ABSTRACT
The synthesis and anti-RSV (Rouse Sarcoma Virus) activity of HMCA, (+/-)-9-(2-hydroxymethyl-cyclopenthyl)-adenine, and its derivatives are described. It has been demonstrated that trans-HMCA has greater anti-RSV activity in tissue culture than cis-HMCA.
Subject(s)
Adenine/analogs & derivatives , Adenine/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Adenine/chemical synthesis , Animals , Antiviral Agents/chemistry , Avian Sarcoma Viruses/drug effects , Chick Embryo , Drug Evaluation, Preclinical , Fibroblasts , HIV-1/drug effects , In Vitro Techniques , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Effects of TA-5707F [6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide] and its sodium salt (TA-5707) on IgE-induced homologous PCA in rats were investigated. 1. Both TA-5707 and TA-5707F were found to be orally effective inhibitors of rat PCA. Maximum activity by oral administration was obtained when they were administered 5 min before the challenge. Their ID50's under these conditions were both approximately 1 mg/kg. Administration 5 min after the challenge was no longer effective. 2. TA-5707 was also effective by intravenous administration, and its ID50, ca. 0.1 mg/kg, was less than that of disodium cromoglycate (DSCG). 3. The PCA-inhibitory activity of TA-5707 was not affected by adrenalectomy and adrenomedullectomy. 4. Daily administration of TA-5707 or TA-5707F for 8 days did not induce drug tolerance. 5. Tachyphylaxis and cross-tachyphylaxis were observed when the PCA-inhibitory activities of TA-5707 and DSCG were tested after intravenous pretreatment with a large dose (ca. 30 times the ID50) of either drug, but not after oral pretreatment with a therapeutic dose of TA-5707 or TA-5707F.