76822-66-7

Upstream product

• 13165-35-0 7-chloroquinazoline-2,4-dione 
• 5900-58-3 2-amino-4-chloro-benzoic acid methyl ester 

Downstream Products

• 220060-39-9 3-ethyl-1,3-dihydro-8-[[[2-[4-(hydroxymethyl)-1-piperidinyl]phenyl]methyl]amino]-2H-imidazo[4,5-g]quinazoline-2-thione 
• 121496-94-4 5,7-Diethyl-2-phenyl-1,5-dihydro-imidazo[4,5-g]quinazoline-6,8-dione 
• 76822-68-9 4-chloro-2-(methylamino)-5-nitro-N-methylbenzamide 

Relevant academic research and scientific papers

Development of a practical synthetic route of a PDE V inhibitor KF31327

An efficient route suitable for a large-scale preparation of KF31327 (1), a potent phosphodiesterase V inhibitor, has been developed. We selected 7-chloro-2,4(1H,3H)-quinazolinedione (15) as a starting material, which gave the desired 6-nitro compound with good selectivity. In the chlorination of 7-ethyl-amino-6-nitro-2,4(1H,3H)-quinazolinedione (17), reaction conditions were optimized to minimize the amount of phosphorus oxychloride, and 2,4-dichloro-7-ethylamino-6-nitroquinazoline (14) was obtained in excellent yield. After the selective substitution at C4 position, the chloro substituent at C2 position was successfully removed by hydrogenation concomitant with the reduction of nitro group. The construction of the imidazothione ring was achieved by using phenyl isothiocyanate as a thiocarbonyl donor instead of extremely flammable carbon disulfide. Multikilograms of drug substance have been successfully prepared by these procedures.

Tricyclic dicarbonyl derivatives

Compounds of general formula (Ia), (Ib) and (II), wherein R1 and R2 each independently signify hydrogen, lower alkyl, lower alkoxy, nitro, trifluoromethyl, amino, halogen, cyano or R3 R4 NS(O)2 -- and R3 and R4 signify lower alkyl, and R2 can additionally signify morpholino or thiomorpholino, a 5- or 6-membered heterocycle with 1-3N atoms optionally substituted by lower alkyl, hydroxy, amino or the group --CH2 NHCH3, a bicyclic heterocycle with 1-3N atoms or a group --NR5 R6 or --OR5 in which R5 and R6 can be the same or different and signify hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl or lower alkylamino-lower alkyl, and X in formula (II) signifies --CH=CH--, --CH=N--, --NH--, --CO-- or --O--, as well as pharmaceutically usable salts of compounds of general formula (Ia), (Ib) and (II). They can be used for the treatment or prevention of illnesses, especially for the treatment or prevention of ischemia, hypoglycaemia, hypoxia, cerebral vascular spasms, spasticity, trauma, hemorrhagia, infection (viral, bacterial, amoebic, prional), epileptic seizures, autoimmune diseases, withdrawal symptoms, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, intoxications, olivoponto-cerebellar atrophy, spinal cord injuries, schizophrenia, depressions, anxiety states, dependence, pains,autism and mental retardation.

Linear Expanded Xanthines

Expansion of the xanthine ring system has been accomplished by linear formation of a benzo, pyrido or pyrazino ring between the pyrimidine and imidazole portions. - Keywords: Anil; Covalent hydrate; Lin-benzo-xanthines; Lin-pyrido-xanthines; Lin-pyrazino-xanthines

Synthesis of lin-Benzofervenulin, lin-Benzotheophylline, and lin-Benzocaffeine

The synthesis of 7,9-dimethylpyrimido-1,2,4-benzotriazine-6,8(7H,9H)-dione (3) as the lin-benzo-separated analogue of fervenulin is reported in five steps from 7-chloro-2,4(1H,3H)-quinazolinedione.The preparation of lin-benzotheophylline (11) is described as arising from 1,3-dimethyl-7-hydrazino-6-nitro-2,4(1H,3H)-quinazolinedione (9) in a procedure originally designed to give 3.Methylation of 11 is shown to yield two products, one of which is lin-benzocaffeine (18).