Search results for "Acetanilide"

ortho-Substituent effects inN-arylacetamides. NMR and molecular mechanics investigation

1995

1H, 13C, 15N and 17O NMR spectra of N-phenylacetamide (acetanilide) and 21 ortho-substituted acetanilides were measured and assigned. The observed NMR parameters are related to the Hammett substituent parameters and conformational characteristics of the acetamido moiety estimated by molecular mechanics calculations. Significant relationships were found for the 13C NMR chemical shifts of C-5 (para to substituent) and the direct spin–spin coupling constant, 1J(C, H), of C-3 (ortho to substituent) with Hammett substituent parameters. For 15N NMR chemical shifts of the amido nitrogen, no general correlation with the Hammett substituent parameters was found. The interactions between functionalit…

Hsp60 Inhibitors and Modulators

2019

In this chapter, we focus on the 60 KDa Heat Shock Protein (Hsp60) and discuss some of its biological, molecular and pathological features. The structural and mechanistic aspect of the Hsp60 folding cycle will be also presented. We further illustrate how Hsp60 may be involved in many diseases and therefore considered as an effective therapeutic or theranostic target. Finally, the state-of-the-art on the development of Hsp60 and bacterial GroEL inhibitors and modulators of their expression will be illustrated. This is discussed in the light of a negative chaperonotherapy, and the consequent development of inhibitors, as well as positive chaperonotherapy, in the event its excessive activity i…

Lower Urinary Tract Symptoms: What's New in Medical Treatment?

2018

Abstract Context Pharmacological treatment is a cornerstone in the management of patients with lower urinary tract symptoms (LUTS). Objective To review emerging evidence in the medical treatment of LUTS. Evidence acquisition An Embase/Pubmed-based literature search was conducted in December 2017, screening for randomized controlled trials (RCTs), prospective and retrospective series, animal model studies, and reviews on medical treatment of LUTS. Evidence synthesis The main medical innovation in recent years in overactive bladder (OAB) has been the approval of the first β 3 -adrenoceptor agonists (mirabegron) and intradetrusor onabotulinum toxin A, while several other drugs such as antiepil…

Hsp60 chaperonopathies and chaperonotherapy: targets and agents

2014

Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms.Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed.The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pa…

Safety and tolerability of β3-adrenoceptor agonists in the treatment of overactive bladder syndrome - insight from transcriptosome and experimental s…

2016

We have reviewed the safety and tolerability of β3-adrenoceptor agonists, specifically mirabegron and solabegron, a newly emerging drug class for the treatment of the overactive bladder syndrome. We discuss them mechanistically in the context of expression and other preclinical data.Based on a systematic PubMed search, incidence of overall adverse events, hypertension, dry mouth, and constipation are comparable between mirabegron or solabegron and placebo. Hypertension is the most frequently observed adverse event, but has a similar incidence with mirabegron and placebo. Nevertheless, severe uncontrolled hypertension has become a contraindication for use of mirabegron based on observation o…

Lorcainide; II. Plasma concentration-effect relationship

1979

On the spectral intermediate at 440 nm formed during mixed function substrate oxidation.

1974

Abstract The spectral shoulder formed at 440 nm in microsomes oxidising hexobarbital and other drugs has been investigated and some of its properties characterised. Hexobarbital, pentobarbital, ethylmorphine and barbital produce this shoulder, while acetanilide, aniline, desmethylimipramine, imipramine, metyrapone and SKF 525-A do not. The formation of the 440 nm shoulder depends on the presence of NADPH and oxygen and is reduced in size when NADH is also present. At saturating substrate concentrations the size of the 440 nm shoulder is correlated to the cytochrome P-450 content. The hexobarbital induced shoulder can be inhibited by drug metabolism inhibitors such as metyrapone, imipramine …

Bioconcentration, metabolism and toxicity of substituted anilines in the zebrafish (Brachydanio rerio).

1991

The LC50 (96 h) values and the bioconcentration factors (BCF) for nine anilines (aniline; 2-, 3-, 4-chloroaniline; 2-, 3-, 4-nitroaniline; 2,4- and 3,4-dichloroaniline) in the zebrafish (Brachydanio rerio) were determined. Biotransformation products of anilines in the zebrafish were analyzed by HPLC. The aim of the investigations was to find relationships between accumulation/elimination/metabolism and toxicity on the one hand and between chemical structure and biotransformation on the other. We found a good correlation of log BCF and of log Pow with log LC50. This concurs with the assumption that the internal dose determines the toxicological effect. All anilines investigated, with the exc…

Aqueous coefficient calculations for chemicals and drugs

1999

Aqueous functional group activity coefficients (AQUAFAC) is a group‐contribution method for estimating the aqueous coefficients. We have written a program for the calculation of these coefficients. The solubility S w of alkanes shows variation of 8 orders of magnitude. The comparison with experiment shows that AQUAFAC gives good S w estimations. For 4'‐substituted acetanilides, I‐, Br‐, nitro‐, Cl‐, F‐ and methoxy‐substituents decrease S w, while formyl‐ and amino‐substituents increase S w. For acetaminophen esters, S w decreases from the acetate to the decanoate. The S w of 29 barbiturates shows typical errors of 0.4 log S w units. For the cyclo‐alkane‐l’,5‐spirobarbituric acids, S w decre…

TRPA1 channel is a cardiac target of mIGF-1/SIRT1 signaling.

2014

Cardiac overexpression of locally acting muscle-restricted (m)IGF-1 and the consequent downstream activation of NAD+-dependent protein deacetylase sirtuin 1 (SIRT1) trigger potent cardiac antioxidative and antihypertrophic effects. Transient receptor potential (TRP) cation channel A1 (TRPA1) belongs to the TRP ion channel family of molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce pain. Recently, it has been shown that TRPA1 activity influences blood pressure, but the significance of TRPA1 in the cardiovascular system remains elusive. In the present work, using genomic screening in mouse hearts, we found that TRPA1 is a target of mIGF-1/SIRT1 sign…