Synthesis of API’s and API’s based Derivative

subtr exertion of APIs and APIs found derivativeTitle of Proposed ProjectEfficient tax deduction of APIs and APIs ground Derivative for their Structure Activity family relationship and Pharmacokinetics ProfileProject lucubrateProject SummaryThis insure concern with the open upment of organic fertilizer deductive reasoning facilities in Department of Chemistry, UNIVERSITY OF KARACHI. The established facilities testament be utilize for the study of BS/M.Sc./MS/M.Phil. And Ph.D. scholars in the field of Organic deductive reasoning. In this pop we provide focus on the establishment of synthetic organic research laboratoryoratory, the implication of the two APIs (Secnidazole atenolol). We atomic number 18 requiring the fol pitiableing basic facilities which we want to establish by this research childbed.Facilities required forOrganic SynthesisFuming HOODs for save, non-hazardous and smooth running(a) at the moment.Inert atmosphere working conditions since many organi c chemical replys requires sloughy condition.Safety equipments i.e. firefighting equipments, washing shower in case of chemic accident and first aid facilities.(UPS) as regular indicator partition results in the unsuccessful reactions and causing faults in the electronic instruments.UV lamp as processing of many reaction monitor under UV light. traffic circle evaporatorPartial availability of glass wares.MAS-II Microwave workstation for repaid synthesis of APIs.Proposed Goals / ObjectivesHypothesis / founding of researchThe nominate of this project is to setup a laboratory which whoremonger design (Organic Synthesis) and synthesize (Organic Synthesis) the APIs for the local Pharmaceutical industry on with the establishment of the required facilities.The undermentioned APIs will be synthesized.atenololEfficient Synthesis of Atenolol.Synthesis of Atenolol ground derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics penSECNIDAZOLEEfficie nt Synthesis of SecnidazoleSynthesis of Secnidazole based derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics inditeGoals / Objectives acclivity up saving of PakistanSynthetic solution for local industry.Provide enough amount of these drugs to prevalent people.INTRODUCTIONAPI stands for active pharmaceutical ingredients and its covers a attracter of pharmaceutically active compounds which has great grandeur in industry as thoroughly as to common people as the insufficiency of these drugs causes hundreds of death. Due to the importance of API we decided to work with the synthesis of API as it will create the encroachment of API research on subject area level. The synthesis of API could decrease the import wag of such active ingredient in Pakistan and in any case opens the opportunity of melodic line. This project could provide a platform to save the foreign currency reserves and supply sufficient amount of drugs to common people at lo w cost.Ours Efforts will be enabling to purpose the more cost-efficient synthesis of complex molecules. In this project we have design the synthesis of the following APIsatenololEfficient Synthesis of Atenolol.Synthesis of Atenolol based derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics inditeSECNIDAZOLEEfficient Synthesis of SecnidazoleSynthesis of Secnidazole based derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics profile4a) Background of the Research Problems to be addressedSecnidazole (Part A)Efficient Synthesis of SecnidazoleSecnidazole is a molecule which belongs to the class of 5-nitroimidazole and it is considerably more effective than opposite imidazole drugs. It is the important API required for the local industry. However it has been used for the intercession of amoebiasis, giardiasis, urogenital trichomoniasis and nonspecific bacterial vaginosis and also a gel face of secnidazole was dev eloped for the word of periodontitis. . All nitroimidazoles are synthetic drugs such as metronidazole. Tinidazole, dimetridazole, secnidazole and ornidazole. Among all these we selected secnidazole because of its High efficacy. Secinidazole is the mainly use for antiprotozoal activity and its exclusive dose possess three daytimes anti protozoal activity. suppose 1 Chemical StructureIUPAC Name1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2-olFigure 2 Proposed trip the light fantastic toe Synthesis route for SecnidazoleAfter observing the reaction condition and UV-Vis absorption, FTIR, ESI-MS and proton magnetic resonance results. The purposed scheme will be optimized.Synthesis of Secnidazole based derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics profilePharmacological and pharmacokinetic properties of liveing drugs cornerstone be enhanced by chemical substance modifications. A prodrug (drug transporter) formation is a great approach to im prove and condition the physio chemical properties of the drug, boost up its concentration at the site of action, bear on its period of action and decrease its toxicity. Regarding 57% of drugs approved world-wide are categorized as prodrug. Prodrugs are the reversible, inactive or little active derivatives of a drug. Prodrugs are hydrolyzed any by enzymatically or non-enzymatically to implode arouse drug while the co-drugs (mutual prodrug) are the special type of prodrug in which two or more pharmacologically active pro moieties exist via chemical bond to release two or more parent drugs upon the cleavage of bond by enzymatically or chemically. The variety of chemical linkages used in the formation of Prodrugs. Although the ester formation is common followed by imides, amide and carbamate derivative. Thats wherefore in this project our aim is to synthesize the prodrug for its better rule of action and their structure activity relationship and their pharmacokinetics profile. ATENOLOL (Part B)Efficient Synthesis of AtenololAtenolol (ATN) belongs to the class of drug called beta-blockers. Beta-blockers (beta adrenoreceptor antagonists) are basically competitive inhibitor thats inhibits the action of stimulating hormones on beta adrenergic receptors in the unquiet system. Atenolol works by competing for receptors sites on cardiac muscle. This slow calibrate the strength of hearts contractions and reduce its oxygen exigencys and the volume of short letter it has to pump. Atenolol is one of the extensive used active pharmaceutical ingredients (API) for the treatment of Hypertension, myocardial infarction (Heart attack), Arrhythmias (rhythms disorder), Angina (chest pain) and disorder arising from decreased circulation of blood.Figure 1 Chemical Structure IUPAC Name2-4-2-hydroxy-3-(propan-2-ylamino) propoxy phenyl acetamideFigure 2 Proposed trip the light fantastic Synthesis route for AtenololThe stereochemistry is important for any molecules. In atenolol (S) isomer is important for its activity the opposite (R) enantiomer may be answerable for the side effects. There have been considerable efforts done in the preparation of enantiomerically pure(S) confirmationSynthesis of Atenolol based derivatives for Structure-Activity Relationship Studies (SARS) and their pharmacokinetics profileOn the basis of the importance of prodrug (mention above part) our aim is to synthesize the prodrug for its better mode of action and their structure activity relationship and their pharmacokinetics profile.4B.RESEARCH PLAN/ METHODOLOGY record/PHASINGEstablishment of Organic Synthesis Facilities In the starting 1st calendar calendar months of this project all the basic and reaction requirement appliance and glassware will be installing.Efficient Synthesis of SECNIDAZOLE After initialization, the starting 3 months will be utilized on the proposed and modified efficient synthesis of Secnidazole to do the maximum yield of required API at minimum co st.Synthesis of SECNIDAZOLE based derivatives for SARS In the 5th and 6th month modification on the molecule of Secnidazole will be applied and study their pharmacokinetics profileSynthesis of ATENOLOL In the period of 7th to 9th month of the project efficient synthesis of atenolol will be doneSynthesis of ATENOLOL based derivatives for SARS In the period of 10th to 11th month of the project clockline, derivatization of atenolol will be carried out and studied their pharmacokinetics profileSummarize results and expand to new project At the end month of this project condemnationline a final project report will be submitted along with findings. Also discuss the achievements and problems faced during this project.4c) ReferencesSecnidazole (Part A)Larina, Lyudmila, and Valentin Lopyrev.Nitroazoles synthesis, structure and applications. New York Springer, 2009.Crozet, Maxime D., Cline Botta, Monique Gasquet, Christophe Curti, Vincent Rmusat, Sbastien Hutter, Olivier Chapelle, Nadine Az as, Michel De Mo, and Patrice Vanelle. Lowering of 5-nitroimidazoles mutagenicity towards optimal antiparasitic pharmacophore.European ledger of healthful chemistry44, no. 2 (2009) 653-659Wang, She-Feng, Yong Yin, Fang Qiao, Xun Wu, Shao Sha, Li Zhang, and Hai-Liang Zhu. Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents.Bioorganic medicinal chemistry22, no. 8 (2014) 2409-2415.Samanta, Himadri Sekhar, and Samit Kumar Ray. Controlled release of tinidazole and theophylline from chitosan based composite hydrogels.Carbohydrate polymers106 (2014) 109-120.Elias, P. curefor affecty.com 2009, 1-11.Shahid, Hafiz Abdullah, Ejaz Hussain, Sajid Jahangir, and Sammer Yousuf. 1-(2-Methyl-5-nitro-1H-imidazol-1-yl) propan-2-yl acetate.Acta Crystallographica ingredient E Structure Reports Online70, no. 3 (2014) o294-o294.Atenolol (Part B)Chaudhari, Vilas, Syed Hussain, and Milind Ubale. International diary of Chemical Studies.Kitaori, Kazuhiro, Yoshikazu TAKEHIRA, Yoshiro FURUKAWA, Hiroshi YOSHIMOTO, and Junzo OTERA. A practical synthesis of optically active atenolol from chiral epichlorohydrin.Chemical and pharmaceutical bulletin45, no. 2 (1997) 412-414.Darnle, Subhash V., Prashant N. Patil, and Manikrao M. Salunkhe. Chemoenzymatic synthesis of (R)-and (S)-atenolol and propranolol employing lipase catalyzed enantioselective esterification and hydrolysis.Synthetic communications29, no. 22 (1999) 3855-3862 push OF PROPOSED RESEARCHThe impact of this project will boost up the economy of Pakistan and will decrease the import bill of Pakistan and also increases the exportation. The project also aims to train the man power and create the skillful hand that can provide the better solution to our local industry. This project also creates the networking between the local industry and researcher. This project also contributes in the providing of the medicine to common people at minimum cost.Estimated Budget For The Proposed Research Period renderingPER YEARAmount (in million Rs)A. Salaries and HonorariumPI One calendar month/Year of Basic Pay 1040000.104 (208000)Student Ships 20,000.00 per month (two)4800000.48 (480000)Secretariat rungPart-time science lab escort 1500 PM180000.018(18000)Subtotal (A)6020000.602(602000)B. Permanent Equipment widely distributed purpose fume hood Pkr 150,000/= (two)3000000.600(600000)The orbitual evaporator r 3 focuses and accessories Pkr 150000015000001.500(1500000)Jacketed reaction apparatus Pkr 169650/= (one)1696500.1695(169650)Glassware, hotplates, stirrer, etc.2500000.250(250000)Laptop (dell core 2i)500000.050(50000)General lab update i.e. Ups and power supply solutions2500000.250(250000)Mas II microwave synthesis system $8000/= (one)8000000.800(800000)Subtotal (B)33196503.319650 (3319650)C. expendable SuppliesChemicals and solvents3000000.300(300000)General lab expenditures ten thousand00.100(myriad0)Spectroscopy te chniques2500000.250(250000)Subtotal (C)6500000.65(650000)D. Others (Literature, documentation, information, online literature search, contingencies, postage, Local Travel conglomerate etc).Journal Publication Fee / Online Material (up to Rs.50,000)500000.050(50000)Stationary/Contingency (10,000/- per year)100000.010(10000)Participation in local conferences, workshops and winter summer schools by PI and students100000.010(10000)Audit Fee (Max. Rs 10,000)100000.010(10000)Accountant Fee (Max. Rs. 10,000)100000.010(10000)Subtotal (D)900000.090(90000)Grand Total(A + B + C + D)46616504.661650(4661650)JUSTIFICATIONSalaries AllowancesTwo Studentships 20,000.00 per month (PM) It is very necessary that at least two full time studentships available to students so that students can perform their work with piece of consciousness so that they have no need to sort part time jobs to meet their day to day expensePart-time Lab Attendant 1500 PM During period of project operations different kind of tasks are assigned to Lab Attendant in addition to their normal job responsibilities. Therefore it is justified to compensate their work with an honorarium.Permanent EquipmentThe Rotary Evaporator and accessories (one) many a(prenominal) organic reactions are in liquid phase and require a lot more time to evaporate on room temperature thats why to save time and fast reaction process need rotary evaporator.General Purpose Fume Hood As many organic reaction, chemicals and solvents are hazardous to human health. For safety and precautionary step need two fuming hoodsJacketed Reaction Apparatus It is the temperature control apparatus. As many reaction are temperature dependent and monitor through varying temperature. to make reaction efficient we need jacketed reaction apparatusGlassware, Hotplates, Stirrer, refwork etc These are the basics requirement for organic synthesis as well as we have dearth of these basics needs thats why we need theseGeneral lab updates i.e. UPS and Powe r Supply solutions Regular breakdown of power supply has resulted in the failure of organic reactions as well as damage of electronic appliances. Therefore a need to establish backup of power supply.Expendable suppliesChemicals and solvents These play key role in all reaction either organic or inorganic and no one can performed reaction without this so these funding are fully justifiedGeneral Lab Expenditures these are the basic need for researcher to meet day to day expensesParticipation in local conferences, workshops and winter/summer schools by PI and students These funding are required to communicate our work on national and international level. Also learn gain information from their experience