کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10585620 | 981372 | 2012 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
7-Substituted-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: A promising approach for treating pain and inflammation
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کلمات کلیدی
HBSSN-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochlorideEDACTRPA1 channelHOBtAITCNGFRNSHEPESDRGTRPA1TRPV1DMEMFBS1-Hydroxybenzotriazole hydrate - 1-Hydroxybenzotriazole هیدرات4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidBSA - BSADulbecco’s modified Eagle medium - Modified Eagle اصلاح شده DulbeccoROS - ROSAsthma - آسمbovine serum albumin - آلبومین سرم گاوinflammation - التهاب( توروم) Allyl isothiocyanate - ایزوتیوسیانات آللییلCho - برایCOPD - بیماری مزمن انسدادی ریهChronic obstructive pulmonary disease - بیماری مزمن انسدادی ریهPain - دردfetal bovine serum - سرم جنین گاوChinese hamster ovary cells - سلول های تخمدان هامستر چینیCinnamaldehyde - سینامالدهید nerve growth factor - فاکتور رشد عصبHanks’ balanced salt solution - محلول نمک متعادل هانکسtransient receptor potential ankyrin 1 - پتانسیل گیرنده گذرا ankyrin 1Transient receptor potential vanilloid 1 - پتانسیل گیرنده گذرا وانیلیوئید 1dorsal root ganglia - گانگلیس ریشه پشتیtrigeminal ganglia - گانگلیس سه گانهreactive nitrogen species - گونه های واکنش پذیر نیتروژنReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The transient receptor potential ankyrin 1 (TRPA1) channel is activated by a series of by-products of oxidative/nitrative stress, produced under inflammatory conditions or in the case of tissue damage, thus generating inflammatory and neuropathic pain and neurogenic inflammatory responses. These findings have identified TRPA1 as an emerging opportunity for the design and synthesis of selective inhibitors as potential analgesic and antiinflammatory agents. Herein we present the synthesis and functional evaluation of a new series of 7-substituted-1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives designed as TRPA1 antagonists. A small library of compounds has been built by the introduction of differently substituted N7-phenylacetamide or N7-[4-(substituted-phenyl)-thiazol-2-yl]-acetamide chains. All the synthesized compounds were assayed to evaluate their ability to block acrolein-mediated activation of native human and rat TRPA1 channels employing a fluorometric calcium imaging assay. Our study led us to the identification of compound 3h which showed considerably improved potency (IC50Â =Â 400Â nM) against human TRPA1 with regard to some of the most representative antagonists previously reported and integrated in our screening program as reference compounds. In addition, 3h proved to maintain its efficacy toward rTRPA1, which designates it as a possible candidate for future evaluation of in vivo efficacy in rodent animal model of inflammatory and neuropathic pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 5, 1 March 2012, Pages 1690-1698
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 5, 1 March 2012, Pages 1690-1698
نویسندگان
Pier Giovanni Baraldi, Romeo Romagnoli, Giulia Saponaro, Mojgan Aghazadeh Tabrizi, Stefania Baraldi, Pamela Pedretti, Camilla Fusi, Romina Nassini, Serena Materazzi, Pierangelo Geppetti, Delia Preti,