BP 501T medicinal chemistry -2 unit -1 5thsem

BP 501T medicinal chemistry -2 unit -1 5thsem

• 1.
  Histamine and antihistamine
• 2.
  • Histamine, meaning'tissue amine' .Histamine functions as a mediator of hypersensitivity phenomena and tissue injury reactions. • Histamine is present mostly within storage Mast cell granules • Histamine is present mostly within storage Mast cell granules of mast cells." Tissues rich in histamine are skin, gastric and intestinal mucosa, lungs, liver and placenta. • Anti-histaminic agents (or histamine antagonists) are the drugs that antagonize the action of histamine.
• 3.
  Histamine • Histamine [2-(imidazol-4-y1)ethylamine] is biosynthesized by decarboxylation of the basic amino acid histidine, is found in all organs and tissues of the human body.
• 4.
  Histamine • Histamine isreleased because of the interaction of an antigen with IgE antibodies on the mast cell surface and plays a central role in immediate hypersensitive reactions. • Systemically, histamine contracts smooth muscles of the lungs and the gastrointestinal system and cause vasodialation, low blood pressure, and increases the heart rate. It also causes symptoms such pressure, and increases the heart rate. It also causes symptoms such as itching, sneezing, watery eye, and running nose. • The release of histamine, in addition to the stimulation of IgE receptors, also activates the phospholipase A2, leading to the production of host mediators, including platelet activating factors and metabolites of arachidonic acid. Leukotriene D4 is also generated, which is a potent constrictor of smooth muscles. This mediates the constriction of bronchi.
• 5.
  Histamine Receptors
• 6.
  Steps involved inthe release of histamine
• 7.
  Histamine and GastricAcid Secretion • Histamine is a powerful gastric acid secretagogue and evokes a copious secretion of acid from the parietal cells by acting on the H2 receptors. • The output of pepsin and intrinsic factors are also increased. However, the secretion of acid is evoked by the stimulation of vagus nerve and by the enteric hormone gastrin. • The mechanism operating at the gastric parietal cells is through H+ K+ ATPase (proton pump), which secretes H+ ions in the apical canaliculi of parietal cells and also which can be activated by histamine. • The therapeutically available antagonists of histamine receptors are used as antiallergic drugs by targeting H1 receptors and as antiulcers by targeting H2 receptors.
• 8.
  Histamine induced gastricacid secretion.
• 10.
  STRUCTURE ACTIVITY RELATIONSHIP—H1RECEPTOR ANTAGONISTS • 1. Aryl groups  The diaryl substitution is essential for significant H1 affinity.  It is present both in first generation and second generation antihistamines.  The optimal antihistaminic activity depends on the co-planarity of two aryl substitutions.
• 11.
  STRUCTURE ACTIVITY RELATIONSHIP—H1RECEPTOR ANTAGONISTS • 2. Nature of X  Antihistamines with X = carbon (pheniramine series) represents the stereo selective receptor binding to the receptors due to its chirality.  The active substitutions of X are as follows:  Where X = oxygen (amino alkyl ether analogue)  X = nitrogen (ethylene-diamine derivative)  X = carbon (mono amino propyl analogue)
• 12.
  STRUCTURE ACTIVITY RELATIONSHIP—H1RECEPTOR ANTAGONISTS • 3. The Alkyl Chain • Most of the antihistamines have ethylene chain, and branching • Most of the antihistamines have ethylene chain, and branching of this chain results in a less active compound.
• 13.
  STRUCTURE ACTIVITY RELATIONSHIP—H1RECEPTOR ANTAGONISTS • 3. Terminal nitrogen atom  The terminal N-atom should be a tertiary amine for maximum activity.  The terminal nitrogen may be a part of heterocyclic ring.  The terminal nitrogen may be a part of heterocyclic ring.  The amino moiety deserves the protonation on interaction with H1 receptor due to the basicity with pka 8.5-10.  For example, antazoline and chlorcyclizine, retains high antihistaminic activity.
• 14.
  Classification of H1-Antagonists •1. H1-Antagonists with classical structures • a) Ethylene diamine derivatives
• 15.
  b) Amino alkylethers
• 16.
  • c) Cyclicbasic chain analogues or piperazine derivatives
• 17.
  d) Tricyclic ringsystems or phenothiazine derivatives
• 18.
  e) Mono aminopropyl analogues
• 19.
  f) Dibenzocyclo heptanes
• 20.
  g) Newer agents Ketotifene7-Chloro ketotifene Dithiadene
• 21.
  2. H1-Antagonists withnon-classical structures Azelastine Tazifylline
• 22.
  3. Nonsedative H1-antihistamines LoratadineEpinastine Rocastine Cetrizine
• 23.
  Inhibition of histaminerelease (mast cells stabilizers) • Cromolyn sodium Nedocromil sodium
• 25.
  Synthesis of Diphenhydramine Uses:  It is frequently used in mild, local allergic reactions due to insect bites.  It possesses sedative, antiemetic and anti-tussive properties  It can be used in seasonal allergic rhinitis, allergic manifestations due to urticaria and allergic conjunctivitis of inhalant allergens.
• 26.
  Dimenhydrinate • Dimenhydrinate isa combination drug as it comprises of diphenhydramine (53- 55.5%) and 8-chloro theophylline (not less than 44-47%) in a salt form, calculated on the dried basis. Uses It is one and half time more as potent as diphenhydramine hydrochloride. It is mostly used as an antinauseant, in motion sickness, radiation sickness and also in nausea of pregnancy.
• 27.
  Doxylamine succinate IUPAC Name:N,N-dimethyl-2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethan-1- amine Uses:  It relieves the symptoms of allergy, hay fever, and common cold.  It relieves sneezing, runny nose, watery eyes, hives, and skin rash, insomnia.  It is used for preventing morning sickness in pregnant women in combination with vitamin B6 (pyridoxine).
• 28.
  • Uses:  Itis an antihistamine having antimuscarinic and moderate sedative properties.  It is used for the symptomatic relief of allergic conditions like rhinitis, urticaria, conjunctivitis, and pruritic skin conditions.
• 29.
  Diphenylpyraline hydrochloride • IUPACName: [4- (diphenyl methoxy) 1- methyl piperidine] hydrochloride • Uses:  It is used for symptomatic relief of rhinitis, pruritic and hay fever.  It is used for relief of cough and common cold.  It can also be useful in the treatment of parkinsonism.
• 30.
  Tripelennamine hydrochloride • IUPAC Name:N-benzyl-N- [(N,N-dimethyl) anmino ethyl] • IUPAC Name: N-benzyl-N- [(N,N-dimethyl) anmino ethyl] pyridine-2-amine • Uses:  It treats the conditions of upper respiratory tract caused due to illnesses and hay fever.  It relieves sneezing, runny nose, itching, watery eyes, hives,  rashes, and other symptoms of allergies and common cold.
• 31.
  Chlorcyclizine hydrochloride • IUPACName: 4-methyl-1 [(P-chlorophenyl)benzyl]piperazine • USES:  It is indicated in the symptomatic relief of urticaria, hay fever, and certain other allergic conditions.
• 32.
  Meclizine hydrochloride • IUPAC Name:4-[(M-methyl)Phenyl]-1 [(P-chloro phenyl) benzyl]Piperazine • Motion sickness,vertigo
• 33.
  Buclizine hydrochloride • (4-[(t-butyl)phenyl)-methyl-1[P-chloro phenyl benzyl] piperazine) hydrochloride • uses • It is highly lipid soluble and cross blood brain barrier. So it is used as CNS depressant. • It is also used as antihistamine, anti-cholinergic, antivertigo and local anaesthetic.
• 34.
  Chlorpheniramine maleate • IUPACName: (2[(N,N dimethyl aminoethyl )-P- chlorobenzyl] pyridine] maleate pyridine] maleate • Uses: • Thís drug is generally combined with Phenylpropanolamine for the treatment of allergy and decongestion. • Along with hydrocodone (Narcotic) chlorpheniramine is used for the treatment of cough and upper respiratory tract allergic conditions.
• 35.
  Triprolidine hydrochloride • IUPACName: 2-[1-(4-methylphenyl)-3-pyrrolidin-1-yl- prop-1-enyl]pyridine prop-1-enyl]pyridine • Used:  It is used for the symptomatic relief of seasonal or perennial allergic rhinitis or non -allergic rhinitis; allergic conjunctivitis; and mild, uncomplicated allergic skin conditions of urticaria and angioedema.  It is used in combination with other agents for the symptomatic relief of symptoms related to common cold.
• 37.
  Phenindamine tartarate • IUPACName: 2-methyl-9- Phenyl tetrahydro Indenopyridine • Uses: • Uses:  Allergies  Hay fever  Watery eyes  Runny nose  Sneezing  Common cold
• 38.
  Promethazine hydrochloride • IUPACName: 10-[2(N,N-dimethyl amino) Propyl] Phenothiazine hydrochloride • It is used as sedative, antiemetic action Also used for anesthetic premedication through I.M with atropine and meperidine
• 39.
  Synthesis of Promethazine
• 40.
  Trimeprazine tartrate • IUPACName: 10-[3(N,N - dimethyl amino -2-(methyl) - propyl ] Phenothiazine tartarate • Uses:  It act as a sedative, hypnotic , and antiemetic for motion sickness.  It is an antipruritic drug.
• 41.
  cyproheptadine hydrochloride • IUPACName: 4-[dibenzo cycloheptene-5-ylidine ] -1 methyl piperidine hydrochloride piperidine hydrochloride • Used in hypersensitivity reactions, perennial, and seasonal allergic rhinitis; vasomotor rhinitis, allergic conjunctivitis, allergic skin manifestations of urticaria and angioedema.
• 42.
  Azatadine maleate IUPAC Name:4[ Benzo cyclohepta pyridine -11-ylidine 1-methyl piperdine piperdine Uses: It is used for upper respiratory mucosal allergic rhinitis
• 43.
  H1- ANTAGONISTS- SECONDGENERATION DRUGS • The second generation antihistaminic (SGAS) may be defined as thoseH1-receptor blockers marketed after 1980 which have one or more of the following properties: • Absence of CNS depressant property. • Absence of CNS depressant property. • HigherH1- selectivity, no anticholinergic side effects
• 44.
  Astemizole • IUPAC Name:1[ (4-Flourophenyl) methyl] N- [1[ 2( P-methoxy phenyl) ethyl ] piperidin-4yl] benzimidazole- 2- amine • Uses:  It is indicated for seasonal allergic rhinitis and chronic urticaria.  It is an effective antiallergic agent giving protection against asthma, hay fever, and chronic urticaria.
• 45.
  Loratadine • IUPAC Name:Ethyl 4-(8-chloro-5,6-dihydro-11H- benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1- piperidinecarboxylate • It is used alone or in combination with pseudoephedrine sulfate for relief of seasonal allergic rhinitis, pruritis, urticaria and erythema.
• 46.
  Cetirizine • [2-[4-[(4-Chlorophenyl)phenylmethyl]-1- • [2-[4-[(4-Chlorophenyl)phenylmethyl]-1- piperazinyl]ethoxy]aceticacid • Seasonal Allergic Rhinitis: It is used for treating symptoms related to seasonal allergic rhinitis caused by allergens. • Chronic Urticaria
• 47.
  Levocetirizine • 2-(2-{4-[(R)-(4-Chlorophenyl)(phenyl)methyl]piperazin-1- yl}ethoxy)acetic acid
• 49.
  Cromoln Sodium • Nebulizedcromolyn sodium is used for prophylactic management of bronchial asthma and bronchospasm. • Its nasal solution is used for allergic rhinitis. • Its eye drops are used to treat allergic conjunctivitis and • Its eye drops are used to treat allergic conjunctivitis and keratitis. • Oral concentrate of cromolyn sodium is used to treat histamine related symptoms like flushing, vomiting, urticaria and itching.
• 50.
  Cimetidine • Cimetidine isused to inhibit stomach acid production and is used in the treatment of heartburn and peptic ulcers
• 51.
  Synthesis of Cimetidine
• 52.
  Ranitidine • IUPAC Name:N-(2-[(5-[(Dimethylamino)methyl]furan-2-yl)methylthio]ethyl)-N'-methyl-2- • IUPAC Name: N-(2-[(5-[(Dimethylamino)methyl]furan-2-yl)methylthio]ethyl)-N'-methyl-2- nitroethene-1,1-diamine • Uses: • Relief of heartburn • Short-term and maintenance therapy of gastric and duodenal ulcers • With nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the risk of ulceration Proton-pump inhibitors (PPIs) are more effective for the prevention of NSAID-induced ulcers. • Pathologic gastrointestinal (GI) hypersecretory conditions such as Zollinger–Ellison syndrome • Gastroesophageal reflux disease (GERD)
• 53.
  Famotidine • IUPAC Name:3-[({2-[(diaminomethylidene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]-N- •IUPAC Name:3-[({2-[(diaminomethylidene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]-N- sulfamoylpropanimidamide • Uses:  Relief of heartburn, acid indigestion, and sour stomach  Treatment for gastric and duodenal ulcers  Treatment for pathologic gastrointestinal hypersecretory conditions such as Zollinger–Ellison syndrome and multiple endocrine adenomas  Treatment for gastroesophageal reflux disease (GERD)  Treatment for esophagitis  Part of a multidrug regimen for Helicobacter pylori eradication, although omeprazole may be somewhat more effective  Prevention of NSAID-induced peptic ulcers.
• 55.
  Omeprazole • IUPAC Name:5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2- yl)methanesulfinyl]-1H-benzimidazole yl)methanesulfinyl]-1H-benzimidazole •Omeprazole can be used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcers, erosive esophagitis, Zollinger– Ellison syndrome, and eosinophilic esophagitis
• 56.
  Pantoprazole • IUPAC Name:(RS)-5-(Difluoromethoxy)-2-[(3,4- dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole • Pantoprazole is used for short-term treatment of erosion and ulceration of the esophagus for adults and children five years of age and older caused by gastroesophageal reflux disease. • Also be used in combination with antibiotics to treat ulcers caused by Helicobacter pylori.
• 57.
  Lansoprazole • IUPAC Name:(RS)-2-([3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2- yl]methylsulfinyl)-1H-benzo[d]imidazole • Uses:  Ulcers of the stomach and duodenum, and NSAID-induced ulcers  Helicobacter pylori infection,  Gastroesophageal reflux disease  Zollinger–Ellison syndrome
• 58.
  Rabeprazole • IUPAC Name:(RS)-2-([4-(3-Methoxypropoxy)-3-methylpyridin-2- yl]methylsulfinyl)-1H-benzo[d]imidazole • Uses :  Rabeprazole is a medicine which reduces the amount of acid produced in your stomach.  It is used to treat heartburn, acid reflux and problems in your oesophagus (which connects your throat to your stomach.  It is also used to prevent and treat stomach ulcers.
• 59.
  Antineoplastic agents By Mr. SarojKanta Bisoyi Asst. Professor RCPHS,BAM
• 60.
  Antineoplastic agents • Drugsused for the treatment of cancer. • Medical term of cancer is neoplasm. • Greek neo means New ,Plasm means formation. • Cancer is a disease characterized by uncontrollable, irreversible independent,autonomous,uncoordinated and relatively unlimited and abnormal over growth of tissues.
• 61.
  • Refers toa group of diseases caused by several agents such as • Exposure of carcinogenic chemical compounds and radiation. • Genetic factor • Life style • Occupation • Virus Cancer or neoplasm
• 62.
  • Characterized byan abnormal and uncontrolled cell division. • Exhibiting varying degrees of malignancy which produce tumors and invade adjacent normal tissue. Cancer or neoplasm
• 63.
  • Cancer cellsseparate themselves from the primary tumor and carried by lymphatic system and reach distant site of the organism. • Where they divide and form the secondary tumors (metastasis). Cancer or neoplasm
• 64.
  • The maincharacteristics of the malignant tumors are: • Autonomous growth, insensitive to the normal control mechanisms that limits cell growth and division. (Apoptosis-cell death program) • Invasiveness of adjacent capillaries and lymph channels. Cancer or neoplasm
• 65.
  Some keywords: • Tumor:Abnormal lump or growth of cells • Benign: when the cells in the tumor are normal, it is benign • Malignant: when the cells are abnormal and can grow uncontrollably they are cancerous cells and the tumor is malignant.
• 66.
  Types of cancer: •Carcinoma: Cancers derived from epithelial cells. Nearly all cancers developing in the breast, prostate, lung, pancreas, and colon are carcinomas. • Sarcoma: Cancer arising from connective tissue. (i.e. bone, cartilage, fat, nerve), each of which develop from cells originating in mesenchymal cells outside of the bone marrow. • Lymphoma and leukemia: These two classes of cancer arise from immature cells that originate in the bone marrow, and are intended to fully differentiate and mature into normal components of the immune system and the blood, respectively. • Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively). • Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue.
• 67.
  Approaches to treatcancer • Surgery- for localized and accessible tumors • Radio therapy • Chemotherapy- for malignant diseases
• 68.
  History of chemotherapy •Higgins demonstrated administration of estrogens for the treatment of metastatic prostate cancer. • Gilman- mechlorethamine Hodgkin’s disease, lympho sarcoma • Antimetabolites • Antibiotics • Plant products
• 69.
  limitations • Normal andneoplastic cells are similar • Agents act by first order kinetics • Solid tumors poorly irrigated by blood • Drugs are highly toxic • Cell develops resistance • Neoplasic cells are not truly foreign to the host so no immunological response.
• 70.
  Classification of antineoplasticagents • Alkylating agents: Meclorethamine, melphalan, cyclophosphamide,ifophosphamide carmustine, lumostine, sptreptozotocin, chlorambucil • Antimetabolites: 5-Flurouracil, 6-mercaptopurine, 6-thioguanine, cytarabine, frludarabine, methotrexate, fluxoridine, azathioprine • Antibiotics: Dactinomycine, daunorubicin, doxorubicin, bleomycin, idarubicin, pilocamycin • Plant products: vincristine, vinblastin, paclitaxol, navelbine, etoposide • Steroid hormones and their antagonists: estrogens, tamoxifen, prednisone, aminoglutethemide, flutamide, leoprolide, groserelin • Miscellaneous: cisplatin and carboplatin, mitotane, asparaginase, interferons procarbazine, hydroxyurea
• 71.
  Alkylating agents • Reactivecompounds that act upon DNA, RNA and certain enzymes. • Nucleophillic attack at 7- position of guanine residue • React with 7-position of guanine of each of the double strands of DNA, causing crosslinking. • This interfers with separation of the strands and prevents mitosis.
• 74.
  • A- adenine •T- thymine • G- guanine • C- cytosine • Results intrastrand linking and crosslinking
• 75.
  Mechanism of action
• 76.
  Classification of alkylatingagents 1. Nitrogen mustards: mechlorethamine, chlorambucil, chlorethylaminouracil, cyclophosphamide, melphalan 2. Nitrosourea: Carmustine (BCNU), Lomustine(CCNU) 3. Azaridines: azatepa, benzatepa, thiotepa 4. Methane sulphonate esters: Busulphan, mannitolbusulphan, piposulphan 5. Epoxides: epoxypiperazine 6. Miscellaneous: dibromodulcitol, dacarbazine (DTIC), pipobroman
• 77.
  Meclorethamine hydrochloride 2,2-Dichloro-N-Mehtyl diethylaminehydrochloride
• 79.
  Uses of Mechlorethamine Treatmentof: • Hodgkin’s disease (lymph nodes in neck, armpits or groin may swell. Fatigue, fever and chills) • Non hodgkin’s lymphoma
• 80.
  Cyclophosphamide: IUPAC nomenclature: N,N-bis(2-chloroethyl)-tetrahydro-2H-1,3,2- oxazaphosphorin-2-amine-oxide Uses: • Multiple myeloma • Chronic lymphocytic leukemia • Acute leukemia in children • Hodgkin’s disease • Breast, ovarian and lungs cancer
• 81.
  Chlorambucil: IUPAC Nomenclature: p-(di-2-chloroethyl)- aminophenylbutyricacid Uses: • Chronic lymphocytic leukemia • Macroglubulinemia
• 82.
  Melphalan: IUPAC Nomenclature: 4-[bis(2-chloroethyl)amino]- L-phenylalanine Uses: •It is effective in multiple myeloma and is widely used as an adjunct to surgery for breast cancer.
• 83.
  Busulphan: IUPAC Nomenclature: 1,4-butanedioldimethane sulphate Uses: • It is the drug of choice in chronic myclonic leukemia.
• 84.
  Thiotepa: IUPAC Nomenclature: Tris(1-aziridyl)phosphate sulphide Uses: • It is used in breast, ovarian, and bronchogenic carcinoma and malignant lymphomas.
• 85.
  Antimetabolites • Antimetabolites arecompounds that prevent the biosynthesis or utilization of normal cellular metabolites. • They usually are closely related in structure to the metabolite that is antagonized. • Many antimetabolites are enzyme inhibitors. • Nearly all of the clinically useful antimetabolites are related to metabolites and cofactors in the biosynthesis of nucleic acids. • Some of the antimetabolite must be transformed biosynthetically (anabolised) into the active inhibitors.
• 86.
  Antimetabolites used incancer chemotherapy can be divided into: 1. Pyrimidine antagonists: Fluorouracil, cytarabine, fluxouridine 2. Purine antagonists: Azathioprine, mercaptopurine, thioguanine 3. Folic acid antagonists: methotrexate, aminopterin 4. Amino acids antagonists: azaserine
• 87.
  Pyrimidine antagonists: Fluorouracil,cytarabine, Floxuridine • Fluorouracil • 2,4-dioxo- 5-fluoropyrimidine • Uses: • This pyrimidine antagonist is the most active drug available for colorectal cancer. • It is effective in palliative management of breast, colon, pancreas, rectum and stomach
• 88.
  Mechanism: • 5-fluorouracil isactivated by anabolism to 5- fluoro-2-deoxyuridylic acid. • This is a powerful competitive inhibitor of thymidylate synthetase, the enzyme that converts 2’-deoxyuridylic acid to thymidylic acid (used for biosynthesis of DNA) • This blockade is probably the main lethal effect of 5-fluorouracil and its metabolites.
• 91.
  Cytarabine • 1-β-D-arabinofuranosylcytosine • 4-amino-1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one • Uses: • Acute myelocytic leukemia • Side effects include severe leucopenia, thrombocytopenia and anemia. It causes orogastrointestinal lesions, giving rise to hepatic and renal toxicity.
• 92.
  Mechanism of actionof cytarabine: • The arabinose moiety is epimeric at the 2’–position with the ribose. • This anabolised to the triphosphate and inhibits the conversion of cytidylic acid to 2’-deoxy cytidylic acid. • Other modes of action include the inhibition of DNA dependent DNA polymerase and mis coding following incorporation into DNA and RNA. • It acts predominately in the S phase of the cell cycle. • A combination of cytosine arabinoside and tetrahydrouridine is presently in clinical trial.
• 93.
  Floxuridine • 5-Fluoro-1-[4-hydroxy-5-(hydroxymethyl)tetrahydrof uran-2-yl]-1H-pyrimidine-2,4-dione • Uses:fluoxouridine is used for palliation of gastrointestinal adenoma metastatic to the liver in patients who are considered incurable by surgery. • It gives the same toxic reactions as fluorouracil.
• 94.
  Purine antagonists: • Mercaptopurine •Thioguanine • Azathioprine
• 95.
  Mercaptopurine • Uses: Treatmentof Leukemia
• 97.
  Mechanism: • 6-MP isan antagonist to purine. • Purine is essential constituents of DNA. • It serves as a specific replacement for hypoxanthine. • It is converted to 6-thioinosinate by the enzyme hypoxanthine guanine phosphoribosyl transferase. • 6-thioinosinate inhibits the conversion of inosinic acid to adinylic acid. • 6-thioinosinate is a potent inhibitor of the conversion of 5- phosphoribosyl pyrophosphate into 5-phosphoribosylamine. It acts as a substrate for a methyl transferase, requiring 5-adenosyl methionine, that converts it into 6-methylthioinosinate.
• 98.
  Side effects ofmercaptopurine • Cause hyper uricemia but usually administered with allopurinol. • Allopurinol is an analogue of hypoxanthine which blocks the conversion of 6-MP to uric acid.
• 99.
  Thioguanine 6-thioguanine • It isused in the treatment of acute myolocytic leukemia in combination with cytarabine.
• 100.
  Azathioprine • 6-[(1-methyl-4-nitroimidazole-5- yl)thio]purine • Itis prepared from 6-MP and 5- chloro-1-methyl-4-nitroimidazole. • It is promercaptopurine. • It is used to prevent the rejection of renal homotransplants. • Immunosuppressants.