Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2-(phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives.

An elevated level of blood uric acid (hyperuricemia) is the underlying cause of gout. Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Allopurinol, a widely used xanthine oxidase inhibitor is the most commonly used drug to treat gout. However, a small but significant portion of the population suffers from adverse effects of allopurinol that includes gastrointestinal upset, skin rashes and hypersensitivity reactions. Moreover, an elevated level of uric acid is considered as an independent risk factor for cardiovascular diseases. Therefore use of allopurinol-like drugs with minimum side effects is the ideal drug of choice against gout. In this study, we report the synthesis of a series of pyrimidin-5-one analogues as effective and a new class of xanthine oxidase inhibitors. All the synthesized pyrimidin-5-one analogues are characterized by spectroscopic techniques and elemental analysis. Four (6a, 6b, 6d and 6f) out of 20 synthesized molecules in this class showed good inhibition against three different sources of xanthine oxidase, which were more potent than allopurinol based on their respective IC(50) values. Molecular modeling and docking studies revealed that the molecule 6a has very good interactions with the Molybdenum-Oxygen-Sulfur (MOS) complex a key component in xanthine oxidase. These results highlight the identification of a new class of xanthine oxidase inhibitors that have potential to be more efficacious, than allopurinol, to treat gout and possibly against cardiovascular diseases.

Benzophenone-N-ethyl piperidine ether analogues--synthesis and efficacy as anti-inflammatory agent.

A sequence of substituted benzophenone-N-ethyl piperidine ether analogues has been synthesized and evaluated as orally active anti-inflammatory agents with reduced side effects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin, and phenylbutazone. These analogues showed an interesting anti-inflammatory activity in carrageenan-induced foot pad edema assay. In the air-pouch test, some of the analogues reduced the total number of leukocytes of the exudate, which indicates inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, in the liver and stomach. None of the compounds illustrated significant side effects compared with standard drugs like indomethacin and naproxen.

Synthesis and antimicrobial study of novel heterocyclic compounds from hydroxybenzophenones.

The triazolothiadiazine analogues 6a-e were obtained via a multistep synthesis sequences beginning with the hydroxybenzophenones 1a-e. Hydroxybenzophenones on reaction with ethyl chloroacetate affords ethyl (2-aroylaryloxy)acetates 2a-e which on treatment with hydrazine hydrate yields 2-(2-aroylaryloxy)acetohydrazides 3a-e. Intramolecular cyclization of 3a-e with carbon disulfide affords 5-(2-aroylaryloxy)methyl-1,3,4-oxadiazole-2-(3H)thiones 4a-e, which on treatment with hydrazine hydrate yields 4-amino-5-(2-aroyl aryloxy)methyl-1,2,4-triazole-3-(2H)thiones 5a-e. Condensation of 5a-e with alpha-halocarbonyl compound results in 3-(2-aroylaryloxy)methyl-6-phenyl-1,2,4-triazolo[3,4-b][1,3,4] thiadiazine 6a-e analogues. The compounds 4a-e, 5a-e and 6a-e were tested against variety of fungal and bacterial strains in comparison to fluconazole and chloramphenicol, respectively.

Synthesis and anti-mildew activity of 5-(2-aroyl)aryloxymethyl-2-phenyl-1 ,3,4-oxadiazoles against downy mildew of pearl millet.

A manipulatively simple, rapid, high-yielding and environmentally benign method for the integration of a heterocyclic ring, 1,3,4-oxadiazole, at the benzophenone nucleus has been achieved through intramolecular cyclization of substituted aroylaryloxyacetohydrazides to substituted 5-(2-aroyl)aryloxymethyl-2-phenyl-1,3,4-oxadiazoles under solventless 'dry' conditions using montmorillonite K10 clay and microwave irradiation. A comparison is made of the microwave-accelerated reaction with conventional heating conditions. Certain of the derivatives tested showed significant anti-mildew activity against Sclerospora graminicola (Sacc) Schroeter, the downy mildew pathogen of pearl millet.

Synthesis and Evaluation of Benzophenone-N-ethyl Morpholine Ethers as Anti-inflammatory Agents.

The synthesis of hydroxy benzophenones and benzophenone-N-ethyl morpholine ethers and the results of anti-inflammatory activity in vivo are described. The structures of the compounds were elucidated by IR, (1)H-NMR, mass spectroscopy and the elementary analysis. The anti-inflammatory activity of the synthesized compounds were determined by carrageenan-induced hind paw oedema test in rats. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than standard drugs. In addition ulcerogenic and cyclooxygenase activities are also described.

Synthesis and antifungal activity of 2-azetidinonyl-5-(2-benzoylphenoxy)methyl-1,3,4-oxadiazoles against seed-borne pathogens of Eleusine coracana (L.) Gaertn.

BACKGROUND: Finger millet is a major food crop as well as feed and fodder for livestock, especially in regions of southern India. A sturdy crop to fluctuating environmental conditions, it can be cultivated in all seasons of the year. Leaf, neck and finger blast caused by Pyricularia grisea Sacc. and Bipolaris setariae (Saw.) Shoem, as well as leaf spot disease, Bipolaris nodulosa (Berk & M.A.Curtis) Shoem, are major production constraints in southern India. Apart from environmental conditions, the use of harvested seeds by farmers is a major reason for disease prevalence. Benzophenone analogues have been investigated for controlling phytopathogenic fungi. In addition, the most important applications of azetidin-2-ones are as antibiotics. Based on this information, the present study was conducted to explore the antifungal activity of integrated 2-azetidinonyl and 1,3,4-oxadiazoles moieties into a benzophenone framework. RESULTS: A simple high-yielding method for the integration of heterocyclic rings, namely 2-azetidinonyl, at the benzophenone nucleus has been achieved, starting from substituted 2-hydroxybenzophenones under mild conditions on a wet solid surface using microwave irradiation. In the present study, an array of newly synthesised compounds, 2-azetidinonyl-5-(2-benzoylphenoxy)methyl-1,3,4-oxadiazoles, were screened for their antifungal property against blast and leaf spot causing fungi associated with the seeds of finger millet, cv. Indof-9. CONCLUSION: Two of the newly synthesised compounds showed promising effects in depleting the incidence of seed-borne pathogenic fungi of finger millet. The suppression of Pyricularia grisea and Bipolaris setariae resulted in enhanced seed germination and seedling growth.

Synthesis and anti-inflammatory activity of benzophenone analogues.

A series of substituted benzophenone analogues has been synthesized and evaluated as orally active anti-inflammatory agents with reduced side effects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin, and phenylbutazone. In carrageenan-induced foot pad edema assay, benzophenone analogues showed an interesting anti-inflammatory activity. In the air-pouch test, some of the analogues reduced the total number of leukocytes of the exudate, which indicates inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, in the liver and stomach. None of the compounds showed significant side effects compared with nonsteroidal anti-inflammatory drugs such as indomethacin and naproxen.