Graduate Medicinal Chemistry Course Descriptions

Graduate Medicinal Chemistry Course List and Syllabi

Medicinal Chemistry 502. Principles of Medicinal Chemistry 2. (3) MCH 502 is a continuation of MCH 501. Drug metabolism, prodrugs and drug delivery systems are discussed in detail, as well as principles of pharmacokinetics and pharmacogenomics. In addition, prototypes of selected drug classes are discussed with a focus on the molecular mechanisms of action of representative drugs. Drug-target interactions at the molecular level will be examined using 3D-visualization techniques, which the students will learn to use. In this course, the medicinal chemistry topics are integrated with relevant topics in biochemistry, physiology, pharmaceutics, pharmacology and structural biology. SPRING Medicinal Chemistry 503. Bio-organic Chemistry. (3) The aims of this course are to develop an understanding of mechanisms of action of biological catalysts and effectors with regard to possible means of selective chemotherapeutic control of biological processes. Topics included are molecular interactions, chemical and kinetic studies of the mechanism of action of enzymes and coenzymes, design and synthesis of active-site directed enzyme inhibitors and receptors. SPRING Medicinal Chemistry 511-511R. Research Problems. (3) Methods of utilizing the literature relating to medicinal chemistry are outlined. Each student must conceive of a research problem unrelated to his previous research activity and prepare a formal written research proposal for this problem. This proposal must be orally defended before the faculty. This course is required of all Ph.D. candidates in the department and is taken during the student's second year. How to Write Your Proposal! (Open only to graduate students in Medicinal Chemistry.) Medicinal Chemistry 512R. Instrumental Analysis. (4) The application of physical methods to the separation and structure determination of organic compounds. Mass spectrometry will be discussed. The discussion of thin-layer, column, and gas-liquid chromatography and of infrared, ultraviolet and nuclear magnetic resonance spectroscopy will normally be followed by laboratory practice. (Lecture/Laboratory) FALL Medicinal Chemistry 615-6. Research. Guidance in research in connection with Graduate thesis or dissertation. Medicinal Chemistry 622-622R. Seminar in Medicinal Chemistry. Attendance at seminar required for all students in the program. May not be taken for more than a total of 3 credit hours. Taken only in the seminar in which the student is presenting a seminar. Medicinal Chemistry 700-700R. Thesis Guidance. Writing and submissions of thesis or dissertation under the supervision of the major professor.

The courses listed below are usually offered in alternate years and are elective topics appropriate for the students' needs and interests.

Medicinal Chemistry 501. Principles of Drug Design and Discovery This course focuses on the fundamental aspects and current methodologies involved in the drug discovery process. The fundamental aspects include the physical, chemical, and pharmaceutical properties of drugs. The methodologies include lead discovery strategies, statistically based 2D and 3D QSAR optimization methods, structure-based and mechanism-based design methods, and combinatorial techniques. Application to the chemotherapy of cancer, viral and microbial diseases will be examined. Medicinal Chemistry 513. Carbohydrates. (3) The organic chemistry of carbohydrates is studied. The discussion emphasizes conformational analysis, steroselective reactions, and the blocking-group chemistry needed for sterospecific transformations. Major attention is given to the biologically important monosaccharides, the carbohydrate portions of nucleosides and antibiotics, and the rare sugars. Medicinal Chemistry 514. Nucleotide and Peptide Chemistry. (3) A study of the chemistry, structure elucidation, and synthesis of nucleosides, nucleotides, nucleic acids and peptides. Medicinal Chemistry 515. Structure Elucidation of Natural Products. (3) A study of methods useful for the proof of structure of the alkaloids and other natural products. Medicinal Chemistry 516. Steroids. (3) A study of the chemistry of steroids. The discussion will focus on interconversions, stereoselective syntheses, and structure-activity relationships of steroids, bile acids, D vitamins, and steroid hormones. Medicinal Chemistry 517. Heterocyclic Chemistry. (3) The synthesis, chemistry, and properties of heteroaromatic heterocycles which represent important drug classes will be studied. Medicinal Chemistry 518. Active Site Chemistry. (2) Chemical approaches to the design of specific inhibitors for labeling the active sites of enzymes. Medicinal Chemistry 519. Kinetics of Model Systems Related to Enzymic Reactions. (3) Kinetics of model reactions related to biochemical reactions are studied. Implications from the results of model studies are applied to their biochemical counterparts with a view to rationalizing biochemical mechanisms using fundamental principles of organic chemistry. Medicinal Chemistry 521. Molecular Structure in Drug Design. (3) A study of the development of quantitative methods useful for the correlation of biological activities with structural properties. Included are empirical de novo, linear free energy, and quantum statistical approaches. Medicinal Chemistry 522. Biosynthesis and Drug Metabolism. (3) Discussion of the methods used in the study of the biosynthesis of selected natural products, in particular, terpenes, acetgenins, and aromatic compounds. Included is an introduction to drug metabolism and the significance of drug metabolism in the design of new agents. Medicinal Chemistry 524. Mechanisms of Drug Action. (3) This course reviews the general principles of drug action and the pharmacological activities of various classes of drugs. The major focus is on the molecular mechanisms of drug action, with a detailed discussion of one or more prototypes of each drug class. Selected examples of drug discovery and development are also discussed. At the completion of the course, students will have a knowledge of the molecular basis of pharmacological activity, the mode of action of major classes of therapeutic agents and be familiar with rational approaches to drug design utilizing mechanistic information. Medicinal Chemistry 525. Structure-based Design of Ligands and Combinatorial Libraries. (3) In the first half of the course various methods, and the relevant background theory, for modeling ligand:protein complexes utilizing protein x-ray or NMR structures as an experimental foundation are covered. These methods, and related theory, include: molecular mechanics calculations, computer graphics and ligand docking techniques, de novo generation of new ligands and the thermodynamics of ligand binding in water. The individual ligand design methods are then used as a basis for evaluating various methods for designing combinatorial libraries of ligands. Contemporary drug targets are used to illustrate these methods. The second half of the course begins with hands-on training in the use of the molecular modeling software package SYBYL with Silicon Graphics terminals. In this half of the course each student completes an individual project wherein a combinatorial library of ligands is designed from a protein structure. Each student also presents to the class a critical evaluation of a current research paper wherein the methods covered in this course were a key component in the work reported. Medicinal Chemistry 525A. Molecular Modeling This course will focus on the current methods in structure-based design and the underlying physical science (e.g. what determines the binding free energy for a protein ligand). The lecture material will initially focus on the design of an individual ligand from the x-ray or NMR structure of the drug target protein (e.g. an enzyme) and subsequently will extend into designing libraries of ligands. There will be no textbook for the course but reading assignments will be given from the current literature, particularly review articles. The first ca. Half of the semester will be mainly formal lectures to give you the necessary background for doing subsequent hands-on modeling experiments. In the second half of the semester training sessions will be given on how to use the Tripos, Inc. Modeling software package SYBYL, and associated software modules, on our UB computer graphics workstations. You will then be given an independent modeling project wherein you will design a library of enzyme inhibitors based upon the structure of an enzyme. Upon completion of this course you will be able to independently carry out molecular modeling studies in support of drug design projects as well as use molecular modeling in support of bioorganic and organic chemistry research projects. Since a large selection of Tripos software, and easily accessible computer graphics workstations, are readily available to you at UB, you will be able to immediately put this new expertise to work in your graduate research projects when suitable, or use the expertise in your later research. Medicinal Chemistry 527. Combinatorial Chemistry. (3) Combinatorial chemistry is a new field within the areas of medicinal/synthetic organic chemistry and chemical information technology. Most pharmaceutical and biotechnology companies have now incorporated combinatorial chemistry into their drug discovery research. Consequently, chemists/medicinal chemists with hands-on experience in this new technology are in high demand. Combinatorial chemistry centers on the design, simultaneous synthesis, and computerized tracking of many new compounds (i.e. "libraries" of compounds) in a highly efficient and automated fashion. This course will focus largely on the medicinal and synthetic organic chemistry aspects of combinatorial chemistry. The first third of the semester will be the lecture module of the course (1 credit) and the last two thirds will be the hands-on laboratory module of the course (2 credits). Students may take only the lecture module of the course, but the laboratory module requires achieving a grade of B- or better in the lecture module, and prior approval from the instructor since the lab has limited enrollment. Equipment and supplies for the laboratory module are generously funded by The Camille & Henry Dreyfus Foundation Special Grant Program in the Chemical Sciences and by the University at Buffalo. (Lecture/Laboratory)