US3684798A

US3684798A - 5-phenyl-7-chloro-1h-1,5-benzodiazepin e-2,4-(3h,5h)-diones

Info

Publication number: US3684798A
Application number: US111716A
Authority: US
Inventors: Karl-Heinz Weber; Karl Zeile; Peter Danneberg; Rolf Giesemann; Karl Heinz Hauptmann
Original assignee: Individual
Current assignee: MARIA HAUPTMANN HEIR; CH Boehringer Sohn AG and Co KG; Boehringer Ingelheim GmbH
Priority date: 1967-02-07
Filing date: 1971-02-01
Publication date: 1972-08-15
Anticipated expiration: 1989-08-15
Also published as: CH509330A; FI61309C; DE1670190A1; FR1574710A; NL6801696A; DK131936C; DK126330B; SE367418B; DK127065B; AT281037B; YU39921B; BE710475A; DE1670305B2; DK131936B; US3707539A; GB1214662A; USRE28935E; SE367416B; CH523894A; US3711509A

Abstract

WHEREIN R1 is hydroxy-alkyl of two to four carbon atoms; haloalkyl of two to four carbon atoms; di(alkyl of two to four carbon atoms)amino-alkyl of two to four carbon atoms; gamma piperidino-propyl; alkoxy of one to two carbon atoms - alkyl of one to four carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkyl of one to four carbon atoms; (alkyl of one to two carbon atoms) mercapto-alkyl of one to four carbon atoms; straight or branched alkenyl of three to five carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkenyl of two to four carbon atoms; or halo-alkenyl of two to four carbon atoms; THE COMPOUNDS ARE USEFUL AS PSYCHOSEDATIVES AND ANTICONVULSIVES.

Compounds of the formula

Description

United States Patent Weber et al.

[54] 5-PHENYL-7-CHLORO-1H-l,5-

BENZODIAZEPIN E-2,4-(3H,5H)- DIONES [73] Assignee: Boehringer lngellheim G.m.b.H., ln-

gqlhe m enlihinezfi r eny 221 Filed: Feb. 1, 1971 211 Appl.No.: 111,716

Related u.s. Application Data [63] Continuation-impart of Ser. No. 89,482, Nov.

13, 1970, which is a continuation-in-part of Ser. No. 703,188, Feb. 5, 1968, abandoned.

[30] Foreign Application Priority Data Feb. 7, 1967 Germany ..B 91071 Jan. 18, 1968 Germany ..B 96281 Jan. 18, 1968 Germany ..B 92682 [52] US. Cl. ..260/239.3 B, 424/244 [51] Int. Cl. ..C07d 53/04 [58] Field of Search ..260/293.3 B

[151 3,684,798 [451 Aug. 15, 1972 [56] References Cited OTHER PUBLICATIONS Buchi et a1., Helo. Chim Acta Vol. 39, pages 95 2- 963 (1956).

Primary Examiner-Henry R. Tiles Assistant ExaminerRobert T. Bond AtrorneyHammond & Littell ABSTRACT Compounds of the formula R1 0 91kt CH2 CI R is hydroxy-alkyl of two to four carbon atoms; haloalkyl of two to four carbon atoms; di(alkyl of two to four carbon atoms)amino-alkyl of two to four carbon atoms; 'y-piperidino-propyl; alkoxy of one to two carbon atoms alkyl of one to four carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkyl of one to four carbon atoms; (alkyl of one to two carbon atoms) mercapto-alkyl of one to four carbon atoms; straight or branched alkenyl of three to five carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkenyl of two to four carbon atoms; or halo-alkenyl of two to four carbon atoms;

the compounds are useful as psychosedatives and anms 8 Claims, No Drawings I i ,N l l xHz 01 N 65H; (I)

wherein R is hydroxy-alkyl of two to four carbon atoms; haloalkyl of two tofour carbon atoms; di(alkyl of two to four carbon atoms)arnino-alkyl of two to four carbon atoms; y-piperidinopropyl; alkoxy of one to two carbon atoms-alkyl of one to four carbon atoms; (alkoxy of one to two carbon' atoms )carbonyl-alkyl of one to four carbon atoms; (alkyl of one to two carbon atoms)mercapto-alkyl of one to four carbon atoms; straight or branched alkenyl of three to five carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkenyl of two to four carbon atoms; or haIo-alkenyl of two to four carbon atoms.

The compounds according to the present invention may be prepared by a number of different methods involving well known chemical principles, among which the following have proved to be particularly convenient and efiicient:

Method A By cyclizing an N-phenyl-N-(Z-amino-S-chlorophenyl)-malonic acid lower alkyl ester amide of the formula m uHr (III) wherein R, has the same meanings as in formula I, with a malonic acid or alkylmalonic acid dihalide and, if

necessary, alkylating the cyclization product thus obtained in the l-position.

In method A the hydrolysis and ring closure proceed smoothly and with good yields in an acid as well as an alkaline medium, preferably in the presence of an alcoholic or aqueous alcoholic solvent; however, other inert solvents such as tetrahydrofuran or dioxan, are also suitable; for-acid cyclization, .acetonitrile may also be used as the solvent. Mineral acids, and particularly hydrohalic acids, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphonic acid and perchloric acid are preferably used as acid cyclization agents. Examples of alkaline cyclization agents are sodium alcoholates and alkali metal hydroxides.

The reaction periods depend upon the quantity of acid or alkali employed and upon the type of solvent used; they vary between several hours and several days.

The preferred reaction temperatures are preferably between +20 C. and the boiling point of the solvent which is used.

The preparation of an end product of the formula I, wherein R is unsubstituted or substituted alkyl, may be carried out in various ways. One may, for instance, start from a compound of formula I wherein R is hydrogen and exchange the same for an alkyl group with the aid of a customary alkylating agent, such as an alkyl halide or an alkyl sulfate, such as a dialkylsulfate. For this purpose an alkali metal salt of a compound of formula I is dissolved or suspended in a suitable solvent, the a] kylating agent is added to the solution or suspension, and the reaction mixture is heated. For the preparation of an end product of the formula I wherein R, is hydroxy-alkyl, a compound of the formula I wherein R is hydrogenrnay be reacted with an alkyleneoxide in the presence of a strong base, such as Triton-B. If the cyclization is carried out under alkaline conditions, the alkylation of the l-position may also be effected after the cyclization is finished, without prior isolation of the l-unsubstituted benzodiazepine-2,4-dione cyclization product. In this case the alkylating agent is added to the cyclization reaction solution containing the cyclization product, and the mixture heated.

In method B the reaction is preferably carried out in the presence of a suitable inert organic solvent, such as benzene, toluene, xylene, tetrahydrofuran, dioxan or dimethylformamide, at room temperature or, more advantageously, at the boiling point of the particular solvent which is used. In some cases the addition of a tertiary organic base, such as pyridine, has proved to have a favorable influence upon the course of the reaction. An end product of the formula I, wherein R is hydrogen, may be subsequently alkylated, as described in conjunction with method A.

If, in a compound of the formula I, R, is hydroxyalkyl, the hydroxyl group may subsequently be replaced by a halogen atom by treatment with a thionyl halide in the presence of dimethylformamide, or converted into an alkoxy group by treatment with a diazoalkane in the presence of borontrifluoride etherate.

If R, in a compound of the formula I is dialkylaminoalkyl, it is possible to introduce a double bond into the alkyl moiety by quaternization and splitting off trialkylarnine.

Furthermore, in a compound of the general formula I, wherein R is alkenyl, this substituent may be partially or completely hydrogenated by known methods.

The N-phenyl-N-( 2-amino-5-chloro-phenyl)- malonic acid lower alkyl ester amides of the formula 11 used as starting materials for method A are also novel. They may be prepared by reacting a correspondingly substituted N-phenyl-N-( 2-nitro 5-chloro-phenyl amine with a malonic acid monoalkyl ester halide to obtain an N-phenyl-N-(2-nitro-5-chloro-phenyl)- malonic acid alkyl ester amide, and subsequently reducing the nitro group according to the following reaction sequence:

O Alkyl Thus, the preparation of an N-phenyl-N-(2-nitro-5- chloro-phenyD-malonic acid alkyl ester amide of the formula IV is carried out, for example, by heating a solution of N-phenyl-N-(2-nitro-5-chloro-phenyl)- amine in a suitable solvent, such as benzene, toluene or xylene, with a malonic acid ester halide, whereby the nitro compound IV is always obtained with good yields (80 percent) and in crystalline form.

The subsequent reduction of compound IV may be effected by nascent or catalytic hydrogenation, for example, by hydrogenation with Raney-nickel or with a mixture of iron and glacial acetic acid.

For the cyclization to form the 5-phenyl-7-chloro-- lH-l,5-benzodiazepine-2,4end product of the formula I it is not absolutely necessary to start from an isolated compound of the formula 11; instead, the solution containing the hydrogenated intermediate product 11 may directly be treated with the cyclization agents mentioned above, after removal of the catalyst.

The starting compounds of the formula III may be prepared by conventional methods, for example, by catalytic reduction of the corresponding 2-nitrodiphenylamine, or analogous to the method described in Chem. Berichte, Volume 34, page 4204 1902), and Volume 37, page 552 (1904), that is, by cyclizing a 2- aminodiphenyl-amine with formic acid, alkylating at the nitrogen atom in the cyclization product by means of an alkyl iodide, and subsequently splitting the ring with an alkali.

The following examples further illustrate the present invention and will enable others skilled in the art to understand it more completely. It should be understood,

however, that the invention is not limited solely to the particular examples given below.

EXAMPLEl 1-( BJ-Iydroxy-ethyl )-5-phenyl-7-chlorol H- l ,5- benzodiazepine-2,4-(3H,5H)-dione by method A A mixture consisting of 28.6 gm (0.1 mol) of 5-phenyl-7-chloro-lH-l,5-benzodiazepine-2,4-( 3H,5H)- dione, 500 ml of methanol, 25 ml of water, 10-15 ml of ethyleneoxide and 1 ml of TritonBtmethanolic 35percent solution of benzyltri'methylammonium hydroxide) was stirred at room temperature for about 8 hours. Thereafter, the clear solution formed thereby was evaporated, the residue was taken up in methylene chloride, and the resulting solution was extracted with water, dried and evaporated. The residue was recrystallized from ethanol, yielding 25.6 gm (78 percent of theory) of the colorless crystalline compound of the formula HOCH2CH2 O I /NG\ O I OH: 01

N 'JeHA \O having a melting point of 208-210 C.

EXAMPLE 2 1-(B-Methoxy-ethyl)-5phenyl-7-chloro- 1 H- 1 ,5 benzodiazepine-2,4-(3H,5H)-dione by method A 28.6 gm (0.1 mol) of 5-phenyl-7-chloro-1H-l,5- benzodiazepine-2,4-(3H,5H)-dione were suspended in 750 ml of absolute tetrahydrofuran, 5 gm of a 50 percent dispersion of sodium hydride in tetrahydrofuran were added to the suspension and the mixture was stirred for 2 hours at room temperature, whereby everything went into solution. 21-28 gm (0.15 0.2 mol) of ,B-bromo-ethyl methyl ether were then added to the solution, and the resulting mixture was refluxed for 15-20 hours. Thereafter, the reaction solution was evaporated in vacuo, the residue was admixed with water, and the aqueous mixture was extracted with methylene chloride. The methylene chloride extract was vacuum-filtered to remove insoluble components, the filtrate was evaporated, and the residue was recrystallized from isopropyl ether, yielding 22 gm (64 percent of theory) of the compound of the formula HzCO-CHz-CHz O Calls 0 having a melting point of 178-180 C.

EXAMPLE 3 was prepared from 7-chloro-5-pheny1-lH-l,5- benzodiazepine-2,4-( 3H,5H)-dione and allyl bromide.

EXAMPLE 4' Using a procedure analogous to that described in Example 2, 1-[isopenten-(4' )-yll ]-7-chloro-5-phenyllH-l ,5 -benzodiazepine-2,4-( 3H,5H )-dione, m.p. l f th iormula.

i from 7-chloro-5-phenyl-lH-l,5- benzodiazepine-2,4-(3H,5l-l)-dione and isopenten-(4)- yl-l bromide.

EXAMPLE 5 Using a procedure analogous to that described in Example 2, 1-dimethylallyl-7-chloro-5-phenyl-1l-I-1,5- benzodiazepine-2,4-(3H,5H)-dione, m.p. 154-l56 19* h mula JuHu was prepared from 7-chloro-5phenyl-lH-l,5-

bezodiazepine-2,4-(3H,5H)-dione and dimethylallyl bromide.

EXAMPLE 6 Using a procedure analogous to that described in Exwas prepared from 7-chloro-5-phenyl-lH-l,5- benzodiazepine-2,4-(3H,5H)-dione and chloroallyl bromide.

EXAMPLE 7 Using a procedure analogous to that described in Example l, l-( l -hydroxy-propyl-2 )-7-chloro-5-phenyl- 1H- 1 ,5-benzodiazepine-2,4-( 3H,5H)-dione, mp. 192 195 C., of the formula Clla was prepared from 7-chloro-5-phenyl-lH-l,5- benzodiazepine-2,4-(3l-l,5l-l)-dione and propyleneoxide.

EXAMPLE8 Using a procedure analogous to that described in Example 2, l-(/3-methoxy-ethyl)-7-chloro-5-phenyl-1H- l,5-benzodiazepine-2,4-( 3H,5I-l)-dione, m.p. 175-178 C., of the formula ts 5555a 513;; ll 7 'h15i5 s" 5iiI i-in i ,s benzodiazepine-2,4-(3H,5H)-dione and B-methoxyethyl bromide.

EXAMPLE 9 EXAMPLE 10 Using a procedure analogous to that described in Example 2, 1-(,B-ethoxyethyl)-7-chloro-5-phenyl-1H-l,5- benzodiazepine-2,4-(3H,5H)-dione, m.p. -l37 C., was prepared from 7-chloro-5-phenyl-1H-l,5- benzodiazepine-2,4-(3H,5H)-dione and B-ethoxyethyl bromide.

EXAMPLE ll Using a procedure analogous to that described in Example l, 1-(B-dimethylamino-ethyl)-7-chloro-5-phenyl-lH-l ,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. l48150 C.; of the formula was prepared from 7-chloro-5-phenyl-1H-1,5- benzodiazepine-2,4-(3H,5H)-dione and B- dimethylamino-ethyl bromide.

EXAMPLE 12 Using a procedure analogous to that described in Example 2, 1-(/3-diethylamino-ethyl)-7-chloro-5-phenyl- EXAMPLE 13 Using a procedure analogous to that described in Example 2, l-(ethoxycarbonylmethyl)-7-chloro-5-phenyll H-l ,5-benzOdiazepine-2,4( 3H,5H)-dione, m.p. 159-l 60 C., of the formula was prepared from 7-chloro-5-Phenyl-1H-l ,5- benzodiazepine-2,4-(3H,5H)-dione and ethoxycarbonylmethylbromide.

EXAMPLE 14 Using a procedure analogous to that described in Example 2, l-('y -chloro-n propyl)-7-chloro-5-phenyl)- lI-ll,5-benzodiazepine-2,4-(3H,5H)-dione,m.p. l56l 58 C., of the formula dlCHzCH-2CH2 o M CH1 o1 flHfl g was prepared fF6 fi*IEii1Z5- 11E1T 1-1H-1,5- benzodiazepine-2,4-(3H,5H)-dione an 1,3-dichloropropane.

EXAMPLE 15 Using a procedure analogous to that described in Example 2, l-(methoxycarbonyl-allyl)-7chloro-5-phenylll-l-l ,5-benzodiazepine-2,4-( 3H,5H)-dione, m.p. l 72174 C., of the formula benzodiazepine-2,4-(3H,5H)-dione and methoxycarbonyl-allyl bromide.

Example 16 Using a procedure analogous to that described in Example 2, l-(B-ethylmercapto-ethyl)-7-chloro-5-phenyl l H- 1 ,5-benzodiazepine-2,4-( 3H,5H)-dione, m.p. 129-131 C., ofthe formula EEK was prepared from 7-chloro-5-phenyl-1l-1-1,5- b enzodiaiepine 2,4-(3H,5H)-Dione and B-ethylmercapto-ethyl bromide.

EXAMPLE 17 Using a procedure analogous to that described in Example 2, 1-('y-hydroxy-n-propyl)-5-phenyl-7-chloro- 11-1-1,5-benzodiazepine-2,4-(3H,5H)-dione, mp. 21 1-2l3 C., was prepared from 5-phenyl-7-chloro-1 H-l,5-benzodiazepine-2,4-(3H,5H)-dione and 3- chloro-propanol.

EXAMPLE 18 Using a procedure analogous to that described in Example 2, l-('y-piperidino-n-propyl)-5-phenyl-7-chlorolH-1,5-benzodiazepine-2,4-(3H,5H)-dione, m.p. 42- 459 .q lrqf mu au was prepared from 5-phenyl-7-chloro-lH-l ,5- benzodiazepine-2,4-(3H,5H)-dione and piperidino-npropyl bromide.

The compounds according to the present invention, that is, those embraced by formula 1 above, have useful phannacodynamic properties. More particularly, they exhibit very efl'ective psychosedative (tranquilizing) and anticon-vulsive activities in warm-blooded animals, such as mice, rats and dogs, coupled with low toxicity.

Particularly efiective are compounds of the formula 1 wherein R is w-hydroxy-alkyl, w-alkoxy-alkyl or dialkylarnino-alkyl, and especially l-(B-hydroxy-ethyl)-5- phenyl-7-chl0ro-lH-1,5-benzodiazepine-2,4-(3 H,5H dione, 1-( methoxy--methyl)-5-phenyl-7-chlorol H- 1,5-benzodiazepine-2,4-(3H,5H)-dione and 1(3- methoxy-ethyl )-5-phenyl7-chlorol H,- 1 ,5 benzodiazepine-2,4-(3H,5H)-dione.

For pharmaceutical purposes the compounds according to the present invention are administered to warm-blooded animals perorally or parenterally as active ingredients in customary dosage unit compositions, that is, compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one effective dosage unit of the active ingredient, such as tablets, coated pills, capsules, wafers, powders, solutions, suspensions, emulsions, syrups, suppositories and the like. One effective dosage unit of the compounds according to the present invention is from 0.0166 to 0.833 mgm/kg body weight, preferably 0.0833 to 0.42 mgrn/kg, and the daily dose rate is from 0.166 to 2.5 mgm/kg.

The following examples illustrate a few dosage unit compositions comprising a compound of the instant inspecified.

EXAMPLE l9 Coated pills The pill core composition was compounded from the following ingredients:

1,S-benzodiazepine-Z,4-(31'1,51-1)-dione 10.0 parts Lactose 28.5 parts Corn starch 15.0 parts Gelatin 1.0 parts Magnesium stearate 0.5 parts Total 55.0 parts Compounding procedure:

The benzodiazepinedione compound was intimately admixed with the lactose and the corn starch, the mixture was moistened with an aqueous percent solution of the gelatin, the moist mass was forced through a 1 mm-mesh screen, and the granulate obtained thereby was dried at 40 C. and again passed through the screen. The dry granulate was admixed with the magnesium stearate, and the mixture was pressed into 55 mgm-pill cores, which were subsequently coated with a thin shell with the aid of an aqueous suspension of sugar,talcum, titanium dioxide and arabic, and the coated pills were polished with beeswax. One coated pill contained 10 mgm of the benzodiazepinedione compound and, when administered to a warm-blooded animal of about 60 kg body weight in need of such treatment, produced very good tranquilizing and anticonvulsive effects.

The same I results were obtained when the benzodiazepinedione compound in the above pill core composition was replaced by an equal amount of one of the following benzodiazepinediones:

a. l-(y-Hydroxy-n-propyD-5-pheny1-7-chlorol H- 1,5-benzodiazepine-2,4(3H,5H)-dione;

1-(B-Methoxy-ethyl)-5-phenyl-7-chloro- 1H- 1 ,5- benzodiazepine-2,4-(3H,5H)-dione; or c. 1-(Dimethylamino-ethyl)-5-phenyl-7-chloro-1H- l ,5-benzodiazepine-2,4( 3H,5H)-dione.

EXAMPLE 20 Suppositories The suppository composition was compounded from the following ingredients: 1-(-y-l-lydroxy-n propyl)-5-phenyl-7-chlorolH-l,5-benmdiazepine-2,4-(3H,5H)-dione 10.0 parts Cocoa butter 1690.0 pans Total 1700.0 parts poured into cooled suppository molds, each holding 1,700 mgm of the mixture. One suppository contained 10 mgm of the ,benzodiazepinedione compound and, when administered by the rectal route to a warmblooded animal of about 60 kg body weight in need of such treatment, produced very good tranquilizing and anticonvulsive efi'ects.

Analogous results were obtained when any one of the other benzodiazepinediones embraced by formula I was substituted for the particular benzodiazepinedione in Examples 19 and 20. Likewise, the amount of active ingredient in these illustrative examples may be varied to achieve the dosage unit range set forth above, and the amounts and nature of the inert pharmaceutical carrier ingredients may be varied to meet particular requirements.

While the present invention has been illustrated with the aid of certain specific embodiments thereof, it will be readily apparentto others skilled in the art that the invention is not limited to these particular embodiments and that various changes and modifications may be made without departing from the spirit of the invention or the scope of the appended claims.

We claim:

1. A compound of the formula R1 0 l l wherein R is hydroxy-alkyl of two to four carbon atoms; haloalkyl of two to four carbon atoms; di(alkyl of two to four carbon atoms)amino-a1kyl of two to four carbon atoms; y-piperidino'propyl; alkoxy of one .to two carbon atoms-alkyl of one to four carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkyl of one to four carbon atoms; (alkyl of one to two carbon atoms)mercapto-alkyl of one to four carbon atoms; straight or branched alkenyl of three to five carbon atoms; (alkoxy of one to two carbon atoms)carbonyl-alkeny1 of two to four carbon atoms; or halo-alkenyl of two to four carbon atoms.

2. A compound according to claim 1, wherein R is w-hydroxy-alkyl of two to three carbon atoms, 7- chloro-n-propyl, ,B-di( alkyl of one to two carbon atoms)amino-ethyl, -piperidino-n-propyl, w-alkoxy of one to two carbon atoms-alkyl of one to two carbon atoms, ethoxycarbonyl-methyl, B-ethylmercapto-ethyl, alkenyl of three to five carbon atoms, y-methoxycarbonyl-allyl or 'y-chloro-allyl.

3. A compound according to claim 1, wherein R is w-hydroxy-alkyl of two to three carbon atoms, w-alkoxy of one to two carbon atoms-alkyl of one to two carbon atoms or B-di(alkyl of one to two carbon atoms)amino-ethyl.

4. A compound according to claim 1, which is l-(B- hydroxy-ethyl-iphenyl-7-chloro-1H- 1 ,5- benzodiazepine-2,4-( 3I-1,5H)-dione.

5. A compound according to claim 1, which is 1-( B- methoxy-ethyl)-5-phenyl-7-chlorol H- 1 ,5- benzodiazepine-2,4-(3H,5H)-dione.

6. A compound according to claim 1, which is lbenzodiazepixze-ZA-(BHISl-lidione. methoxymethyl-S-phenyl-7-chloro-lH-l ,5- 8. A compound according to claim 1, which is l-(B- benzodiazepine-2,4-( 3H,5H)-dione. dimethylamino-ethyl)-5-phenyl:7-chlorol H- l ,5-

7. A compound according to claim 1, which is l-(ybenmdlaZePme'2,4'(3H,5H)d1nehydroxy-n-propyl-5-phenyl-7-chloro-1H,l,5- 5

Claims

2. A compound according to claim 1, wherein R1 is omega -hydroxy-alkyl of two to three carbon atoms, gamma -chloro-n-propyl, Beta -di(alkyl of one to two carbon atoms)amino-ethyl, gamma -piperidino-n-propyl, omega -alkoxy of one to two carbon atoms-alkyl of one to two carbon atoms, ethoxycarbonyl-methyl, Beta -ethylmercapto-ethyl, alkenyl of three to five carbon atoms, gamma -methoxycarbonyl-allyl or gamma -chloro-allyl.
3. A compound according to claim 1, wherein R1 is omega -hydroxy-alkyl of two to three carbon atoms, omega -alkoxy of one to two carbon atoms-alkyl of one to two carbon atoms or Beta -di(alkyl of one to two carbon atoms)amino-ethyl.
4. A compound according to claim 1, which is 1-( Beta -hydroxy-ethyl-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.
5. A compound according to claim 1, which is 1-( Beta -methoxy-ethyl)-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.
6. A compound according to claim 1, which is 1-methoxymethyl-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione.
7. A compound according to claim 1, which is 1-( gamma -hydroxy-n-propyl-5-phenyl-7-chloro-1H,1,5-benzodiazepine-2,4-(3H,5H)-dione.
8. A compound according to claim 1, which is 1-( Beta -dimethylamino-ethyl)-5-phenyl-7-chloro-1H-1,5-benzodiazepine-2,4-(3H,5H) -dione.