Drug candidates development

HMR 1556 was a drug candidate developed for treatment of hypertension. It was 14C-labeled and investigated in a rat mass balance study to determine the pattern and rate of excretion, the residual concentrations at the end of the study 168 h after administration and the mass balance following oral and intravenous route of administration. 

During early stages of drug candidate development, raw materials and isolated process intermediates may be included in the finished goods essential peak set until the appropriate analytical and process-control strategies are implemented. Once the appropriate controls are in place as the candidate approaches commercialization, it may be possible to eliminate some of these components from the component set. 

Triazoles are an interesting class of heterocyclic units widely used in the discovery and modulation of drug candidates, development of new materials, supramolecular chemistry, design of new supported organocatalysts, and biotechnology area [55], Therefore, several elegant methods for the synthesis of this classic nitrogen heterocyclic compounds have been reported by 1,3-dipolar cycloaddition of azides with alkynes under thermal [56] conditions as well as copper catalysis. 

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

In particular, in silico methods are expected to speed up the drug discovery process, to provide a quicker and cheaper alternative to in vitro tests, and to reduce the number of compounds with unfavorable pharmacological properties at an early stage of drug development. Bad ADMET profiles are a reason for attrition of new drug candidates during the development process [9, 10]. The major reasons for attrition of new drugs are ... 

The development of the key intermediate, 5-(2-methoxy-4-nitrophenyl)oxazole (25), in the preparation of the hepatitis C drug candidate, VX-497, utilizes a van Leusen reaction of aldehyde 24 with TosMIC. ... 

Taxol s journey to the clinic was slow and arduous. Initial difficulties with aqueous solubility and lack of knowledge regarding its mechanism, of action delayed its development until 1979 when, in another seminal paper in the field, S.B.Horwitz and her collaborators disclosed their findings on the interaction of taxol with microtubules.4 Taxol s unique biological action, which includes promotion of microtubule formation and microtubule stabilization, stimulated a renewed interest in taxol as a potential drug candidate. The problem of procuring adequate supplies of taxol became even... 

Ganter B, Tugendreich S, Pearson Cl, Ayanoglu E, Baumhueter S, Bostian KA, et al. Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. J Biotechnol 2005 119 219-44. 

An example is a view given to us by a discovery manager that if a drug candidate could not reach a successful market launch, the next best thing for a discovery team would be to have their compound progress to late stages of development before failure, because this implies that any problem was hard to predict, for example, a rare event. Yet this is exactly the most expensive kind of failure. 

Shen M, Xiao Y, Golbraikh A, Gombar VK, Tropsha A. Development and validation of k-nearest-neighbor QSPR models of metabolic stability of drug candidates. J Med Chem 2003 46 3013-20. 

Curatolo, W. Physical chemical properties of oral drug candidates in the discovery and exploratory development settings. Pharm. Sci. Technol. Today 1998, 1, 387-393. 

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