First Edition : 1994Twelfth Edition : 2017Thirteenth Revised Edition : 2018(As per Revised Syllabus)Fourteenth Edition : 2019

(Revised syllabus as per credit based and grading system)

T.Y.B.Sc.(Applied Component)

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© AuthorsNo part of this publication may be reproduced, stored in a retrieval system, or transmittedin any form or by any means, electronic, mechanical, photocopying, recording and/orotherwise without the prior written permission of the authors and the publisher.

Dr. Tanuja ParulekarAssociate Professor,

Department of Chemistry,S.I.W.S. College,

Wadala, Mumbai.

Dr. Gomathi ShridharAssociate Professor,

Head, Dept. of Chemistry,V.K. Krishna Menon College of

Commerce, Economics & Science,Bhandup, Mumbai.

Dr. Bholanath MukherjeeAssociate Professor,

Head, Dept. of Chemistry,K.V. Pendharkar College,

Dombivli.

R.S. RaoVice-Principal & Associate Professor,

Department of Chemistry,G.N. Khalsa College of Arts, Science and

Commerce,Matunga, Mumbai.

INTRODUCTION TO

SYNTHETICDRUGS AND DYES

(ii)

SYLLABUS

SEMESTER V

CHEMISTRY OF DRUGSUNIT I1.1 General Introduction to Drugs (8L)

1.1.1 Definition of a drug, sources of drugs, requirements of an idealdrug, classification of drugs (based on therapeutic action).

1.1.2 Nomenclature of drugs: Generic name, Brand name, Systematicname.

1.1.3 Definition of the following medicinal terms: Pharmacon,Pharmacology, Pharmacophore, Prodrug, Half-life efficiency,LD50, ED50, GI50 Therapeutic Index.

1.1.4 Brief idea of the following terms: Receptors, Agonists,Antagonists, Drug-receptor interaction, Drug Potency,Bioavailability, Drug toxicity, Drug addiction, Spurious Drugs,Misbranded Drugs, Adulterated Drugs, Pharmacopoeia.

1.2 Routes of Drug Administration and Dosage Forms (3L)1.2.1 Oral and Parenteral routes with advantages and disadvantages.1.2.2 Formulations and combination formulation, Different dosage

forms (including Patches and Adhesives, emphasis on Sustainedrelease formulations and Enteric coated tablets).

1.3 Pharmacodynamic Agents (4L)A brief introduction of the following pharmacodynamic agents and thestudy with respect to their chemical structure, chemical class,therapeutic uses, and side effects.

1.3.1 CNS Drugs (4L)Classification based on pharmacological actions: CNSDepressants and CNS Stimulants. Concept of Sedation andHypnosis, Anaesthesia. Phenytoin (Hydantoin) Trimethadione (Oxazolidinediones) (Synthesis from

acetone) Alprazolam (Benzodiazepines) Levetiracetam (Pyrrolidines)

PREFACE

This book has been written according to revised syllabus, as percredit based semester and grading system, for Applied Component Paperon Drugs and Dyes prescribed for T.Y.B.Sc. classes by University ofMumbai, effective from academic year 2018-19.

In the section on drugs, important pharmacological terms are definedfirst. The classification of drugs on the basis of chemical structure andbiological activity has been given. The aspects of drug discovery anddesign development, will be interesting to students. The mode of actionand drug metabolism as well as routes of drug administration and dosageforms are explained. The individual classes of drugs have been explainedin detail with examples. The synthesis of drug intermediates is included.The topics like sustained release formulations and use of nanoparticles inmedicinal chemistry will expose the students to the current research inthe field. An idea of different pharmacopoeia is also given.

In the section on dyes, nomenclature and definition of related termsare given in the beginning. This is followed by chemical classification ofdyes with examples. The concept of colour and its relationship to chemicalstructure has been explained clearly. The types of fibers, the dye fibreforces and methods of application of dyes are included. The importanceof unit processes, intermediates and their conversion into dye stuffs hasbeen dealt in later chapters. The students are made aware of the currentconcern about the toxicity of dyes, its effect on environment andremediation methods of physical, chemical and biochemical nature toovercome this problem.

The book will be useful to students to prepare them for appliedcomponent papers in T.Y.B.Sc. examinations. Any suggestions for theimprovement of the book from teachers and students will be appreciated.Finally, the authors thank the publisher and the staff for bringing the fineedition of the book.

Authors(iii) (v)

Amphetamine (Phenethylamine) (Asymmetric synthesisfrom phenyl acetic acid)

Chlorpromazine (Phenothiazines)UNIT II2.1 Analgesics, Antipyretics and Anti-inflammatory Drugs (4L)

2.1.1 Analgesics and Antipyretics Morphine (Phenanthrene alkaloids) Tramadol (Cyclohexanols) (Synthesis from salicylic acid) Aspirin (Salicylates) Paracetamol (p-Amino phenols)

2.1.2 Anti-inflammatory DrugsMechanism of inflammation and various inflammatoryconditions. Steroids: Prednisolone, Betamethasone Sodium Diclofenac, Aceclofenac (N-Aryl anthranilic acids)

(Synthesis from 2,6-dichlorodiphenyl amine)2.2 Antihistaminic Drugs (2L)

Diphenhydramine (Ethanol amines) Cetrizene (Piperazine) (Synthesis from 4-Chlorobenzhydryl

chloride) Chlorpheniramine maleate (Ethyl amines) Pantoprazole (Benzimidazoles)

2.3 Cardiovascular Drugs (3L)Classification based on pharmacological action

Isosorbide dinitrate (Nitrates) Valsartan (Amino acids) (structure not expected) Atenolol (Aryloxy propanol amines) (Synthesis from 3-

Hydroxy phenyl acetamide) Amlodipine (Pyridines) Frusemide/Furosemide (Sulfamoyl benzoic acid) Rosuvastatin (Pyrimidine)

2.4 Antidiabetic Agents (2L)General idea and types of diabetes; Insulin therapy

Glibenclamide (Sulphonyl ureas) Metformin (Biguanides) Dapagliflozin (Pyranose) Pioglitazone (Thiazolidinediones) (Synthesis from 2-

(5-ethylpyridin-2-yl) ethanol)

2.5 Antiparkinsonism Drugs (2L)Idea of Parkinson’s disease

Procyclidine hydrochloride (Pyrrolidines) Ethopropazine hydrochloride (Phenothiiazines) Levodopa (Amino acids) (Synthesis from Vanillin)

2.6 Drugs for Respiratory SystemGeneral idea of: Expectorants; Mucolytes; Bronchodilators;Decongestants; Antitussives (2L)

Ambroxol (Cyclohexanol) (Synthesis from paracetamol) Salbutamol (Phenyl ethyl amines) Oxymetazoline (Imidazolines) Codeine Phosphate (Opiates)

UNIT III3.1 Introduction to the Dye-stuff Industry (5L)

3.1.1 DyesDefinition of dyes, Requirements of a good dye, i.e., Colour,Chromophore and Auxochrome, Solubility, Linearity, Coplanarity,Fastness, Substantivity, Economic viability.Definition of fastness and its properties and Mordants withexamplesExplanation of nomenclature or abbreviations of commercial dyeswith at least one example suffixes – G, O, R, B, K, L, C, S, H, 6B,GK, 6GKNaming of dyes by colour index (two examples) used in dyeindustries.

3.1.2 Natural and Synthetic DyesNatural Dyes: Definition and limitations of natural dyes.Examples and uses of natural dyes w.r.t. Heena, Turmeric, Saffron,Indigo, Madder, Chlorophyll – names of the chief dyeing material/s in each natural dye [structures not expected],Synthetic dyes: Definition of synthetic dyes, primaries andintermediates. Important milestones in the development ofsynthetic dyes – Emphasis on Name of the Scientist, dyes andthe year of the discovery is required (structure is not expected).

3.2 Substrates for Dyes: Types of Fibres (3L)3.2.1 Natural: cellulosic and proteinaceous fibres, examples – wool,

silk and cotton structures and names of dyes applied on each ofthem.

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3.2.2 Semi-synthetic: definition and examples [structures not expected].3.2.3 Synthetic: Nylon, Polyesters and Polyamides structures and

names of dyes applied on each of them.3.2.4 Blended fabrics: definition and examples [structures not

expected].3.2.5 Binding forces of dyes on substrate: ionic forces, covalent

linkages, hydrogen bonding, vander-waals forces.3.3 Classification of Dyes based on Applications and Dyeing Methods (7L)

3.3.1 Dyeing methodsBasic operations involved in dyeing process:(i) Preparation of fibres (ii) Preparation of dyebath

(iii) Application of dyes (iv) FinishingDyeing method of Cotton Fibres:(i) Direct dyeing (ii) Vat dyeing

(iii) Mordant dyeing (iv) Disperse dyeing3.3.2 Classification of dyes based on applicability on substrates

(examples with structures).(a) Acid Dyes – Orange II(b) Basic Dyes – Methyl Violet(c) Direct Cotton Dyes – Benzofast Yellow 5GL(d) Azoic Dyes – Diazo components; Fast Yellow G, Fast Orange

RCoupling components – Naphthol AS, Naphthol ASG(e) Mordant Dyes – Eriochrome Black A, Alizarin(f) Vat Dyes – Indanthrene Brown RRD(g) Sulphur Dyes – Sulphur Black T (no structure)(h) Disperse Dyes – Celliton Fast Brown 3R(i) Reactive Dyes – Cibacron Brilliant Red B

3.3.3 Optical Brighteners:General idea, Important characteristics of optical brighteners andtheir classes [Stilbene, Coumarin, Heterocyclic vinylenederivatives, Diaryl pyrazolines, Naphthylamide derivatives],General structure of each class.

UNIT IV4.1 Colour and Chemical Constitution of Dyes (4L)

4.1.1 Absorption of visible light, Colour of wavelength absorbed,Complementary colour.

4.1.2 Relation between colour and chemical constitution.(i) Armstrong Theory (Quinonoid Theory) and its limitations.(ii) Witt’s Theory: Chromophore, Auxochrome, Bathochromic

and Hypsochromic Shift, Hypochromic and Hyperchromiceffect.

(iii) Valence Bond Theory, comparative study and relation ofcolour in the following classes of compounds/dyes:Benzene, Nitrobenzene, Nitroanilines, Nitrophenols,Benzoquinones, Azo, Triphenyl Methane, Anthraquinones.

(iv) Molecular Orbital Theory.4.2 Unit Process and Dye Intermediates

4.2.1 A brief idea of Unit Processes (3L)Introduction to primaries and intermediatesUnit processes: definition and brief ideas of below unit processes:(a) Nitration(b) Sulphonation(c) Halogenation(d) Diazotization (3 different methods and its importance)(e) Ammonolysis(f) OxidationNB: Definition, Reagents, Examples of each unit processesmentioned above with reaction conditions (mechanism is notexpected)

4.2.2 Preparation of the Following Intermediates (8L)Benzene derivatives: Benzenesulphonic acid; 1,3-Benzenedisulphonic acid; sulphanilic acid; o-, m-, p-chloronitrobenzenes; o-, m-, p-nitroanilines; o-, m-, p-phenylenediamines; Naphthol ASG.Naphthalene Derivatives: Schaeffer acid; Tobias acid; Naphthionicacid; N.W. acid; Cleve-6-acid; H-acid; Naphthol AS.Anthracene Derivatives: 1-Nitroanthraquinone; 1-Aminoanthraquinone Anthraquinone-2-sulphonic acid;Benzanthrone.

(viii) (ix)

SEMESTER VI

CHEMISTRY OF DRUGSUNIT V5.1 Drug Discovery, Design and Development (6L)

5.1.1 Discovery of a Lead compound: Screening, drug metabolismstudies and clinical observation, Lipinski’s rule of 5.

5.1.2 Medicinal properties of compounds from Natural Sources:Antiinfective and anticancer properties of Turmeric (Curcumin).

5.1.3 Development of drug: The Pharmacophore identification,modification of structure or functional group, Structure activityrelationship (Sulphonamides).

5.1.4 Structure modification to increase potency: Homologation, Chainbranching and Extension of the structure.

1.1.5 Computer assisted drug design.5.2 Drug Metabolism (3L)

Introduction, Absorption, Distribution, Biotransformation, ExcretionDifferent types of chemical transformation of drugs with specific examples.

5.3 Chemotherapeutic Agents:Study of the following chemotherapeutic agents with respect to theirchemical structure, chemical class, therapeutic uses, side effects andintroduction to MDR wherever applicable.

5.3.1 Antibiotics and antivirals: Definition, (2L) Amoxicillin (-lactum antibiotics) Cefpodoxime (Cephalosporins) Doxycycline (Tetracyclines) Levofloxacin (Quinolones) (Synthesis from 2,3,4- Trifluro-

1-nitrobenzene) Aciclovir/Acyclovir (Purines)

5.3.2 Antimalarials: (2L)Types of Malaria; Symptoms; Pathological detection duringwindow period (Life cycle of the parasites not to be discussed) Chloroquine (3-Amino quinolones) Artemether (Benzodioxepins)

Following combination to be discussed: Atremether-Lumefantrine (no structure)

5.3.3 Anthelmintics and Antifungal Agents (2L)Drugs effective in the treatment of Nematodes and Cestodesinfestations.

Diethyl carbamazine (Piperazines) Albendazole (Benzimidazoles) (Synthesis from 2-

Nitroaniline) Clotrimazole (Imidazole) Fluconazole (Triazole) (Synthesis from 1-Bromo-2,4-

difluorobenzene)UNIT VI6.1 Antiamoebic Drugs (1L)

Types of Amoebiasis Metronidazole, Ornidazole, Tinidazole (Imidazole)

Synthesis of Metronidazole from glyoxal by Debus-Radziszewski imidazole synthesis route

Following combination therapy to be discussed: Ciprofloxacin-Tinidazole

6.2 Antitubercular and Antileprotic Drugs (3L)Types of Tuberculosis; Symptoms and diagnosis of Tuberculosis.Types of Leprosy.General idea of Antibiotics used in their treatment.

PAS (Amino salicylates) Isoniazide (Hydrazides) Pyrazinamide (Pyrazines) (+) Ethambutol (Aliphatic diamines) (Synthesis from 1-

Nitropropane) Dapsone (Sulphonamides) (Synthesis from 4-

Chloronitrobenzene) Clofazimine (Phenazines) Bedaquiline (Quinoline)

Following combination therapy to be discussed:(i) Rifampin + Ethambutol + Pyrazinamide(ii) Rifampin + Isoniazide + Pyrazinamide

6.3 Anti-Neoplastic Drugs (2L)Idea of malignancy; Causes of cancerBrief idea of Immuno stimulants and Immuno depressants Lomoustine (Nitrosoureas) Anastrozole(Triazoles) (Synthesis from 3,5-bis

(bromomethyl) toluene) Cisplatin (Chloro Platinum) Vincristine, Vinblastine, Vindesine) (Vinca alkaloids)

(structure not expected)(x) (xi)

6.4 Anti-HIV Drugs (1L)Idea of HIV pathogenicity, Symptoms of AIDS AZT/Zidovudine, Lamivudine, DDI (Purines)

6.5 Drug Intermediates: Synthesis and Uses (2L)1. 2,3,6-Triamino-6-hydroxypyrimidine from Guanidine2. p-[2 -(5-Chloro-2-methoxy benzamido) ethyl]-

benzenesulphonamide from Methyl-5-chloro-2-methoxybenzene3. 3-(p-Chlorophenyl)-3-hydroxypiperidine from

3-Chloroacetophenone4. p-Acetyl amino benzenesulphonyl chloride from Aniline5. Epichlorohydrine from propene

6.6 Nano Particles in Medicinal Chemistry (4L)Introduction; Carbon nano particles (structures) and Carbonnano tubes: Functionalization for Pharmaceutical applications Targeted drug delivery In Vaccine (Foot and mouth disease) Use in Bio-physical treatment.

Gold nano particles in treatment of: Cancer; Parkinsonism;Alzheimer.Silver nano particles: Antimicrobial activity.

6.7 Drugs and Environmental Aspects (2L) Impact of Pharma-industry on environment. International regulation for human experimentation with

reference to “The Nuremberg Code” and “The HelsinkiDeclaration”.

UNIT VII7.1 Classification of Dyes based on Chemical Constitution and Synthesis

of Selected Dyes (synthesis of the dyes marked with * is expected)(12L)

(i) Nitro Dye: Naphthol Yellow S(ii) Nitroso Dye: Gambine Y(iii) Azo dyes:

(a) Monoazo dyes: Orange IV*(from sulphanilic acid) andEriochrome Black T* (from -naphthol)

(b) Bisazo dyes: Congo Red* (from nitrobenzene)(c) Trisazo Dye: Direct Deep Black EW* (from benzidine)

(iv) Diphenylmethane dye: Auramine O* (from N,N-dimethyl aniline)

(v) Triphenylmethane dyes:(a) Diamine series: Malachite Green* (from benzaldehyde)(b) Triamine series: Acid Magenta(c) Phenol series: Rosolic acid

(vi) Heterocyclic Dyes:(a) Thiazine dyes: Methylene Blue(b) Azine dyes: Safranin T* (from o-toluidine)(c) Xanthene Dyes: Eosin* (from phthalic anhydride)(d) Oxazine Dyes: Capri Blue(e) Acridine Dyes: Acriflavine

(vii) Quinone Dyes:(a) Naphthaquinone: Naphthazarin(b) Anthraquinone Dyes: Indanthrene Blue* (from

anthraquinone)(viii) Indigoid Dyes: Indigo* (from aniline + monochloroacetic acid)

(ix) Phthalocyanine Dyes: Monastral Fast Blue B7.2 Health and Environmental Hazards of Synthetic Dyes and their

Remediation Processes (3L)7.2.1 Impact of the textile and leather dye industry on the environment

with special emphasis on water pollution.7.2.2 Health Hazards: Toxicity of dyes w.r.t. food colours.7.2.3 Effluent Treatment Strategies:

Brief introduction to effluent treatment plants (ETP).Primary Remediation processes (Physical Processes):Sedimentation, Aeration, Sorption (activated charcoal, fly ash etc.).Secondary Remediation processes: Biological Remediation –Biosorption, bioremediation and biodegradation.Chemical Remediation: Oxidation Processes (chlorination),Coagulation-Flocculation-Precipitation

UNIT VIII8.1 Non-textile uses of dyes: (8L)

8.1.1 Biomedical Uses of Dyes(i) Dyes used in formulations (Tablets, capsules, syrups, etc.)

Indigo carmine, Sunset yellow, Tartrazine(ii) Biological staining agents Methylene blue, Crystal violet

and Safranine T(iii) DNA markers

Bromophenol blue, Orange G, Cresol red

(xii) (xiii)

(iv) Dyes as therapeuticsMercurochrome, Acriflavine, Crystal Violet, Prontosil

8.1.2 Dyes used in food and cosmetics(i) Properties of dyes used in food and cosmetics.(ii) Introduction to FDA and FSSAI.(iii) Commonly used food colours and their limits.

8.1.3 Paper and leather dyes(i) Structural features of paper and leather.(ii) Dyes applicable to paper and leather.

8.1.4 Miscellaneous dyes(i) Hair dyes(ii) Laser dyes(iii) Indicators(iv) Security inks(iv) Coloured smokes and camouflage colours

8.2 Pigments (3L)Definition of pigments, examples, properties of pigments, differencebetween dyes and pigments.Definition of Lakes and Toners.

4.3 Dyestuff Industry - Indian Perspective (4L)4.3.1 Growth and development of the Indian Dyestuff Industry.4.3.2 Strengths, Weaknesses, Opportunities and Challenges of the

Dyestuff industry in India.4.3.3 Make in India – Future Prospects of the Dye Industry.

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SEMESTER VCHEMISTRY OF DRUGS

Unit Chapter Topic Name Page No.

I 1.1 General Introduction to Drugs (8L) 3 – 171.2 Routes of Drug Administration and

Dosage Forms (3L) 18 – 28

1.3 Pharmacodynamic Agents (4L) 29 – 38Central Nervous System (CNS) Drugs

II 2.1.1 Analgesics and Antipyretics (2L) 39 – 44

2.1.2 Anti-Inflammatory Drugs (2L) 45 – 49

2.2 Antihistaminic Drugs (2L) 50 – 54

2.3 Cardiovascular Drugs (3L) 55 – 61

2.4 Antidiabetic Agents (2L) 62 – 68

2.5 Antiparkinsonism Drugs (2L) 69 – 73

2.6 Drugs for Respiratory System (2L) 74 – 80

CHEMISTRY OF DYESTUFFS

III 3.1 Introduction to Dyestuff Industry (5L) 81 – 92

3.2 Substrates for Dyes: Types of Fibres (3L) 93 – 102

3.3 Classification of Dyes based onApplications and Dyeing Methods (7L) 103 – 118

IV 4.1 Colour and Chemical Constitution of Dyes (4L) 119 – 135

4.2 Unit Process and Dye Intermediates (11L) 136 – 153

CONTENTS

SEMESTER VICHEMISTRY OF DRUGS

Unit Chapter Topic Name Page No.

V 5.1 Drug Discovery, Design and Development (6L) 3 – 225.2 Drug Metabolism (3L) 23 – 32

5.3 Chemotherapeutic Agents

5.3.1 Antibiotics and Antivirals (2L) 33 – 42

5.3.2 Antimalarials (2L) 43 – 47

5.3.3 Anthelmintics and Antifungal Agents (2L) 48 – 54

VI 6.1 Antiamoebic Drugs (1L) 55 – 59

6.2 Antitubercular and Antileprotic Drugs (3L) 60 – 71

6.3 Anti-Neoplastic Drugs (2L) 72 – 81

6.4 Anti-HIV Drugs (1L) 82 – 87

6.5 Drug Intermediates (2L) 88 – 91

6.6 Nano Particles in Medicinal Chemistry (4L) 92 – 100

6.7 Drugs and Environmental Aspects (2L) 101 – 118

CHEMISTRY OF DYESTUFFS

VII 7.1 Classification of Dyes Based on ChemicalConstitution and Synthesis of Selected Dyes (12L) 119 – 135

7.2 Health and Environmental Hazards ofSynthetic Dyes and their RemediationProcess (3L) 136 – 143

VIII 8.1 Non-textile Uses of Dyes (8L) 144 – 166

8.2 Pigments (3L) 167 – 174

8.3 Dyestuff Industry – Indian Perspective (4L) 175 – 178

(xv) (xvi)

INTRODUCTION TO

SYNTHETICDRUGS AND DYES

The pharmacodynamic agents are the drugs used to correct thedisorders in the physiological functions and restore them to normalconditions. Thus, they bring relief from the symptoms of discomfort byeither stimulating or depressing the physiological functions which areabnormal. They are used to restore the functions such as blood pressure,blood sugar, body temperature, electrolytes etc.

1.3.1 Central Nervous System (CNS) Drugs

The drugs which act on the CNS are known as CNS drugs.Anatomically, the nervous system is made-up of CNS and Peripheral

nervous system consisting of somatic and autonomic nerve fibres. Thecentral nervous system consists of cerebrum, cerebellum, medula andthe spinal cord.

Functionally the CNS consists of billions of neurons organised toform several neuronal system with nuclei and their tracts. Each is concernedwith certain specialised function as motor activity, perception and regulationof various body functions. These systems are esentially interdependentand disturbances in any one may produce repercussions in other systemas well.

Pharmacodynamic AgentsCentral Nervous System (CNS) Drugs

CHAPTER 1.3

29

(A) Classification of CNS Drugs :Based on their pharmacological activity, the CNS drugs are classified

into three types:(a) CNS depressants(b) CNS stimulants(c) CNS modifiers(a) CNS depressants: ‘The drugs which have a depressant action

on the CNS as its principal pharmacological action are known as CNSdepressant. They are of two types;

(1) Non-selective CNS depressants are drugs which produce ageneralised depressant action on the central nervous system. They include,

(i) Hypnotic and sedatives(ii) General anaesthetics(iii) Central muscle relaxants(2) Selective CNS depressants: Those drugs which selectively

depress certain region or portion of the CNS are known as selective CNSdepressants. They include,

(i) Tranquillizers(ii) Analgesics(iii) Anti-convalsants(b) CNS Stimulants: The drugs which stimulate and reactivate the

CNS are known as CNS stimulants or anti depressants. The CNS stimulantsare used for a variety of purposes such as treatment of depressive state,maintainence of wakefulness, restoration of respiration and blood pressureand restoration of normal reflexes.

The CNS stimulants are broadly classified into the following fourclasses

(i) Cerebral stimulants(ii) Respiratory stimulants(iii) Analeptics (restorative)(iv) Psychomotor stimulantsAnalepsis is a Greek word meaning “picking up those who have

been cast down”. Hence, Analeptics are drugs which stimulate the CNSincluding the respiratory centres depressed by narcotics. Hence, thesedrugs have wide range of action.

(c) CNS Modifiers (Tranquillizers): These are the drugs employedin the treatment of mental disorders. They produce a specific improvementin the mood and behaviour of the patient. They also decrease pschomotoractivity without causing sedation and hence they are also known aspsycholeptics. A tranquillizer should have following characteristics,

(i) It should not have toxic effects.

(ii) It should not produce other undesirable side effects.

(iii) It should have calming effect without causing sedation.

(iv) It should not result in unconsciousness.

They are of two types:

(1) Major Tranquillizers (Antipsychotics)

They are used to reduce the agitation and disturbed behaviour whichare associated with delusion and hallucinations in schizophrenia. Reserpineis an alkaloid, obtained from the plant Rauwolfia serpentina, which hasbeen used for longtime in treatment of serious mental disorders. Nowsynthetic derivatives of phenothiazine, thioxanthene, indole, buterophenoneetc. are used.

(2) Minor Tranquillizers

These are antianxiety agents which have a calming effect in patientsin anxiety state associated with neurotic personality. They are furtherclassified as muscle relaxants and ataractics which cause the mind tobecome cool, calm and collected.

(B) Concept of Hypnosis and Sedation and AnaesthesiaThe sedation and hypnosis are closely related terms which mean the

different extents to which CNS is depressed. A hypnotic is a drug whichproduces sleep resembling natural sleep. A sedative is a drug whichproduces mild depression and calms anxiety without causing drowsinessor impaired performance.

Hypnotics and sedatives differ in their action quantitatively. A sedativewhen given in large dosage acts as a hypnotic. Similarly, a hypnotic whengiven in small dosage acts as a sedative. Further, it is observed that increasedamount of dosage can lead to anaesthesia and finally coma. However, ifthe depression reaches the medulla region then it causes death. The effectof increasing order of depression can be represented as:

Sedation Hypnosis Anaesthesia Coma Death.

30 Introduction to Synthetic Drugs and Dyes Pharmacodynamic Agents 31

The hypnotics and sedatives are mainly used for the treatment ofinsomnia. An ideal hypnotic and a sedative should possess the followingcharacteristics,

(i) The administration should be easy and oral.

(ii) Its action should be rapid on administration.

(iii) Tolerance should not be developed on prolonged use.

(iv) Should not be habit forming.

Anaesthesia

General anaesthetics are depressant drugs that produce partial ortotal loss of sense of pain which may be accompanied by loss ofconsciousness. This state of insensibility is known as anaesthesia.Anaesthesia may be also defined as the absolute loss of sensation. It isderived from a Greek word which means insensitivity or lack of feeling.

Types of anaesthesia

According to Guedel, anaesthesia occurs in four stages:

Stage I Analgesia: It is accompanied by mild depression of highercortical centers. This stage is suitable for surgical procedures not requiringextensive muscular relaxation.

Stage II Delirium or excitement: The patient looses consciousnessas a result of depression of cortical motor centers resulting in possibleextensive involuntary activity.

Stage III Surgical anaesthesia: During surgical procedures thereis progressive increase in depth of anaesthesia in the following order;loss of spinal reflexes, deceased muscle reflexes, paralysis of intercostalmuscles and finally disappearance of muscle tone.

Stage IV Respiratory paralysis or medullary paralysis

More correctly it is refered to as toxic or overdose stage involvingrespiratory and vasomotor cessation. This is the stage when surgicaloperations are carried out.

(C) Classification based on Pharmacological Actions:(1) Phenytoin or Dilantin (5, 5-Diphenyl hydantoin) Hydantoins:

This was the first anticonvalsant drug which showed a clear differencebetween anticonvulsant activity and a sedative-hypnotic activity. It alsoacts as a sodium channel blocker.

NHR1

R2

R3

N C = OO34

5

2

1

Hydantoin

C H6 5

C H6 5

NH

H

N C = OO

Phenytoin

(i) It can also be used in treatment of all types of epilepsy and fortrigeminal neuralgia.

(ii) It is useful for treating cardiac arrhythmia especially inducedby digitalis.

Side effect : Dizziness, itching, skin rashes, vomiting with blurredvision, tremors and fever.

(2) Trimethadone or Tridone (Oxazolidinediones): When the N–Hgroup at position 1 of a hydantoin nucleus is replaced with an oxygen atom itforms oxazolidine -2, 4-dione system.

1234

5

R3

R1

R2

CH3

CH3

CH3

NN

O

O O

O

OO

Tridone (3, 5, 5-Trimethyl-2, 4-oxazolidinedione)

CH3

CH3

CH3

CH3

C = O HCN CCN

OHH SO /C H OH2 4 2 5

i) Hydrolysisii) Esterification Cyanohydrin

CH3 CH3

CH3 CH3

C CC C(CH ) SO3 2 4NaOH–NH3

C CO O

OO

NH N – CH3

O O

Trimethadione

Synthesis:

CH3 CH3H N2H N2

H N2

Urea

CH3 CH3

C C CO

C C H Na2 5O–C H OH2 5

C C

OHOH

O

OC H2 5O O

+

NH

32 Introduction to Synthetic Drugs and Dyes Pharmacodynamic Agents 33

(4) Levetiracetam (Keppra) (Pyrrolidones): These are pyrrolidonesubstituted derivatives of amides. They are mild mood elevators causing asense of well being. Thus they have a favourable effect on mind andsometimes they are called nootropics.

HC

N

C NH2

OH C2

H C3

O

The cyanohydrin of acetone is hydrolysed and esterified to get ethyldimethyl glycolate. This is condensed with urea in presence of sodiumethoxide to get oxazolidenedione derivative. Finally, it is methylated withdimethyl sulphate in alkaline medium to get trimethadione.

Use: It is mainly used as a anticonvulsant in treatment of grand malepilepsy. In combination with phenytoin it is used to treat petit mal epilepsywhen other drugs are not effective.

Side effects: Rashes, exfoliative dermatitis, blood dyscrasia, kidneydamage and hepatitis.

(3) Alprazolam (Benzodiazepines): In benzodiazepines the aromaticring is fused to the seven membered heterocyclic ring with an aryl groupsubstituted at 5 position. The benzodiazepines are drugs which have adepressant action on the CNS. Hence, they are known as CNS depressants.The 1, 4-benzodiazepines class of drugs are mainly used as anti-anxietyagents, as sedatives and hypnotics. It is also found to possessanticonvulsant and muscle relaxant properties.

Structure of Benzodiazepines:

N

N

NN

CH3

Cl

Alprazolam

It is optically active and dextro form is found to be more potent thanlaevo form. It is used in treatment of narcolepsy and alcoholism.

Side effect: Their prolonged use results in a psychotic state ofsuspicion and paranoia.

Synthesis:

(1) Phenyl acetic acid is subjected to thermal acylation anddecarboxylation to give phenyl acetone. Phenyl acetone on treatment withhydroxylamine hydrochloride under mildly basic conditions gives the oxime,which is then reduced to give Amphetamine.

CH2

RN

Y C

C

N

X

1 23

456

7

89

Where, R = H or alkyl,X = O or S; Y = Cl or NO2

When another heterocyclic ring is fused at 1,2 positions it gives 1,2-annelated-1,4-benzodiazepines, which are found to be better anti-anxiety agents.

Alprozolam is obtained by fusing a triazole ring at 1,2 position of1,4-benzodiazepin. It is an anti-anxiety agent and also used as sleep inducer.

Use: It is an anticonvulsant and is used to treat epilepsy. It is usedfor partial onset, myoclonic, or tonic-clonic seizures. It is found to beuseful for other psychiatric and neurological conditions such as Tourettesyndrome, anxiety disorder, and Alzheimer’s disease.

Side effects: Drowsiness, dizziness, unusual tiredness or weaknessmay occur.

(5) Amphetamine (Phenyl propyl amines): There are twosubclasses, i.e., phenyl-n-propyl amines and phenyl isopropylamines. Bothare used as anti-depressants. They are also used in treatment of obesity,as they reduce the appetite.

(i) Amphetamine is a derivative of phenyl isopropyl amines.

CH – CH – CH2 3

NH2

Side effect: causes drowsiness and lethargy.

34 Introduction to Synthetic Drugs and Dyes Pharmacodynamic Agents 35

(2) Assymmetric synthesis of d-Amphetamine

Phenyl acetone (Methyl benzyl ketone) on treatment with chiral -methyl benzylamine resulted in the formation of an imine, which wasreduced with Raney nickel at 50 psi to give (I).

Hydrogenolysis of the N-benzyl group of (I), over 10% Pd/C gave(d)-amphetamine of high optical purity

CH – COOH + CH COOH2 3 H C – CH – C – CH5 6 2 3

Phenyl acetic acidPhenyl acetone

, High temp. acetylation

decarboxylation –CO , –H O2 2

O

N

S

Cl

CH – CH – CH – N2 2 2

CH3

CH3

N

S

R112

3456

7

89

10

CH – CH – CH – N2 2

R2

R2R3

R1 3

2 3

3 3

= H, Cl, CFR = CHR = H, CH

General Structure of phenothiazine

(6) Chloropromazine (Thorazine) (Phenothiazines): These drugshave a heterocyclic ring system called phenothiazine having substitutionin 2 and 10 positions.

CH – C = NOH2Oxime

NH OH, NaOH4

CH3

CH – CH – NH 2 2

Amphetamine

Na, MeOHReduction

CH3

The activity of phenothiazines increases if substituted at-2-position.

Chloropromazine is given orally or by intramuscular or by intravenousinjection. In patients with major psychosis with agitation, it producespsycomotor slowing, emotional quitening and decrease of anxiety withoutaffecting wakefulness. The subject will become quiet and showindifference to the events around him.

Chlorpromazine blocks condition avoidance response so that theperson forgets what he has learnt. Chloropromazine is also used in minorpsychatric disorders or neurosis such as anxiety states. It depresses thechemoreceptor trigger zone (CTZ) and thus acts as a powerful anti-emeticagent. It is also used for blocking certain actions of adrenaline and nor-adrenaline as it possesses adrenergic blocking effect. It also has musclerelaxant property.

Questions1. What are pharmacodynamic drugs?2. What are CNS drugs? How are they classified on the basis of their

pharmacological action?3. Explain sedation, hypnosis, anaesthesia. How are they interelated?4. What is anesthesia? What are the types? What are the different stages

in which it occurs?

CH 2 CH 3

(I)

O

100% eeAmphetamine

-Methyl benzyl amineRaney-Ni, H 2 , HCl

H N2

HNNH2

10% Pd/C, H , MeOH2

Phenyl acetone

+

36 Introduction to Synthetic Drugs and Dyes Pharmacodynamic Agents 37

5. Explain the following CNS drugs giving their general structure oneexample, uses and side reactions(i) Hydantoins (ii) Oxazolidinediones

(iii) Benzodiazepines (iv) Pyrrolidones(v) Phenyl propyl amines (vi) Phenothiazines

6. Give the synthesis and uses of the following drugs(i) Trimethadione (ii) Amphetamine

Objective Questions(A) Fill in the blanks:

(i) Hypnotics and sedatives belong to the class of ________.(ii) Sedative is a drug which produces ________.(iii) Hypnotic when given in small dosage act as ________.(iv) ________ are depressant drugs that produce partial or total loss of

sense of pain which may be accompanied by loss of consciousness.(v) Phenytoin is an example of the class ________.

(B) State whether True or False(i) General anaesthetics belong to the class of CNS stimulants.(ii) Tranquilizers are an example of selective CNS depressants.(iii) Sedative when given in large dosage act as hypnotic.(iv) Alprazolam is an example of oxazolidinediones.

(C) Match the followings: (A) (B)

1. Hypnotics and sedatives (a) Amphetamine2. Hydantoin (b) Alprazolam3. Oxazolidinediones (c) Levetiracetam4. Benzodiazepines (d) CNS depressants5. Pyrrolidones (e) Phenytoin6. Phenothiazines (f) Trimethadone7. Phenyl propyl amines (g) Chlorpromazine

38 Introduction to Synthetic Drugs and Dyes