PST Level 5 Semester 1

NTA Level 5 • Semester 1 • PST05106 Structure – Activity Relationship of Sulphonamides Pharmaceutical Organic Chemistry • Source Session/Topic 29 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 29: Structure – Activity Relationship of Sulphonamides. Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: • Define Sulphonamides • Explain chemical structure of sulphonamides • Explain the structure – activity relationship of sulphonamides Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Brainstorming |Definition of Sulphonamides. | | | |Presentation | | |3 |40 minutes |Presentation |Chemical Structure of Sulphonamides.| |4 |45 minutes | Group |Structure – Activity Relationship of| | | |discussion |Sulphonamides. | | | |Presentation | | |5 |10 minutes |Presentation |Key Points | | 6 |10 minutes |Presentation |Evaluation | SESSION CONTENTS. STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify. ASK students if they have any questions before continuing. STEP 2: Definition of Sulphonamides (10 minutes). |Activity: Brainstorming (5 minutes) | | | |Ask students to brainstorm on the following question: | | | |What are Sulphonamides? | | | |ALLOW few students to respond. | | | |WRITE their responses on the flip chart/ board. | | | |CLARIFY and SUMMARISE by using the table below | Sulphonamides are antibacterial agents which acts against cell metabolism (antimetabolites). Sulfonamides: • Once known as ‘wonder drug’. • Once mainstays of antimicrobial chemotherapy. • The relative cheapness of the sulphonamides is one of their most attractive features and accounts for much of their persistence in the market. STEP 3: Chemical Structure of Sulphonamides (40 minutes). • Sulphonamides are composed of a sulphur atom that has two sets of double bonds to two oxygen atoms, a carbon-based side group, and a nitrogen atom bonded to the sulphur itself. • In organic chemistry, an amide contains a carbonyl group bonded to a nitrogen atom. • Sulphonamides are similar, but the carbonyl group is replaced with sulfone sulphur with two oxygen atoms). • That's why the term 'amide' appears in the name. [pic] General structure of amides and sulphonamides. • The 'R' groups in the figure simply represent any generic carbon-based side chain and could be virtually anything. • For example, R could be a methyl group, a benzene ring, an alkane ring, or some other group. • If the nitrogen atom contains two hydrogens, the sulphonamide is classified primary, if there is one hydrogen it's secondary, and if no hydrogens are present on the nitrogen, it's a tertiary sulphonamide [pic] Structures of primary, secondary, and tertiary sulphonamides. Important Sulfonamide Derivatives • Sulfamethoxazole • Sulfamethoxazole is another sulfonamide with antibacterial activity and is commonly used in the treatment of urinary tract infections and bronchitis. • Sulfamethoxazole looks very similar to sulfanilamide in terms of its structure but contains an extra ring system called an oxazole. [pic] STEP 4: Structure – Activity Relationship of Sulphonamides (45 minutes). |Activity: Small Group Discussion (20 minutes). | | | |DIVIDE students into small manageable groups. | | | |ASK students to discuss on the following question. | |What is the importance of SAR of sulphonamides? | | | |ALLOW students to discuss for 15 minutes. | | | |ALLOW few groups to present and the rest to add points not mentioned. | | | |CLARIFY and SUMMARIZE by using the contents below | The synthesis of a large number of sulphonamide analogues led to the following conclusions [pic] Sulfonamides analogues • The para -amino group is essential for activity and must be unsubstituted (i.e. R1=H). The only exception is when R1=acyl (i.e. amides). • The amides themselves are inactive but can be metabolized in the body to regenerate the active compound. • Thus, amides can be used as sulfonamide prodrugs. • Incorporation of other groups (halogen, alkyl, etc.) destroys the activity. [pic] Metabolism of acyl group to regenerate active compound • The aromatic ring and the sulphonamide functional group are both required. • Total loss of antibacterial activity occurs if sulphonamide group is replaced by other acidic groups (sulfonic, phosphoric etc.) • The aromatic ring must be para -substituted only. • Extra substitution eliminates activity for steric reasons. • The sulfonamide nitrogen must be primary (sulfanilamide) or secondary (acidic proton is essential for antibacterial activity). • R2 is the only possible site that can be varied in sulfonamides. Sulphonamide analogues • R2 can be varied by incorporating a large range of heterocyclic or aromatic structures, which affects the extent to which the drug binds to plasma protein. • This in turn controls the blood levels of the drug such that it can be short acting or long acting. • Thus, a drug which binds strongly to plasma protein will be slowly released into the blood circulation and will be longer lasting. • R2 affects pharmacokinetic properties but not the pharmacodynamics properties. Sulfonamide analogues with reduced toxicity • Changing the nature of the group R2 has also helped to reduce the toxicity of some sulfonamides. • The primary amino groups of sulfonamides are acetylated in the body and the resulting amides have reduced solubility which can lead to toxic effects. • For example, the metabolite formed from sulfathiazole is poorly soluble and can prove fatal if it blocks the kidney tubules [pic] Insoluble • It was discovered that the solubility problem could be overcome by replacing the thiazole ring in sulfathiazole with a pyrimidine ring to give sulfadiazine. [pic] • Its metabolites will also be water soluble • The reason for the improved solubility lies in the acidity of the sulphonamide NH proton. • In sulfathiazole, this proton

NTA Level 5 • Semester 1 • PST05106 Structure – Activity Relationship of Aspirin Pharmaceutical Organic Chemistry • Source Session/Topic 30 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 30: Structure – Activity Relationship of Aspirin. Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: • Define Aspirin • Explain Chemical structure of aspirin • Explain the structure – activity relationship of aspirin Resources Needed: • Flip charts, marker pens, and masking tape. • Black/white board and chalk/whiteboard markers. SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Brainstorming |Definition of Aspirin | | | |Presentation | | |3 |40 minutes |Presentation |Chemical Structure of Aspirin | |4 |45 minutes |Group |Structure – Activity Relationship of| | | |discussion |Aspirin | | | |Presentation | | |5 |10 minutes |Presentation |Key Points | | 6 |10 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify. ASK students if they have any questions before continuing. STEP 2: Definition of Aspirin (10 minutes). |Activity: Brainstorming (5 minutes) | | | |Ask students to brainstorm on the following question: | | | |What is Aspirin? | | | |ALLOW few students to respond | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY and SUMMARISE by using the table below | • Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body. • It also prevents blood clots (i.e., is antithrombotic). As a group, NSAIDs are non-narcotic relievers of mild to moderate pain of many causes, including o Headaches, o Injury, o Menstrual cramps, o Arthritis, and other musculoskeletal conditions • Other members of this class include o ibuprofen (Motrin), o indomethacin (Indocin), o nabumetone (Relafen) and several others. • They all work by reducing the levels of prostaglandins, chemicals that are released when there is inflammation and that cause pain and fever. • NSAIDs block the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower concentrations of prostaglandins. • As a consequence, inflammation, pain, and fever are reduced. • Inhibition of prostaglandins also reduces the function of platelets and the ability of blood to clot. STEP 3: Chemical Structure of Aspirin (40 minutes). • Acetylsalicylic acid –or, as it is more commonly known, aspirin –has a simple chemical structure. • It consists of a small number of carbons, hydrogen and oxygen atoms that form the chemical bonding patterns shown below. • Aspirin Acetylsalicylic acid C9H8O4 [pic] • One of the best-known aromatic acetates is acetylsalicylic acid, or aspirin, which is prepared by the esterification of the phenolic hydroxyl group of salicylic acid. [pic] • Aspirin possesses a number of properties that make it the most often recommended drug which are; o analgesia, leading to pain relief o anti-inflammatory effect, providing some relief from the swelling associated with arthritis and minor injuries. o antipyretic effect, which means it reduces fever. Synthesis • The key compound in the synthesis of aspirin, salicylic acid, is prepared from phenol by Kolbe synthesis (also known as the Kolbe- Schmitt reaction) whereby sodium phenoxide is heated with CO2 under pressure and the reaction mixture is subsequently acidified to yield salicylic acid. [pic] STEP 4: Structure – Activity relationship of Aspirin (45 minutes). |Activity: Small Group Discussion (20 minutes) | | | |DIVIDE students into small manageable groups. | | | |ASK students to discuss on the following question | |What is the importance of SAR of aspirin? | | | |ALLOW students to discuss for 15 minutes. | | | |ALLOW few groups to present and the rest to add points not mentioned. | | | |CLARIFY and SUMMARIZE by using the contents below | • Despite the vast effort that has been expended in the search to find a “better” aspirin—that is, one possessing fewer GI side effects, but a greater potency and a longer duration of action yet is inexpensive and an antipyretic, analgetic, and anti-inflammatory agent that is overall superior to aspirin—none has yet to be discovered. The following structure–activity relationships have been established: [pic] • Possesses a free carboxylic acid (COOH) for an ionic interaction with the positively charged arginine residue at the active site of the cyclooxygenases (i.e., Arg-120 in COX-1 or Arg-106 in COX-2 isozymes). • This acidic moiety is further linked to an aromatic (or heteroaromatic) ring for binding to either the Δ5-double-bond or Δ8- double-bond binding regions. • The active moiety appears to the salicylate anion. • The side effects of aspirin, particularly the GI effects, appear to be associated with the carboxylic acid function. • Reducing the acidity of this group (e.g., converting to an amide, salicylamide) maintains the analgesic actions of salicylic acid derivatives but eliminates the anti-inflammatory properties. • Substitution on either the carboxyl or phenolic hydroxyl groups may affect potency and toxicity. • Benzoic acid itself has only weak anti-inflammatory activity. • Placing the phenolic hydroxyl group meta or para to the carboxyl group abolishes this activity. • Substitution of halogen atoms on the aromatic ring enhances potency and toxicity. • Substitution of aromatic rings at the 5-position of salicylic acid increases anti-inflammatory activity (e.g., diflunisal). STEP 5: Key Points (10 minutes). • Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body. • Aspirin possesses a free carboxylic acid (COOH) for an ionic interaction with the positively charged arginine residue at the active site of the cyclooxygenases. • Modification of carboxylic acid function group of aspirin may help in reducing its GI toxicity. STEP 6: Evaluation (10 minutes). • What is Aspirin? • Draw chemical structure of aspirin. • What

NTA Level 5 • Semester 1 • PST05106 Structure – Activity Relationship of Paracetamol Pharmaceutical Organic Chemistry • Source Session/Topic 31 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 31: Structure – Activity Relationship of Paracetamol. Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: • Define Paracetamol • Explain Chemical structure of paracetamol • Explain the structure – activity relationship of paracetamol Resources Needed: • Flip charts, marker pens, and masking tape. • Black/white board and chalk/whiteboard markers. SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Brainstorming |Definition of Paracetamol | | | |Presentation | | |3 |40 minutes |Presentation |Chemical Structure of Paracetamol | |4 |45 minutes |Group |Structure – Activity Relationship of| | | |discussion |Paracetamol | | | |Presentation | | |5 |10 minutes |Presentation |Key Points | | 6 |10 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes). READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Definition of Paracetamol (10 minutes). |Activity: Brainstorming (5 minutes) | | | |Ask students to brainstorm on the following question: | | | |What is paracetamol? | | | |ALLOW few students to respond. | | | |WRITE their responses on the flip chart/ board. | | | |CLARIFY and SUMMARISE by using the table below | • Paracetamol also known as acetaminophen is an analgesic antipyretic derivative of acetanilide. • Acetaminophen has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. • Acetaminophen is a p-aminophenol derivative with analgesic and antipyretic activities. • Although the exact mechanism through which acetaminophen exert its effects has yet to be fully determined, acetaminophen may inhibit the nitric oxide (NO) pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate (NMDA) and substance P, resulting in elevation of the pain threshold. • The antipyretic activity may result from inhibition of prostaglandin synthesis and release in the central nervous system (CNS) and prostaglandin-mediated effects on the heat-regulating center in the anterior hypothalamus. • Acetaminophen is a widely used nonprescription analgesic and antipyretic medication for mild-to-moderate pain and fever. • Harmless at low doses, acetaminophen has direct hepatotoxic potential when taken as an overdose and can cause acute liver injury and death from acute liver failure. • Even in therapeutic doses, acetaminophen can cause transient serum aminotransferase elevations. Summary • Paracetamol (acetaminophen) is a pain reliever and a fever reducer. • Paracetamol is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers. It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint. STEP 3: Chemical Structure of Paracetamol (40 minutes). • The acetaminophen has the IUPAC name N-(4-hydroxyphenyl) acetamide and its chemical formula us C8H9NO2 and its extended formula is HOC6H4NHCOCH3. • Its molar mass is 151.165 g mol-1. • The molecule is formed by an aromatic phenyl ring, which has two substituents in position -para (1,4). • The first substituent is an amide group (acetamide) and the second is a hydroxy group (-OH). • The molecule is planar with 7 carbon atoms with sp2 hybridization. • Its chemical structure can be written as below, in the common representations used for organic molecules. [pic] STEP 4: Structure – Activity relationship of Paracetamol (45 minutes) |Activity: Small Group Discussion (20 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question. | |What is the importance of SAR of paracetamol? | | | | | |ALLOW students to discuss for 15 minutes. | | | |ALLOW few groups to present for 5 minutes and the rest to add points | |not mentioned. | | | |CLARIFY and SUMMARIZE by using the contents below | • Paracetamol consists of a benzene ring core, substituted by one hydroxyl group and the nitrogen atom of an amide group in the para (1,4) pattern. • The amide group is acetamide (ethanamide). • It is an extensively conjugated system, as the lone pair on the hydroxyl oxygen, the benzene pi cloud, the nitrogen lone pair, the p orbital on the carbonyl carbon, and the lone pair on the carbonyl oxygen is all conjugated. • The presence of two activating groups also makes the benzene ring highly reactive toward electrophilic aromatic substitution. • As the substituents are ortho,para-directing and para with respect to each other, all positions on the ring are more or less equally activated. • The conjugation also greatly reduces the basicity of the oxygens and the nitrogen, while making the hydroxyl acidic through delocalisation of charge developed on the phenoxide anion. • Structure and reactivity of acetaminophen accounts for its chemical properties • Based on the comparative toxicity of acetanilide and acetaminophen, aminophenols are less toxic than the corresponding aniline derivatives, although p-aminophenol itself is too toxic for therapeutic purposes. • Etherification of the phenolic function with methyl or propyl groups produces derivatives with greater side effects than with ethyl groups. Substituent • The nitrogen atoms that reduce basicity reduce activity unless that substituent is metabolically labile (e.g., acetyl). • Amides derived from aromatic acids (e.g., N-phenylbenzamide) are less active or inactive. • As indicated, both acetanilide and phenacetin are metabolized to acetaminophen. Additionally, both undergo hydrolysis to yield Aniline derivatives that produce directly, or through their conversion to hydroxylamine derivatives, significant methemoglobinemia and hemolytic anemia, which resulted in their removal from the U.S. market. STEP 5: Key Points (10 minutes) • Paracetamol also known as acetaminophen is an analgesic antipyretic derivative of acetanilide • The SAR of paracetamol may

NTA Level 5 • Semester 1 • PST05106 Biotransformation of Medicinal Products Pharmaceutical Organic Chemistry • Source Session/Topic 32 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 32: Biotransformation of Medicinal Products. Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: • Define biotransformation • Explain metabolism of different organic compounds • Explain the importance of biotransformation Resources Needed: • Flip charts, marker pens, and masking tape. • Black/white board and chalk/whiteboard markers. SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Brainstorming |Definition of Biotransformation | | | |Presentation | | |3 |60 minutes |Presentation |Metabolism of Organic Compounds | |4 |25 minutes |Group |Importance of Biotransformation | | | |discussion | | | | |Presentation | | |5 |10 minutes |Presentation |Key Points | | 6 |10 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Definition of Biotransformation (10 minutes). |Activity: Brainstorming (5 minutes) | | | |Ask students to brainstorm on the following question: | | | |What is Biotransformation? | | | |ALLOW few students to respond. | | | |WRITE their responses on the flip chart/ board. | | | |CLARIFY and SUMMARISE by using the table below | • Biotransformation is Chemical alteration of the drug in body that converts non-polar or lipid soluble compounds to polar or lipid insoluble compounds. OR • Biochemical alteration of chemicals such as (but not limited to) nutrients, amino acids, toxins, and drugs in the body. • It is also needed to render non-polar compounds polar so that they are not reabsorbed in renal tubules and are excreted. • The body typically deals with a foreign compound (DRUGS) by making it more water-soluble, to increase the rate of its excretion through the urine. STEP 3: Metabolism of Organic Compounds (60 minutes). • Termination of drug effect is by the process of drug elimination which involves mainly 2 processes: one of them is drug metabolism. • Metabolism is predominantly done in the liver due to its richness in enzymes • The enzymes that are responsible for drug metabolism in the liver are; o Microsomal mixed function oxidases (MFOs) system involved. o Cytochrome P450 enzymes play important role. • Other organs responsible for drug metabolism are; o Lungs o Kidney o Intestine o Placenta o Skin o Brain o Testes o Muscle o Spleen • Metabolism of drugs makes them: o More polar o Ionizable o Water soluble to enhance renal excretion o More active (for pro drugs) Drug Metabolism in the Liver • There are two phases of drug metabolism in the liver. • Phase I reaction • Phase II reaction PHASE I REACTIONS • A polar group is introduced/ unmasked to make the drug molecule more water-soluble & less active to be excreted. • Reactions are non-synthetic in nature. • The majority of metabolites are generated by a common hydroxylating enzyme system known as Cytochrome P450. o Oxidation o Reduction o Hydrolytic cleavage o Dealkylation o Ring cyclization o N-carboxylation o Dimerization o Transamidation o Isomerization o Decarboxylation • Oxidation of aromatic carbon atoms (aromatic hydroxylation): [pic] • Oxidation of olefins (C=C bonds): o Oxidation of non-aromatic C=C bonds is analogous to aromatic hydroxylation. i.e. it proceeds via formation of epoxides to yield 1,2- dihydrodiols [pic] • Oxidation of Benzylic Carbon Atoms o Carbon atoms attached directly to the aromatic ring are hydroxylated. [pic] • Oxidation of Allylic carbon Atoms o Carbon atoms adjacent to Olefinic double bonds (are allylic carbon atoms) also undergo hydroxylation in a manner similar to Benzylic Carbons. [pic] • Oxidation of Carbon Atoms Alpha to Carbonyls and Imines o Several Benzodiazepines contain a carbon atom (C-3) alpha to both Carbonyl (C=0) and imino (C=N) function which readily undergoes Hydroxylation. [pic] • Oxidation of Aliphatic Carbon Atoms (Aliphatic Hydroxylation) o Terminal hydroxylation of methyl group yields primary alcohols which undergoes further oxidation to aldehydes and then to carboxylic acid. [pic] • Oxidation of Alicyclic Carbon Atoms (Alicyclic Hydroxylation) o Cyclohexane (alicyclic) and piperidine (non-aromatic heterocyclic) rings are commonly found in a number of molecules. o Such rings are generally hydroxylated at C-3 or C-4 positions. [pic] • Oxidation Of Carbon-Heteroatom Systems o Biotransformation of C-N, C-0 & C-S system proceed in one of the two ways: ▪ Hydroxylation of carbon atom attached to the heteroatom and subsequent cleavage at carbon-heteroatom bond. E.g. N-, O- & S- dealkylation, oxidative deamination & desulfuration. ▪ Oxidation of the heteroatom itself. E.g. N- & S- oxidation. • Oxidation of Carbon-Nitrogen System o N-DEALKYLATION: ▪ Mechanism of N-dealkylation involve oxidation of α-carbon to generate an intermediate carbinolamine which rearranges by cleavage of C-N bond to yield the N dealkylated product and the corresponding carbonyl of the alkyl group. [pic] ▪ A tertiary nitrogen attached to different alkyl groups undergoes dealkylation by removal of smaller alkyl group first. Example: o 2º aliphatic amine e.g. Methamphetamine. o 3º aliphatic amine e.g. imipramine o 3º alicyclic amine e.g. hexobarbital o Amides e.g. Diazepam o N-HYDROXYLATION: ▪ Converse to basic compounds that form N-oxide, N- hydroxy formation is usually displayed by non-basic nitrogen atoms such as amide Nitrogen. [pic] • Oxidation of Carbon-Sulfur Systems o S-DEALKYLATION: ▪ The mechanism of S-Dealkylation of thioethers is analogous to N- dealkylation .IT proceed via α-carbon hydroxylation. ▪ The C-S bond cleavage results in formation of a thiol and a carbonyl product. [pic] • Desulfuration: o This reaction also involves cleavage of carbon-sulfur bond (C=S). o The product is the one with C=0 bond. o Such a desulfuration reaction is commonly observed in thioamides such as thiopental [pic]

NTA Level 5 • Semester 1 • PST05106 Pharmaceutical Organic Chemistry – Complete Full Notes Complete educational source text in one page Completeness safeguard: this page keeps the complete educational module/source wording in one place so learning material is not lost when browsing topic by topic. Presenter/tutor metadata is intentionally excluded. UNITED REPUBLIC OF TANZANIA [pic] Ministry of Health, Community Development, Gender, Elderly and Children Facilitator Guide Copyright © Ministry of Health, Community Development, Gender, Elderly and Children – 2018 Table of Contents Table of Contents iii Background iv Acknowledgment v Introduction vii Abbreviations/Acronym xi Session 1: Introduction to Pharmaceutical Organic Chemistry. 1 Session 2: Classification of Organic Compounds. 8 Session 3: Classification of Drugs According to Their Chemical Nature. 14 Session 4: Nomenclature of Organic Compounds. 17 Session 5: General Properties of Organic Compounds. 23 Session 6: Chemical Reaction in Organic Compounds. 32 Session 7: Isomerism. 38 Session 8: Alkanes of Pharmaceutical Importance. 48 Session 9: Alkenes of Pharmaceutical Importance. 57 Session 10: Alkynes of Pharmaceutical Importance. 73 Session 11: Alcohols of Pharmaceutical Importance. 84 Session 12: Carboxylic Acids of Pharmaceutical Importance. 101 Session 13: Esters of Pharmaceutical Importance. 114 Session 14: Acyl Chlorides of Pharmaceutical Importance. 122 Session 15: Ethers of Pharmaceutical importance. 128 Session 16: Aldehydes of Pharmaceutical Importance. 138 Session 17: Ketones of Pharmaceutical Importance. 148 Session 18: Aromatic Organic Compounds of Pharmaceutical Importance . 161 Session 19: Phenols of Pharmaceutical Importance. 175 Session 20: Aryl Halides of Pharmaceutical Importance. 188 Session 21: Amines of Pharmaceutical Importance. 200 Session 22: Amides of Pharmaceutical Importance. 216 Session 23: Introduction to Heterocyclic Compounds. 224 Session 24: Chemical Reactions of Heterocyclic Compounds. 234 Session 25: Introduction to Structure – Activity Relationship of Drugs. 243 Session 26: Structure – Activity Relationship of Penicillins. 247 Session 27: Structure – Activity Relationship of Cephalosporins. 257 Session 28: Structure – Activity Relationship of Quinolones. 264 Session 29: Structure – Activity Relationship of Sulphonamides. 271 Session 30: Structure – Activity Relationship of Aspirin. 279 Session 31: Structure – Activity Relationship of Paracetamol. 285 Session 32: Biotransformation of Medicinal Products. 290 Background There is currently an ever-increasing demand for pharmaceutical personnel in Tanzania. This is due to expanding investment in public and private pharmaceutical sector. Shortage of trained pharmaceutical human resource contributes to poor quality of pharmaceutical services and low access to medicines in the country (GIZ, 2012). Through Public-Private-Partnership (PPP) the Pharmacy Council (PC) together with Development Partners (DPs) in Germany and Pharmaceutical Training Institutions (PTIs) worked together to address the shortage of human resource for pharmacy by designing a project named “Supporting Training Institutions for Improved Pharmaceutical Services in Tanzania” in order to improve quality and capacity of PTIs in training, particularly of lower cadre pharmaceutical personnel. The Pharmacy Council formed a Steering committee that conducted a stakeholder’s workshop from18th – 22ndAugust 2014 in Morogoro to initiate the implementation of the project. Key activities in the implementation of this project included carrying out situational analysis, curriculum review and harmonization, development of training manual/facilitators guide, development of assessment plan, training of trainers and supportive supervision. After the curricula were reviewed and harmonized, the process of developing standardised training materials started through Writer’s Workshop approach. The approach included a number of workshops for developing, reviewing, editing and formatting the sessions of the modules. The goals of writer’s workshops were to build capacity of tutors in the development of training materials and to develop high-quality, standardized teaching materials. The training package for pharmacy cadres includes a facilitator guide, assessment plan and practicum. There are 11 modules for NTA level 5 making 11 facilitator guides including one practicum guide. Acknowledgment The development of standardized training materials of a competence-based curriculum for pharmaceutical sciences has been accomplished through involvement of different stakeholders. Special thanks go to the Pharmacy Council for spearheading the harmonization of training materials in the pharmacy after noticing that training institutions in Tanzania were using different curricula and train their students differently. I would also like to extend my gratitude to Christian Social Service Commission (CSSC) for their tireless efforts to mobilize funds from development partners. Special thanks to Multi Actors Partnership (MAP) for the financial and technical support. Particular thanks are due to those who led this important process to its completion, Centre for Education Development in Health Arusha (CEDHA), Ms. Diana Gamuya, Mr. Dickson Mtalitinya and Members from the secretariat of National Council for Technical Education (NACTE) for facilitating the process. Finally, I very much appreciate the contributions of the tutors and content experts representing PTIs, hospitals, and other health training institutions. Their participation in meetings and workshops, and their input in the development of this training manual/facilitators guide have been invaluable. These participants are listed with our gratitude below: Ms. Elizabeth Shekalaghe Registrar, Pharmacy Council of Tanzania Dr. Catherine Jincen Principal, CEDHA Dr. Saitore Laizer Deputy Principal, CEDHA Dr. Sungwa N. Kabissi Project Manager – MAP, CSSC Ms. Diana Gamuya CEDHA Ms. Emily Mwakibolwa Pharmacy Council Ms. Tumaini H. Lyombe MUHAS Ms. Dilisi J. Makawia KSP Director of Human Resources Development Ministry of Health, Community Development, Gender, Elderly and Children Introduction Module Overview This module content is a guide for tutors of Pharmaceutical schools for training of students. The session contents are based on sub-enabling outcomes and their related tasks of the curriculum for Basic Technician Course in Pharmaceutical Sciences. The module sub-enabling outcomes and their related tasks are as indicated in the Ordinary Technician Certificate in Pharmaceutical Sciences (NTA Level 5) Curriculum. Target Audience This module is intended for use primarily by tutors of pharmaceutical schools. The module’s sessions give guidance on the time, activities and provide information on how to teach the session. The sessions include different activities which focus on increasing students’ knowledge, skills and attitudes. Organization of the Module The module consists of thirty-two (32) sessions; each session is divided into several parts as indicated below: • Session Title: The name of the session • Total Session Time: The estimated time for teaching the session, indicated in