Medicinal   Chemistry

One of the largest frustrations in pharmaceutical R&D occurs when a project fails to reach fruition. Oftentimes this disappointment happens because the compound does not have enough exposure at the site of action. Otherwise potent candidates fail because of barriers to exposure, such as low aqueous solubility, poor permeability, high plasma protein binding, and poor tissue partitioning. These factors are all related to the lipophilicity of the compound.

Moreover, about two thirds of the compounds in the world drug index are electrolytes (i.e., not neutral over the pH range of the Gl tract). In fact, it is common for the solubility and lipophilicity to vary by several orders of magnitude throughout the Gl tract.

Taking these factors together, we can see that the pH profile of logD and solubility are critical factors governing the relationship between dose and exposure. ACD/Labs has long set the standard for predicting pH-dependent logD and solubility, creating definitive solutions to the challenges of predictive accuracy and practical application for these properties. In addition ACD/Labs offers other solutions relative to the medicinal chemist outside of the physical chemistry realm.

Optimization of Drug Libraries

An understanding of the relationship between ADME characteristics, physical properties, and structure are extremely important when designing and filtering compounds in a library or class. Reduce the costs of screening by eliminating non-drug-like molecules from the reaction pool according to their predicted properties. Since the shotgun approach to library design has produced disappointing results, the industry paradigm is shifting toward pre-filtering libraries candidates to actively avoid wasting resources on those compounds with highly undesirable properties. For example, compounds with extremely poor predicted solubility (S), lipophilicity (logP, logD), molecular weights and other similar properties can be easily and reliably screened in seconds using ACD/Labs industry standard predictors.

To learn more about the molecular physical property predictions that we offer, click here.

Improve Selected ADME Properties by Modifying Chemical Structures

Promising leads often cannot be used as such, prompting the search for derivatives and analogs with better PK properties. Synthetic improvements of absorption and distribution properties are generally guided by trial and error as well by the judicious application of rules of thumb and experience. Speed up and simplify the search by systematically modifying lead structure to meet specific solubility, ionization state (pK_a), and lipophilicity (logP and logD) targets with minimum disturbance of the key active site by using ACD/Labs physicochemical property predictors and structure design tools.

Relevant Software: ACD/Structure Design Suite

Chemical Naming for Chemical Patenting and Litigation

Clear and accurate naming is essential in these documents to ensure that the information is communicated clearly. To conduct comprehensive literature and patent searches, the ability to derive chemical structures from names is often required. Read more here.

Save Time Reporting and Publishing Results

Quickly assemble quality reports and publications for departmental meetings or project reviews to illustrate progress and production. To learn how to quickly create high-quality comprehensive reports, visit here.

Streamline Interpretation of Analytical Data

With the heavy emphasis of a medicinal chemist's work on chemical synthesis, reducing the tedious and non-core research tasks of sample processing, analysis, and assisted verification will leave time for more important tasks. Read about our verification solutions here.

Retrieve and Review Chemical and Analytical Data

Access and contribute accumulated structures, reactions, and structural data in an easily searchable repository that can be shared throughout the group/department.

Relevant Software: ACD/ChemFolder

Speed Chiral Purification

One of the problems facing medicinal chemistry organizations is efficient purification of materials prior to testing. Since chiral chromatographic separations often require specialized method development, some analytical laboratories do thousands of injections per week investigating chiral methods for purification of samples. To learn how to speed up sample turnaround, visit here.