Month: November 2022

He, Fazhong published the artcileTRIB3 rs6037475 is a potential biomarker for predicting felodipine drug response in Chinese patients with hypertension, Formula: C18H19Cl2NO4, the main research area is felodipine hypertension biomarker Chinese; Tribbles homolog 3 (TRIB3); felodipine; hypertension; individualized drug therapy; pharmacogenetics.

Background: In this study, we aimed at exploring and validating the effect of TRIB3 polymorphism on antihypertensive drugs responses. Methods: A total of 830 hypertensive patients, who were administered with open-labeled hydrochlorothiazide (12.5 mg once daily) and randomly assigned to off-labeled felodipine (5 mg) or a matched placebo combination treatment (1:1), were selected from the Felodipine Event Reduction (FEVER) study. A strategy of screening 259 samples and validating the remaining 531 samples was implemented. Results: We found that TRIB3 rs6037475 CC genotype was associated with a reduction of diastolic blood pressure (DBP) (P=6.3×10-3) in the felodipine treatment group of screening set, and was also associated with a reduction of systolic blood pressure (SBP) (P=0.021), DBP (P=6.0×10-3) and mean arterial pressure (MAP) (P=0.021) in the felodipine treatment group of the validation set. Combined screening and validation set anal. found that patients with TRIB3 rs6037475 CC genotype had a significant higher mean SBP, DBP and MAP than those with TT genotype in the felodipine treatment group (CC vs. TT -10.2±0.74 vs. -17.8±0.21, P=7.8×10-3; -4.6±0.50 vs. -10.2±0.23, P=3.0×10-4; -6.5±0.54 vs. -12.7±0.14, P=3.0×10-4, resp.). Conclusions: These results suggest that TRIB3 rs6037475 genetic variation can be useful as a bio-marker for predicting felodipine drug response in Chinese patients with hypertension.

Annals of Translational Medicine published new progress about Antihypertensives. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Yongle published the artcileBenidipine, an anti-hypertensive drug, relaxes mouse airway smooth muscle, Computed Properties of 21829-25-4, the main research area is benidipine antihypertensive agent airway smooth muscle; Airway smooth muscle; Benidipine; Ca(2+) influx; L-type voltage-dependent Ca(2+) channels; Non-selective cation channels; Relaxation.

Benidipine is a dihydropyridine (DHP) derived Ca2+ antagonist, can block triple Ca2+ channels (L, N, and T). It has been used as a safety anti-hypertensive drug because of its long-acting relaxant effect on vascular smooth muscle (VSM). However, whether benidipine has similar pharmacol. actions in airway smooth muscle (ASM) is unknown. This research aims to reveal the relaxant property and Ca2+ antagonistic effect of benidipine on ASM. The relaxant property of mouse ASM was investigated by tissue tension tests, and Ca2+ antagonistic effect was evaluated through patch-clamp techniques. Benidipine caused dose-dependent relaxations on high K+ (80 mM) induced precontraction in mouse ASM, which relied on inhibition of extracellular Ca2+ influx, and 1μM benidipine totally blocked L-type voltage-dependent Ca2+ channels (LVDCCs) currents in airway smooth muscle cells (ASMCs). Benidipine also showed dose-dependent inhibition of ACh-induced precontraction with or without the LVDCCs blocker nifedipine, and 100μM benidipine blocked ACh-stimulated Ca2+ influx through not only LVDCCs but also non-selective cation channels (NSCCs). Benidipine blocked LVDCCs and NSCCs to abolish these channels-mediated Ca2+ influx, which relaxed precontracted ASM. This study represented benidipine with a new potential medicinal value for ASM hypercontractility.

Life Sciences published new progress about Antihypertensives. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Computed Properties of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Cui, Haiming published the artcileThe effects of renin-angiotensin system inhibitors (RASI) in coronavirus disease (COVID-19) with hypertension: A retrospective, single-center trial, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is human covid19 renin angiotensin system inhibitor; Coronavirus disease 2019; Enfermedad Coronavirus 2019; Hipertensión; Hypertension; Renin-inhibidores del sistema de angiotensina; Renin–angiotensin system inhibitors.

A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension.In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clin. Center from Jan. 25, 2020 to Jan. 31, 2020, were analyzed for clin. features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. Comparing the two groups, we did not found statistically significant differences in clin. symptoms and laboratory tests. Furthermore, cough was not aggravated. Through the anal. of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further anal. with a larger sampling size is required to explore the underlying mechanisms.

Medicina Clinica published new progress about Antihypertensives. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Yifan published the artcileInvolvement of p75NTR in the effects of Aβ on L-type Ca2+ channel in cultured neuronal networks, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is NTR calcium channel cultured neuronal network; AD; Aβ; L-type Ca(2+) channel; p75NTR.

Ca2+ overload in neurons has been implicated in Alzheimer’s Disease (AD). Upregulation of Ca2+ through L-type Ca2+ channels was known to be involved in the neurodegeneration induced by amyloid-β (Aβ) peptides in AD. However, little is known about the mechanism by which upregulation of L-type Ca2+ channel currents is linked to Aβ-induced neuronal toxicity. In the present study, we found that the L-type Ca2+ current in transgenic AD mice (Tg2576) neurons is greater than in wild-type (WT) neurons, and this Ca2+ channel current change were rescued in Tg2576/p75NTR+/- (p75 neurotrophin receptor) neurons. We further examined the changes in the gating of L-type Ca2+ channels following Aβ42 treatment, and the results showed that the L-type Ca2+ channel current was significantly increased by Aβ42 treatment in WT hippocampal neurons. Blocking or decreasing the expression of p75NTR eliminated the influence of Aβ42 on the L-type Ca2+ channel current in WT hippocampal neurons. We also evaluated how Aβ42 affected the voltage-dependent activation and inactivation of L-type Ca2+ channels in cultured WT neurons. The results indicated that the half-maximal activation voltage (V1/2) was left shifted, and the half-inactivation voltage (V1/2) displayed a right shift in neuron treated by Aβ42. Decreasing the expression of p75NTR eliminated the effect of Aβ42 on voltage-dependent activation and inactivation of the L-type Ca2+ channel. These results indicate that Aβ42 changes L-type Ca2+ channel currents by modulating the channel’s activation and inactivation dynamics, while decreasing p75NTR expression can remove this effect.

Life Sciences published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Cumming, Jared N. published the artcileStructure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor, Quality Control of 917471-30-8, the main research area is iminohydantoin imidazolidinone propynylpyridinylphenyl preparation BACE1 inhibitor Alzheimers.

From an initial lead 2-imino-1-methyl-4,4-diphenyl-5-imidazolidinone, a structure-based design approach led to identification of the novel, high-affinity iminohydantoin BACE1 inhibitor I that lowers CNS-derived Aβ following oral administration to rats. SAR development in the S3 and F’ subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for I are reported.

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Quality Control of 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

de Jong, Daan L. K. published the artcileEffects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease: A Randomized Trial, Product Details of C17H18N2O6, the main research area is Alzheimers disease nilvadipine cerebral blood flow; Alzheimer disease; blood pressure; disease progression; hippocampus; nilvadipine.

Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 mo of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest including the hippocampus. Fifty-eight patients were randomly assigned (29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medication compliant over 6 mo. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ = -11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ = 5.4 [95% CI, -6.4 to 17.2] mL/100 g per min; P = 0.36). CBF in the hippocampus increased (left: Δ = 24.4 [95% CI, 4.3-44.5] mL/100 g per min; P = 0.02; right: Δ = 20.1 [95% CI, -0.6 to 40.8] mL/100 g per min; P = 0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ = 5.2 [95% CI, -16.5 to 27.0] mL/100 g per min; P = 0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Hypertension published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Dyer, Adam H. published the artcileIs ongoing anticholinergic burden associated with greater cognitive decline and dementia severity in mild to moderate alzheimer’s Disease?, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nilvadipine anticholinergic agent cognition dementia Alzheimer disease; Alzheimers; Cognitive aging; Drug related; Medication.

Use of anticholinergic medication is associated with an increased risk of cognitive impairment and/or dementia. Despite this, the impact of continuing medication with anticholinergic properties in those diagnosed with Alzheimer’s Disease (AD) is not clear. Anal. of data from NILVAD, an 18-mo randomized controlled trial of Nilvadipine in AD. Effects of ongoing Anticholinergic Cognitive Burden (ACB) on cognition (ADAS-Cog: Alzheimer’s Disease Cog Subsection) and dementia severity (CDR-sb: Clin. Dementia Rating – Sum of Boxes/DAD: Disability Assessment for Dementia) over 18 mo was evaluated adjusting for important clin. covariates. Just over one-quarter (27.90%, n = 142/510) of patients with mild to moderate AD were prescribed a potential/definite anticholinergic. While ACB score was not associated with greater progression on the ADAS-Cog/CDR-sb over time, a higher total ACB predicted greater dementia severity on the DAD, which persisted after robust covariate adjustment (β Coef: -1.53, 95% CI: -2.83 to -0.23, p = .021). There was a significant interaction between APOE ε4 status and ACB score, with carriers experiencing greater progression on both the CDR-Sb (β Coef: 0.36, 95% CI: 0.05-0.67, p = .021) and DAD (β Coef: -3.84, 95% CI: -7.65 to 0.03, p = .049). Ongoing use of anticholinergic medication was associated with greater dementia progression on the DAD, but not the CDR-sb. APOE ε 4 carriers may be particularly vulnerable to the effect of ongoing anticholinergic medication on dementia severity, with significant APOE ε 4 x ACB score interactions demonstrated on both the DAD and CDR-sb.

Journals of Gerontology, Series A: Biological Sciences and Medical Sciences published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

de Heus, Rianne A. A. published the artcileBlood pressure lowering with nilvadipine in patients with mild-to-moderate Alzheimer disease does not increase the prevalence of orthostatic hypotension, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Alzheimer disease orthostatic hypotension nilvadipine blood pressure; Alzheimer disease; adverse drug event; antihypertensive agent; calcium channel blocker; orthostatic hypotension; randomized controlled trial.

This secondary anal. of randomized controlled trial assessed whether antihypertensive treatment increases prevalence of orthostatic hypotension in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 wk. Presence of OH (blood pressure drop â‰?0/â‰?0 mm Hg after 1 min of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 ± 8.2 years and mean Mini-Mental State Examination score was 20.4 ± 3.8. Baseline blood pressure was 137.8 ± 14.0/77.0 ± 8.6 mm Hg. Grade I hypertension was present in 53.4%. After 13 wk, blood pressure had fallen by 7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo . Across the 78-wk intervention period, there was no difference between groups in the proportion of patients with OH at study visit, nor in proportion of visits where a patient met criteria for OH, corrected for number of visits. OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.

Journal of the American Heart Association published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mandal, Mihirbaran published the artcileDesign and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme-1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation, Synthetic Route of 917471-30-8, the main research area is bicyclic iminopyrimidinone preparation BACE1 inhibitor amyloid Alzheimer’s.

On the basis of our observation that the biaryl substituent of iminopyrimidinone 7 must be in a pseudoaxial conformation to occupy the contiguous S1-S3 subsites of BACE1, we have designed a novel fused bicyclic iminopyrimidinone scaffold intended to favor this bioactive conformation. Strategic incorporation of a nitrogen atom in the new constrained ring allowed us to develop SAR around the S2′ binding pocket and ultimately resulted in analogs with low nanomolar potency for BACE1. In particular, optimization of the prime side substituent led to major improvements in potency by displacement of two conserved water mols. from a region near S2′. Further optimization of the pharmacokinetic properties of this fused pyrrolidine series, in conjunction with facile access to a rat pharmacodynamic model, led to identification of compound 43, which is an orally active, brain penetrant inhibitor that reduces Aβ40 in the plasma, CSF, and cortex of rats in a dose-dependent manner.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Synthetic Route of 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ciordia, Myriam published the artcileApplication of Free Energy Perturbation for the Design of BACE1 Inhibitors, Product Details of C8H8BNO2, the main research area is free energy perturbation calculation BACE1 inhibitor drug design Alzheimer.

Novel spiroaminodihydropyrroles probing for optimized interactions at the P3 pocket of β-secretase 1 (BACE1) were designed with the use of free energy perturbation (FEP) calculations The resulting mols. showed pIC50 potencies in enzymic BACE1 inhibition assays ranging from approx. 5 to 7. Good correlation was observed between the predicted activity from the FEP calculations and exptl. activity. Simulations run with a default 5 ns approach delivered a mean unsigned error (MUE) between prediction and experiment of 0.58 and 0.91 kcal/mol for retrospective and prospective applications, resp. With longer simulations of 10 and 20 ns, the MUE was in both cases 0.57 kcal/mol for the retrospective application, and 0.69 and 0.59 kcal/mol for the prospective application. Other considerations that impact the quality of the calculations are discussed. This work provides an example of the value of FEP as a computational tool for drug discovery.

Journal of Chemical Information and Modeling published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Product Details of C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem