Patent GB-1120461-A (GB)
Title: Derivatives of fluoreno-[1,9-ef]1,4-diazepine-1-oxide
Inventor: RIDDER RENE RACHEL DE
IPC: A61K31/55
Filed: 1964-07-06
Abstract: Compounds of the general Formula (I) <FORM:1120461/C2/1> wherein R3 and R5, which may be the same or different, represent hydrogen atoms or methyl or ethyl groups, R4 represents a hydrogen atom or a halogen atom in position 5 or 7, and R1 represents a hydrogen atom and R2 represents a hydrogen atom, a C1- 6 alkyl group, an alkenyl, benzyl, cyclohexyl, b -phenylethyl, alkylaryl, hydroxyalkyl, amino, amidino, furfuryl, alkylheterocyclic or dialkylaminoalkyl group or a group of the formula <FORM:1120461/C2/2> (in which <FORM:1120461/C2/3> is a nitrogen-containing heterocyclic group which may be substituted), or R1 and R2 form together with the adjacent nitrogen atom a heterocyclic group (which may be subtituted) or a dimethylamino group, and their acid addition salts are prepared by (a) reacting a compound of the Formula (III) <FORM:1120461/C2/4> wherein X represents a halogen atom, with R2NH2 in the presence of a solvent, a heterocyclic amine (other than morpholine) in the presence of methanol, or dimethylamine or (b) reacting a compound of the Formula (III) with methanol or ethanol in the presence of sec.-butylamine, tert.-butylamine, cyclohexylamine, N-ethylethanolamine, diethylamine, isopropylamine, ethanolamine, N-methylpiperazine, N-(b  - hydroxyethyl) - piperazine, hexamethyleneimine or a tertiary amine carrying no primary or secondary amine groups and reacting the resulting compound of the Formula (IV) <FORM:1120461/C2/5> wherein R represents a methyl or ethyl group, with ammonia, guanidine, hydrazine, methylamine, ethylamine, ethanolamine, propylamine, isopropylamine, allylamine, butylamine, isobutylamine, amylamine, isoamylamine, hexylamine, benzylamine, phenethylamine or a heterocyclic amine, optionally followed in either case by salt formation.  The compounds of the Formula (III) may be prepared by cyclizing a compound of the Formula (V) <FORM:1120461/C2/6> and the compounds of the Formula (V) may be prepared by (a) reacting a compound of the Formula (VI) <FORM:1120461/C2/7> with hydroxylamine or (b) reacting a compound of the Formula (VIII) <FORM:1120461/C2/8> with a compound of the Formula (VII) <FORM:1120461/C2/9> wherein X1 represents a halogen atom.  The compounds of the Formulae (VI) and (VIII) may be prepared by reacting the appropriate 1 - aminofluorenone with an appropriate compound of the Formula (VII) or hydroxylamine, respectively.  1 - Aminofluorenoneoxime hydrochloride is prepared from the free base, and 2- and 4-chloro-1-aminofluorenone are prepared by chlorinating 1-aminofluorenone.  When a compound of the Formula (III) is reacted, in methanol, with pyrrolidine, piperidine or a substituted piperazine, a mixture of a compound of the Formula (I) with a compound of the Formula (II) <FORM:1120461/C2/100> may be obtained.  The compounds of the Formula (I) and their salts possess sedative, tranquilizing, hypnotic, pre-narcotic, anticonvulsant, anti-parkinson and antispasmodic activity, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier or excipient.