Advanced Drug Design And Development: Medicinal Chemistry Approach (Ellis Horwood Series in Pharmace

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Since their introduction in the early s, CDSs have also generated considerable research work, especially for brain and eye targeting of various therapeutic agents, including those that cannot cross the blood-brain barrier or the blood-retinal barrier on their own. Within this approach, three major general CDS classes have been identified:. This concept has been extended to many drugs and peptides, its importance illustrated by the fact that its first applications and uses were published in Science [25] [26] [27] in , and Its extension to the targeted brain-delivery of neuropeptides was included by the Harvard Health Letter [28] as one of the top 10 medical advances of Several compounds have reached advanced clinical development phase, such as.

The second example involves eye-specific delivery of betaxoxime , the oxime derivative of betaxolol. These retrometabolic design strategies were introduced by Nicholas Bodor, one of the first and most prominent advocates for the early integration of metabolism, pharmacokinetic and general physicochemical considerations in the drug design process. The importance of this field is reviewed in a book dedicated to the subject Bodor, N.

The FDA and the Pharmaceutical Industry

Bodor's work on these design concepts developed during the late s and early s, and came to prominence during the mids. Loteprednol etabonate, a soft corticosteroid designed and patented [35] [36] by Bodor received final Food and Drug Administration FDA approval in as the active ingredient of two ophthalmic preparations Lotemax and Alrex , currently the only corticosteroid approved by the FDA for use in all inflammatory and allergy-related ophthalmic disorders.

Its safety for long-term use [37] further supports the soft drug concept, and in , loteprednol etabonate [38] [39] [40] was also approved as part of a combination product Zylet. A second generation of soft corticosteroids such as etiprednol dicloacetate [41] is in development for a full spectrum of other possible applications such as nasal spray for rhinitis or inhalation products for asthma. The soft drug concept ignited research work in both academic e. A number of new chemical entities NCE were developed based on these principles, such as E 2 -CDS Estredox [29] or betaxoxime [30] are in advanced clinical development phases.

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A review of ongoing research using the general retrometabolic design approaches is conducted biennially at the Retrometabolism Based Drug Design and Targeting Conference , an international series of symposia developed and organized by Nicholas Bodor. Proceedings of each conference held have been published in the international pharmaceutical journal Pharmazie. Past conferences, and their published proceedings are:. From Wikipedia, the free encyclopedia.

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Wiegrebe, Electron impact induced fragmentation of 4-aryl-4,6,7,8-tetrahydro-1H,3H-quinazolinone-2,5-diones. Heterocycles 48 , Dove, Computermethoden im Arzneimitteldesign. Structure-activity relationships of arginine derivatives and hybrid compounds with arpromidine-like partial structures.

Dove, Configurational and conformational isomeric antiaromatic [28]tetraoxaporphyrinoids 4. A new type of molecular dynamics in macrocyclic systems. Acta 80 , A Verification of the Topographic Model. Role of the Guanidine Group.

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Schunack, H1 agonistic 2-heteroaryl and 2-phenylhistamines: CoMFA and possible receptor binding sites. Gruska, Physicochemical properties and drug action: An example of considering effectuation models in biological data interpretation and QSAR. Franke, Activity data decomposition - levels, methods and principles.


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Rational approaches in the design of bioactive compounds , Pharmacochem. Medicamentum 32 , Dove since R.

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