A5011497691- Cardiac electrophysiology and arrhythmias
- Corporate Taxation and Avoidance
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer Treatment and Pharmacology
- Chemical synthesis and alkaloids
- Synthetic Organic Chemistry Methods
- Ion channel regulation and function
- Catalytic C–H Functionalization Methods
- Atrial Fibrillation Management and Outcomes
- Taxation and Legal Issues
- Apelin-related biomedical research
- Diabetes Management and Research
- Pharmacology and Obesity Treatment
- Lipoproteins and Cardiovascular Health
- Alkaloids: synthesis and pharmacology
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Advanced Synthetic Organic Chemistry
- Gut microbiota and health
- Synthesis and Catalytic Reactions
- Eicosanoids and Hypertension Pharmacology
- Finance, Taxation, and Governance
- Cryospheric studies and observations
- Nuclear Receptors and Signaling
- Avian ecology and behavior
- Cardiovascular Health and Risk Factors
United States Fish and Wildlife Service
2025
University of Alabama in Huntsville
2022
Bristol-Myers Squibb (United States)
2001-2022
Syngene International (India)
2017
Biocon (India)
2016-2017
Bristol-Myers Squibb (India)
2016
Bristol-Myers Squibb (Germany)
2015
Columbia University
2000-2002
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSelective Functionalization of Amino Acids in Water: A Synthetic Method via Catalytic C−H Bond ActivationBrian D. Dangel, James A. Johnson, and Dalibor SamesView Author Information Department Chemistry, Columbia University New York, York 10027 Cite this: J. Am. Chem. Soc. 2001, 123, 33, 8149–8150Publication Date (Web):July 31, 2001Publication History Received25 May 2001Revised2 July 2001Published online31 inissue 1 August...
The antitumor agent (−)-rhazinilam was synthesized in three major steps, namely the pyrrole synthesis, selective C−H bond activation, and direct macrolactam formation. key step involved asymmetric functionalization (dehydrogenation) of diethyl group segment intermediate 6. This achieved by attachment chiral platinum complexes to proximal nitrogen atom. A high degree selectivity (60−75% ee) via use oxazolinyl ketone auxiliaries.
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTC−H Bond Activation of Hydrocarbon Segments in Complex Organic Molecules: Total Synthesis the Antimitotic RhazinilamJames A. Johnson and Dalibor SamesView Author Information Department Chemistry, Columbia University New York, York 10027 Cite this: J. Am. Chem. Soc. 2000, 122, 26, 6321–6322Publication Date (Web):June 16, 2000Publication History Received31 January 2000Published online16 June inissue 1 July...
Several lactam analogues of the epothilones were prepared using a concise semisynthetic approach starting with unprotected natural products. Highlighted in this strategy is novel regio- and stereoselective Pd(0)-catalyzed azidation reaction macrocyclic lactone. Subsequent reduction macrolactamization resulting azide acid intermediates provided desired macrolactams satisfactory overall yields. The entire three-step sequence was streamlined into "one-pot" process for epothilone B-lactam,...
On 29 May 2023, Pohlen discovered an adult male Kentish Plover (Anarhynchus alexandrinus) at Eareckson Air Station, Shemya Island, Aleutian Islands, Alaska—a first record for North America. Features identifying the bird as a and distinguishing it from similar Snowy (A. nivosus) include rufous or tawny tinge to crown, solidly black lores, limited auricular patch. The weather patterns leading up discovery were conducive drift vagrancy Asia.
Abstract One approach to improving predictions about a species’ response projected environmental changes is compare populations in current environments that represent expected future conditions. However, we often know more species at the core of its range, where numbers usually are greatest, which can skew inference. We studied Kittlitz's murrelet ( Brachyramphus brevirostris ), an ice‐associated seabird conservation concern, northern edge breeding range northwestern Alaska, USA, 2022–2023....
The human urinary microbiome is thought to affect the development and progression of tract infections (UTI), particularly recurrent UTIs in aging populations women. To understand possible interactions pathogens with commensal bacteria inhabiting bladder, we conducted an initial functional assessment a representative set lactobacilli that dominate this niche postmenopausal We created repository bladder isolated
A semisynthetic route to epothilone cyclopropanes from epothilones and B is described. Of significance, the deoxygenation of 12,13-epoxide give corresponding olefin was achieved with high efficiency. The title compounds (8, 9) were active in both tubulin polymerization cytotoxicity assays, which direct contrast a previously published report. These results provide further evidence that role largely conformational argue against some current pharmacophore models.
[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from A. The final semisynthetic route involves a formal double-inversion stereochemistry at both the C12 and C13 positions. All aziridine analogues tested for effects on tubulin binding polymerization cytotoxicity. results indicate that moiety is viable isosteric replacement epoxide case epothilones.
Apelin-13 is an endogenous peptidic agonist of the apelin receptor (APJ) with potential for improving cardiac function in heart failure patients. However, low plasma stability apelin-13 necessitates continuous intravenous infusion therapeutic use. There are several approaches to increase including attachment pharmacokinetic enhancing groups, stabilized peptides, and Fc-fusion approaches. We sought a small-molecule APJ approach target compound profile amenable chronic oral administration....
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, an acceptable preclinical PK profile. Upon further characterization in vivo, compound demonstrated unacceptable level of brain penetration. In effort to reduce the penetration while maintaining overall profile, SAR was developed at C2' position for series close analogues by employing hydrogen bond donors. As...
Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show excellent efficacy and minimal bleeding in preclinical models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimization P' groups led to a series highly potent selective TF-FVIIa inhibitors displayed poor permeability. Fluorination reduced basicity P1 group significantly improved The resulting lead compound was potent, selective, achieved good...
A new series of phenylquinazoline inhibitors Kv 1.5 is disclosed. The was optimized for potency, selectivity versus hERG, pharmacokinetic exposure, and pharmacodynamic potency. 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine (13k) identified as a potent ion channel selective inhibitor with robust efficacy in the preclinical rat ventricular effective refractory period (VERP) model rabbit atrial (AERP) model.
The apelin receptor (APJ) is a significant regulator of cardiovascular function and involved in heart failure other diseases. (Pyr1)apelin-13 one the endogenous agonists APJ receptor. Administration increases cardiac output preclinical models humans. Recently we disclosed clinical lead BMS-986224 (1), C3 oxadiazole pyridinone agonist with robust pharmacodynamic effects similar to an acute rat pressure-volume loop model. Herein describe structure-activity relationship carboxamides as...
Endothelial lipase (EL) selectively metabolizes high density lipoprotein (HDL) particles. Inhibition of EL has been shown to increase HDL concentration in preclinical animal models and was targeted as a potential treatment atherosclerosis. We describe the introduction an α-sulfone moiety benzothiazole series inhibitors resulting increased potency versus EL. Optimization for selectivity hepatic pharmacokinetic properties resulted discovery 24, which showed good vitro bioavailability but,...
Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting reduction plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery series oxadiazole ketones, which upon optimization, led identification compound 12. Compound 12 was evaluated mouse...
Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and the potential to treat a range of diseases. Many reported synthetic contain phenylurea, which appears be necessary for activity chemotypes. We set out find isosteres phenylurea focused our efforts on heteroaryl rings. The wide potencies with heterocyclic demonstrates how electronic effects heteroatom placement impact molecular recognition. Herein, we report discovery benzimidazole...
<table width="593" border="1" cellspacing="0" cellpadding="0"><tbody><tr><td rowspan="2" valign="top" width="387">The purpose of this meta-analysis was to examine the impact ethnicity and obesity as it relates Type-2 Diabetes (T2D) in specific Central American countries. A conducted determine association ethnicity, obesity, T2D. Four studies that qualified for inclusion were identified by searching MEDLINE PubMed databases. The on T2D had a combined population...