery in IC models.
Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), have an unclear impact on bladder mucosal physiology. This study investigates UPEC's effects on the urothelium and lamina propria using an ex vivo porcine bladder model. Bladder mucosal strips were analysed for contractile responses to acetylcholine, serotonin, and neurokinin A.
