Radioprotective effects of 2-imino-3-[(chromone-2-yl)carbonyl] thiazolidines against gamma-irradiation in mice

A series of 2-imino-3-[(chromone-2-yl) carbonyl]thiazolidines substituted at the C-5 and/or C-7 positions of a chromone ring were synthesized. The in vivo toxicity and radioprotective efficacy of these agents were evaluated in male NMRI mice against cobalt-60 gamma-rays. The LD50 values as determined by a Probit analysis, were 659, 1216 and 790 mg/kg for compounds, 2, 3 and 4, respectively. For studying radioprotective effects, one half of the toxic LD50 values were used, namely 330, 605 and 395 mg/kg for compounds 2, 3 and 4, respectively. The dose reduced factor (DRF) was determined by dividing the LD50/30 values obtained from the radiation survival curve in the presence of a radioprotective agent by the LD50/30 value obtained from a control radiation survival curve. A compound with a hydroxyl group substituent at the C-5 position afforded better radioprotective activity than those without this substituent. The radioprotective effect of chromone having a hydroxyl group at only the C-7 position was similar to that of the unsubstituted chromone. The most active compound has hydroxyl groups at the C-5 and C-7 positions of the chromone ring; it had a DRF of 1.48.     

Structure-cytotoxicity relationship in a series of N-phosphorus substituted E,E-3,5-bis(3-pyridinylmethylene)- and E,E-3,5-bis(4-pyridinylmethylene)piperid-4-ones

In order to give further insight on the influence of the aromatic ring nature and the presence of the phosphorus substituent at the piperidone nitrogen atom of E,E-3,5-bis((hetero)arylidene)piperid-4-ones on their antitumor properties, a series of phosphorus substituted E,E-3,5-bis(pyridinylmethylene)piperid-4-ones bearing either 3-pyridine or 4-pyridine rings was obtained. Novel NH-3,5-bis(pyridinylmethylene)piperid-4-ones 1a,b were converted into the corresponding N-phosphorylated derivatives 3a-c, 4a-c differing in the substitution at the phosphorus atom (amidophosphates and amidophosphonates), via direct phosphorylation while N-(ω-phosphorylalkyl)-substituted compounds 8a-c were obtained via aldol-crotonic condensation of preformed N-phosphorylalkyl substituted piperidones with the corresponding pyridinecarboxaldehyde. The cytotoxicity screen has revealed that phosphorylated compounds based on E,E-3,5-bis(4-pyridinylmethylene)piperid-4-one framework displayed higher inhibitory properties toward Caov3, A549, KB 3-1 and KB 8-5 human carcinoma cell lines comparing with their analogues with 3-pyridine rings. Introduction of the phosphorus moiety substantially increased the antitumor properties in the case of E,E-3,5-bis(3-pyridinylmethylene)piperid-4-ones derivatives but this influence less pronounced for more active analogues bearing 4-pyridinyl rings. Most of the compounds tested are potent against multi-drug resistant cell line KB 8-5 affording some guidelines for the search of perspective drug-candidates among phosphorus substituted E,E-3,5-bis((hetero)arylidene)piperid-4-ones.     

Synthesis and antimicrobial activities of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines carrying thioalkyl and sulphonyl phenoxy moieties

Thirty one new 6-aryl-3-{(4-substituted phenoxy) methyl}-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (6a-s) and 6-aryl-3-[(4-substituted phenoxy methyl]-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (7a-l) have been synthesized from 4-thioalkyl phenols (1a-b) through a multi-step reaction sequence. Compounds 1a-b reacted with ethyl chloroacetate in presence of acetone and potassium carbonate to give ethyl [4-(thioalkyl) phenoxy] acetates (2a-b). Further, 2a was oxidized to [4-(methyl sulphonyl) phenoxy] acetate (2c) using hydrogen peroxide in acetic acid. Reactions of (2a-c) with hydrazine hydrate in alcoholic medium furnished 2-[4-thiosubstituted phenoxy] acetohydrazides (3a-b) and 2-[4-methyl sulphonyl phenoxy] acetohydrazide (3c) which on treatment with carbon disulphide and methanolic potassium hydroxide yielded corresponding potassium dithiocarbazates (4a-c). They were then converted to 4-amino-5-[(4-thioalkyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiols (5a-b) and 4-amino-5-[(4-methyl sulphonyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiol (5c) by refluxing them with aqueous hydrazine hydrate. The title compounds 6a-s were prepared by condensing 5a-c with various aromatic carboxylic acids in presence of phosphorus oxychloride. The intermediates 5a-c, on condensation with various substituted phenacyl bromides afforded a series of title compounds (7a-l). The structures of new compounds 2a-7l were established on the basis of their elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. All the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against three fungi. Preliminary results indicate that some of them exhibited promising activities and they deserve more consideration as potential antimicrobials.     

Synthesis and in vivo analgesic and anti-inflammatory activity of some bi heterocyclic coumarin derivatives

Sets of coumarinyl ethers having chromone, benzofuranyl and 4-hydroxy coumarins (4, 5, 6) were prepared and tested for analgesic and antiinflammatory activity. The 4-(4'-acetyl-3'-hydroxy-phenoxymethyl)-coumarin 3 were synthesised by the reaction of 4-bromo methyl coumarin with 2, 4-dihydroxy acetophenones, were found to less active. Further compound 3 having the ortho hydroxy moiety was cyclised to chromones 4 and benzofurans 5 were found to enhance the analgesic and anti-inflammatory activity. The cyclisation to 4-hydroxy coumarin 6 was found to be reducing the anti-inflammatory and analgesic activity in this series. These newly synthesized compounds were found to produce less toxicity and less ulcerogenic effects.     

Stereoselective synthesis and QSAR study of cytotoxic 2-(4-oxo-thiazolidin-2-ylidene)-2-cyano-N-arylacetamides

(2Z,5Z) 2-[(5-Arylidene-4-oxo-3-phenyl)-thiazolidin-2-ylidine]-2-cyano-N-arylacetamides 4a-l were stereoselectively prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a-c. The latters were obtained via electrophilic attack of phenylisothiocyanate on 2-cyano-N-arylacetamides 1a-c followed by reaction with chloroacetyl chloride under basic condition. Single crystal X-ray study of 3a allows good confirmation for the assigned structure. Additionally, 5-arylhydrazono analogs 5a-e were prepared via condensation of the appropriate diazonium salts with 4-thiazolidinones 3a,b. Many of the synthesized compounds exhibited promising antitumor properties against colon HCT116, breast MCF7 and liver HEPG2 cell lines. 3D-Pharmacophore modeling and QSAR analysis were combined to explain the observed antitumor properties.     

Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles

Reaction of 1-adamantanecarbonyl chloride with certain carboxylic acid hydrazides in pyridine yielded the corresponding N-acyl adamantane-1-carbohydrazide derivatives 3a-j, which were cyclized to the corresponding 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles 4a-j via heating with phosphorus oxychloride. Treatment of 1-adamantylisothiocyanate with some carboxylic acid hydrazides in ethanol yielded the corresponding 1-acyl-4-(1-adamantyl)-3-thiosemicarbazides 7a-g, which were cyclized to the corresponding 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazole derivatives 8a-g. Compounds 4a-j, 7a-g, and 8a-g were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against the tested Gram-positive bacteria Bacillus subtilis. Meanwhile, compounds 4i and 8g displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. The oxadiazole derivatives 4c, 4g, 4i and 4j produced good dose-dependent anti-inflammatory activity.     

Synthesis and antimicrobial activities of some new 1-(5-phenylamino-[1,3,4]thiadiazol-2-yl)methyl-5-oxo-[1,2,4]triazole and 1-(4-phenyl-5-thioxo-[1,2,4]triazol-3-yl)methyl-5-oxo- [1,2,4]triazole derivatives

Acetic acid ethyl esters containing 5-oxo-[1,2,4]triazole ring (2) were synthesized by the condensation of compounds 1a-f with ethyl bromoacetate in basic media. The reaction of compounds 2a-f with hydrazine hydrate led to the formation of acid hydrazides (3a-f). The treatment of compounds 3 with two divers aromatic aldehydes resulted in the formation of arylidene hydrazides as cis-trans conformers (4a,c,e,f, 5a,e,f). The thiosemicarbazide derivatives (6a,c,d,f) were afforded by the reaction of corresponding compounds 3 with phenylisothiocyanate. The treatment of compounds 6a,c,d,f with sulfuric acidic caused the conversion of side-chain of compounds 6a,c,d,f into 1,3,4-thiadiazol ring; thus, compounds 7a,c,d,f were obtained. On the other hand, the cyclization of compounds 6a,c,d,f in the presence of 2 N NaOH resulted in the formation of compounds 8a,c,d,f containing two [1,2,4]triazole rings which are linked to each other via a methylene bridge. Compounds 4a, f, 5a, 7a, d, f, 8a and d have shown antimicrobial activity against one or more microorganism, but no antifungal activity has been observed against yeast like fungi. Also inhibitory effect on mycelial growth by compounds 4e, 7d and 8f has been observed. Compounds 4c and 5f were found to possess antitumor active towards breast cancer.     

Synthesis of compounds with antiproliferative activity as analogues of prenylated natural products existing in Brazilian propolis

This work describes the syntheses and antitumoral properties of five prenyl compounds from which antiproliferative activities were predicted by using the TOPS-MODE approach, a computational method for drug design. The syntheses of 2-(3-methylbut-2-enyloxy)acetophenone (2), 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone (3), 2-hydroxy-3-(1,1-dimethylallyl)acetophenone (4), and 5-(3-methylbut-2-enyl)-2-(3-methylbut-2-enyloxy)acetophenone (5) were realized by O-prenylation of phenolic compounds with prenyl bromide and by Claisen rearrangement, respectively. Reaction of 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone 3 under Vilsmeier-Haack conditions with phosphoryl chloride and N,N-dimethylformamide yielded 6-(3-methylbut-2-enyl)chromone-3-carbaldehyde (6). The compounds were tested for their cytotoxicity toward a diverse panel of cultured human tumor cell lines. Compound 3 showed significant selective cytotoxic activity (IC(50) < 9 microg/ml).     

Synthesis and structure-activity relationships of new arylpiperazines: para substitution with electron-withdrawing groups decrease binding to 5-HT(1A) and D(2A) receptors

Compounds in which N-phenylpiperazines were linked by a propyloxy chain to position 6 or 7 of a coumarin ring were designed and synthesised, and their affinities for 5-HT(1A) and D(2A) receptors were determined by radioligand binding assays. The influence of para substitution in the phenyl ring, substitution at position 4 of the coumarin system, and the coumarin position at which the piperazinylalkyl chain is linked was explored. Electron-withdrawing phenyl ring substituents para to the piperazine strongly reduced activity at both receptors. Binding at 5HT(1A) was influenced by the bulk of substituents at position 4 of the coumarin system, and binding at D(2A) by their electronic properties. Neither binding affinity was significantly affected by whether the piperazinylalkyl chain was inserted at position 6 or 7 of the coumarin system.     

Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl]thiomorpholines and related compounds

Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl]thiomorpholines 5-7(a-c) and some related compounds 8a-c and 9a-c were described. The anti-H. pylori activity of target compounds along with commercially available antibiotics such as metronidazole and amoxicillin was evaluated by comparing the inhibition zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates, it is evident that most compounds still had strong activity at 4 and 2mug/disc (average of inhibition zone >20mm) while metronidazole had little activity at these doses. Nitrofuran analog 7b containing thiomorpholine S,S-dioxide moiety was the most potent compound tested.     

New acyclic nucleosides analogues as potential analgesic, anti-inflammatory, anti-oxidant and anti-microbial derived from pyrimido[4,5-b]quinolines

Synthesis of 2-thioxopyrimido[4,5-b]quinoline 3a-c by microwave oven was used as a base to synthesis acyclic nucleosides analogue of types, 3-(penta-O-acetyl-glycosyl)-6-(4-chlorophenyl)-10-(4-chlorophenylmethylene)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]-pyrimido[4,5-b]quinolin-4-ones (7a-c), 2-tetra-O-acetyl-glycosylhydrazon-N3-acetyl-5-(4-chlorophenyl)-9-(4-chlorophenylmethylene)-6,7,8,9-pentahydro-1H-pyrimido[4,5-b]-quinolin-4-ones (10a-c) and 3-(glycosyl)-6-(4-chlorophenyl)-10-(4-chlorophenylmethylene)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-b]quinolin-4-ones (8a-c), (12a-c). The title compounds were investigated for analgesic, anti-inflammatory, anti-oxidant and anti-microbial activities. Compounds 8a,b and 12a,b exhibited highly significant activity towards gram-negative and gram-positive bacteria, showed more potent anti-inflammatory and analgesic activities than the acetylated glycoside derivatives 7a,b and 10a,b and exhibited high anti-oxidant activity when compared to the ascorbic acid.     

Synthesis and antitumor activity of cis-dichloroplatinum(II) complexes of 1-(2-aminophenyl)-1,2,3,4-tetrahydroisoquinolines

Fifteen cis-dichloroplatinum complexes (5a-5o) were synthesized by treatment of 1-(2-aminophenyl)-1,2,3,4-THIQs (4a-4o) with K(2)PtCl(4). The antitumor activity of these compounds was examined against four different human tumor cell lines. Their structure-activity relationships for antitumor activity are reported. All of these compounds exhibited activity against MCF-7 cell line and showed good activity against WiDr cell line except 5c and 5f. On the other hand, compounds 5j and 5o are more active than the other compounds against Hepa59T/VGH cell line. The electron-donating group at the 6-position of isoquinoline ring seems to decrease the antitumor activity and the chloro substituent at the C-4 position of the aniline ring shown the highest potency. The "trans influence" dominates the control of the stability of [1-(2-aminophenyl)-1,2,3,4-THIQ]dichloroplatinums(II).     

Synthesis and antifolate evaluation of the aminopterin analogue with a bicyclo

N-[4-[[2,4-diamino-6-pteridinyl)methyl]amino]bicyclo[2.2.2]octane-1-carbonyl]-L-glutamic acid (1) was synthesized and tested for antifolate activity. N-(4-Aminobicyclo[2.2.2]octane-1-carbonyl-L-glutamic acid dimethyl ester (6), the side chain precursor to subject compound 1, was synthesized readily via reported bicyclo[2.2.2]octane-1,4-dicarboxylic acid monoethyl ester (2). The side chain precursor 6 was alkylated by 6-(bromomethyl)-2,4-pteridinediamine (7). Subsequent ester hydrolysis then afforded 1. Antifolate and antitumor evaluation of 1 verses L1210 dihydrofolate reductase (DHFR) and three tumor cell lines (L1210, S180, and HL60) showed it to be ineffective. Although compound 1 was very similar to aminopterin structurally, the bicyclo[2.2.2]octane ring system in place of the phenyl ring in the p-aminobenzoate moiety effectively negates the stoichiometric binding displayed by many classical DHFR inhibitors bearing appropriate aromatic ring systems in the side chain.     

Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents

Four series of pyrazolyl benzenesulfonamide derivatives have been synthesized. The first series was prepared by cyclization of the intermediate N,N-dimethylaminomethylene-4[3-phenyl-4-(substituted thiosemicarbamoyl hydrazonomethyl)-1H-pyrazol-1-yl]benzenesulfonamide 2a-c with ethyl bromoacetate to afford the corresponding thiazolidinyl derivatives 3a-c. The second series was prepared by cyclization of the key intermediates 2a-c with 4-bromophenacyl bromide giving rise to thiazolinyl derivatives 4a-c. Thiadiazolyl derivatives 5a-c were obtained by heating 2a-c with 2M FeCl(3) solution. Refluxing the intermediates 2a-c in acetic anhydride yielded the corresponding thiadiazolinyl derivatives 6a-c. All the target compounds showed anti-inflammatory activity and three of them 3b, 3c and 4c surpassed that of indomethacin both locally and systemically in the cotton pellet granuloma and rat paw edema bioassay. The active compounds showed selective inhibitory activity towards COX-2 enzyme as revealed by the in vitro enzymatic assay. All the tested compounds proved to have superior gastrointestinal (GI) safety profiles as compared to indomethacin, when tested for their ulcerogenic effects. The acute toxicity study of compounds having promising anti-inflammatory activity (3b, 3c and 4c) indicated that they are well tolerated both orally and parenterally. Antimicrobial activity tests expressed as minimal inhibitory concentrations (MIC), revealed that compounds 3b and 4a showed comparable antibacterial activity to that of ampicillin against Escherichia coli, while compounds 3a, 3c and 4a possessed about half the activity of ampicillin against Staphylococcus aureus. On the other hand, the results showed that all the tested compounds have weak or no antifungal activity against Candida albicans except for compounds 6b and 6c that showed half the activity of the control antifungal drug used (clotrimazole).     

Synthesis of novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)-guanidine derivatives as potential antitumor agents

Novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives have been synthesized as potential anticancer agents. The in vitro antitumor activity of these compounds has been evaluated in the US National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. The prominent compound was 1-allyl-2-[4-chloro-5-(4-chlorophenylcarbamoyl)-2-methylthiobenzenesulfonyl]-3-(5-nitrofurfurylideneamino)guanidine (8) with remarkable activity against 21 human tumor cell lines representing leukemia, lung, colon, melanoma, ovarian, renal, prostate and breast (GI(50)=0.3-3.0microM), and selectivity toward leukemia RPMI-8226 cell line (GI(50)=0.3microM, TGI=1.4microM).     

In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.     

Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives

Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC₅₀ values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.     

Synthesis, anticonvulsant activity and 5-HT1A, 5-HT2A receptor affinity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione

The synthesis, physicochemical and pharmacological properties of new N-[(4-arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane- (8a-c, 10a-d) and [4.5]decane-1,3-dione (9a-c, 11a-d) derivatives were described. The antiepileptic effects of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (sc. PTZ) tests, and their neurotoxicity was determined using a rota-rod test. Compounds 8c, 9c, 10c, d, 11c, d with a CF(3) group at the 3-position of the 4-arylpiperazine fragment exhibited anti-seizure properties in the MES model; in contrast, their 2-CH(3) and 2-OCH(3) analogues were inactive in both the tests used. Moreover, since the investigated compounds belong to the class of long-chain arylpiperazines, their serotonin 5-HT(1A) and 5-HT(2A) receptor affinity was determined. The relationship between the length of alkylene spacer and 5-HT(1A)/5-HT(2A) receptor activity was observed. Compounds with an ethylene and a propylene bridge (10a-d and 11a-d) were 3-80-fold more potent (K(i) ranged from 3.1 to 94 nM for 5-HT(1A) and 32-465 nM for 5-HT(2A)) than their methylene analogues (8a-c and 9a-c; K(i) ranged from 81 to 370 nM for 5-HT(1A) and 126-1370 nM for 5-HT(2A)). The highest 5-HT(1A) receptor affinity was displayed by 2-OCH(3) and 3-CF(3) phenyl derivatives (10b, 11b: K(i)=6.8 and 5.7 nM, respectively, and 10c, 11c: K(i)=6.0 and 3.1 nM, respectively), while in the case of 5-HT(2A) receptor the highest affinity was observed for the 3-CF(3) phenyl derivatives 10c, d, 11c, d (K(i) ranged from 32 to 86 nM).     

Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflammatory and analgesic activities

The 5,10-dihydro-2-thioxo-pyrimido[4,5-b]quinolines (2a-c) and its oxidized form 3 were prepared and used as key intermediates for the synthesis of thiazolo[3',2':1,2]pyrimido[4,5-b]-quinolines (5a-c), isoxazolo[5',4':4',5']thiazolo[3',2':1,2]pyrimido[4,5-b]quinolines (6a-c), 4-chloro-2-methylthio-pyrimido[4,5-b]quinoline, its amino derivatives (19-21) and 10,11,12,13-tetrahydro-5H-quino[2',3':4,5]pyrimido[6,1-b]quinazoline (22). The newly synthesized compounds were characterized by IR, NMR (1H, 13C) and mass spectral studies. Representative of the synthesized compounds was tested and evaluated for anti-oxidant, anti-inflammatory and analgesic activities. Compounds 2a-c showed the highest inhibitory anti-oxidant activity either using erythrocyte hemolysis or ABTS methods. Compounds 2a, 10b, 16, and 17a manifested the best protective effect against DNA damage induced by bleomycin. Compounds 2c, 5a, 20a, 2a, and 2b exhibited a potent anti-inflammatory activity using carrageenan-induced paw edema test in rats.