New Treatments for Incontinence

MacLachlan, Lara S.

doi:10.1053/j.ackd.2015.03.003

Cited by 13 publications

(3 citation statements)

References 61 publications

(66 reference statements)

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“…This metaphor was able to bind TAR RNA with a high affinity for the HIV type-1 tat protein ( Figure 55) [180]. Squaramides have been used to design a novel series of adenosine 5'-triphosphate-sensitive potassium (KATP) channel openers for the treatment of urge urinary incontinence (UUI) [181]. Furthermore, these studies identified that the N-cyanoguanidine moiety of pinacidil can be replaced with a squaramide to give the analogue ( Figure 56) [112].…”

Section: Structure Of Squaramide Hgc-27mentioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

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Section: Structure Of Squaramide Hgc-27mentioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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“…19 Among treated patients, drug side effects (e.g., dry mouth, constipation, reduced ejaculation), morbidity associated with surgery, co-morbid illnesses, cost and many other factors can negate the benefits of intervention across LUTS conditions. For urinary incontinence (UI), first-line treatments—including pelvic floor muscle training for stress UI (SUI) and behavioral therapy for urgency UI (UUI)—improve outcomes in many patients 21 but depend in large part on the patient's ability to self-manage, which is affected by psychological, cognitive, and social factors. Many second and third-line treatments for SUI and UUI have inconsistent outcomes, uncertain durability, and high risk of complications.…”

Section: Challenges With Current Treatment Of Lutsmentioning

confidence: 99%

“…Many second and third-line treatments for SUI and UUI have inconsistent outcomes, uncertain durability, and high risk of complications. 2122 For LUTS associated with benign prostatic hyperplasia (BPH), randomized clinical trials (RCT) have demonstrated the efficacy of commonly used pharmacologic therapies in men, but the beneficial effects of treatment may not be generalizable, can be costly because of long-term use, and produce numerous, often intolerable side-effects, which reduces adherence. 23 For interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), numerous medical interventions have been proposed; however, effective treatment remains elusive.…”

Section: Challenges With Current Treatment Of Lutsmentioning

confidence: 99%

Advancing a Comprehensive Approach to the Study of Lower Urinary Tract Symptoms

et al. 2016

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Purpose Lower urinary tract symptoms (LUTS) are common in the United States leading to a significant economic, quality-of-life, and public health burden. This burden will increase as the population ages and risk factors for LUTS such as diabetes and obesity remain highly prevalent. Improving clinical management and establishing the knowledge base to prevent LUTS will require a comprehensive research approach that examines factors beyond the lower urinary tract (LUT). While the study of these “extra-LUT” factors has increased recently, current urologic research does not systematically account for the broad set of potential LUTS contributors that span biologic, behavioral, psychological/executive function, and sociocultural factors. A comprehensive assessment of potential contributors to LUTS risk, treatment response, and progression is necessary to reduce the burden of this condition within the United States. Materials and Methods We consider challenges to continuing the predominantly LUT dysfunctioncentric approach that has dominated previous LUTS research, and propose a new, comprehensive framework for future urology research that includes a broader set of potential LUTS contributors. Results and Conclusions This comprehensive approach should help reduce the medical and economic burden of LUTS in the U.S. population.

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