Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension

Wong, Gavin WK; Boyda, Heidi N.; Wright, James M

doi:10.1002/14651858.cd007450.pub2

Cited by 18 publications

(6 citation statements)

References 29 publications

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“…Phentolamine, 35 an anti-hypertensive drug ( 11i ), also reacted efficiently. Lastly, indolebased molecules such as pindolol ( 11j , a β-blocker) 36 and serotonin ( 11k , a neurotransmitter) 37 provided the corresponding products in high yields in the presence of the copper reagent.…”

Section: Resultsmentioning

confidence: 99%

A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins

et al. 2018

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Conjugates between proteins and small molecules enable access to a vast chemical space that is not achievable with either type of molecule alone; however, the paucity of specific reactions capable of functionalizing proteins and natural products has presented a formidable challenge for preparing conjugates. Here we report a strategy for conjugating electron-rich (hetero)arenes to polypeptides and proteins. Our bioconjugation technique exploits the electrophilic reactivity of an oxidized selenocysteine residue in polypeptides and proteins, and the electron-rich character of certain small molecules to provide bioconjugates in excellent yields under mild conditions. This conjugation chemistry enabled the synthesis of peptide-vancomycin conjugates without prefunctionalization of vancomycin. These conjugates had enhanced in vitro potency for resistant Gram-positive and Gram-negative pathogens. Additionally, we showed that a 6 kDa affibody protein and a 150 kDa IgG antibody could be modified without diminishing bioactivity.

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Section: Resultsmentioning

confidence: 99%

A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins

et al. 2018

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“…first-line therapy for hypertension. [56][57][58][59][60][61][62] In total, these meta-analyses included 316 RCTs. We excluded the trials and trial arms of medications and medication dosages that were not indicated in the BNF.…”

Section: Evidence Base For Medicationsmentioning

confidence: 99%

How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 randomised controlled trials assessing exercise and medication effects on systolic blood pressure

et al. 2018

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ObjectiveTo compare the effect of exercise regimens and medications on systolic blood pressure (SBP).Data sourcesMedline (via PubMed) and the Cochrane Library.Eligibility criteriaRandomised controlled trials (RCTs) of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-2 receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs) and diuretics were identified from existing Cochrane reviews. A previously published meta-analysis of exercise interventions was updated to identify recent RCTs that tested the SBP-lowering effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions (up to September 2018).DesignRandom-effects network meta-analysis.OutcomeDifference in mean change from baseline SBP between comparator treatments (change from baseline in one group minus that in the other group) and its 95% credible interval (95% CrI), measured in mmHg.ResultsWe included a total of 391 RCTs, 197 of which evaluated exercise interventions (10 461 participants) and 194 evaluated antihypertensive medications (29 281 participants). No RCTs compared directly exercise against medications. While all medication trials included hypertensive populations, only 56 exercise trials included hypertensive participants (≥140 mmHg), corresponding to 3508 individuals. In a 10% random sample, risk of bias was higher in exercise RCTs, primarily due to lack of blinding and incomplete outcome data. In analyses that combined all populations, antihypertensive medications achieved higher reductions in baseline SBP compared with exercise interventions (mean difference −3.96 mmHg, 95% CrI −5.02 to −2.91). Compared with control, all types of exercise (including combination of endurance and resistance) and all classes of antihypertensive medications were effective in lowering baseline SBP. Among hypertensive populations, there were no detectable differences in the SBP-lowering effects of ACE-I, ARB, β-blocker and diuretic medications when compared with endurance or dynamic resistance exercise. There was no detectable inconsistency between direct and indirect comparisons. Although there was evidence of small-study effects, this affected both medication and exercise trials.ConclusionsThe effect of exercise interventions on SBP remains under-studied, especially among hypertensive populations. Our findings confirm modest but consistent reductions in SBP in many studied exercise interventions across all populations but individuals receiving medications generally achieved greater reductions than those following structured exercise regimens. Assuming equally reliable estimates, the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications. Generalisability of these findings to real-world clinical settings should be further evaluated.

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“…We believe that this is the first example of C2-selective tryptophan deuteration. Efficient C2- and C3-deuteration of the clinically approved beta blocker pindolol/Visken was achieved ( 4l : 57% D incorporation at C2 and 34% at C3); however, no reduction of C3-deuteration was observed after treatment with K 2 CO 3 , even when 3 equivalents of the base were used.…”

Section: Reaction Scopementioning

confidence: 99%

Programmable Deuteration of Indoles via Reverse Deuterium Exchange

et al. 2023

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Methods for selective deuterium incorporation into drug-like molecules have become extremely valuable due to the commercial, mechanistic, and biological importance of deuterated compounds. Herein, we report a programmable labeling platform that allows access to C2, C3, or C2-and C3deuterated indoles under mild, user-friendly conditions. The C2-deuterated indoles are accessed using a reverse hydrogen isotope exchange strategy which represents the first non-directed C2-deuteration of indoles.

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Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension

Cited by 18 publications

References 29 publications

A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins

A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins

How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 randomised controlled trials assessing exercise and medication effects on systolic blood pressure

Programmable Deuteration of Indoles via Reverse Deuterium Exchange

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