ABSTRACT
A series of 6,8-disubstituted 3-[5- [[2-hydroxy-3-[(substituted phenyl)amino]propyl]thio]-1,3,4-thiadizol-2-yl] 2-methyl-4(3)- quinazolinones were synthesized whose structures were confirmed by elemental analyses, IR, NMR and mass spectral studies. All these compounds were evaluated in vivo for anticonvulsant and analgesic activities and in vitro for monoamine oxidase and succinate dehydrogenase enzyme inhibitory activities using rat brain homogenate as a source of enzyme at final concentration of 1 x 10(-4) mol/l. ALD50 values indicated their relatively nontoxic nature.
Subject(s)
Anticonvulsants/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Quinazolines/pharmacology , Analgesics , Animals , Brain/drug effects , Brain/enzymology , Female , In Vitro Techniques , Male , Mice , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/pharmacology , Quinazolines/chemical synthesis , Quinazolines/toxicity , Rats , Succinate Dehydrogenase/antagonists & inhibitorsABSTRACT
Sixteen new 2,3-dihydro-N-(substituted phenyl)-spiro (benzo [b] cyclopenta [e][1,4] diazepine-10(1H), 1'-cyclopentane)-9(10aH)-ethanamines, whose structures were confirmed by correct elemental analyses, IR, NMR and mass spectral studies, were synthesized and evaluated for anticonvulsant and analgesic activity in vivo and monoamine oxidase (MAO) inhibitory activities in vitro. The compounds exhibiting significant anticonvulsant and analgesic activity also showed marked inhibition of the enzyme MAO. The low toxicity of these compounds was reflected by their high approximate LD50 values.
Subject(s)
Anticonvulsants , Benzodiazepines/pharmacology , Monoamine Oxidase Inhibitors , Analgesics , Animals , Benzodiazepines/chemical synthesis , Benzodiazepines/chemistry , Brain/drug effects , Brain/enzymology , Female , In Vitro Techniques , Lethal Dose 50 , Male , Mice , RatsABSTRACT
Eight substituted quinazolonoformazans were synthesized and evaluated for anti-inflammatory activity. The degree of protection provided by seven of these compounds, at a dose of 100 mg/kg, po, against carrageenin-induced edema in rat paw ranged from 26 to 57%. The four active substituted quinazolonoformazans (1, 2, 6, 8), on further evaluation for antiwrithmogenic activity, provided 10-80% protection against the aconitine-induced writhing response in mice. The ulcerogenic liabilities of two of the most active compounds were also determined. The doses producing ulcers in 50% of the treated rats (UD50) were 155 and 260 mg/kg, ip, for 2 and 8, respectively. The low toxicities possessed by these substituted quinazolonoformazans were indicated by their LD50 values which ranged from 600 to 1300 mg/kg, ip, in mice.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Azo Compounds/chemical synthesis , Formazans/chemical synthesis , Quinazolines/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Carrageenan , Chemical Phenomena , Chemistry , Edema/chemically induced , Edema/drug therapy , Female , Formazans/pharmacology , Formazans/toxicity , Male , Mice , Quinazolines/pharmacology , Quinazolines/toxicity , Rats , Stomach Ulcer/chemically inducedABSTRACT
Various new formazans of substituted oxadiazole 2(3H)-thiones were tested for their anti-inflammatory activity against carrageenin-induced paw oedema in albino rats. Among these, two most potent derivatives were evaluated in detail using cotton pellet implantation methods in albino rats of either sex. These two active analogues were also tested for their analgesic activity in albino mice and ulcerogenic liability in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 value in albino mice. An attempt has also been made to establish the structure-activity relationship.
Subject(s)
Analgesics , Anti-Inflammatory Agents, Non-Steroidal , Oxadiazoles/pharmacology , Aconitine/pharmacology , Animals , Carrageenan , Edema/chemically induced , Edema/prevention & control , Female , Gossypium , Lethal Dose 50 , Male , Oxadiazoles/toxicity , Phenylbutazone/pharmacology , RatsABSTRACT
Various new substituted formazans were synthesized and characterized by elemental analyses, IR and mass spectral data. The compounds were evaluated for their ability to protect against inflammation by carrageenin-induced paw edema in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 on albino mice. An attempt has also been made to establish a structure-activity relationship.
Subject(s)
Analgesics , Anti-Inflammatory Agents, Non-Steroidal , Azo Compounds/pharmacology , Formazans/pharmacology , Animals , Edema/prevention & control , Female , Formazans/chemical synthesis , Formazans/toxicity , Lethal Dose 50 , Male , Mice , Pain/drug therapy , Rats , Structure-Activity Relationship , Ulcer/chemically inducedABSTRACT
Substituted 1,5-diaryl-3(4-chlorophenyl)-delta 2-pyrazolines were synthesized and evaluated for anticonvulsant activity. Most pyrazolines (100 mg/kg) provided 20-80% protection against pentylenetetrazol-induced convulsions in mice. All compounds inhibited rat brain mitochondrial monoamine oxidase (MAO) and succinic dehydrogenase (SDH) and exhibited low toxicity as reflected by approximate LD50 values (500 to greater than 1000 mg/kg) in mice.
