Molecular structure, drugs

Most practical implementations of drug-likeness use a computational model which takes as input the molecular structure, together with various properties, and predicts whether the molecule is drug-like or not. Some of these models may be very simple, such as a series of substructural filters. Only those molecules which pass all of these filters are output, Such filters can be used to eliminate molecules that contain inappropriate functionality. 

There are now extensive databases of molecular structures and properties. There are some research efforts, such as drug design, in which it is desirable to hnd all molecules that are very similai to a molecule which has the desired property. Thus, there are now techniques for searching large databases of structures to hnd compounds with the highest molecular similarity. This results in hnding a collection of known structures that are most similar to a specihc compound. 

Once a number of lead compounds have been found, computational and laboratory techniques are very successful in rehning the molecular structures to yield greater drug activity and fewer side elfects. This is done both in the laboratory and computationally by examining the molecular structures to determine which aspects are responsible for both the drug activity and the side effects. These are the QSAR techniques described in Chapter 30. Recently, 3D QSAR has become very popular for this type of application. These techniques have been very successful in the rehnement of lead compounds. 

Drug (trade name) CAS Registry Molecular Molecular Structure... 

Blood-brain barrier permeation of 7, among other drugs, was predicted from its three-dimensional molecular structure by a computational method (0OJMC2204). The combination of molecular topological methods using 137 quinolones, including 7 provided an excellent tool for the design of new... 

Many drug-like molecules have aromatic substituents and thus have limited aqueous solubility. A routine practice is to dissolve stock drugs in a solvent known to dissolve many types of molecular structures. One such solvent is... 

Moreover, molecular modeling is one key method of a wide range of computer-assisted methods to analyze and predict relationships between protein sequence, 3D-molecular structure, and biological function (sequence-structure-function relationships). In molecular pharmacology these methods focus predominantly on analysis of interactions between different proteins, and between ligands (hormones, drugs) and proteins as well gaining information at the amino acid and even to atomic level. 

Gvesthe exact chemical makeup of the drug and placing of the atoms or molecular structure it is not capitalized. 

Many new drugs are discovered by studying the properties of compounds found in plants or other materials that have been used as medicines for centuries (Fig. F. 1). Once chemists have extracted a biologically active compound from a natural product, they identify its molecular structure so that it can be manufactured. This section focuses on the first step in identifying the molecular structure, the determination of the empirical and molecular formulas of the compound. 

Understanding the relationship between molecular structure and materials piroperties or biological activity is one of the most important facets of biomaterials synthesis and new-drug design. This is especially true for polyphosphazenes, where the molecular structure and properties can be varied so widely by small modifications to the substitutive method of synthesis. 

Molecular structure has been shown to influence absorption. By examining the structural characteristics of drugs that were in use, certain common characteristics of well-absorbed molecules were identified, commonly referred to as the rule of five. Some investigators have used this as a basis for characterizing the drug-likeness of a lead chemical. Other factors also come into play including receptor activity, metabolism profile and for CNS-active compounds, an ability to cross the blood-brain barrier. 

Epilepsy is a clinical disorder characterized by spontaneous, recurrent seizures arising from excessive electrical activity in certain parts of the brain [51]. Currently available drugs, such as phenytoin, carbamazepine, valproic acid, lamotrigine, and topiramate (for molecular structures see Fig. 6), provide symptomatic seizure suppression in only 60-70% of those receiving treatment [52-54]. These drugs are also associated with unwanted side... 

Fig. 6 Molecular structures of currently available antiepUeptic drugs. These molecules possess several severe life-threatening adverse effects [51-54]...

Molecular structure and properties are key concepts in drug design, but they may not mean the same to all medicinal chemists, not to mention other researchers involved in drug discovery and development such as biochemists, pharmacologists and toxicologists (see Chapter 2). It is therefore the merit of this book to offer a rationalization of these concepts with a view to advocating their value and clarifying their use. 

Testa, B. Drugs as chemical messages molecular structure, biological context, and structure-activity relationships. Med. Chem. Res. 1997, 7, 340-365. 

Testa, B., Kier, L. B. The concept of molecular structure in structure-activity relationship studies and drug design. Med. Res. Rev. 1991, 11, 35 8. 

Nuclear magnetic resonance (NMR) spectroscopy is, next to X-ray diffraction, the most important method to elucidate molecular structures of small molecules up to large bio macromolecules. It is used as a routine method in every chemical laboratory and it is not the aim of this article to give a comprehensive review about NMR in structural analysis. We will concentrate here on liquid-state applications with respect to drugs or drug-like molecules to emphasize techniques for conformational analysis including recent developments in the field. 

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