عنوان مقاله
دراگ گورو : یک برنامه نرم افزار کامپیوتری برای طراحی دارو با استفاده از قوانین شیمی دارویی
فهرست مطالب
چکیده
مقدمه
مواد و روش ها
نتایج
نتیجه گیری
بخشی از مقاله
ساختار ورودی
ساختار شیمیایی از طریق کد شناسه شرکتی ، برنامه رسم فنی، یا فایل شرکتی، به صورت فردی یا گروهی وارد می گردد. نمونه ساختارهای ورودی عبارتنداز ساختار اصلی کنونی برای پروژه خاص، ترکیب رقیب یا لیگاند طبیعی. بعد از ورود ساختار ورودی، کاربر دکمه اجرا را بدون نیاز به اطلاعات دیگر انتخاب می کند. کلیه روندهای تبدیل عمومی به این سبک بکار گرفته شده اند.
کلمات کلیدی:
Drug Guru: A computer software program for drug design using medicinal chemistry rules Kent D. Stewart,a,* Melisa Shirodaa and Craig A. Jamesb a Abbott Laboratories, Global Pharmaceuticals Research and Development, Abbott Park, IL 60064, USA b Moonview Consulting, LLC, San Diego, CA, USA Received 27 April 2006; revised 6 June 2006; accepted 8 June 2006 Available online 25 July 2006 Abstract—Drug GuruTM (drug generation using rules) is a new web-based computer software program for medicinal chemists that applies a set of transformations, that is, rules, to an input structure. The transformations correspond to medicinal chemistry design rules-of-thumb taken from the historical lore of drug discovery programs. The output of the program is a list of target analogs that can be evaluated for possible future synthesis. A discussion of the features of the program is followed by an example of the software applied to sildenafil (Viagra) in generating ideas for target analogs for phosphodiesterase inhibition. Comparison with other computer-assisted drug design software is given. 2006 Elsevier Ltd. All rights reserved. 1. Introduction A rich tradition of analog design strategies has evolved for creating new compounds within medicinal chemistry research for biological evaluation. When similar physical properties between lead compound and analog are desired, ‘bioisosteric’ replacements are commonly employed. Where more structurally altered yet still compatible differences between lead compound and analog are desired, non-classical replacements are considered. This latter situation occurs when a chemist desires structures that are outside of the intellectual property of a competitor or when attempting to achieve more dramatic changes in potency or bioavailability. Collectively, these replacements are known to experienced medicinal chemists as ‘rules-of-thumb’ for drug design. Two examples of well-known design rules-of-thumb, the carboxylateto-tetrazole and amide-to-retroamide replacements, illustrated in Figure 1, have historically been considered to yield analogs of high interest in medicinal chemistry programs. Hundreds of these structural transformations have been reported in the literature and have potential for general applicability and acceptance as design rules.1–9 While no single rule is ever guaranteed to achieve the desired endpoint, the traditional rules represent a useful starting place in a drug discovery effort, particularly when other knowledge such as pharmacophore models, 3D receptor structure, or structure– activity relationship data is limited, low quality, or non-existent. We have written a web-based computer application, called ‘Drug Guru,’10 that contains the historical rulesof-thumb as lines of SMIRKS code.11 The name of the program is an acronym for drug generation using rules. The program applies a library of rules to any input structure and then permits visual or computational evaluation of the output structures. To our knowledge, no previously described or commercially available software
