Heterocyclicchemistry is one of the most interesting, applied branches of organic chemistryand of utmost practical and theoretical importance. It is a vast and expandingarea of chemistry because of obvious applications of compounds derived fromheterocyclic rings in pharmacy, medicine, agriculture, plastic, polymer andother fields. Heterocycliccompounds are present in abundance in our surroundings. They owe theirimportance in the biological system due to uniqueness in their structuralskeleton parts. All thesenatural and synthetic heterocyclic compounds can and do participate in chemicalreactions in the human body.
Furthermore, all biological processes are chemicalin nature. Nitrogen containing heterocyclic compounds are importantclass of heterocyclic compounds that has paid significant contribution towardsmedicinal chemistry. The types of compounds depend upon number of nitrogenatoms and their position.Ex: Pyrimidines, triazoles, pyrazoles, imidazoles ect., Heterocycliccompounds played a vital role in the metabolism of all living cells. Some ofthe common heterocyclic compounds used in the medicines are amino acids likeproline, histidine and tryptophan, the vitamins and coenzyme precursors such asthiamine, riboflavin, pyridoxine, folic acid, biotin, B12 and E families of thevitamins. There are a vast number of pharmacologically active heterocycliccompounds, many of which are in regular clinical use such as cholesterol-reducingAtorvastatin, anti-inflammatory Celecoxib, antiulcerative Cimetidine,antifungal Fluconazole, and antihypertensive Losartan ect.
Literature surveyreveals that when one biologically active heterocyclic system is coupled withanother, there will be an increase in the biological activity of the resultantmolecule. Keeping in view of these facts, number of bi heterocyclic compoundshave been synthesized and examined their biological activities. Thieno2,3-dpyrimidines Pyrimidinehas always been a unique interesting heterocyclic moiety for the medicinalchemists. An exhaustive research has been done on the pyrimidines that led to thediscovery and introduction of several drugs into the market. This ring system is present in cytosine,adenine, guanine and thiamine, which form a part of ribonucleic acid (RNA) anddeoxyribonucleic acid (DNA) and vitamins like vitamin B2 (Riboflavin) andvitamin B6 (Pyridoxine) co-enzyme and other purines 1. Fromthe standpoint of biological activity, fused hetero aromatic systems are oftenof much greater interest than the constituent monocyclic compounds. Fusedpyrimidines have also been attracted a considerable interest in medicinalchemistry research due to their versatility and a broad bioactive potential. The heterocyclic fusion of thiophenering with pyrimidine ring system resulted in the formation of thieno pyrimidine,a structural analogue of quinazoline, an important class of heterocycliccompounds which possesses broad spectrum of biological activities.
Sincelast four decades research has been focused on the design and synthesis ofnovel thienopyrimidines as medicinal agents, a large number of reports havebeen documented on thienopyrimidines. Theseare three isomeric thienopyrimidines corresponding to the three possible typesof annulations of thiophene to the pyrimidine ring. Thieno2,3-dpyrimidine (1), thieno3,2-dpyrimidine (2), andthieno3,4-dpyrimidine (3). Amongthienopyrimidines, thieno2,3-dpyrimidines have extreme importance in medicinal chemistry,exhibiting pharmacological and therapeutic properties such as antioxidant 2,antibacterial 3,4,5, antifungal 6, anti-inflammatory 7,8, anti platelet 9,antihypertensive 10, herbicidal 11, and anticancer 12 ect.
So the present studyfocuses only on thieno2,3-dpyrimidines. Syntheticroutes of thieno2,3-dpyrimidinederivatives1. Interaction of2-amino-3-carbethoxythiophenes with amides 2. Interaction of2-amino-3-cyano/carbethoxythiophenes with thioamides 3. Interaction of 2-aminothiophene-3-carboxylateswith imidic esters 4. Interactionof 2-aminothiophene-3-carboxylates with thiourea 5. Interactionof 2-acylaminothiophene-3-carboxylates with hydrazine 1,2,3-triazoles Themedicinal chemists have considered the synthesis of 1, 2, 3-triazole basedheterocyclic compounds as the corner stone of medicinal chemistry due to theirimportant biological activities. This could be understood from the fact thateven in the early part of the twentieth century the researchers started workingon the possibility of using 1,2,3-triazolo4,5-d pyrimidines(8-azapurines) for the treatment of cancer and malignant tumors.
1, 2,3-triazoles cause peptidomimetic inhibition of tyrosinase, an enzyme whichcauses the browning of plant based foodstuffs and human skin diseases. The featurespossessed by the 1, 2, 3-triazoles make them pharmaceutically importantmolecules. They are stable to reduction and oxidation as well as to hydrolysisin acidic and basic conditions, which indicates their high aromaticstabilization. 1,2,3-triazoles have a high dipole moment (about 5 D) and areable to participate actively in hydrogen bond formation as well as indipole–dipole and ? stacking interactions which helps them in binding easilywith the biological targets and improves their solubility. There arefew 1,2,3–triazole bearing drugs available on the market like Refinamide,Tazobactum, Cefatrizine etc.
The clickchemistry approach invented by Sharpless using copper (I)-catalyzed azide alkynecycloaddition (CuAAC) has resulted in the production of large number of 1,4-disubstituted 1, 2, 3-triazoles in very high yields 13. Regioselective “Click” reaction In 2002, two research groupsindependently reported that CuAAC proceeds as much as 107 times morerapidly than the un catalyzed version. More importantly, at room temperature orwith only moderate heating, use of the copper catalyst affords the exclusiveformation of the 1, 4-regioisomer. Importance of ClickReaction:Ø Functional group tolerance Ø Aqueous conditions Ø Shorter reaction time Ø High yield Ø High purity Ø Regioselectivity and economica Proposed catalytic cycle for Cu (I) catalyzed ligation The use of copper(I) as a catalyst in the reaction dramatically accelerates the rate of reactionand accomplishes region specificity by the formation of 1,4-substitutedproducts only and it requires simple purification as filtration orcrystallization.
The click reaction proceeds most rapidly in water orwater-co-solvent mixtures in highest yield.
