Heterocyclic Building Blocks

Acridines

Acridine (dibenzo(b,e)pyridine; 2,3,5,6-dibenzopyridine; 2,3-benzoquinoline; 10-azaanthracene) alkaloids are flat (planar) aromatic, hydrophobic nitrogen heterocycles, structurally related to anthracene, with one of the central CH groups replaced by nitrogen. Acridine derivatives have a long history in medicinal chemistry, beginning with antimicrobial activity that was reported by Ehrlich and Benda in 1912. They also exhibit anticancer, antibiotic anti-AChE, antiprion, antileukemic, antimalarial, antipsychotic, antidepressant, anti-dimentia, antinociceptive, and telomerase inhibition drug properties. Their hydrophobicity allows them to diffuse into the cell membrane and complex with (intercalate) DNA and RNA. This component results in their inherent drug properties and causes fluorescence that can be used to study cellular processes, e.g. cell cycle determination, stain nucleic acids, and flow cytometry. 9-Aminoacridine hydrochloride monohydrate is a mutagen, but appropriately substituted 9-arylaminoacridine anticancer drugs act via interference with the mammalian topoisomerase II enzyme. We offer several acridine derivatives to facilitate drug discovery.

Azaindoles

Azaindoles have a bicyclic structure that consists of a pyridine ring fused to a pyrrole ring. These compounds exhibit significant biological activity and help facilitate the generation of new therapeutic leads. The azaindole moiety exhibits excellent potential as a bioisostere of the indole ring system, differing from indole only by the presence of an additional ring of nitrogen. 7-Azaindoles are of particular interest because of their ability to mimic purines in their role as hydrogen-bonding partners.

Benzimidazoles

A benzimidazole is a heterocyclic aromatic organic compound consisting of a fusion of benzene and imidazole. Benzimidazoles are used as an extension of the well-elaborated imidazole system, as a carbon skeleton for N-heterocyclic carbenes, and as a ligand for transition metal complexes. Pharmacological compounds of benzimidazole derivatives are potent inhibitors for a variety of enzymes. Benzimidazoles have a variety of therapeutic uses, including antitumor, antifungal, antiparasitic, analgesics, antiviral, and antihistamine activities, as well as use in cardiovascular disease, neurology, endocrinology, and ophthalmology.

Benzodioxanes

Benzodioxane derivatives, bicyclic heterocyclic systems consisting of a benzene ring fused to a heterocyclic dioxane ring, represent a series of synthetic and natural compounds of considerable medicinal importance. Compounds containing the dioxane or the 1,4-benzodioxane moiety exhibit various biological activities, such as antihepatotoxic (hepatoprotective), α-adrenergic blocking agent, anti-inflammatory, antigrastic, spasmolytic, antipsychotic, anxiolytic, and D2 antagonist/5-HT1A partial agonist activities.

Benzofurans

Benzofuran, also known as coumarone, is a heterocyclic compound consisting of fused benzene and furan rings. Benzofuran derivatives have shown biological activities, ranging from antifungal and antimicrobial properties to acting as antagonists for the H3 receptor and angiotensin II.

Benzopyrans

Benzopyrans, also called chromenes, are bicyclic heterocyclic systems consisting of a benzene ring fused to a heterocyclic pyran ring. Benzopyran derivatives (chromones and flavones) are potentially useful anti-inflammatory agents due to their ability to inhibit protein kinase-dependent signal transduction pathways. Furthermore, some natural benzopyran derivatives exhibit inhibitory activity of prostaglandin E2 (PGE2) production. Benzopyran derivatives are also an attractive template for the identification of potential anticancer agents.

Benzothiophenes

Benzothiophenes, a benzene ring fused to a thiophene ring, are an important class of heterocycles with privileged structures. They are used as starting materials for the synthesis of bioactive structures and are present in pharmaceuticals; such as selective estrogen receptor modulators, leukotriene synthesis inhibitors, and antifungals, and many natural products. Different substitution patterns in these heterocycles provide new opportunities for drug discoveries and other applications in materials science.

Benzotriazoles

Benzotriazoles, bicyclic heterocyclic systems containing three nitrogen atoms and a fused benzene ring, show a wide range of biological and pharmacological activities as well as applications in materials science. They are used in industry as fixing agents in photographic emulsions, as anti-tarnish agents for copper and its alloys, as a corrosion inhibitor, and in antifreeze and water coolant systems. Some synthetic methods of benzotriazole include N-alkylation of benzotriazole under solvent-free conditions and copper-free “click” methods, the preparation of a-nitro ketones, oxazolines and thiazolines under microwave irradiation, and the utility of N-acylbenzotriazoles continues to expand.

Benzotriazole derivatives have been commonly employed as a leaving group and used extensively as a novel synthetic auxiliary. Much of their attractiveness lies in their ability to be introduced readily and easily removed during synthesis, and activate other parts of the molecule.

A plethora of methods for the formation of the peptide bond have been reported. The most successful approaches known today involve active ester formation with uronium/guanidinium salts. The most popular members of this family are peptide synthesis reagents based on benzotriazole derivatives, such as HOBt or HOAt, both of which are also commonly used as additives in carbodiimide mediated peptide coupling.

Carbazoles

Carbazole derivatives are tricyclic aromatic heterocycles consisting of two benzene rings fused on either side of a five-membered nitrogen-containing ring. The intriguing structural features and promising pharmacological activities of these natural products have led to enormous growth in carbazole chemistry. Carbazole alkaloid derivatives are well known for their various pharmacological activities, including anti-HIV, anticancer, antibacterial and antifungal activities. Carbazole derivatives, such as N-vinylcarbazole and poly(vinylcarbazole) also have applications in industry and materials science as optoelectronic materials.

Coumarins

Coumarins are a group of plant-derived polyphenolic compounds. They belong to the benzopyrones family and possess a wide range of pharmaceutical applications including cytoprotective and modulatory functions, which may be translated into therapeutic potential for multiple diseases. Coumarin derivatives are found in antibiotic, antimitotic, immunomodulating, antiviral, anticancer, anti-inflammatory, anticoagulant, antifungal, antioxidant, and cytotoxic agents, as well as some biological assays.

Coumarins have additional industrial applications. The fluorescence of coumarins, such as 7-hydroxycoumarin, is widely used as a research tool in polymer science. Coumarins are used as laser dye-sensitized photoinitiators, for incorporation into polymer chains by co-polymerization, in the estimation of polymer solvent effects, for various structural characterizations, in the monitoring of the releasing properties of poly(methylmethacrylate) nanospheres and for polymeric fluorescent solar collectors.

Furans

Furans, consisting of a five-membered aromatic ring with one oxygen atom, are an important class of heterocyclic compounds that possess important biological properties. The furan ring system is the basic skeleton of numerous compounds possessing cardiovascular activities. An iodinated lipophilic furan derivative is widely used in the treatment of ventricular and arterial fibrillation. These moieties are widely found in antibacterial, antiviral, anti-inflammatory, antifungal, antitumor, antihyperglycemic analgesic, anticonvulsant, and other agents. Slight changes in substitution patterns in the furan nucleus cause distinguishable differences in their biological activities. Furan derivatives have been found to be inhibitors of biofilm formation for several bacterial species, as well as possess quorum-sensing inhibitory activities. In addition to being synthetic building blocks, derivatives are promising lignocellulosic biofuels.

Homopiperidines

Homopiperidines, also known as azepanes, are saturated heterocycles containing a nitrogen in a seven-membered ring, and are precursors to several drugs and pesticides. They have been investigated as small-molecule modulators of calcium-activated potassium channels.

Imidazoles

An imidazole is a planar five-member ring containing two nitrogens (C₃N₂H₄). While other azole heterocycles are prevalent in a wide range of bioactive natural products, the imidazole ring occurs largely in the context of the natural amino acid histidine. In addition, the imidazole ring appears as a component of unnatural cyclic peptides and is used as an ester isostere in peptidomimetic studies. However, the applications of imidazole are not limited to the realm of peptides and peptidomimetics. Imidazoles are present in the large family of bromopyrrole-imidazole alkaloids isolated from marine sponges containingthe common metabolite oroidin that feature significant biological activities. The imidazole ring is also present in the pilocarpine alkaloids, which are potential therapeutic agents for thrombosis, cancer, and inflammatory diseases.

Imidazolines/Imidazolidines

Imidazolines and imidazolidines are important heterocycles found in many biologically-active compounds. Imidazolines are used as chiral catalysts, chiral auxiliaries, and ligands for asymmetric catalysis. They exhibit a range of biological activities, including antihyperglycemic, anti-inflammatory, antihypertensive, anticancer, and antihypercholesterolemic agents, as well as antiulcer, antiviral, antifungal, antibacterial, antitubercular, antiasthmatic, anti-diabetic and antiprotozoal activities. Imidazolines, such as fatty acid imidazolines, have industrial applications as corrosion inhibitors.

Indazoles

Indazole moieties are heterocyclic aromatic compounds with a benzene fused to a pyrazole. They differ from indole only by the presence of an additional ring of nitrogen, and thus exhibit excellent potential as bioisosteres of the indole ring system. Various indazoles display significant activity as antifungals, anti-inflammatory agents, antiarrhythmic agents, analgesics, and nitric oxide synthase inhibitors.

Indoles

Indoles are benzene rings fused with a pyrrole ring. The indole subunit is a near-ubiquitous component of biologically active natural products, and its study has been a major focus of research for generations. They are capable of binding to multiple receptors with high affinity, and thus have applications across a wide range of therapeutic areas. Due to this activity, it is not surprising that the indole ring system has become an important building block or intermediate in heterocyclic synthesis.

Indolines

Indolines are aromatic bicyclic heterocycles consisting of a benzene ring fused to a five-membered nitrogen-containing ring. Indole alkaloids are extensively studied for their biological activities in several pharmaceutical areas, such as anticancer and antitumor. Among this chemical family, indolinone displays very promising antitumor properties by inhibiting various kinase families. These small molecules have a low molecular weight and most of them bind to protein kinases, competing with ATP for the ATP-binding site. In addition to being building blocks in heterocyclic synthesis, indolines also have industrial applications as sensitizers in solar cells.

Isoquinolines

Isoquinolines, structural isomers of quinolines, are benzopyridines, composed of a benzene ring fused to a pyridine ring. Because of their wide range of activities, the synthesis of isoquinolines if of considerable interest and many synthetic approaches allow access to these structures.

Isoxazoles

Isoxazole, an azole with an oxygen, derivatives are found in some natural products, such as ibotenic acid, as well as several drugs, including a COX-2 inhibitor, and furoxan, a nitric oxide donor. Isoxazoles are useful isosteres of pyridine and have been found to inhibit voltage-gated sodium channels to control pain, enable the construction of tetracycline antibiotic derivatives, and are used as treatments for depression.

Morpholines/Thiomorpholines

Morpholines are six-membered heterocycles featuring both amine and ether functional groups. Substituted morpholine derivatives are the core of various natural products and biologically active compounds. This class of compounds has found important applications in pharmaceuticals and in agricultural use. Chiral morpholine derivatives have found numerous applications in asymmetric synthesis as chiral auxiliaries as well as chiral ligands. Morpholine derivatives from synthesis and natural products have exhibited activity as antidepressants, appetite suppressants, antitumor agents, antioxidants, antibiotics, selective α1-agonists in the treatment of dementia and other central nervous system (CNS) disorders characterized by symptoms of noradrenergic insufficiency, as well as potent long acting human neurokinin-1 (hNK-1) receptor antagonists. Morpholines have several industrial applications, such as corrosion inhibitors, optical bleaching agents, in textile dying, and for fruit preservation.

Oxadiazoles

Oxadiazoles are five-membered heterocyclic aromatic compounds consisting of one oxygen atom, two nitrogen atoms and two carbon atoms. Depending on the placement of the nitrogens in the ring, several isomers exist such as 1,2,4-; 1,2,5-; and 1,3,4-oxadiazole. Oxadiazoles form a major class of compounds with a heterocyclic nucleus for drug development and were among the first effective chemotherapeutic and antibiotic agents. Interest in oxadiazoles ranges from medicinal chemistry to the polymer industry. Oxadiazoles have antibacterial, anti-inflammatory, anticonvulsant, anticancer, antitubercular, anti-diabetic, antihelmintic, and analgesic CNS depressant activities, among others. Due to their broad biological activity potential, the synthesis of oxadiazole derivatives is of interest to medicinal chemists working in drug development.

Oxazoles

Oxazoles are heterocyclic aromatic compounds containing an oxygen atom and a nitrogen atom separated by one carbon atom. Oxazole derivatives have become increasingly important because of their use as intermediates for the preparation of new biological materials. The oxazole ring is present in numerous pharmacologically important compounds, including those used as antibiotics and antiproliferative agents. The wide range of biological activities of oxazoles includes anti-inflammatory, analgesic, antibacterial, antifungal, hypoglycemic, antiproliferative, anti-tuberculosis, muscle relaxant and HIV inhibitor activity. In addition, oxazole derivatives are useful synthetic intermediates and can be used as diversity scaffolds in combinatorial chemistry and as peptidomimetics.

Oxazolines/Oxazolidines

Oxazolines consist of a five-membered heterocyclic ring containing one oxygen and one nitrogen atom, and oxazolidines (also called 1,3-oxazolidines) are the reduced form of oxazolines. Isoxazolidines are isomers of oxazolidines where the nitrogen and oxygen atoms are adjacent. Oxazolines are attractive heterocyclic compounds not only because of their unique structures and varied applications, but also because they serve as structural elements in a variety of natural products and pharmaceuticals. Examples of these compounds include an antimycobacterial oxazole-containing alkaloid, a tubulin polymerization inhibitor, and anticancer agents that comprise 2,5-disubstituted oxazoline elements. Moreover, oxazoline derivatives can also be employed as corrosion inhibitors in industrial settings and as chiral ligands in asymmetric synthesis. Polymers of 2-oxazoline are regarded as pseudopeptide bioinspired polymers. Because of the important applications of oxazoline derivatives, various synthetic methodologies have been developed for the production of these compounds. Generally, oxazole derivatives are synthesized by three typical methods: cyclization of acyclic precursors, oxidation of oxazolines, and coupling of the prefunctionalized oxazoles with other organometallic reagents. Chiral bis(oxazoline) (BOX) ligands are used in the asymmetric catalysis of a variety of reactions.

Oxetanes

Oxetanes, a four-membered ring with three carbon atoms and one oxygen atom, are close homologs of epoxides and are attractive modules for drug discovery. Rogers-Evans, Carreira, and co-workers reported that replacing a gem-dimethyl unit with an oxetane unit demonstrated improved physio- and biochemical properties of a molecular scaffold. They also showed the use of 1,6-substituted azaspiro[3.3]heptanes containing an oxetane ring as alternatives to unstable 1,3-heteroatom substituted cyclohexanes. The oxetane ring can also function as a surrogate for a carbonyl group. In most cases, 3-oxetanone was the principal building block employed by the authors to install the oxetane unit.

The presence of the oxetane moiety in drug-like and biologically active molecules is nothing new to synthetic and medicinal chemists. Perhaps the best-known examples of oxetane-containing drugs are the natural product paclitaxel (Taxol^®) and its synthetic analog docetaxel. Joëlle Dubois and co-workers studied the effect of the deletion of the oxetane ring in analogs of docetaxel and found the analogs to be less active than docetaxel in biological assays. Merrilactone A shows promise as a nonpeptidal neurotropic agent, and the β-amino acid oxetin has demonstrated both herbicidal and antibiotic activity.

Piperazines

The piperazine scaffold is a six-membered ring with two nitrogens in opposite positions and is frequently found in biologically active compounds across different therapeutic areas. Some of these therapeutic areas include antifungals, antidepressants, antiviral, and serotonin receptor (5-HT) antagonists/agonists. Simple N-substituted piperazines are found in numerous drug molecules. Industrial applications for piperazines include the manufacture of plastics, resins, pesticides, and break fluid.

Piperidines

Piperidines and their derivatives have become increasingly popular building blocks in a vast array of synthetic protocols. The piperidine ring, a six-membered ring containing one nitrogen atom, can be recognized not only in the structure of more than half of the alkaloids known today, but also in many natural or synthetic compounds with interesting biological activities. 1-Boc-2-(aminomethyl)piperidine has been used in a post-Ugi carbonylation/intramolecular amidation approach to a series of eight-membered macrolactams with multiple points of diversity. Additionally, the unprotected analogue has been employed in the synthesis of melanocortin 4 receptor antagonists. These antagonists are potentially useful in the therapeutic treatment of involuntary weight loss. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, such as in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and numerous degradation reactions.

Piperidones

The piperidone pharmacophore, a nitrogen-containing heterocycle with a carbonyl group, possess a greater affinity towards cellular thiols than towards amino and hydroxyl groups. Thus, compounds of this nature may be devoid of the genotoxic side effects associated with many alkylating agents. As α,β-unsaturated ketones, these compounds are capable of undergoing Michael addition, resulting in alkylation of cellular nucleophiles. Piperidones exhibit anticancer, anti-inflammatory, and antimicrobial activity, and also inhibit the NF-κB signaling pathway. 2-Piperidone and 4-piperidone are important intermediates in alkaloid synthesis and in the preparation of medicinal agents. Mannich–Michael, and aza-Diels–Alder reactions involving an imino dienophile and a conjugated diene and enones have been applied to the synthesis of piperidine derivatives.

Purines

Vital to life as we know it—pyrimidine and purine bases are included in the structures of DNA and RNA. Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle found in nature.

Pyrans

Pyran is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom and contain two double bonds. Pyran derivatives, such as pyranoflavonoids, are biologically important. Monosaccharides containing a six-membered ring are known as pyranoses.

Pyrazines

Pyrazines (paradiazines) are heterocyclic six-membered aromatic compounds containing para nitrogen atoms. Pyrazine derivatives are known for antitumor, antibiotic, anticonvulsant, antituberculosis and diuretic activities, as well as kinase, enzymatic, and potent tubulin and FtsZ polymerization inhibition. Pyrazines are volatile compounds that are also of interest to the cosmetic, food, flavor, and fragrance industries.

Pyrazoles

Pyrazole, a five-membered heterocyclic diazole alkaloid composed of three carbon atoms and two nitrogen atoms in adjacent positions, is a prevalent scaffold in drug discovery programs. Derivatives of pyrazole are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle-relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities. The pyrazole ring is present as the core in a variety of leading nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. They have also found use as bifunctional ligands for metal catalysis.

Pyridazines

Pyridazine, sometimes called 1,2-diazine, is a six-membered ring containing two adjacent nitrogen atoms. Pyridazine can be used as an isosteric replacement of phenyl or heteroaromatic rings. Pyridazines can improve the physiochemical properties of drug molecules by increasing their water solubility, participating as hydrogen bond acceptors, and have a high capacity to complex with targets due to their dipole moment. Pyridazine confers bioavailability, especially to the CNS, and can reduce toxicity. Pyridazine is a part of several drug molecules, and the pyridazine pharmacophore has led to a variety of pharmacologically active compounds.

Pyridines

Pyridines are heterocyclic six-membered aromatic compounds containing a single nitrogen atom. Pyridines are a class of important heterocycles and appear in many naturally occurring bioactive compounds, pharmaceutical molecules, and chiral ligands in polysubstituted forms. The pyridine moiety is present in countless molecules with applications as varied as catalysis, drug design, molecular recognition, and natural product synthesis. Examples of pyridines include the well-known alkaloids lycodine, the A₃ adenosine receptor antagonist, and a N,N-dimethylaminopyridine (DMAP) analogue commonly applied in organic synthesis. Pyridine derivatives have also been implicated as small molecule α-helical mimetics in the inhibition of protein-protein interactions, and functionally selective GABA_A ligands. Halogenated pyridines are particularly attractive building blocks for various cross-coupling methodologies, including Suzuki-Miyaura cross-coupling reactions.

Pyrimidines

Pyrimidines are heterocyclic aromatic organic compounds similar to pyridine but contain two nitrogen atoms at positions 1 and 3 of the six-membered ring. The ring is isomeric with two other forms of diazine: pyridazine, with the nitrogen atoms in positions 1 and 2; and pyrazine, with the nitrogen atoms in positions 1 and 4. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have vast biological applications. For example, pyrimidine derivatives are of use in research on DNA repair with implications in cancer and epigenetics.

Pyrroles

Pyrroles (1H-pyrroles) are heterocyclic aromatic compounds consisting of a five-membered ring containing a nitrogen atom. Pyrroles are important synthons in the synthesis of natural products. They exhibit remarkable biological properties such as hypolipidemic, antimicrobial, anti-inflammatory and antitumor activities and can inhibit retroviral reverse transcriptases [i.e., human immunodeficiency virus type 1 (HIV-1)], cellular DNA polymerases and protein kinases. Furthermore, some of these compounds are useful intermediates in the synthesis of biologically important naturally occurring alkaloids and unnatural heterocyclic derivatives. Phosphino-substituted N-aryl pyrroles, a novel class of sterically demanding and electron rich biaryl phosphine ligands, exhibit high turnover rates and low catalyst loadings.

Pyrrolidines

Pyrrolidines are cyclic secondary amines with a five-membered ring, containing four carbon atoms and one nitrogen atom. The pyrrolidine ring is the central structure of the amino acid proline and its derivatives. Chiral pyrrolidines play an important role both as chiral building blocks for auxiliaries as well as key structures relevant to biologically active substances. Derivatives of the methylpyrrolidinyl fragment are common structural motifs present in several inhibitors and antagonists, including a series of HIV-1 reverse transcriptase inhibitors and histamine H3 receptor and dopamine D4 antagonists. The majority of pyrrolidines we offer are available as racemates or in either enantiomeric form.

Pyrrolines

Pyrrolines, nitrogen-containing five-membered heterocycles, are common structural scaffolds in natural products and pharmaceutical agents. Pyrroline derivatives include natural and synthetic compounds with notable biological and pharmacological properties. Pyrrolines are intermediates in the syntheses of biologically active pyrroles and pyrrolidines. Examples of medicinally important pyrroline-based compounds include protein kinase inhibitor staurosporine and geranylgeranyltransferase inhibitor.

Quinazolines

Quinazoline, 1,3-diazanaphthalene, is composed of fused benzene and pyrimidine rings. They are outstanding scaffolds for synthetic manipulations with huge pharmacological activities due to the predictable reactivity of the rings in electrophilic and nucleophilic substitution. Quinazoline derivatives have found applications as anti-malarial agents and in cancer treatment.

Quinolines

Quinoline derivatives, a benzene ring fused to a pyridine ring, have antiseptic, antipyretic, and antiperiodic properties and are used as antimalarials and for preparing other antimalarial drugs. The discovery of chloroquine, the most famous drug containing this scaffold, resulted in control and treatment of malaria for decades. Quinoline and its derivatives are widely used as fungicides, biocides, antibiotics, alkaloids, dyes, rubber chemicals, and flavoring agents. Additional industrial applications include their use as corrosion inhibitors, preservatives, and as solvents for resins and terpenes, and in transition-metal complex catalysis for uniform polymerization and luminescence chemistry. They are also used in manufacturing oil soluble dyes, food colorants, pharmaceuticals, pH indicators and other organic compounds. Quinoline is a catabolite of tryptophan, a fundamental structure in some antihypertensive agents such as the peripheral vasodilators prazosin and doxazosin.

Quinoxalines

Quinoxalines (also called 1,4-diazanaphthalenes or benzopyrines) are bicyclic heterocycles containing a benzene ring fused to a pyrazine ring. Quinoxaline derivatives are important components of pharmacologically active compounds, including antibacterial, antibiotic, and antitumor agents, anti-fungal, anti-inflammatory, and analgesic activities, as well as use in RNA synthesis inhibition, reactive dyes and pigments, azo dyes, fluroscein dyes, corrosion inhibition, and photovoltaic polymers.

Quinuclidines

Quinuclidine, a bicyclic amine, has found numerous applications, most notably as a ligand employed in studies on the OsO₄-catalyzed dihydroxylation of olefins. These nitrogen containing heterocycles have also been used to form onium salts for testing of PAC-antagonist activity. 3-Quinuclidinol is a synthon for the preparation of cholinergic receptor ligands and anesthetics as well as a catalyst for condensation of methyl vinyl ketone with aldehydes.

Tetrazoles

Tetrazoles, a five-membered ring containing four nitrogens, have applications in both materials science and pharmaceuticals. Tetrazoles can tolerate a wide range of chemical environments, from strongly acidic to basic as well as oxidizing and reducing conditions. Tetrazoles are metabolically stable bioisosteres of the carboxylic acid group and can serve as precursors to a variety of nitrogen-containing heterocycles by the Huisgen rearrangement. They also function as simple lipophilic spacers displaying two substituents in the appropriate manner, where the connectivity patterns of the embedded tetrazole units bear a striking resemblance to those of their 1,2,3-triazole analogues.

Thiadiazoles

Thiadiazole derivatives, five-membered rings containing two nitrogens and a sulfur, have been investigated for anticonvulsant and antimicrobial activities. Derivatives of 1,3,4-thiadiazoles are known to exhibit antibacterial and antifungal activities.

Thiazines

Thiazines (also called 1,4-thiazines) consist of a six-membered ring containing a sulfur and a nitrogen atom para to each other. They exhibit diverse pharmacological and biological activities, such as anticancer, antimicrobial, anti-inflammatory, and antipyretic activities, as well as act as central nervous system depressants. Additionally, thiazine derivatives are also used for dyes, tranquilizers, and insecticides.

Thiazoles

Thiazoles, a five-membered ring containing a nitrogen and sulfur, exhibit an exceptional range of antitumor, antiviral, and antibiotic activities. Their presence in peptides, or their ability to bind to proteins, DNA, and RNA, have directed numerous synthetic studies and new applications. The thiazole ring has been identified as a central feature of a myriad of natural products, perhaps the best known being the epothilones. Additionally, thiazoles frequently appear in peptide research. Thiazoles can also serve as a protected formyl group that can be liberated in the late stages of a complex natural product synthesis.

Thiazolines/Thiazolidines

Thiazolines are five-membered heterocyclic compounds containing a sulfur atom and a nitrogen atom. Thiazolidine is the reduced form of thiazoline. Cysteine residues are commonly post-transcriptionally modified into thiazolines. Thiazoline derivatives are activators of PPARγ, which improves insulin resistance and lowers blood glucose levels in type 2 diabetes, as well as anticancer agents via inhibition of the Raf/MEK/extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades.

Thiophenes

Thiophenes (thiofurans) are important sulfur-containing heterocyclic compounds that function as analogues of furans and pyrroles, and are widely used as building blocks in many agrochemicals and pharmaceuticals as well as materials science. Benzothiophene and dibenzothiophene contain the thiophene ring fused with one and two benzene rings, respectively. As a consequence of its aromaticity, thiophene does not exhibit the same properties seen for conventional thioethers. For example, the sulfur atom in a thiophene resists alkylation and oxidation. Thiophene can also serve as a bioisostere of the benzene ring, such as in the NSAID lornoxicam, the thiophene analog of piroxicam.

Triazines

Triazine derivatives consist of a six-membered aromatic ring containing three nitrogen atoms. Isomeric forms include 1,2,3-; 1,2,4-; and 1,3,5-triazine. Tri-substituted 1,3,5-triazines are one of the oldest classes of organic compounds that continue to be used as important core structures in many chemotherapeutic agents due to their effective pharmacological properties, including anticancer, anti-angiogenesis, anti-HIV, antimalarial, antibacterial, and antimicrobial activities. These compounds have also been used as subunits in the formation of supramolecular structures because they possess good optical and electronic properties and are able to form multiple hydrogen bonds. Triazine derivatives have also been found to be PI3K and mTOR inhibitors, as well as efficient corrosion inhibitors for mild steel in acidic solutions.

Triazoles

Triazole rings, a five-membered ring containing three nitrogen atoms, exhibit biological activity, notably as antifungals, antimicrobials, and enzymatic inhibitors. The azide-alkyne Huisgen cycloaddition is a mild and selective reaction that produces 1,2,3-triazoles as products. The reaction has been widely used in bio-orthogonal chemistry and in organic synthesis. Triazole rings are relatively stable functional groups, and triazole linkages can be used in a variety of applications, such as replacement of the phosphate backbone of DNA.