Graduate
  1. Physical Chemistry  1.1. Thermodynamics  1.1.1. Laws of Thermodynamics  1.1.2. Enthalpy and heat capacity  1.1.3. Entropy and free energy  1.1.4. Phase Equilibrium  1.1.5. Statistical thermodynamics  1.1.6. Thermodynamic cycle  1.1.7. Fugacity and activity  1.2. Quantum Chemistry  1.2.1. Principles of quantum mechanics  1.2.2. Schrödinger Equation  1.2.3. Particle in a box  1.2.4. Operators and eigenvalues  1.2.5. Atomic orbitals  1.2.6. Molecular orbital theory  1.2.7. Perturbation theory  1.2.8. Valence bond theory  1.2.9. Hybridization and chemical bonding  1.3. Chemical kinetics  1.3.1. Rate laws and reaction mechanisms  1.3.2. Collision theory  1.3.3. Transition state theory  1.3.4. Enzyme Kinetics  1.3.5. Chain Reactions and Polymerization  1.3.6. Photochemical reactions  1.4. Statistical mechanics  1.4.1. Partitioning functions  1.4.2. Molecular distribution functions  1.4.3. Boltzmann Distribution  1.4.4. Bose–Einstein and Fermi–Dirac statistics  1.5. Spectroscopy  1.5.1. Rotational Spectroscopy  1.5.2. Vibrational Spectroscopy  1.5.3. Electronic Spectroscopy  1.5.4. Nuclear magnetic resonance spectroscopy  1.5.5. Mass Spectrometry  1.5.6. Raman Spectroscopy  1.5.7. Electron paramagnetic resonance spectroscopy  1.6. Surface and colloidal chemistry  1.6.1. Absorption isotherm  1.6.2. Surface tension and wetting  1.6.3. Colloidal Stability  1.6.4. Catalysis  1.6.5. Emulsions and micelles  1.7. Electrochemistry  1.7.1. Nernst equation  1.7.2. Electrochemical cells  1.7.3. Conductivity and mobility  1.7.4. War  1.7.5. Fuel cells  1.7.6. Electrolysis
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic reactions  2.2. Spectroscopy and structural determination  2.2.1. UV-Vis Spectroscopy  2.2.2. IR Spectroscopy  2.2.3. NMR Spectroscopy  2.2.4. Mass Spectrometry  2.2.5. X-ray crystallography  2.3. Stereoscopic  2.3.1. Chirality and optical activity  2.3.2. Structural analysis  2.3.3. Geometrical isomerism  2.3.4. Dynamic Stereochemistry  2.4. Organometallic Chemistry  2.4.1. Organolithium and organomagnesium reagents  2.4.2. Palladium-catalyzed cross-coupling reactions  2.4.3. Transition Metal Complexes  2.4.4. Metal–carbon bond  2.5. Polymer chemistry  2.5.1. Polymerization mechanism  2.5.2. Polymer Characteristics  2.5.3. Biodegradable Polymer  2.5.4. Conducting polymer  2.5.5. Supramolecular polymers  2.6. Medicinal chemistry  2.6.1. Drug design and development  2.6.2. Pharmacokinetics and pharmacodynamics  2.6.3. Structure-activity relationships  2.6.4. Molecular docking and drug screening
  3. Inorganic chemistry  3.1. Coordination chemistry  3.1.1. Crystal field theory  3.1.2. Ligand field theory  3.1.3. Spectrochemical Series  3.1.4. Chelation and stability  3.2. Organometallic Chemistry  3.2.1. Metal Carbonyls  3.2.2. Catalysis by organometallic complexes  3.2.3. Metallocenes  3.3. Bio-inorganic chemistry  3.3.1. Metalloproteins and enzymes  3.3.2. The role of metals in biological systems  3.3.3. Metal ion transport and storage  3.4. Solid state chemistry  3.4.1. Crystal Structures  3.4.2. Band theory of solids  3.4.3. Superconductors  3.4.4. Defects in the crystal  3.5. Lanthanides and Actinides  3.5.1. Electronic configuration in lanthanides and actinides  3.5.2. Coordination chemistry of the lanthanides  3.5.3. Magnetic Properties of Lanthanides
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.2. Spectroscopic Techniques  4.2.1. Atomic absorption spectroscopy  4.2.2. X-ray diffraction  4.2.3. Inductively coupled plasma spectroscopy  4.3. Electroanalytical methods  4.3.1. Potentiometry  4.3.2. Voltammetry  4.3.3. Colometry  4.4. Mass Spectrometry  4.4.1. Ionization Technique  4.4.2. Fragmentation Pattern  4.5. Chemometrics  4.5.1. Multidisciplinary analysis  4.5.2. Machine Learning in Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.1.1. Force fields and energy minimization  5.1.2. Monte Carlo simulation in molecular dynamics simulations  5.2. Quantum chemical methods  5.2.1. Hartree–Fock theory  5.2.2. Density functional theory  5.2.3. Semi-empirical methods  5.3. Computational drug design  5.3.1. Molecular Docking  5.3.2. QSAR Modeling  5.3.3. Virtual Screening
  6. Biochemistry  6.1. Enzyme Kinetics  6.1.1. Michaelis-Menten kinetics  6.1.2. Inhibition mechanism  6.2. Metabolism and Bioenergetics  6.2.1. Glycolysis  6.2.2. Citric acid cycle  6.2.3. Electron transport chain  6.3. molecular Biology  6.3.1. DNA replication and repair  6.3.2. Protein synthesis  6.3.3. Gene Regulation  6.4. Structural Biochemistry  6.4.1. Protein Folding  6.4.2. Membrane Biophysics
  7. Environmental Chemistry  7.1. Atmospheric Chemistry  7.1.1. Greenhouse gases  7.1.2. Ozone depletion  7.1.3. Air pollutants and smoke  7.2. Water Chemistry  7.2.1. pH and water hardness  7.2.2. Wastewater treatment  7.2.3. Aquatic Chemistry  7.3. Soil Chemistry  7.3.1. Heavy metal contamination  7.3.2. Soil pH and Buffering  7.3.3. Nutrient cycling  7.4. Toxicology and Chemical Safety  7.4.1. Toxicokinetics  7.4.2. Risk Assessment in Toxicology and Chemical Safety in Environmental Chemistry  7.4.3. Effects of pollutants on the environment

Graduate → Organic chemistry → Medicinal chemistry ↓


Drug design and development


Drug design and development is a fascinating and complex field within medicinal chemistry, a sub-discipline of organic chemistry. It involves the creation of new medicines to treat various diseases and medical conditions. The process requires an interdisciplinary approach, involving chemistry, biology, and pharmacology, among other fields. This detailed essay will discuss in depth the key aspects of drug design and development, providing insight into the processes, challenges, and scientific principles that underlie this field.

Understanding drug design

Drug design refers to the inventive process of finding new drugs based on knowledge of a biological target. The biological target is usually a protein, enzyme, or receptor that plays a critical role in a disease. The design of drugs is a challenging task that can be divided into two primary approaches: structure-based drug design (SBDD) and ligand-based drug design (LBDD).

Structure-based drug design (SBDD)

Structure-based drug design involves understanding the 3D structure of a biological target molecule. This information can often come from techniques such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy, which help to view the molecule at the atomic level. By knowing the structure, medicinal chemists can design a drug that will fit into the target's active site like a key in a lock. This method allows for the rational design of potent inhibitors or modulators.

Target Molecules Active site

Ligand-based drug design (LBDD)

In cases where the 3D structure of the target is unknown, ligand-based drug design is used. This approach involves studying molecules that are known to bind to the target. By understanding the properties of these ligands, researchers can predict potential new drugs. This can involve analyzing molecular shapes, pharmacophores, and using computational models to design analogs that will bind equally or better than known drugs.

Stages of drug development

Drug development is an extensive process that involves several stages, from initial discovery to clinical trials and ultimately market approval. These stages ensure that any new drug is safe, effective, and of high quality for patient use.

Search phase

The discovery phase is the beginning of drug development. It involves identifying viable drug targets and potential candidates. This phase typically involves screening thousands of compounds to find those that show promising biological activity. High-throughput screening (HTS) is often used to test large chemical libraries against biological targets to rapidly identify effective compounds.

Preclinical phase

Once potential drug candidates are identified, preclinical testing begins. This phase involves rigorous in vitro (test tube) and in vivo (animal studies) testing to evaluate the drug's safety, effectiveness, and pharmacokinetics. Preclinical testing provides crucial data but does not yet involve any human participants.

Clinical trials

Step 1

The first stage of human testing is Phase I trials. These trials are conducted on a small group of healthy volunteers to assess the drug's safety, tolerable dose range, and pharmacokinetics.

Phase II

If Phase I is successful, the drug moves to Phase II, where it is tested on a larger group that includes patients with the targeted disease. The purpose of this phase is to assess the drug's efficacy, monitor side effects, and further evaluate safety.

Phase III

Phase III trials involve even larger patient groups and compare the new drug to standard treatments. These trials collect more extensive data on effectiveness and monitor adverse reactions. If successful, the drug manufacturer will apply for regulatory approval.

Step 1 Phase II Phase III

Regulatory approval and Phase IV

After successful Phase III trials, the drug manufacturer applies for regulatory approval with agencies such as the FDA (US) or EMA (Europe). This approval allows the drug to be marketed and sold. Post-marketing studies, known as Phase IV, continue to monitor the drug's long-term safety and effectiveness in the general population.

Challenges in drug development

Drug development is often fraught with challenges. A primary issue is the high cost and time required, which often amounts to billions of dollars and takes more than a decade. Another significant challenge is the high attrition rate, where many promising compounds fail during the testing phases. Achieving the optimal balance of efficacy, safety, and patient compliance is another complex task, requiring adjustments in formulation and dosing.

Role of computational chemistry

Computational chemistry plays a vital role in modern drug design. Using computer simulations and models, researchers can predict how drugs will behave in the body, how they will interact with their target molecules, and what their potential side effects might be. This method helps to significantly reduce the cost and time of drug development by allowing virtual screening of compounds.

Example: Using docking simulations to predict binding affinities of drug candidates to the target protein.

Case study: Discovery of a new antiviral drug

Imagine a scenario where researchers aim to find a drug to combat a new viral infection. They start with a known viral enzyme structure using SBDD. Computational models are created to investigate potential inhibitors, leading to the synthesis of several potential compounds. Preclinical trials on these candidates reveal one with high efficacy and safety. Successfully undergoing clinical trials, the drug receives approval and is introduced to the market, effectively managing the viral outbreak.

In this case, drug designers achieved their goal by integrating structure understanding, computational chemistry, rigorous testing phases, and regulatory navigation.

Conclusion

Drug design and development is an essential and multifaceted process in medicinal chemistry. Understanding biological targets, adopting various design strategies and navigating complex development stages are crucial to bringing new therapies to market. Despite the challenges and the need for substantial investment, advances in technology, particularly in computational chemistry, continue to open up new possibilities in the development of effective, safe and life-saving drugs.


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Drug design and development

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