63376-35-2

Upstream product

• 4233-33-4 4-Phenyl-1,2,4-triazolidine-3,5-dione 
• 64-17-5 ethanol 
• 15988-11-1 4-Phenylurazole 
• 103-71-9 phenyl isocyanate 

Relevant academic research and scientific papers

Synthesis and hypolipidemic activity of 4-substituted 1-acyl-1,2,4- triazolidine-3,5-diones in rodents

A series of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones demonstrated potent activity in CF1 mice when administered intraperitoneally at 20 mg/kg/day, lowering both serum cholesterol and triglyceride levels significantly. The 4-(4-chlorophenyl)-substituted compounds demonstrated better hypolipidemic activity in rodents than 4-methoxy-4-nitro-, and 4-t- butylphenyl substitutions. Aryl and alkyl substitutions rather than benzoyl substitutions at position 4 demonstrated good hypocholesterolemic activity. Selected compounds were examined for the mode of action in rats in which serum cholesterol and triglyceride levels were reduced after administration of 20 mg/kg/day orally; tissue lipids were reduced after 14 days of administration, and bile and fecal lipids were increased by 44-250%. Serum lipoprotein levels were also modulated by the agents, with cholesterol levels in very low density lipoprotein and low density lipoprotein fractions being reduced by 2-57%. Cholesterol levels in the high density lipoprotein fraction were elevated by 94-341%. Activities of mouse hepatic enzymes were suppressed by the agents in a manner that suggested that the compounds interfere with de novo synthesis of lipids.

Method for control of hyperlipidemia

The present invention is directed to a method of controlling hyperlipidemia in mammals which comprises administering to a mammal an amount effective to control hyperlipidemia of a compound having hypolipidemic activity and the structural formula: STR1 wherein R1 is hydrogen, a C1 to C18 alkyl or substituted alkyl, a C2 to C18 alkenyl or substituted alkenyl, a C2 to C18 alkynyl or substituted alkynyl, a C4 to C10 cycloalkyl or substituted cycloalkyl, a C4 to C10 cycloalkenyl or substituted cycloalkenyl, phenyl, a substituted phenyl, cyano, phenalkyl, --CO--R9 or --Y--CO--R9 ; R2 is STR2 R3 and R4 can be the same or different and are each the same as R1 ; R5, R6 and R7 can be the same or different and are each hydrogen, a C1 to C18 alkyl or substituted alkyl, a C2 to C18 alkenyl or substituted alkenyl, a C1 to C18 alkynyl or substituted alkynyl, a C4 to C10 cycloalkyl or substituted cycloalkyl, a C4 to C10 cycloalkenyl or substituted cycloalkenyl, phenyl or substituted phenyl, phenalkyl, --CO--R9, or --Y--CO--R9, with the proviso that R5 and R6 together cannot be so bulky as to cause the compound to decompose; R8 is hydrogen, a C1 to C5 alkyl, a C4 to C10 cycloalkyl, --CO--R9 or Y--CO--R9 ; R9 is hydrogen, a C1 to C5 alkyl or substituted alkyl, a C2 to C5 alkenyl or substituted alkenyl, a C2 to C5 alkynyl or substituted alkynyl, phenyl or substituted phenyl, phenoxy or substituted phenoxy, a C1 to C5 alkoxy or substituted alkoxy, a C4 to C10 cycloalkyl or substituted cycloalkyl, a C4 to C10 cycloalkenyl or substituted cycloalkenyl, --NHC6 C5l , --NR10 R11 wherein R10 and R11 can be the same or different and are each hydrogen, a C1 to C5 alkyl or substituted alkyl, phenyl or substituted phenyl; Y is a C1 to C10 alkylene or substituted alkylene; R12 is --CO, --COH, --CS, --CSH, or a C1 to C4 alkylene group; and and the pharmaceutically acceptable salts, and mixtures thereof.

Triazolinediones. Conversion to Deaza Dimers by Electron-Transfer Catalysis. A Possible Radical Anion Diels-Alder Reaction

1,2,4-Triazolidines, 4-RTAD (1), are converted to dimeric products (deaza dimers 2) with loss of dinitrogen by a variety of agents of which the most effective are good single-electron donors (sodium naphthalenide, sodium iodide, sodium metal).The reaction is retarded by tetracyanoethylene or lead tetraacetate (electron acceptors).A radical anion chain reaction is proposed (Scheme IV and eq 9-12) in which the overall result is the reaction of two RTAD --> deaza dimer 2 + N2, catalyzed by electron donors.The sequence suggested includes the cycloaddition of RTAD anion radical with the dienophile RTAD, the first example (of which we are aware) of a radical anion Diels-Alder reaction.In the presence of an alcohol (e.g., methanol) PhTAD is converted, again in a catalyzed reaction (e.g., sodium iodide), to a methanol addition product, formulated as 3a (eq 5a, 15, and 17 and Scheme V).

Decomposition Reactions of a Cis-Diacyl Diimide. 4-Phenyl-1,2,4-triazoline-3,5-dione

The cis-diacyl diimide 4-phenyl-1,2,4-triazoline-3,5-dione (1) was decomposed in a variety of solvent systems.In nonnucleophilic solvents under 80 deg C 1 underwent nitrogen evolution and was converted to 2,6-diphenyltriazolo-s-triazole-1,3,5,7-tetrone (2).At higher temperatures 1 gave phenyl isocyanate (3).In nucleophilic solvent systems (acetic acid, alcohols, or water) 1 underwent loss of nitrogen and formed mixtures containing varying amounts of 2, 1-(N-phenylcarbamoyl)-4-phenylurazole (5), 4-phenylurazole (11), diphenylurea (12), N-phenylcarbamtes (13), and 1-(alkoxycarbonyl)-4-phenylurazoles (14), depending on the decomposition conditions employed.The mechanistic pathways leading to the various products are discussed.