Years of cumulative research can result in the development of a clinically useful drug, providing either a cure for a particular disease or symptomatic relief from a physiological disorder. A lead compound with a desired pharmacological activity may have associated with it undesirable side effects, characteristics that limit its bioavailability, or structural features which adversely influence its metabolism and excretion from the body. Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. The concept of bioisosterism is often considered to be qualitative and intuitive.1 The prevalence of the use of bioisosteric replacements in drug design need not be emphasized. This topic has been reviewed in previous years.2-5 The objective of this review is to provide an overview of bioisosteres that incorporates sufficient detail to enable the reader to understand the concepts being delineated. While a few popular examples of the successful use of bioisosteres have been included, the George Patani graduated with a B.Pharm. in 1992 from the College of Pharmaceutical Sciences, Mangalore University at Manipal, India. In 1996, he received his M.S. in Pharmaceutical Science at Rutgers University under the direction of Professor Edmond J. LaVoie. He is presently pursuing graduate studies in pharmaceutics. His current research interests are focused on drug design and controlled drug delivery.

https://www.mch.estranky.sk/file/228/1996chemrev96-3147-76_bioisosterism.pdf

Bioisosterism: A Rational Approach in Drug Design.

Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of activities. The combination of different pharmacophores in a pyrrole ring system has led to the formation of more active compounds. Pyrrole containing analogs are considered as a potential source of biologically active compounds that contains a significant set of advantageous properties and can be found in many natural products. The marketed drugs containing a pyrrole ring system are known to have many biological properties such as antipsychotic, β-adrenergic antagonist, anxiolytic, anticancer (leukemia, lymphoma and myelofibrosis etc.), antibacterial, antifungal, antiprotozoal, antimalarial and many more. Due to the diversity of these analogs in the therapeutic response profile, many researchers have been working to explore this skeleton to its maximum potential against several diseases or disorders. In this review, attempts have been made to disclose various tactical approaches to synthesize pyrrole and pyrrole containing analogs. The structure–activity relationship studies have been discussed along with their therapeutic applications which have been reported during last decade. Some molecules as the main components of the market and clinical trials have also been discussed.

/pdf/pyrrole-a-resourceful-small-molecule-in-key-medicinal-hetero-c6dc7ae6wv.pdf

Pyrrole: a resourceful small molecule in key medicinal hetero-aromatics

Utilization of operational schemes for analog synthesis in drug design

Rationale for Design of Biologically Reversible Drug Derivatives: Prodrugs

A comprehensive overview on homogeneous catalytic hydrogenation of carboxylic acids and its derivatives as well as carbonic acid derivatives with transition metal-based molecular catalysts is described. Despite the tremendous potential in the hydrogenation of these less electrophilic carbonyl compounds using molecular hydrogen in synthetic organic chemistry, their reduction still relies mostly on the stoichiometric use of metal hydride reagents, such as LiAlH4, NaBH4, and their derivatives. For the past decade, a significant and rapid progress in particularly ester hydrogenation has been achieved by utilization of conceptually new bifunctional molecular catalysts originating from the metal–ligand cooperation effects. The bifunctional-catalyst-promoted hydrogenation using molecular hydrogen is now realized to be a practical tool in synthetic organic chemistry in both academia and industry. The industrial outlook for the present hydrogenation is bright because of its operational simplicity, scope, economic ...

Catalytic Reductive Transformations of Carboxylic and Carbonic Acid Derivatives Using Molecular Hydrogen

Reduction of cyclic anhydrides with sodium borohydride. Versatile lactone synthesis

A series of aryloxy alkyl diketones II was synthesized and screened in vitro for antiviral activity The effect of various substituents on the phenyl ring, as well as the length of the alkyl bridge, was examined to establish the requirements for optimum activity One of the most active members of the series, 4-[6-(2-chloro-4-methoxy)phenoxy]hexyl-3,5-heptanedione (56), exhibited a high level of activity against both DNA and RNA viruses in both the tissue culture and organ culture screens and was particularly effective against herpesvirus type 1 and 2

Robert E. Johnson

Papers

Reduction of cyclic anhydrides with sodium borohydride. Versatile lactone synthesis

Antiviral activity of some .beta.-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses

The Anomalous Stille Reactions of Methyl .alpha.-(Tributylstannyl)acrylate: Evidence for a Palladium Carbene Intermediate

Pyrrole antibacterial agents. 2. 4,5-Dihalopyrrole-2-carboxylic acid derivatives

Synthesis of novel tetrahydrobenzazepinones