Biomaterial Database

Synthesis of some carbon-3 substituted 1,4-benzodiazepin-2-ones and their central nervous system effects. 1979

T Kovac, and F Kajfez, and V Sunjić, and N Blazević, and D Kolbah

Starting from 3-hydroxy-1,4-benzodiazepin-2-ones 1--3, via 3-chloro derivatives 4--6, 13 new C(3)-substituted 1,4-benzodiazepin-2-ones were synthesized. Reaction of 4--6 with ethylene glycol yielded 3-(beta-hydroxyethyl) derivatives 7--9. Similar reaction with the isopropylidene derivative of glycerol afforded 10--12, which on hydrolysis of the isopropylidene group hielded glycerol derivatives 13--15. Reaction of trichloroacetyl chloride with oxazepam and temazepam yielded the corresponding trichloroacetyl esters 16 and 17. The beta-hydroxyethyl derivative 7 was conjugated with an acetylated glucopyranose derivative to give isomeric 18 and 19. Partition coefficients (log Poct) and central nervous system activities (in six stranded tests) were determined for 7--15 as well as several standard compounds. Most of the compounds exhibiting beneficial central nervous system activity had Poct values between 1.71 and 2.48. No correlation between lipophilicity and central nervous system activity could be discerned for these compounds.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D002490	Central Nervous System	The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.	Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D004952	Esters	Compounds derived from organic or inorganic acids in which at least one hydroxyl group is replaced by an –O-alkyl or another organic group. They can be represented by the structure formula RCOOR’ and are usually formed by the reaction between an acid and an alcohol with elimination of water.	Ester
D004987	Ethers	Organic compounds having two alkyl or aryl groups bonded to an oxygen atom, as in the formula R1–O–R2.
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001570	Benzodiazepinones
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus