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The proof of the pudding: A proof-of-concept study using γ-secretase inhibitors as a model has shown that sulfonimidamides act as bioisosteres for sulfonamides. Detailed in vitro and in vivo profiling reveal that the sulfonimidamide motif imparts desirable properties such as decreased lipophilicity and plasma protein binding, accompanied by increased solubility. Our data support a wider use of this unique functional group in the design of new pharmacologically active agents.
Medicinal Chemistry, iScience, CNSP iMed, AstraZeneca R&D Södertälje, Västra Mälarehamnen 9, 151 85 Södertälje (Sweden).
This article was published in the following journal.
The first described reaction between N-tosylhydrazone and SO2 is reported to provide alkyl sulfonamides in the presence of various amines. In this procedurally simple method, hydrazones of both unsatu...
Incorporation of selenocysteine (Sec) in bacteria requires a UGA codon that is reassigned to Sec by the Sec-specific elongation factor SelB and a conserved mRNA motif (SECIS element). These requiremen...
Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose....
No evidence-based approach to the evaluation of CKD has been established. We sought to identify clinical criteria to guide a rational diagnostic approach for the initial evaluation of CKD.
Rational pathway design is the invention of an optimally efficient route from one state (e.g. chemical structure, state of differentiation, physiological state) to another, based on knowledge of biolo...
Subjects are healthy adult volunteers either at high risk for HIV infection or already known to be seropositive, who will donate blood for in vitro tests of T-cell function and in vitro re...
To compare the safety and efficacy of aerosolized pentamidine and dapsone in the prevention of Pneumocystis carinii pneumonia (PCP) in high-risk HIV-infected patients who are intolerant to...
Oxytocin is normally administered following delivery in pregnant patients to reduce postpartum bleeding by increasing uterine tone. It is unclear whether the use of intravenous oxytocin al...
Continuous albuterol has become the standard of care for patients in status asthmaticus. We have previously performed an in-vitro study comparing 4 different brands of continuous nebulizer...
Methods of infertility treatment may involve in vitro fertilization or IVF. Though effective, IVF is complex and expensive. Methods using no gonadotropin hormone stimulation of the ovaries...
Biologically functional sequences of DNA chemically synthesized in vitro.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.
Studies designed to assess the efficacy of programs. They may include the evaluation of cost-effectiveness, the extent to which objectives are met, or impact.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...