Synthesis, immunomodulating effects and structure-activity relationships of new N-phenyl-5-amino-3-methylisoxazole-4-carboxamides

Ryng, Stanisław; Machoń, Z; Wieczorek, Z; Zimecki, Michał; Mokrosz, Maria J.

doi:10.1016/s0223-5234(99)80035-x

Cited by 25 publications

(18 citation statements)

References 17 publications

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“…This effect suggests that the substituents in the phenyl ring not only change the electron density distribution within this ring but also influence the electron density in the amide function, which we have already observed before [3]. We did not find any correlation between the IL-6 determination test and either σ or σ* constants, which suggests that the effect of substituents on the biological activity of the compounds, demonstrated in this test, is more complex than that observed in the proliferation and TNF-α tests.…”

Section: Quantitative Structure-activity Relationshipssupporting

confidence: 73%

“…Our previous studies on these compounds in the mouse model showed that compound 9, and particularly compound 11, strongly stimulated both humoral as well as cellular immune response [3] . Significant stimulation of the immune response by compound 11 correlated with its ability to upregulate TNF-α production in human PBMC (Table 3).…”

Section: Resultsmentioning

confidence: 94%

“…In the studies of our laboratory group [3][4][5] , the isoxazoles possessing immunological activity represent the most important field of research. In our last report [3] we described the synthesis, immunomodulating activity, and structure-activity relationships of the 5-amino-3-methylisoxazole-4-carboxylic acid phenylamides 3 ( Figure 2) in the mouse model.…”

Section: Introductionmentioning

confidence: 99%

“…In our last report [3] we described the synthesis, immunomodulating activity, and structure-activity relationships of the 5-amino-3-methylisoxazole-4-carboxylic acid phenylamides 3 ( Figure 2) in the mouse model. Interesting results were obtained, showing stimulatory influence of these compounds on the magnitude of the humoral immune response to sheep red blood cells (SRBC) in vitro and in vivo, and on the delayed type hypersensitivity (DTH) reaction to SRBC.…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulating Action and Structure-Activity Relationships of Substituted Phenylamides of 5-Amino-3-methylisoxazole-4-carboxylic Acid

Ryng¹,

Zimecki

Sonnenberg

et al. 1999

Arch. Pharm. Pharm. Med. Chem.

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A series of 5‐amino‐3‐methylisoxazole‐4‐carboxylic acid amides has been prepared by condensation of 5‐amino‐3‐methylisoxazole‐4‐carboxylic acid with ethyl chloroformate. The resulting mixed anhydride undergoes condensation with appropriate phenylamides to form the corresponding amides 6‐16. The compounds obtained were evaluated for their immunological activities in cultures of human peripheral blood mononuclear cells (PMBC). We found that the activities of the compounds in the proliferation test and in the lipopolysaccharide (LPS)‐induced cytokine production in PBMC cultures were differential. The stimulatory or inhibitory effects depended strongly on the origin and location of substituents in the phenyl ring which is described in the discussion and was supported by QSAR studies.

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Section: Quantitative Structure-activity Relationshipssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunomodulating Action and Structure-Activity Relationships of Substituted Phenylamides of 5-Amino-3-methylisoxazole-4-carboxylic Acid

Ryng¹,

Zimecki

Sonnenberg

et al. 1999

Arch. Pharm. Pharm. Med. Chem.

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“…In the last few years we have synthesized novel isoxazole compounds exhibiting immunostimulatory [1] and immunosuppressory [2,3] activities. In our research program, aimed at the quantum mechanical study of immunomodulatory agents, we focused our attention on recently described 5-aminomethinimino-3-methylisoxazole-4-carboxylic acid derivatives [2].…”

Section: Introductionmentioning

confidence: 99%

A Quantum Chemical Study of the 5-Aminomethinimino-3-methylisoxazole-4-carboxylic Acid Phenylamides-A New Lead Structure in the Immunosuppressing Agents

Ryng¹,

Zimecki

Fedorowicz

et al. 1999

Quant. Struct.-Act. Relat.

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In this paper we describe structure-activity relationships of 5-aminomethin-imino-3-methylisoxazole-4-carboxylic acid phenylamide (AMIAP) derivatives in various immunological tests in vivo and in vitro. We found a strong relationship between atom charges in the amide group in AMIAP derivatives and their activities in the HIR in vitro experiments. In particular, the hydrogen's charge within the amide group is best correlated with the immune activity. In general, decrease of the electrostatic potential around the amide groups is associated with increase of the immunological activity.The studied derivatives may be divided into two groups based on their structure and immunological activity which may be low (compound 1 and 3) or high (compound 2, 4, 5, 7 and 8). That division is associated with the presence of hydrogen at the R H substituent, which plays a key role in the immune activity, or, as in the case of compound 2, with the presence of a ethoxy group which is a stronger electrondonor as compared to a Cl group.Studying the effects of the compounds on CIR we found a relationship between atom charges of atoms C5, C6 and chlorine substituent with activity of AMIAP derivatives. In addition, the nitrogen atom (N14) from the isoxazole ring has a strong charge versus activity relationship. The change of the chlorine substituent to an ethoxy one did not have any effect on CIR. Studying the effect of AMIAP derivatives on HIR in vivo we found that atom charges of atom C6, and connected to it hydrogen H25, correlated with immunological activities.The overall biological activity of AMIAP is also re¯ected by the HOMO orbital.

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Reactions of 5-Amino-3-methylisoxazole-4-carboxylic Acid Hydrazide with Carbonyl Compounds: Immunological Activity and QSAR Studies of Products

Ryng¹,

Zimecki

Fedorowicz

et al. 2001

Arch. Pharm. Pharm. Med. Chem.

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Synthesis, immunomodulating effects and structure-activity relationships of new N-phenyl-5-amino-3-methylisoxazole-4-carboxamides

Cited by 25 publications

References 17 publications

Immunomodulating Action and Structure-Activity Relationships of Substituted Phenylamides of 5-Amino-3-methylisoxazole-4-carboxylic Acid

Immunomodulating Action and Structure-Activity Relationships of Substituted Phenylamides of 5-Amino-3-methylisoxazole-4-carboxylic Acid

A Quantum Chemical Study of the 5-Aminomethinimino-3-methylisoxazole-4-carboxylic Acid Phenylamides-A New Lead Structure in the Immunosuppressing Agents

Reactions of 5-Amino-3-methylisoxazole-4-carboxylic Acid Hydrazide with Carbonyl Compounds: Immunological Activity and QSAR Studies of Products

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