ADVANCED PHARMACEUTICAL ORGANIC CHEMISTRY – II

Synthetic Reagents and Applications: Lead tetra acetate (LTA), n-bromo succinamide (NBS), osmonium tetraoxide, lithium aluminium hydride (LAH), sodium borohydride, DCC (Dicyclohexyl carbodimide), and 2,3-dichlro-5,6-dicyano-1,4-benzoquinone (DDQ).

Mechanism and applications of reactions and reagents:

            a. Claisen ester condensation, 

            b. Mannich reaction, 

            c. Micheal addition, 

            d. Witting reaction, 

            e. Synthetic applications of ethyl aceto acetate, diethyl malonate, ethylcyano acetate.

Development & scale up of process for the manufacture of new pharmaceuticals: 

            1. Introduction, synthetic route selection, development and scale up, optimization of synthetic routes-yield improvement, investigative approach, streamlining the process.

            2. A brief account on Green Chemistry: principles, and applications.

  

Synthetic Strategies: Introduction to disconnection approach, consecutive vs convergent synthesis, various strategic approaches in retro synthesis, strategic bond approach-preliminary scan, criteria in disconnection of strategic bonds, identifying strategic bonds in rings.

Combinatorial Chemistry: Introduction, solid phase techniques, parallel synthesis, mixed combinatorial chemistry, deconvulution techniques, tagging, photolithography, limitations of combinatorial chemistry, planning and designing of combinatorial synthesis.

ADVANCED MEDICINAL CHEMISTRY – II

Computer aided drug design (CADD): 

            1. Virtual screening: concept, drug likeness screening, focused screening libraries for lead identification, pharmacophore screening, structure based virtual screening and applications.

            2. Molecular modeling: Molecular mechanics, quantam mechanics, modeling ligands for known receptors and unknown receptors.

Rational Drug design: Quantitative structure activity relationship (QSAR): Physico chemical properties: hydrophobicity, electronic effects, steric factors-Taft’s steric factor (Es), molar refractivity, verloop steric parameter, other physico chemical parameters.

Methods used to correlate physico chemical parameters with biological activity: Hansch analysis, Free and Wilson approach, Topliss scheme, bioisosteres, planning a QSAR study. 3D QSAR, molecular graphics based drug design and mathematical methods.

  

Enzyme Inhibitors: A detailed study of the following types of enzyme inhibitors, related drugs and their pharmaceutical significance.

            • P.G. Synthease (Cyclooxygenase and Lipoxygenase) inhibitors, 

            • Phosphodiesterase (PDE) inhibitors, 

            • HMG Co A reductase inhibitors,

            • Xanthine oxidase inhibitors,

            • Angiotensin convertin enzyme (ACE) inhibitors.  

Anti Viral Agents: Viruses, viral diseases, structure and life cycle of viruses; antiviral agents used against DNA viruses- herpes, chicken pox; and RNA viruses – HIV, influenza.

Chemotherapy of Cancer: Molecular biology of caner: introduction, biochemical basis of cancer, types of cancer, SAR and mechanism of action of anticancer agents, alkylating agents, antimetabolites, antitumor antibiotics. A brief account on cancer chemotherapy and drug resistance.

DRUG SCREENING METHODS AND BIOSTATISTICS

Bio-statistics: Regression and correlation: Linear regressions, Method of least squares; correlation coefficients, rank correlation, multiple regression tests of significance: testing hypotheses, tests of significance based on normal distribution. T-test; significance of correlation coefficient. F-test, Analysis of variance: 1-way, 2-way and 3-way classification, Chi-square test of (i) Variance of a normal population (ii) Goodness of fit, (iii) Independence in contingency tables. 

Design of experiment: Principles of randomization, replication and local control, completely randomized block of the above designs in pharmaceutical research, Statistical quality control, process control, control charts, acceptance sampling – sampling plans. 

High throughput screening: introduction, bioassay design, and screen construction-assay design, assay construction, homogenous and non homogeneous biochemical assays and cellular assays.

          1. Bioassay: Different types: dose effect relationships, calculation of LD₅₀, ED₅₀ – Probit analysis. 

          2. In vivo screening methods: Antihypertensive, antiarrythmic, cardiotonic, and anticancer and diuretic drugs.

   In vivo screening methods: Analgesic, anti-inflammatory, antiepileptic, antidiabetic, and antifertility drugs. 

SCIENTIFIC AND TECHNICAL WRITING

Course Objectives: 

            • To be able to appreciate and understand importance of writing scientifically.

            • To develop competence in writing and abstracting skills.

            • To write either a draft research proposal or a chapter of dissertation.

COLLECTION AND EVALUATION OF INFORMATION

Identification, sources, searching information, classifying information under fact/opinion, tabulating information, summarizing a text and presenting sequence of topics in different forms.

 WRITING AS A MEANS OF COMMUNICATION

-  Different forms of scientific and technical writing.

- Articles in journals, research notes and reports, review articles, monographs, dissertations, bibliographies.

How to formulate outlines: The reasons for preparing outlines

            • as a guide for plan of writing

            • as skeleton for the manuscript

Kinds of outline: topic outlines, conceptual outline, sentence outlines and combination of topic and sentence outlines

DRAFTING TITLES, SUB TITLES, TABLES, ILLUSTRATIONS

Tables as systematic means of presenting data in rows and columns and lucid way of indicating relationships and results.

Formatting Tables: Title, Body stab, Stab Column, Column Head, Spanner Head, Box Head

Appendices: use and guidelines.

The Writing process: Getting started, Use outline as a starting device, Drafting, Reflecting and Re-reading. Checking: Organization, Headings, Content, Clarity and Grammar.

Brevity and Precision in writing - Drafting and Re-drafting based on critical evaluation

 PARTS OF DISSERTATION/RESEARCH REPORT/ARTICLE

Introduction, Review of Literature, Methodology, Results and Discussion. Ask questions related to: content, continuity, clarify, validity internal consistency and objectivity during writing each of the above parts.

WRITING FOR GRANTS

            - Clearly state the question to be addressed

            - Rationale and importance of the question being address

            - Emperial and theoretical conceptualization

            - Presenting pilot study/data

            - Research proposal, clarity, specificity of method

            - Clear organization

            - Outcome of study and its implications 

            - Budgeting, available infra-structure and recourses