Synthesis and antihistaminic activity of some thiazolidin-4-ones.

A new series of 2-(4- and 3-substituted phenyl)-3-[3-(N,N-dimethylamino) propyl]-1,3-thiazolidin-4-ones were synthesized, characterized, and evaluated for their ability to inhibit the contractions induced by histamine on guinea pig ileum. The measurement of pA2 values suggested that the reported compounds showed H1-antagonism. The more active compounds 5, 9, and 13 exhibited activity close to that of mepyramine.

Synthesis and antimicrobial activity of 1-(p-substituted)phenyl-3-(p-alkoxy)phenyl-4-phenyl-azetidin-2-ones.

A series of 1-(p-substituted)phenyl-3-(p-alkoxy)phenyl-4-phenyl-azetidin-2-one s 1a-20a, was synthesized and characterized. Their antimicrobial activity, against Gram+ and Gram- bacteria and Fungi, was tested. The compounds 8a, 13a, 14a, 18a and 6a, 9a, 10a showed remarkable activity respectively against Pseudomonas aeruginosa and against Fungi.

Synthesis and antimicrobial activity of hydroxy-isophthalaldehyde acid derivatives.

4-hydroxy-isophthalaldehyde acid (1), its alkyl esters (methyl, ethyl, propyl and butyl) and alkyl ethers (propyl, butyl, pentyl and esyl), as well as 6-hydroxy-isophthalaldehyde acid (2) ita alkyl esters (methyl and ethyl), 4-hydroxy-5-iodo-isophthalaldehyde acid (3) and its methyl ester were synthesized and characterized. Antimicrobial and antifungal activity was tested and the LD50 of the most active compound 4 was determined.

N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines and their methyl esters: synthesis and antimicrobial activity.

The N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines (1-6) and the corresponding 5-carbomethoxy derivatives (7-12) were synthesized and characterized. Antimicrobial and antifungal activity was tested against Gram+ and Gram- bacteria and Fungi.

Synthesis and antimicrobial activity of 1,3,4-triaryl-2-azetidinones.

A set of substituted 1,3,4-triaryl-2-azetidinones were synthesized and characterized. Their antimicrobial activity, against Gram+ and Gram- bacteria and Fungi, was tested. The compounds 23 and 30 showed remarkable activity against Pseudomonas aeruginosa.

[Experimental observations on the iodination of phenols in the preparation of intermediates of pharmaceutical interest]. / Osservazioni sperimentali sulla iodurazione di composti fenolici per la preparazione di "intermedi" d'interesse chimico farmaceutico.

A study has been made on the iodination of phenols by elemental iodine in Na2CO3 solution. The results attained by applying the suggested procedure to a number of practical cases have been very encouraging. This method gives rise to the iodine derivatives of aldehydes (2-hydroxy- and 4-hydroxy-3,5-diiodobenzaldehyd), ketones (2-hydroxy-5-iodo-, 2-hydroxy-3,5-diiodo- and 4-hydroxy-3,5-diiodo-acetophenone, 4-hydroxy-3,5-diiodo-propiophenone), acids (3,5-diiodo-4-hydroxybenzoic acid, 3-formyl-4-hydroxy-5-iodobenzoic acid), aminoacids (3-iodo- and 3,5-diiodo-tyrosine), esters (methyl ester of 2-hydroxy- and 4-hydroxy-3,5-diiodobenzoic acid, methyl ester of 3-iodo-5-chloro-, 3-iodo-5-bromo- and 3,4,5-triiodosalicylic acid, dimethyl- and diethyl-ester of 4-hydroxy-5-iodo-isophthalic acid), amides (2-hydroxy-3,5-diiodobenzamide) and benzoxazole derivatives (2-(2'-hydroxy-3',5'-diiodophenyl)benzoxazole).

[Hydrazide derivatives of fluorobenzoic acids and their antimicrobial activity]. / Derivati idrazidici di acidi fluorobenzoici ad attivita' anti microbica.

The compounds of formula (A) were prepared by reaction between Rn-substituted benzoyl hydrazides and R-substituted benzoyl chlorides; the compounds of formula (B) were obtained by condensing R-substituted benzoyl chlorides with isonicotinic hydrazide. All the compounds were tested for in vitro activity against five Gram+ bacteria (S. aureus, S. epidermidis, B. subtilis, B. anthracis, M. paratuberculosis ATCC 607), seven Gram-bacteria (S. paratyphi A, S. paratyphi B, E. coli, B. abortus, B. melitensis, P. aeruginosa, P. mirabilis) and three fungi (C. albicans, A. niger, S. cerevisiae), by agar-diffusion method (Kirby-Bauer modified). The prepared compounds generally showed inhibitory activity against Gram+ bacteria. The greatest activity was observed in the compounds of general formula (B); they were especially inhibitory toward M. paratuberculosis ATCC 607.

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. V. Pharmacological activity of substituted 2-phenyl-3-(N,N-dimethylaminoprophyl)-1,3-thiazolidin-4-one .

The following 2-substituted phenyl-3-(N,N-dimethylaminopropyl)-1,3-thiazolidin-4-one of general formula (A): [formula: see text] where: X = H (I), 3-F (II), 3-Cl (III), 3-Br (IV), 3-CH3 (V), 3-OCH3 (VI), 3-NO2 (VII), 4-F (VIII), 4-Cl (IX), 4-Br (X), 4-CH3 (XI), 4-OCH3 (XII), 4-NO2 (XIII) were prepared and tested for antihistamine activity. The synthetic procedure involves the cyclocondensation of the appropriate Schiff base with thioglycolic acid in refluxing dry benzene. The compounds herein presented were tested for their ability to inhibit the contraction inducted by histamine 5.10(-7) M "in vitro", on guinea pig ileum. The results are reported as contraction of test compound causing 50% of submaximal contraction induced by histamine (IC50), and related to mepyramine as control. The results of the antihistamine tests showed an interesting degree of activity of some of the new thiazolidinone-derivatives. Compounds II, III, V, X, and XI showed IC50 values near the value of the control, compound XI being the most active. These compounds seem to be worthy of further investigation.

"Food allergy in children: an attempt to improve the effects of the elimination diet with an immunomodulating agent (thymomodulin). A double-blind clinical trial".

During 90 days of elimination diet nineteen children with food allergy manifesting atopic dermatitis were treated with either 120 mg/day of thymomodulin (10 subjects) or placebo (9 subjects) in a double blind design. After this period an improvement in skin lesions was observed in both groups. Subsequently a food challenge was performed for two weeks: in the group treated with thymomodulin skin lesions did not modify while they worsened in the placebo group and the comparison was statistically significant (p less than 0.01). Before the beginning of the trial laboratory assessments evidenced an increase in total and specific IgE serum levels, which decreased by the end of the study only in the group receiving the thymic derivative (p less than 0.05).

Biological activity of 4-hydroxy-5-formylbenzoic acid derivatives.

A group of thirty 4-hydroxy-5-formylbenzoic acid derivatives of general formula: (formula; see text) where (formula; see text) have been prepared and characterized in an attempt to make available for testing a representative selection of hitherto undescribed hydroxyformylbenzoic acid derivatives. The products, which are listed in Table I, with pertinent data, have been obtained in satisfactory yield and in a good state of purity. The prepared compounds have been tested for "in vitro" activity against three fungi (A. niger, C. albicans, S. cerevisiae), six Gram- bacteria (E. coli Bb, S. typhi, S. infantis, S. paratyphi A, B. melitensis, P. mirabilis) and four Gram+ bacteria (M. paratuberculosis ATCC 607; S. epidermidis, B. subtilis, B. anthracis), by the agar diffusion method (Kirby-Bauer modified). In general, the results of the tests indicated that most of the compounds: a) didn't exhibit antifungal activity "in vitro"; b) had little activity on Gram- bacteria; showed inhibitory activity toward Gram+ species, in particular toward M. paratuberculosis. Other activities of pharmaceutical interest will be tested; the screening program includes tests for cardiac activity. The results of these studies will be published as soon as they are complete.

[Biological activity of 4-hydroxy-5-formylbenzoic acid derivatives. II. Esters and Schiff bases with antimicrobial activity]. / Attivita' biologica di derivati dell'acido 4-idrossi-5-formil benzoico. II. Esteri e basi di Schiff ad attività antimicrobica.

A number of hitherto undescribed 4-hydroxy-5-formylbenzoic acid derivatives (A), have been prepared and characterized. (formula; see text) Esters (X = CH3) and Schiff's bases (Z = N-aryl) were prepared by conventional methods and were obtained in satisfactory yield and in a good state of purity. The prepared compounds have been tested for "in vitro" activity against Gram+ bacteria (S.epidermidis, B.subtilis, B.anthracis, M.paratuberculosis), Gram- bacteria (P.aeruginosa, S.typhi murium, E.coli Bb, S.typhi O, S.typhi infantis, S.paratyphi A, S.paratyphi B) and fungi (C.albicans, A.niger, S.cerevisiae) by agar-diffusion method (Kirby-Bauer modified). The prepared compounds, generally, showed inhibitory activity against Gram+ bacteria. Esters (A: X = CH3) showed antibacteric and antimycotic activity. The greatest activity was observed in the methyl ester (XV) of 4-hydroxy-5-formylbenzoic acid (I).

Biological activity of 4-hydroxyisophthalic acid derivatives. II. Anilides with antimicrobial activity.

A series of 1,3 -bis-anilides of 4-hydroxyisophthalic acid was prepared and tested for antibacterial and antifungal activity. The prepared compounds (I-XVIII), of general structure (A), (Formula: see text) where Xn = H (I); 2-F (II); 3-F (III); 4-F (IV); 2-Cl (V); 3-Cl (VI); 4-Cl (VII); 2-Br (VIII); 3-Br (IX); 4-Br (X); 2-J (XI); 3-J (XII); 4-J (XIII); 2,5-Cl2 (XIV); 2,4-Br2 (XV); 2,3,4-Cl3 (XVI), 2,4,5-Cl3 (XVII); 2,4,6-Cl3 (XVIII), were investigated for the purpose of determining the effect of halogen-substitution on the aniline rings of (A). All of these compounds were prepared in satisfactory hield by reaction of 4-hydroxyisophthalic acid with the appropriate aromatic amine at 175 degrees for 3 hours. The 1,3-bis-anilides prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, B. subtilis, B. anthracis, M. paratuberculosis 607, E. coli Bb, S. typhi, S. typhimurium, S. paratyphi B, Pr. vulgaris, Kl. pneumoniae, Ps. aeruginosa, C. albicans, and A. niger. The results of this investigation indicated that most of the 1,3-bis-(halogen-anilides) of 4-hydroxyisophthalic acid had little or no antifungal activity "in vitro", while showed significant activity against Gram+ and Gram- bacteria. Some fluoro-derivatives showed inhibitory activity especially toward S. aureus and M. paratuberculosis. Iodo-derivatives showed broad-spectrum "in vitro" antimicrobial activity, and had some antifungal activity.

Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. Antimicrobial activity of monohalogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine-2,4' (1H)-diones.

The following halogenated 3'-phenyl [3H-indole-3,2'-thiazolidine]-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI). The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha-mercaptoalkanoic acids, to give spirothiazolidinones of type (A). The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, S. typhi, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified. The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. 3-Fluoro-derivative (III) showed inhibitory activity especially toward S. aureus and C. albicans. Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S. aureus, E. coli, and S. Typhi. Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M. paratuberculosis.

Studies on heterocyclic compounds: spiro [indole-3,2'-thiazolidine] derivatives. II. Antimicrobial activity of halogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine -2,4 (1H)-diones.

The following polyhalogenated 3'-phenyl 3H-indole-3,2'-thiazolidine -2,4' (1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity. (formula: see text) where: X = H (I, III, V, VII, IX, XI), CH3 (II, IV, VI, VIII, X, XII); Y = H (I, II), 2,4-F2 (III, IV), 2,4-Cl2 (V, VI), 3,4-Cl2 (VII, VIII), 2,6-Cl2 (IX, X), 2,4,6-Cl3 (XI, XII). The general synthetic route involves the preparation of variously substituted isatin-3-imines, which are subjected to cyclocondensation with thioglycolic acid to give compounds I, III, V, VII, IX, XI, or thiolactic acid to give compounds II, IV, VI, VII, X, XII. The prepared compounds were screened against S. aureus, B. cereus, M. paratuberculosis, E. coli, Pr. mirabilis, Ps. aeruginosa, C. albicans, S. cerevisiae, A. niger by a disk-diffusion assay (Kirby-Bauer modified). The results of the antimicrobial screening showed that the polyhalogenated derivatives of type (A) exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. Compound (III) showed a significant activity toward A. niger, moreover compound (IV) was active toward C. albicans. Compound (IX) was very active toward S. typhi and Ps. aeruginosa. Compounds (VII), (IX) and (XII) were very active toward M. paratuberculosis.

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. IV. Biological activity of variously substituted 2,3-diaryl-1,3-thiazolidin-4-ones.

The following 2,3-diaryl-1,3-thiazolidin-4-ones of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV, XVII, XIX, XXI, XXIII), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI, XVIII, XX, XXII, XXIV); R = H (I, II, V, VI, VII, VIII, XI, XIII), 4-CH3 (XXI, XXII, XXIII, XXIV), 4-Br (III, IV, IX, X), 2-NO2 (XIII, XIV), 3-NO2 (XV, XVI), 4-NO2 (XVII, XVIII), 4-OCH3 (XIX, XX); R' = H (I, II, III, IV, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII), 4-CH3 (XXIII, XXIV), 3-Br (V, VI), 4-Br (VII, VIII, IX, X), 4-J (XI, XII). These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids. The prepared compounds were screened against S. aureus, S. beta-haemolititicus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps, aeruginosa, C. albicans, A. niger, S. cerevisiae by a disk-diffusion assay (Kirby-Bauer modified). The results obtained in this investigation showed that the prepared compounds exhibited varying degrees of antimicrobial activity. They were especially inhibitory toward Gram-positive bacteria, and fungi. 4-Nitroderivatives (XVII), (XVIII), and 2-nitroderivatives (XIV) and (XIII) possessed marked antimicrobial activity against S. aureus, S. beta-haemoliticus, and B. subtilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological activity of 4-hydroxyisophthalic acid derivatives. III. Variously substituted anilides with antimicrobial activity.

A series of 1,3-bis-anilides of 4-hydroxyisophthalic acid was prepared and investigated for antibacterial and antifungal activities. The prepared compounds (I-XIV), of the general formula (A), where Xn = 2-NO2 (I); 2,4-(NO2)2 (II); 2,4-NO2, Cl (III); 2,4-NO2,CF3 (IV); 3,4-NO2,Cl (V); 2,4-Cl,NO2 (VI); 2,5-Cl,NO2 (VII); 2,4,6-Cl,NO2,Cl (VIII); 2,4-Br, NO2 (IX); 2-CF3 (X); 3-CF3 (XI); 2,5-Cl,CF3 (XII); 2,5-CH3,Cl (XIII); 3,4-Cl,CH3 (XIV), were obtained in satisfactory yield by reacting 4-hydroxyisophthalic acid with the appropriate substituted aniline. (Formula: see text). The prepared compounds were tested for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were the following: S. aureus, B. subtilis, B. anthracis, M. paratuberculosis 607, E. coli Bb, S. typhi, S. typhimurium, S. paratyphi B, Pr. vulgaris, K1. pneumoniae, Ps. aeruginosa, C. albicans, and A. niger. The results of the antimicrobial screening showed that a number of substituted anilides exhibited varying degrees of activity against Gram-positive and Gram-negative bacteria, and fungi, nitro-halogen-derivatives being the most interesting members of the series.

Biological activity of 4-hydroxyisophthalic acid derivatives. Hydrazones with antimicrobial activity.

The following hydrazono derivatives (I-XIX) of type (A) (sequence in text) where Rn = (sequence in text ) (I-XVII); (sequence in text) (XVIII); -CCl3 (XIX); and Xn = H (I); 2-Cl (II); 3-Cl (III); 4-Cl (IV); 2-NO2 (V); 3-NO2 (VI); 4-NO2 (VII); 2-OH (VIII); 3-OH (IX); 4-OH (X); 4-F (XI); 3,4-OCH3,OH (XII); 3,4,5-OCH3,OH,J (XIII); 3,4-OCH3,OCH3 (XIV); 2,4-Cl2 (XV); 3,4-Cl2 (XVI); 2,6-Cl2 (XVII); were prepared and characterized in an attempt to make available for testing a representative selection of hitherto unreported 4-hydroxyisophthalic acid derivatives. The new compounds in question were obtained in satisfactory yield by condensation of 4-hydroxyisophthalic acid hydrazide with the appropriate aldehydes. The prepared compounds were tested for their possible activity against Gram-positive (S. epidermidis, B. subtilis, B. anthracis) and Gram-negative bacteria (P. aeruginosa, B. melitensis, S. typhi O, S. typhi H, S. infantis, S. paratyphi B, E. coli Bb, E. coli 7075), and fungi (C. albicans, A. niger, S. cerevisiae). The "in vitro" antimicrobial assays were carried out using the paper disk technique (Kirby-Bauer modified). The influence of certain structural modifications on the antimicrobial activity was evaluated.

Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. III. Biological activity of halogenated 2,3-diaryl-1,3-thiazolidin-4-ones.

In previous communications from these laboratories, thiazolidinone derivatives of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H, CH3 Ar = phenyl Ar' = fluorinated or chlorinated phenyl The present communication is in part concerned with further extension of these studies to variously halogenated thiazolidinones of general formula (B). (formula; see text) where: X = H, CH3 R = H, 2-F, 3-F, 4-F, 3-Cl, 4-Cl R' = H, 4-F, 4-Cl These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The general synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids such as thioglycolic and thiolactic acid. The prepared compounds were tested for their possible activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were: S. aureus, S. beta-haemoliticus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps. aeruginosa, C. albicans, A. niger, S. cerevisiae. The results of this antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. The second half of this report deals with the structure-activity relationships in all the compounds prepared and studied in this research program. For comparison of antimicrobial activity, the growth inhibitory activity of all the halogenated thiazolidinones of type (A) and (B), prepared and screened in this SARs study, were tabulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure-activity relationships of hydrazono derivatives of biological interest.

The following hydrazono derivatives (I-XXIII) of type (A), (formula; see text) where: X = NO2 (II, IV, VI, VIII, X, XIV-XXIII), X = H (I, III, V, VII, IX, XI, XII, XIII), and Y = H (I, II); 3-Cl (III, IV); 4-Cl (V, VI); 3,4-Cl2 (VII, VIII); 2,6-Cl2 (IX, X); 2-NO2 (XI); 3-NO2 (XII); 4-NO2 (XIII, XIV); 2-F (XV); 3-F (XVI); 4-F (XVII); 2-OH (XVIII); 4-OH (XIX); 2,4-(OH)2(XX); 2,4,6-(OH)3(XXI); 2,3-(OH,NO2) (XXII); 2,4-(NO2)2 (XXIII), were prepared and tested for antibacterial and antifungal activity. All of these compounds were prepared in satisfactory yield by reaction of aromatic aldehydes with 2-furoyl and 5-nitro-2-furoyl hydrazide. The hydrazono derivatives I-XXIII prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, S. -haemoliticus, B. subtilis, M. paratuberculosis, E. coli, S. typhi, Ps. aeruginosa, K1. pneumoniae, A. niger, S. cerevisiae, C. albicans. The results of this study showed that a number of the prepared hydrazono derivatives exhibited varying degrees of activity against Gram-positive and Gram-negative bacteria. Compounds IV and XV possessed broad spectrum "in vitro" against Gram-positive and Gram-negative bacteria. Compounds XII greater than IV greater than XV showed inhibitory activity especially toward S. aureus. Compounds IV greater than XV greater than XVI were especially active against E. coli. Compounds XV greater than IV were especially inhibitory toward S. typhi and most of the prepared compounds inhibited considerably Ps. aeruginosa and K1. pneumoniae.