A5102024242- Mitochondrial Function and Pathology
- Chemical Synthesis and Analysis
- Immunotherapy and Immune Responses
- Metabolism and Genetic Disorders
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Muscle Physiology and Disorders
- Quinazolinone synthesis and applications
- Synthesis and Biological Activity
- HIV Research and Treatment
- Phenothiazines and Benzothiazines Synthesis and Activities
- Diet and metabolism studies
- Cancer therapeutics and mechanisms
- Carbohydrate Chemistry and Synthesis
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- HIV/AIDS drug development and treatment
- Polyamine Metabolism and Applications
- Hepatitis B Virus Studies
- Hepatitis C virus research
- RNA and protein synthesis mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Neurological and metabolic disorders
- Pediatric Urology and Nephrology Studies
- Urological Disorders and Treatments
Alcon (United States)
2023
Pfizer (United States)
2009-2017
Massachusetts General Hospital
1973-2015
Harvard University
1974-2015
Novartis (Switzerland)
2014
Novartis (United States)
2014
Providence St. Vincent Medical Center
2013
Pfizer (United Kingdom)
2006-2010
Scripps Research Institute
2001-2010
Trent University
2008
A series of acidic diaryl ether heterocyclic sulfonamides that are potent and subtype selective NaV1.7 inhibitors is described. Optimization early lead matter focused on removal structural alerts, improving metabolic stability reducing cytochrome P450 inhibition driven drug-drug interaction concerns to deliver the desired balance preclinical in vitro properties. Concerns over nonmetabolic routes clearance, variable clearance species, subsequent low confidence human pharmacokinetic...
Hirsch, Martin S.1; Ellis, David A.1; Black, Paul H.1; Monaco, Anthony P.2; Wood, Mary L.2 Author Information
Activation of murine leukemia viruses, as detected by the mixed culture cytopathogenicity (XC) assay, followed transplantation A/J skin onto immunosuppressed BALB/c mice. Virus was found in most mice receiving both grafts and antilymphocyte serum, but not animals either serum alone, graft or no treatment.
Preventing entry of HIV into human host cells has emerged as an attractive approach to controlling viral replication. Maraviroc 1 is approved antagonist the CCR5 receptor which prevents HIV. Herein, we report design and discovery a series imidazopiperidine antagonists retain antiviral profile window over hERG activity maraviroc 1, combined with improved absorption profiles in rat dog. Furthermore, this compounds been shown against laboratory generated maraviroc-resistant HIV-1 strain,...
The cysteine protease adenain is the essential of adenovirus and, as such, represents a promising target for treatment ocular and other adenoviral infections. Through concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 pyrimidine 2 complementary starting points inhibition. These hits enabled first high-resolution X-ray cocrystal structures with inhibitors bound revealed binding mode 2. screening were optimized by structure-guided medicinal chemistry strategy into...
Conditions for the formation of serine-derived organozinc reagent 1 in THF, together with transmetallation to zinc-copper 2, are described. Reactions these reagents substituted propargyl tosylates, an acetylenic bromide, and bromocyanopyridines gave corresponding protected amino acids.
The development of a facile and general method for the preparation enone derived α-amino acids is described. key step involves Horner–Wadsworth–Emmons reaction between an aspartic acid β-keto phosphonate ester range aldehydes resulting in formation highly functionalised good yields. An efficient two-stage deprotection process using mild conditions was developed to give parent acids. Application this methodology has produced novel fluorescent that potential as biological marker.
Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of work reported in this paper was to combine high levels PDE5 potency selectivity with dose-independent bioavailability, minimize impact on Cmax any interactions coadministered drugs clinic. This goal achieved...
The CT appearance of the adrenal glands was investigated in 30 patients with congenital renal anomalies (17 cases unilateral agenesis, 11 inferior ectopy, and 2 crossed fused ectopy). ipsilateral clearly identified 83% these patients; all them, a paraspinal disk-shaped organ, which appeared linear on CT. Conversely, adrenals retained their normal shape control group 20 acquired atrophy or prior simple nephrectomy.
An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, water-soluble JAK inhibitors as immunomodulating agents topical ocular disposition. focused library known 3-(4-(2-(arylamino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitriles was evaluated molecular...
1. Acid extracts of muscle-fibre preparations from human biopsies incubated with [U-14C]glucose were chromatographically analysed. 2. Radioactivity fructose was significantly greater in muscle childhood dystrophy patients and also female carriers the disease compared normal, foetal, neurogenic polymyositis control groups. 3. Measurements activity polyol-NADP oxidoreductase (EC 1.1.1.21) L-iditol-NAD 1.1.1.14) ability to dephosphorylate 6-phosphate, indicated that probable route formation...
We present a general route for the synthesis of triazacyclononane functionalised with one, two or three pendant phosphine arms and exemplify method N-(diphenylphosphinopropyl) 1,4,7-triazacyclonoane (L) crystal structure its zinc(II) complex [Zn2L2Cl3][ClO4].
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRing size effects in phenol-phenolate tungsten (VI) chelatesMartha D. Morton, Joseph A. Heppert, Steven Dietz, Wayne H. Huang, David Ellis, Tiffany Grant, Nancy W. Eilerts, Denise L. Barnes, Fusao Takusagawa, and VanderVeldeCite this: J. Am. Chem. Soc. 1993, 115, 17, 7916–7917Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://doi.org/10.1021/ja00070a063RIGHTS &...
The synthesis and examination of a novel class reversed CPyI analogues CC-1065 the duocarmycins are described. Capable unique metal cation activation DNA alkylation, these agents allowed effects binding domain (104-fold increase in alkylation rate efficiency) to be partitioned into two components: that derived from enhanced affinity selectivity (10−80-fold) contribution catalysis (250−5000-fold). In addition, enantiomeric sequence selective alkylating provides further strong support for...