34245-14-2Relevant academic research and scientific papers
Design, synthesis and evaluation of 9-hydroxy-7H-furo [3,2-g]chromen-7-one derivatives as new potential vasodilatory agents
Wang, Cheng,Wang, Tao,Zhou, Nan,Pan, Xiao-Yan,He, Huai-Zhen
, p. 304 - 311 (2014/02/14)
Two new 9-hydroxy-7H-furo[3,2-g]chromen-7-one derivatives were designed, synthesized and evaluated for their in vitro vasodilatory activity. The structures of two compounds were elucidated by infrared, 1H NMR, and mass spectral data. The invitro pharmacological evaluation indicated that both of them possessed well vasodilatory activity compared with imperatorin. The molecule docking also showed two target compounds docked well with L-calcium channel (PDB code: 3G43). The result suggested that they would be potential vasodilatory agents for hypertension.
Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro - amitriptyline and verapamil as model compounds
Rousu, Timo,Herttuainen, Jukka,Tolonen, Ari
experimental part, p. 939 - 957 (2011/10/19)
Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time- and cost-effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early-phase 'one lab visit only' approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time-of-flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ-Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q-Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high-important accurate mass data, they suffered from many false negatives, and especially with the QqQ, from very high overall time consumption.
A panel of cytochrome P450 BM3 variants to produce drug metabolites and diversify lead compounds
Sawayama, Andrew M.,Chen, Michael M. Y.,Kulanthaivel, Palaniappan,Kuo, Ming-Shang,Hemmerle, Horst,Arnold, Frances H.
supporting information; scheme or table, p. 11723 - 11729 (2010/04/29)
Herein we demonstrate that a small panel of variants of cytochrome P450 BM3 from Bacillus megaterium covers the breadth of reactivity of human P450s by producing 12 of 13 mammalian metabolites for two marketed drugs, verapamil and astemizole, and one research compound. The most active enzymes support preparation of individual metabolites for preclinical bioactivity and toxicology evaluations. Underscoring their potential utility in drug lead diversification, engineered P450 BM3 variants also produce novel metabolites by catalyzing reactions at carbon centers beyond those targeted by animal and human P450s. Production of a specific metabolite can be improved by directed evolution of the enzyme catalyst. Some variants are more active on the more hydrophobic parent drug than on its metabolites, which limits production of multiply-hydroxylated species, a preference that appears to depend on the evolutionary history of the P450 variant.
PHENYLACETONITRILE DERIVATIVES AND HAIR TONICS AND EXTERNAL PREPARATIONS FOR SKIN CONTAINING THE DERIVATIVES
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Page 19-20, (2010/02/09)
A hair growth promoting composition comprising, as an effective ingredient, a phenylacetonitrile derivative or a pharmacologically acceptable salt thereof expressed by the following Formula (I): wherein each of R1 and R2 is hydrogen atom, a C1-10 alkyl group, a C2-10 alkenyl group or C2-10 acyl group, or NR1R2 may be a heterocycle having 3-7 members; R3 is a C1-5 alkyl group; and each of R4, R5 and R6 is hydrogen atom or a C1-4 alkoxy group. The present invention provides a hair growth promoting composition having excellent effects on promoting hair regrowth, preventing or inhibiting hair loss, and the like in human by compounding above-specified phenylacetonitrile derivative as a effective ingredient thereto.
Antagonistes calciques. I. Remplacement du groupe dimethoxy-3,4- phenylethyle du verapamil
Laguerre, M.,Boyer, C.,Carpy, A.,Panconi, E.,Cognic, F.,Vaugien, B.
, p. 351 - 359 (2007/10/02)
In the verapamil structure, the 3,4-dimethoxy phenylethyl group has been replaced by several moieties belonging to α- and β-blockers or other classes of calcium channel blockers.The best derivatives, as calcium blockers, were prepared with β-blocker fragments like aryloxypropanolamines (AOPA) with an ortho substituent on the aromatic ring.
