Advanced Medicinal Chemistry - Lecture 2

A multi-step process from target identification to candidate drug development.

Lead compounds can originate from chance discoveries, natural products, clinical observations, and more.

Discovering new lead compounds through unintended or unplanned observations.

Lead compounds obtained directly from natural sources like plants or microorganisms.

Identifying lead compounds through observing treatment effects in patients.

Identifying molecules that show some activity, but not necessarily strong activity on the target.

Improving the initial active molecules—modifying them to increase activity and decrease toxicity.

Further improving the lead compound to increase potency and reduce side effects.

Substances found in nature that interact with specific receptors in the body.

Drugs developed by modifying existing successful drugs to improve their effectiveness or address specific limitations.

A process used to rapidly test many different molecules to identify those with desired biological activity.

A chemical group that has similar chemical properties and interactions to an existing chemical group in a natural ligand.

A specific type of chemical group or compound found in certain hormones and medicinal agents.

Drug with problems of short-duration and multiple side effects and compatibility conflicts.

Concerns about the protection of intellectual property rights for existing drugs.

Bronchodilators; drugs used to relax bronchial tubes/muscles, improving breathing.

A chemical compound that shows potential for development into a drug. It has some beneficial activity against the target but needs further optimization.

A specific molecule or biological pathway in the body that a drug aims to affect. For example, a target could be a protein involved in disease progression.

A target that is suitable and feasible for drug development. It's likely that drugs can be developed to affect this target.

Around 50-70% of new drug projects start with High Throughput Screening (HTS).

A good target for High Throughput Screening (HTS) is one that is validated (proven to be involved in the disease) and tractable (we can effectively screen compounds against it).

These are the techniques used to screen vast libraries of compounds against a target. Examples include fluorescence, luminescence, radioactivity, or even cell-based assays.

Small, multi-well plates used in HTS. They allow for efficient testing of hundreds or thousands of compounds at once, like miniature test tubes for high-throughput experiments.

A technique used for HTS, especially with radioligand binding assays. It involves radioactive labels and beads that emit light upon binding to the target molecule, enabling high-throughput screening.

A sophisticated machine that measures fluorescence changes in microtiter plates, often used in HTS to study calcium signaling in cells, allowing for real-time analysis of hundreds of wells simultaneously.

A library of chemical compounds, organized for high-throughput screening (HTS). The quality of the collection is crucial for the success of HTS.

A diverse compound collection increases the chances of finding hits for different targets. It's like having a wide variety of tools for different tasks.

There can be redundancy within a collection (similar compounds). Lack of diversity can limit the chances of finding hits for certain targets.

To improve the chances of finding hits in HTS by ensuring the collection has the right diversity and quality of compounds. It's like upgrading a toolbox with better tools.

Redundancy within a compound collection can lead to wasted time and resources as similar compounds are tested, reducing the efficiency of the screen.

Chemical diversity ensures that the compound collection is diverse in structure and properties, increasing the chances of finding hits against different targets.

HTS automates and speeds up the process of screening large libraries of compounds, allowing researchers to quickly identify potential drug candidates.

Automation in HTS allows for high-throughput screening of thousands or even millions of compounds in a shorter amount of time and with greater accuracy.

HTS is a powerful tool for identifying potential drug candidates. It significantly speeds up the early stages of drug discovery, enabling researchers to quickly test large libraries of compounds.

HTS is not without limitations. It can be expensive to establish and maintain, and the screening process may generate vast amounts of data that require sophisticated analysis.

A decentralized model that integrates chemistry and biology research, with chemistry embedded in research areas, fostering collaboration and innovation.

A collection of readily available chemical building blocks and reactions for rapid and efficient synthesis of various compounds.

The three primary reactions used in CCE include amide coupling, sulfonamide formation, and reductive amination. These reactions are versatile and efficiently produce a wide range of compounds.

A chemical reaction that joins two molecules by forming an amide bond, which is commonly used in CCE to create complex molecules.

A reaction that generates a sulfonamide group, which is often found in drug molecules, and frequently employed in CCE.

A process used in CCE to form an amine bond by combining a ketone or aldehyde with an amine in the presence of a reducing agent. This is a powerful method for creating diverse molecules.

A stepwise reaction involving protonation, nucleophilic attack, and deprotonation, resulting in the formation of an amide bond.

The reaction proceeds via a nucleophilic attack of an amine on a sulfonyl chloride, followed by deprotonation, leading to the formation of a sulfonamide.

A multi-step process involving nucleophilic addition, protonation, reduction, and deprotonation resulting in an amine bond formation.

A technique that rapidly screens large numbers of molecules against a biological target to identify potential drug leads.

A key part of CCE that integrates biological expertise, providing essential information for the design and optimization of drug candidates.

The core of CCE dedicated to designing and synthesizing drug candidates, guided by biological data and chemical expertise.

A crucial aspect of CCE, bridging chemistry and biology through computational tools to analyze, predict, and design novel compounds.

Central to CCE, employing computer simulations and calculations to predict the properties and behavior of molecules, aiding in drug design.

The critical link that manages and analyzes vast chemical and biological data, enabling informed decisions in drug discovery.