Some transformations of 3-amino-4-alkoxycarbonyl-6-hydroxy-2H-1-benzopyran-2-ones. The synthesis of [1] benzopyrano[3,4-d]-[1,3]oxazine and [1] benzopyrano[3,4-d]pyrimidine derivatives

Acylation of 4-alkoxycarbonyl-3-amino-6-hydroxy-2H-1-benzopyran-2-one derivatives 3 and 4 gave under mild conditions the O-substituted derivatives 5–10, N,O -disubstituted derivative 11 and N,N-disubstituted derivative 12 . The compound 4 was transformed with benzoyl chloride under more drastic conditions into 13 , a derivative of a new heterocyclic system 2-benzopyrano[3,4-d][1,3]oxazine. The derivatives of 1-benzopyrano-[3,4-d]pyrimidine 19 and 20 were prepared either from 3 and 4 through the corresponding N-heteroarylformamidines 14 and 15 and N-heteroarylformamide oximes 17 and 18 or by cyclization of thiourea derivative 20 .     

Part 1: Synthesis of Polyfused Heterocyclic Systems Derived From 3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione

3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 1 ) was condensed with o -aminothiophenol, 2-amino-ethanol or cystamine to afford compounds 2-4 respectively. Treatment of compound 1 with dimethylthiomethylenemalononitrile yielded the corresponding pyrano[3,2- f ][1,2,4]triazolo[3,4- b ]-[1,3,4]thiadiazepine derivative 5 . 7-[5-Amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 6 ) was obtained by treating compound 1 with CS 2 and chloroacetonitrile. Thiation of compound 1 gave the corresponding thioanalog 7 , which in turn was condensed with malononitrile to give 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6-one-8-ylidenemalononitrile ( 8 ). On treating compound 8 with benzaldehyde or p -nitrobenzaldehyde, pyrano[1,2,4]triazolo[1,3,4]thiadiazepin derivatives 9a , b , respectively, were obtained. Compound 8 was treated with CS 2 and methyl iodid to give the corresponding dithiomethylmethylene derivative 10 which was subjected to react with aniline to give pyrido[1,2,4]triazolo[1,3,4]thiadiazepine derivative 11 . Compound 8 was treated with 3-aminopyridine, o -aminothiophenol, or o -phenylenediamene to yield compounds 12 and 13a , b respectively. Finally, tertiary amines or activated phenols were condensed with compound 8 to yield compounds 14 and 15a , b respectively.     

Synthesis,Characterization, and Antioxidant Evaluation of Some Novel Pyrazolo[3,4‐c][1,2]diazepine and Pyrazolo[3,4‐c]pyrazole Derivatives

5‐Hydrazineyl‐3‐methyl‐1H‐pyrazole ( 1 ) was used as a starting material for the synthesis of novel pyrazolo[3,4‐c][1,2]diazepine derivatives 3 , 4 , and 6a,b by its reaction with acetylacetone, ethyl acetoacetate, and isatylidene derivatives 5a,b , respectively. Also, pyrazolo[3,4‐c][1,2]diazepine derivative 11 was synthesized via multicomponent reaction of 1 , benzaldehyde, and malononitrile. Moreover, compound 1 was used for synthesis novel pyrazolo[3,4‐c]pyrazole derivative 7 by its reaction with isatin. In addition, pyrazolo[3,4‐c]pyrazole derivatives 18a–c were synthesized by treatment of 2‐cyano‐N′‐(3‐methyl‐1H‐pyrazol‐5‐yl)acetohydrazide ( 13 ) with aromatic aldehydes 16a–c . The newly synthesized compounds were valeted by means of analytical and spectral data. All newly synthesized compounds were screened for their antioxidant activities. Compounds 3 , 13 , 18b , and 18c showed higher radical‐scavenging activities.     

Potential antitumor agents. III. Synthesis of pyrazolo[3,4-e]pyrrolo[3,4-g]indolizine and 1H-pyrazolo[3,4-e]indolizine derivatives

The preparation of 5-dimethylaminoethyl-4,6-dioxo-1-phenyl-1,4,5,6-tetrahydropyrazolo[3,4-e]pyrrolo-[3,4-g]indolizine, a derivative of the still unknown tetracyclic parent ring pyrazolo[3,4-e]pyrrolo[3,4-g]indolizine, is reported starting from 1-phenyl-5-(1-pyrryl)pyrazole-4-acetonitrile by PPA catalyzed double cyclization of the related oxalylcyanomethyl derivative and subsequent alkylation. The synthesis of 4,5-bis(isopro-pylaminocarbonyloxymethyl) and 4,5-bis-(cyclohexylaminocarbonyloxymethyl) derivatives of 1-phenyl-1H-pyrazolo[3,4-e]indolizine is also described. The new tricyclic and tetracyclic derivatives were tested as potential antitumor agents.     

Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.     

Cyclization of substituted 3,4-diaminopyridines into 1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxide derivatives during the nitration process

The nitration of pyridine-3,4-diamine, its N,N′-diacetyl derivative, and N ⁴-alkylpyridine-3,4-diamines with excess nitric acid in concentrated sulfuric acid at 60°C was accompanied by cyclization with formation of the corresponding 1-substituted 4-nitro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxides. 4-Chloro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxide derivatives were obtained under analogous conditions from 2-chloropyridine-3,4-diamine, its N,N′-diacetyl derivative, and 2-chloro-N ⁴-methylpyridine-3,4-diamine. The nitration of these compounds at 80–90°C gave 4-chloro-7-nitro-1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxides.     

4,5-Dihydropyrazolo[3,4-f]quinazolines

By reaction of 6-dimethylamino-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinazoline with hydrazine, phenylhydrazine, 4-bromo-, 4-chlorophenylhydrazines, and also reaction of 6-dimethylaminomethylene-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazoline with hydrazine, 4-methoxy- and 2-carboxyphenylhydrazines, we have obtained the corresponding 7-phenyl(4-pyridyl)-substituted 1H(2H)- or 1-aryl-4,5-dihydropyrazolo[3,4-f]quinazolines. Methylation of 7-phenyl-4,5-dihydro-1(2H)-pyrazolo[3,4-f]quinazoline by methyl iodide led to its 2-methyl derivative.     

Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]-pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5-c]pyrimidine derivatives

Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3H)one and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15 a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16 a,b and 17 a,b. Reactions of compounds 17 a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19 a,b, respectively.     

Synthesis of 1,2-diazepino[3,4-b]quinoxalines and pyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxalines via a 1,3-dipolar cycloaddition reaction

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with furfural, 3-methyl-2-thiophene-carbaldehyde, 2-pyrrolecarbaldehyde, 4-pyridinecarbaldehyde and pyridoxal hydrochloride gave 6-chloro-2-[2-(2-furylmethylene)-1-methylhydrazino]quinoxaline 4-oxide 5a , 6-chloro-2-[1-methyl-2-(3-methyl-2-thienyl-methylene)hydrazino]quinoxaline 4-oxide 5b , 6-chloro-2-[1-methyl-2-(2-pyrrolylmethylene)hydrazino]quinoxa-line 4-oxide 5c , 6-chloro-2-[1-methyl-2-(4-pyridylmethylene)hydrazino]quinoxaline 4-oxide 5d and 6-chloro-2-[2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridylmethylene)-1-methylhydrazino]quinoxalme 4-oxide 5e , respectively. The reaction of compound 5a or 5b with 2-chloroacrylonitrile afforded 8-chloro-3-(2-furyl)-4-hydroxy-1-methyl-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6a or 8-chloro-4-hydroxy-1-methyl-3-(3-methyl-2-thienyl)-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6b , respectively, while the reaction of compound 5e with 2-chloroacrylonitrile furnished 11-chloro-7,13-dihydro-4-hydroxy-methyl-5,14-methano-1,7-dimethyl-16-oxopyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxaline 7.     

Synthesis of 4H-[1]benzopyrano[3,4-c][1,2,5]thyadiazol-4-one and its reactions with some nucleophilic and electrophilic agents

The reaction of 3,4-diaminocoumarin with thionyl chloride gave 4H-[1]benzopyrano[3,4-c][1,2,5]thiadiazol-4-one (II), which was cleaved by the action of nucleophilic agents to the corresponding 4-(2-hydroxyphenyl)-1,2,5-thiadiazole-3-carboxylic acid derivatives. The nitration of II leads to the 8-nitro or 6,8-dinitro derivative; the latter was isolated in the form of 4-(2-hydroxy-3,5-dinitrophenyl)-1,2,5-thiadiazole-3-carboxylic acid.See [3] for our preliminary communication.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 977–981, July, 1988.     

Synthesis of [1,5-A]Pyrimidinone Ring Derivatives

Cyclodehydrogenation of the benzalhydrazino derivatives 5 and 6 gave 6-cyano-7-(4-methoxyphenyl)- 2-phenyl-5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (8) and 6-cyano-7-(4-methoxyphenyl)-4-methyl-2-phenyl- 5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (9) respectively. Melhylation, acetylation and benzylation of 8 gave the corresponding N-methyl, acetyl and benzyl derivatives 10-12 . Methylation of 5 with dimethylsulfate gave 2-benzalhydrazino-5-cyano-3-methyl-6-(4-methoxyphenyl)-3,4-dihydropyrimidin-4-one (6) , of which the reaction with acetic anhydride in pyridine afforded the N-acetylbenzalhydrazino derivative 15 . The latter was also prepared from acetylation of 5 followed by medthylation with iodomethane. Acetylation of 5 with boiling acetic anhydride afforded the diacetyl derivative 16 , whereas its benzylation gave the mono-N-benzyl derivative 14 .     

The chemistry of 1,2,5-thiadiazoles V. Synthesis of 3,4-diamino-1,2,5-thiadiazole and [1,2,5] thiadiazolo[3,4-b]pyrazines

The o-diamine, 3,4-diamino-1,2,5-thiadiazole ( 2 ), was synthesized from 3,4-dichloro-1,2,5-thiadiazole ( 3 ) hy three methods. Aqueous glyoxal cyclized 2 into [1,2,5]thiadiazolo[3,4–6]-pyrazine ( 14 ). 3,4-Dichloro-1,2,5-thiadiazole 1,1-dioxide ( 18 ) reaeted with 2 to give 1,3-dihydro-bis[1,2,5]thiadiazolo[3,4-b:3′,4′-e]pyrazine 2,2-dioxide ( 19 ). The reaction of 2 with selenium oxyehloride led to [1,2,5]selenadiazolo[3,4-c] [1,2,5]thiadiazole ( 12 ). Ring closure of 2,3-diaminoquinoxaline ( 4 ) with thionyl chloride or selenium oxychloride gave [1,2,5]thiadiazolo-[3,4-b]quinoxaline ( 21 ) and [1,2,5]selenadiazolo[3,4-b]quinoxaline ( 22 ), respectively. Sulfurous acid reduced 21 to the 4,9-dihydro derivative 23 , which was reoxidized to 21 with chloranil. Aqueous hase hydrolyzed 21 to 4 via the hydrated intermediate 24 . Aqueous glyoxal cyclized 4 to the covalent hydrate of pyrazino[2,3-b]quinoxaline ( 26 ), 27 , which was dehydrated to 26 . Compound 26 underwent rapid addition of two alcohols in a process analogous to covalent hydration.     

Nitrogen bridgehead compounds. Part 86. Synthesis and reactivity of 7,12-dihydropyrimido[1′,2′;1,2]pyrido[3,4-b]indol-4(6H)-ones. Debenzologues of rutaecarpine alkaloids

A series of 7,12-dihydropyrimido[1′2′:1,2]pyrido[3,4-b]mdole-4(6H)-ones was prepared by Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrirmdin-4-ones. Quantum chemical calculations (ab initio and AM1) indicate that position 3 of 7,12-dihydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indole-4(6H)-one can be involved in electrophilic substitutions, while position 2 is sensitive towards nucleophilic attack. Bromination of 6-methyl-7,12-tetrahydropyrimido[1′,2′:1,2]pyrido-[3,4-b]indol-4(6H)-one 16 with bromine afforded 3-bromo derivative 25 , which was reacted with cyclic amines to give 2-ammo-7,12-dihydropyrirmdo[1′2′:1,2]pyrido[3,4-b]indol-4(6H)-ones 26–30 in an addition-elimination reaction. Vielsmeier-Haack formylation of compound 16 gave 12-formyl 31 and 3,12-diformyl 32 derivatives (an N-formyl-1-deaza derivative of nauclefidine alkaloid 34 ) at 60° and 100°, respectively. 3,12-Diformyl compound 32 was oxidized to 3-carboxyl derivative 33 with potassium permanganate. The quaternary salt 35 , obtained from compound 16 with dimethyl sulfate, suffered a ring opening on the action of aqueous sodium hydroxide. The new compounds have been characterized by elemental analyses uv, ¹H nmr and in some cases by ¹³C ruler, CD spectra and X-ray investigations.     

Nitrogen bridgehead compounds. Part 88. Synthesis of 3H, 7H-[1,4]diazepino[3,4-b]quinazoline-3,7-diones

3H,7H-[1,4]Diazepino[3,4-b]quinazolone-3,7-diones 9, 11 were synthesized starting from 2-(1-bromo-ethyl)quinazolin-4(3H)-ones 3 and 17 via 2-[1-(4-methoxyphenylamino)ethyl]quinazolin-4(3H)-ones 4 and 18. Cyclization of 3-[2-(1-bromoethyl)-4-oxo-3,4-dihydroquinazolin-3-yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7H-[1,4]oxazepino[3,4-b]quinazoline-3,7-dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and ¹H nmr spectroscopy.     

Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

Liquid crystalline hexa-amides and side chain polysiloxanes of azacrown [18]-N6

The hexa-4-dodecyloxybenzoyl derivative 1 of azacrown [18]-N₆ was originally reported to have a 'tubular' mesophase on the basis of its large central ring and 6-fold symmetry. Starting in the mesophase, annealing of 1 under a cover slip results in formation of a new crystalline phase that melts directly to an isotropic liquid at the temperature previously observed for the mesophase to isotropic transition. Thus the phase behaviour of 1 is kinetically controlled. The analogous hexa-3,4-bisdodecyloxybenzoyl derivative 2 of azacrown [18]-N₆ has no kinetic limitations to its phase changes and has an enantiotropic columnar liquid crystalline phase. We have synthesized side chain copolysiloxanes with a (CH₂)₁₁ spacer and 75-84 per cent by weight of the same 4-dodecyloxybenzoyl-[18]-N₆ mesogen. The polysiloxanes also display a liquid crystalline phase.     

Simultaneous Formation of 8H-Isoquino[2,1-b][2,7]naphthyridin-8-ones and 13H-Pyrido[4′,3′:3,4]pyrrolo[2,1-b][3]benzazepin-13-ones,a Novel Potential Alkaloidal System

Condensation of 3,4-dihydro-6,7-dimethoxyisoquinoline ( 4 ) with 4-methylnicotinoyl chloride ( 12 ) in refluxing pyridine gives 5,6,13,13a-tetrahydro-2,3-dimethoxy-8H-isoquino[2,1-b][2,7] naphthyridin-8-one ( 11 ), along with some of its 13,13a-didehydro derivative 7 . A similar reaction of 4 with 4-(chloromethyl)nicotinoyl chloride ( 14 ) affords, in addition to 7 , the isomeric product 10,11-dihydro-7,8-dimethoxy-13H-pyrido[4′,3′:3,4]pyrrolo[2,1- b][3]benzazepin-13-one ( 3 ). Analogous pairs of products are obtained from 3,4-dihydro-6,7-(methylenedioxy)- and 3,4-dihydro-6,7,8-trimethoxy-isoquinolines ( 15 and 18 , resp.). The structure of 3 was established by extensive NMR data and confirmed by single-crystal X-ray studies. Structure 7 has the ring system of the Alangium alkaloids like alangimarinc ( 1 ), while the isomeric ring system 3 is predicted to be present in nature on biogenetic reasoning.     

Reactions with dimethylformamide‐dimethylacetal: Synthesis and reactions of several new pyridine and pyrazolo[3,4‐b]pyridine derivatives

6‐Aminopyridine‐2(1H)‐thiones 1a,b reacted with dimethylformamide‐dimethylacetal (DMF‐DMA) to give the corresponding 6‐{[(N,N‐dimethylamino)methylene]amino}pyridine derivatives 2a,b . The latter compounds reacted with hydrazine hydrate to afford the 3,6‐diamino‐1H‐pyrazolo[3,4‐b]pyridine derivative 4 and 3‐amino‐5‐hydrazino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine derivative 7 , respectively. Compound 4 condensed with DMF‐DMA to yield the 3,6‐bis{[(N,N‐dimethylamino)methylene]amino}‐1H‐pyrazolo[3,4‐b]pyridine derivative 10 , which reacted with malononitrile to give the corresponding pyridopyrazolopyrimidine derivative 15 . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:399–404, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20312     

1,3-Dioxopyrrolo[3,4-b]porphyrins: synthesis and chemistry

A novel 1,3-dioxopyrrolo[3,4-b]porphyrin (2) has been synthesized in 70% yield following a [4 + 2] cycloaddition reaction of pyrrolo[3,4-b]porphyrin 1 with (1)O(2). The new imide was used as a template to other 1,3-dioxopyrrolo[3,4-b]porphyrins and to the corresponding open counterparts. The UV/vis absorption spectra of the new compounds show significant red-shifts when compared with those of the nonsubstituted analogues. The structure of an imide derivative was confirmed by single-crystal X-ray diffraction.     

Imidazo[2,1-b]benzothiazoles. II. Synthesis and antiinflammatory activity of some imidazo[2,1-b]benzothiazoles

3-[2-[p-(Un)substituted phenyl]imidazo [2,1-b]benzothiazol-3- yl]propionic acid derivatives (2a--e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (1a--e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a--e produced methyl esters (3a--e). Upon the interaction of 3a with m-chloroperbenzoic acid, the S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3- yl]formaldehyde derivatives (6a--e). Derivatives 6a--e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol- 3-yl]propionate esters (7a--e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a--e showed weak or no activity in the carrageein-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.