Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives.

Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding beta-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin.

Synthesis, X-ray structure, and pharmacological activity of some 6,6-disubstituted chromeno[4,3-b]- and chromeno- [3,4-c]-quinolines.

Some chromeno[4,3-b]quinolines 4a-i were obtained from beta-chloro carboxyaldehydes 3a-c with different aniline derivatives namely, aniline, 4-fluoroaniline, and 2-aminophenol. Surprisingly, 3a-c reacted with 2-aminothiophenol and afforded the chromeno[3,4-c]quinoline derivatives 5a-c. Single-crystal X-ray diffraction studies of 4e and 5b provided good support for the established structure. Compounds 4b and 5b showed significant anti-inflammatory and ulcerogenic score activities compared to that of indomethacin.

Novel synthesis of [1]-benzothiepino[5,4-b]pyridine-3-carbonitriles and their anti-inflammatory properties.

Reaction of 4-arylmethylene-3,4-dihydro-[1]-benzothiepin-5(2H)-ones 1 with malononitrile in the appropriate alcohol in the presence of sodium afforded the 2-alkoxy-4-aryl-5,6-dihydro-[1]-benzothiepino[5,4-b]pyridine-3-carbonitriles 2 and not the isomeric forms [1]-benzothiepino[4,5-c]pyridine-1-carbonitriles 3 in high regioselective manner. The assumed structure of 2 was inferred through independent synthetic reaction of 3,4-dihydro-[1]-benzothiepin-5(2H)-one (4) with ylidenemalononitriles 5 under the same applied reaction conditions and confirmed by single crystal X-ray diffraction studies. However, reaction of 4 with arylidenecyanothioacetamides 6 in refluxing ethanol in the presence of basic catalyst (piperidine or morpholine) does not afford the expected 4-aryl-3-cyano-5,6-dihydro-[1]-benzothiepino[5,4-b]pyridine-2(1H)-thiones 7 and instead 4-aryl-3,5-dicyano-6-thioxo-2(1H)-pyridinethiolate monohydrates were isolated as piperidinium or morpholinium salts 8. On the other hand, reaction of 6 with cyanothioacetamide in the presence of a sufficient amount of basic catalyst yielded exclusively 2-amino-4-aryl-3,5-dicyano-2-pyridinethiolates as piperidinium or morpholinium salts 9. Meanwhile, 7 were prepared through the reaction of 1 with cyanothioacetamide in refluxing ethanol in the presence of a catalytic amount of piperidine. Anti-inflammatory activity screening of the prepared compounds using in vivo acute carrageenan-induced paw oedema in rats exhibited that all the tested compounds possess considerable activity. In addition, few synthesized derivatives reveal remarkable anti-inflammatory properties (2d, k, l) comparable with indomethacin which was used as a reference standard during the pharmacological activity screening studies.

Synthesis of novel vasodilatory active nicotinate esters with amino acid function.

A variety of N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]amino acid esters 6a-h were synthesized through the reaction of 2-bromonicotinates 4 with a number of primary amino acid ester hydrochlorides 5 in refluxing tetrahydrofuran in the presence of triethylamine as dehydrohalogenating agent. Similarly, reaction of 4 with N-glycylglycine ethyl ester hydrochloride 7 'as a representative example of dipeptide derivative' afforded smoothly the corresponding N-[(ethyl-4,6-diaryl-3-pyridinecarboxylate)-2-yl]-N'-glycylglycine ethyl ester analogues 8. However, reaction of 4 with 5 in refluxing pyridine yielded the unexpected 2-aminonicotinate esters 9. Vasodilation activity screening for the synthesized nicotinate esters was investigated in vitro on the contractile response of vascular thoracic aorta smooth muscle from Wistar rats, where all the tested compounds exhibit considerable vasodilatory properties. In addition, few prepared compounds especially, 6b, 6h and 9b reveal remarkable vasodilation potency (IC(50)).

Facile synthesis of non-steroidal anti-inflammatory active bisbenzamide-containing compounds.

A variety of N,N'-bis{2-[1,2-ethanediylbis(oxy-2,1-phenylene)]-1-(substituted carbonyl)ethenyl}benzamides 7a-c, 9a-d were synthesized via nucleophilic attack of either primary 8 or secondary amines 6 on bisoxazol-5(4H)-one 5. The latter was obtained through the reaction of 2,2'-[1,2-ethanediylbis(oxy)]bisbenzaldehyde (4) with hippuric acid in acetic anhydride in the presence of anhydrous sodium acetate. The anti-inflammatory properties of the prepared compounds were screened using carrageenan-induced paw oedema in rats. Many of the prepared bisbenzamide-containing compounds show considerable in vivo anti-inflammatory activity, especially 7b which reveals remarkable pharmacological properties comparable with ketoprofen (which was used as a reference standard) at successive time intervals (1, 2, 3, 4 and 24h).

Synthesis and evaluation of some 1,2,3,4-tetrahydropyrimidine-2-thione and condensed pyrimidine derivatives as potential antihypertensive agents.

Some new tetrahydropyrimidine-2-thione, octahydroquinazoline-2-thione and thiazolo[3,2-a]pyrimidine derivatives have been synthesized and tested for their antihypertensive activity. Among them, compounds 1 and 2b can be considered more potent than the reference, nifedipine (CAS 21829-25-4), while compounds 3b and 10a are equipotent to it. In addition, compound 6 showed significant antihypertensive activity.

Synthesis, anticonvulsant, and anti-inflammatory activities of some new benzofuran-based heterocycles.

Treatment of 2-bromoacetylbenzofuran (2) with pyridine afforded its corresponding pyridinium bromide 3. The latter salt reacted with some activated alkenes and acetylenes to give the corresponding indolizine derivatives. Treatment of the salt 3 with benzylidenemalononitriles 9 afforded polysubstituted aniline derivatives, however with arylidenecyanothioacetamides 15 it gave the corresponding 4,5-dihydrothiophenes. Bromide 3 also coupled with p-chlorobenzenediazonium salt followed by ammonium acetate to give the corresponding 1,2,4,5-tetrazine derivative. The biological activity of the newly synthesized compounds was examined and some of them were found to possess anticonvulsant and anti-inflammatory activities.

Synthesis, anticonvulsant, and anti-inflammatory evaluation of some new benzotriazole and benzofuran-based heterocycles.

Treatment of 2-bromoacetylbenzofuran with 1H-benzotriazole afforded 1-(benzofuran-2-yl)-2-(benzotriazol-1-yl)ethanone which reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivatives. Treatment of the latter ethanone and thioacetanilide derivatives with hydrazonoyl chlorides afforded the corresponding pyrazole and 1,3,4-thiadiazole derivatives. The thioacetanilide derivative reacted with alpha-haloketones and alpha-halodiketones to afford thiophene and thiazole derivatives, respectively. The newly synthesized compounds were found to possess anticonvulsant and anti-inflammatory activities with the same mechanism of action of selective COX-2 inhibitors.