JPS58154574A - Alkylene dioxybenzene derivatives and their acid addition salts - Google Patents

Abstract

NEW MATERIAL:An alkylenedioxybenzene derivative of formulaI m, n are 1-3 respectively; X is formula II (l is 0-2), formula III (R is H, lower alkyl, acyl, carbamoyl), formula IV (R' is lower alkyl), NHCO and its acid adduct salt. EXAMPLE:5- 2- (1,4-benzoxan-2-ylmethyl)amino ethylthio -1,3-benzodioxol. USE:It is used as a drug, because of its hypotensive activity. Its pharmaceutical effect rapidly develops and continues durably. Further, it is relatively weak in accute toxicity with high safety. PREPARATION:The reaction between a halogenoalkoxyalkylenedioxybenzene derivative of formula V (Y is halogen) and an amine of formula VI is carried out in a solvent such as dioxane at room temperature to 150 deg.C to give the compound of formulaI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to alkylene dioxybenzene derivatives and acid addition salts thereof that have a hypotensive effect.

The compound of the present invention has the general formula (I) of the lower manure. It is indicated by.

In the above general formula, vrr, nli! % Indicates an integer of J.

R' represents a hydrogen atom, a lower alkyl group, an acyl group or a carbamoyl group, and R' represents a lower alkyl group. Specifically, the lower alcoholic number 1 is, for example, a vertical prime number l~≦
Examples include:

Examples of the acyl group include vertical prime number/-Jo4.

The method for producing the compound of the present invention will be explained below.

The compound of the present invention has the following general formula (I) (in the above general formula, m, n, and I are m in the general formula (1),
It is obtained by the reaction of a halogenoalkoxyalkylenedioxybenzene derivative represented by n,] (synonymous with , Y represents a halogen atom) and an amine represented by the following formula (1).

The above halogenoalkoxyalkylene dioxybenzene derivative and amine react in a ratio of 1:1, respectively, but the reaction usually proceeds more smoothly when the amine is used in excess. Therefore, the amine is used in an amount of 7 to 10 mol per 1 mol of the halogenoalkoxyalkylene dioxyben.

Although the reaction proceeds satisfactorily even without a solvent, an inert solvent may be used to facilitate the reaction.

As the solvent, water, dioxane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, lower alcohol, or a mixture of two or more of these solvents is used.

Reaction temperature 11jti Not particularly limited, but usually from room temperature to 1r
It is oC.

The reaction time varies depending on the reaction temperature, the reactivity of the raw materials, and the type of solvent, but is usually in the range of 70 minutes to 10 hours.

A base Ill may be added to collect the hydrogen halide generated by the chemotactic reaction and accelerate the reaction. Examples of the bases include inorganic salts such as potassium hydroxide, potassium carbonate, sodium hydroxide, sodium hydroxide, and sodium carbonate, and tertiary organic amines such as pyridine and triethylamine. The amount used is usually 7 to 7 mol per 1 mol of the amine of formula (7).

In order to obtain a desired acid addition salt, after the reaction is complete, excess amine and solvent are removed by distillation or washing with water, and a strong aqueous base solution such as sodium hydroxide or potassium hydroxide is added to form the free alkylene dioxybenzene derivative. ,
The compound is then extracted with solvents such as ether, chloroform, benzene, and toluene. Further, by neutralizing by adding a desired acid, the desired acid addition salt can be obtained.

The alcohol used can be any acid commonly used to obtain an acid addition salt of a compound, such as inorganic acids such as cyclohydric acid, oxalic acid, sulfuric acid, phosphoric acid, and nitric acid, acetic acid, and succinic acid. , adipic acid, propionic acid, tartaric acid, 7-malic acid, ■
Examples include organic acids such as leic acid, oxalic acid, citric acid, benzoic acid, toluenesulfonic acid, and methanesulfonic acid.

In addition, the alkylenedioxybenzene derivative represented by the following general formula (in the above general formula, m and n are defined in general formula (1) and are synonymous with n) obtained as above. By reducing with a gold-hydride such as L1mlH4, the following general formula (in the above general formula, m and n are defined by the general formula (1) and 7j
It is synonymous with m and n. ) can be obtained.

In addition, in the presence of an alkylene dioxybenzene derivative represented by the general formula (It/), a benzyl/S ride and an inorganic base such as potassium carbonate or a tertiary organic ammonium such as triethylamine, in an inert solvent such as water, Acetone, alcohol.

By treating with dimethylformamide, dioxane, tetrahydrofuran, etc., H-benzyl represented by the following general formula (Vl) (in the above general formula, 1m' and n are defined by the general formula (1) and are nen and osha) derivatives can be obtained. This compound was prepared by the following general formula (in the above general formula, m and n are defined in general formula (1) It is possible to obtain an alkylene dioxybenzene derivative represented by

By treating a compound of general formula (■) with an alkanoic acid anhydride, an alkanoic acid halide, or an alkoxycarbonyl chloride (alkyl chloroformate) in a basic solvent such as pyridine or in the presence of an inorganic base such as potassium carbonate. , by treating the isocyanate in an acidic solvent such as acetic acid, or by treating it with an alkyl halide in the presence of an organic base such as triethylamine, or an inorganic salt such as potassium carbonate, or by treating the isocyanate with an alkyl halide in the presence of an organic base such as triethylamine, or an inorganic salt such as potassium carbonate; The following general formula (to) (in the above general formula, in, n and R have the same meanings as m, n and R in general formula (1) (except when R is a hydrogen atom) ) can be obtained. By hydrogenolyzing this under a metal catalyst such as palladium or platinum, the following general formula (IK) (in the above general formula, m, n, R
is as defined by general formula (1). However, R
Except when is a hydrogen atom. )) can be obtained.

In addition, these alkylene dioxybenzene derivatives are
Acid addition salts can be prepared in the same manner as above.

Specific examples of the compounds according to the present invention are illustrated below.

ter[-1((/,e-benzoxan-2-ylmethyl)ainocoethylthio)-/, J-benzodioxole! -[-1((t,a-benzodioxan-1-ylmethyl)aminocoethersulfinyl]-1,3-benzodioxole!-[-1((t,a-penzodioxan-1-ylmethyl) methyl)aminocoethylsulfonyl]-7,3-benzodioxole N-(co((/,bait-penzodioxane-coylmethyl)aminocoacetyl)-3,u-methylenedioxyaniline N-[ -1((t,U-benzodioxane-ylmethyl)aminocoethyl) -i,a-methylenedioxyaniline N-[-1((t,U-penzodioxane-ylmethyl)aminocoethyl) -N-foru-ru 3. Hiro-methylenedioxyaniline M-(co((t,a-penzodioxane-coylmethyl)amino]ethyl)-y-
Acetyl-J,%-methylenedioxyaniline N-(co(t,4t-benzodioxa/-1-ylmethyl)
aminocoethyl)-N-propionyl-J, Hiro-methylenedioxyaniline N-(J-((7,1'-benzodioxane-ylmethel)amino]ethyl]-γ-methyl-3, termethylenedioxy Aniline-3, bait-methylenedioxyaniline N-[λ-((/,bait-hensosioxan-ylmethyl)aino]ethyl)-M-propyl-!, bait-methylenedioxyaniline N- [co((/, Hiro-penzodioxane-coylmethyl)ahno]ethyl)-M-methoxycarbonyl-3,-1methylenedioxyaniline N-(J-[:(/, Hiro-penzo dioxane-coylmethyl)aminocoethyl)-N-ethoxycarbonyl-
3J-methylenedioxyaniline M-[J-((t, seapenzodioxane-coylmethyl)aguino]ethyl] -N-force λbamoyl) )
In the case where m=/, n'=t, the corresponding compounds where n is 4 and J are also all exemplified as compounds of the present invention.

≦-[λ-[(t, a-penzodioxane-coylmethyl)annocoetherthio) -t, a-benzodioxane 6-[λ-[(t, U-benzodioxane--ylmethyl) aminocoethersulfinyl]-/, seabenzodioxane 4-[-1[(/--be/zodioki?/-coylmethel)aξno]ethersulfol]-l hiro-benzodioxane M-[-1 (l--benzodioxane-ylmethyl)amino]acedel]-1--dimedelenedioxyaniline-[-1((t-benzodioxane-coylmethyl)adenno]ethyl)- J, @-dimelenedioxyaniline)i-[λ-((t,a-benzodioxane-ylmethyl)adenno]ethyl]-ken-phorζruJ,!-dimethylenedioxyaniline M-(-1[(/,-1pen7dioxane111ylmethel)anno]ether]-acetel-J,%-dimethylydioxyaniline N-
[Co[(/,dobenzodioxane-coylmethyl)amine]ethyl]-M-propionyl-! , Hiro-dimedelenedioxyae, Lin N-[Co((/, Bait-penzodioxane-coylmedel)aminocoethyl)-
M-methyl-3,--dimethylenedioxyaniline N-
[--C(/,bait-penzodioxane-coylmethyl)aminocoethyl)-M-ethyl-7,4t-dimethylenedioxyaniline N-(-1[(l1μmpenzodioxane-ylmethyl)aminocoethyl) )-N-propyl-j, B-dimethylenedioxyaniline N-(co[(/,Hiro-penzoquoxane-coylmethyl)adeno]ethyl)-M-methoxycarbonyl-J, li-dimethyledioxy Aniline N-[co((t,s=-pe/zodioxan--ylmethel)aminocoethyl)-N-ethoxycarbonyl-
3, Hiro-dimeteredioxyaniline N-[co((/,a-penzodioxane-coylmedel)amino]ethyl]-N-carbamoyl-3,F-
Dimethylenedioxyaniline The above examples are general formula (1)
In the case of mz co, n-/, corresponding compounds where n is co and J are also all exemplified as compounds of the present invention.

7-[co[(1,%-penzodioxane-ylmethyl)adenno]etherdeo] -t,r-penzodioxebine 7-[co[(l-penzodioxane-coyl) methyl)aminocoethylsulfinyl]-/r-penzodioxebine 7-[co((/, Hiro-penzodioxane-coylmethyl)aono]ethylsulfonyl]-l-nerpenzodioxebine N-( -1[(/-1penzodioxane-choylmethyl)aminocoacetyl)-S,a-)dimethylenedioxyanilineN-[co((/,μmpenzodioquinane-choylmethyl)a is nocoethyl )-i, u-trimeprenedioxyaniline N-[co[(/,bait-penzodioxane-coylmethyl)aminocoethyl)-M-hol-ken-ru-jl-hiro-trimethylenedioxyaniline M-(co(( /, dobenzodioquiten-co-ylmethyl)adenno]ethyl]-N
-acetyl-j,e-)rimethylenedioxyaniline N
-[-1((t,a-benzodioxane-ylmethyl)adeno]ethyl)-M-propionyl-3,4 to 1-trimethylenedioxyaniline −
Penzodioxane-ylmethyl)aminoethyl
-N-Methyl-3,μ-trimethylenedioxyaniline M-(-1[:(/,%-benzodioxane-coylmethyl)aminocoethyl) -N-ethyl-J,%-)
IJ methylenedioxyaniline M (-2-((z,
a-penzodioxane-ylmethyl)a-enno]ethyl]-fukiichipropyl-3, Hiro-trimethylenedioxyaniline N-(co[(/, penzodioxane-coylmethyl)akenno] ethyl)-M-methoxycarbonyl-3,sc-trimethylenedioxyaniline N-(-1[(1,bait-benzodioxane-11ylmethyl)adeno]ethyl]-y-nitoxycarbonyl-,
t, 4t-) Rimeteredioxyaerin Summer - [Co((/, Bait-Benzodione-Ilmetel)Akenno]Ethyl]-Fukiichi Carbamoyl-3-Trimethylenedioxyaerin or more An example is the general formula (1)
In the case of ml-J and nx/, all the corresponding compounds where n is co and J are also exemplified as compounds of the present invention.

Also included within the scope of the present invention are pharmaceutically acceptable acid addition salts of the above compounds.

The blood pressure lowering effect of the compound of the present invention will be explained below.

The antihypertensive effect of the compounds of the present invention can be examined by the following method.

That is, the animals were spontaneously hypertensive rats (8HR) (3
00-170f, ~7 months old) was excised using a catheter inserted through the caudal artery under ether anesthesia, and 1.
! After calculating the average pressure and heart rate before administering the drug, administer the drug every hour.
.

J, 10 da/kt was orally administered and the antihypertensive effect was determined;
It was expressed as the rate of decrease from the pre-administration value. The results are shown in Table 1.

In addition, the acute toxicity value (LDso) was determined using Tus.

It was calculated by the Litchfiela-Wilcoxon method, and the results are shown in Table 1.

As shown in Table 1, the compounds of the present invention exhibit a sufficient hypotensive effect upon oral administration of 3 to 1 kp, have rapid onset of efficacy, and have a sustained action. or.

Acute toxicity is also relatively weak, and considering the amount of medicinal efficacy expressed, it is presumed to be a very safe drug.

Table No. 1): Expressed as the maximum decrease rate from the pre-administration mean blood pressure measured by conventional blood pressure measurement of unanesthetized 8HR (spontaneous hypertensive rats).

Note: The structure of the compound is listed in the corresponding column in Table C.

Although the compound of the present invention can be administered by any method, the following method is preferably carried out.

i.e., subcutaneous, intravenous, and intramuscular injections.

Parenteral administration, such as intraperitoneal injection, and oral administration are also possible.

The dosage is determined according to the patient's age, health condition, weight, type of concurrent treatment, if any, frequency of treatment, nature of desired effect, etc.

Generally, the daily dosage of the active ingredient is 0. /~100 da/k
t weight 1 normal / -30■ / kt weight.

Administered 7 or more times.

When the compound of the present invention is administered orally, it is in the form of a tablet, tablet, capsule, powder, liquid, elixir, etc. When it is administered parenterally, it is in the form of a sterile liquid i-form such as a liquid or a suspension. When used in the forms described above, solid or liquid non-toxic pharmaceutical carriers can be included in the composition.

As an example of a solid phase, conventional gelatin-type capsules are used. It was. The active ingredient is packaged as a tablet or powder with or without adjuvants.

These capsules, tablets, and powders are commonly used in Kr~de! Yu,
Preferably -1-? Contains 09t weight of active ingredient.

That is, these dosage forms preferably contain the active ingredient of 100ml of tlil Mikoko IO Misaki.

As the liquid carrier, water or petroleum, animal, vegetable, ultra-thick, or synthetic ponds such as peanut oil, soybean oil, mineral oil, sesame oil, etc. are used.

Also commonly saline, dextrose or similar sugar solutions, and ethylene glycol.

Glycols such as propylene glycol and polyethylene glycol are preferred as liquid carriers, and in particular, in the case of injections using physiological saline, the active ingredient is usually 03 to -09 g, preferably ij / - / 0 - weight. do.

In the case of solutions for oral administration, suspensions or syrups containing o,5-to-96 weight of active ingredient are preferred.

The carrier used in this case is a flavoring agent, a syrup, or an aqueous vehicle in the form of pharmaceutical micelles.

As explained above, the compounds of the present invention can be effectively used as antihypertensive agents.

Example / N-(J-p roloprohionyl)-J, μm methylenedioxyaniline (/θf) t-dimethylformamide (
rOd), bait-benzodioxane-choylmedelamine (r,7F) and trietheramine (
/,? f ) and ! Stir at θC for 40 hours. After the reaction is complete, water is added and extracted with ethyl acetate. After washing with saturated brine, drying with anhydrous sodium sulfate, and distilling off the solvent. The resulting residue was dissolved in ethyl acetate, 10% hydrogen chloride/ethyl acetate was added, and the resulting crystals were poured into a PBS and recrystallized from ethanol to give N-(j-((/, bait-
Penzodioquinan-choylmethyl)annocopropionyl]-3,4t-methylenedioxyanili/hydrochloride (
ij, yf, 779G yield).

The physical properties of this compound are shown in the corrosion column of Table 1.

Example Co N- (J- After dissolving penzodioxane-ylmethyl)amino]globionyl]-J,-mesolenodioxyaniline!, σf in acetone 4ONl, anhydrous potassium carbonate/, FW and benzylbromidena, O2
and stir at room temperature for an hour. Thereafter, the reaction mixture was dried under reduced pressure, and ethyl acetate and water were added to the residue to separate the mixture into 1 layer. The ethyl acetate layer is washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and dried under reduced pressure to obtain a syrup.

Next, this syrup is dissolved in tetrahydrofuran O-, and added to a suspension of lithium aluminum hydride/f of tetrahybee 7 lancona ds, and stirred under reflux for a period of time.

The reaction solution is treated in a conventional manner, and after removing the insoluble portion P, solution F is dried to dryness under reduced pressure, and ethyl acetate and water are added to the residue to separate the layers. After that, the mixture was washed with saturated saline and anhydrous sulfuric acid). After drying with IJium, ethyl acetate was dried under reduced pressure to obtain N-[7-(N-benzyl (1, bait-penzodioxane-choylmethyl)).
aminocopropyl] -i, a-methylenedioxyaniline/0. /f as syrup. (yield λ
J*) The physical properties of this compound are shown in column A6/ of Section-2.

Example 3 N-[7-((/,gubenzodioxan-λ-ylmethyl)amino]glopyl]-y-acetelium 3.Termetere/dioxyaniline/hydrochloride N-[7-(N-benzyl(/, Dobenzodioxane-ylmethyl)amino]globil]-3. Bait - After dissolving methylenedioxyaniline j, l17 f in pyridinco 1, add Wil to acetic anhydride under ice-cooling, and stir for μ hours at room temperature. Thereafter, the reaction solution is dried under reduced pressure, and ethyl acetate and water are added to the residue to separate the layers.The ethyl acetate layer is
Wash sequentially with an aqueous sodium hydroxide solution, water, and saturated brine, dry with anhydrous sulfuric acid and thorium, and then add -0-hydrogen chloride-ethyl vinegar under cooling with water. After dissolving the precipitated crystals in F*,
Normally mixed with palladium black.

Measurement is carried out using hydrogen for 4 hours under stirring at normal pressure. Before and after catalyst P, the P solution was dried under reduced pressure, and the residue was crystallized from a7to/-ethyl ether to give N-(J-((/, &-henzodioxane-ylmethyl)aminocopropyl)- N-acetel-J--methylenedioxyaniline hydrochloride/,
Get It.

(Yield deλ,!4) The physical properties of this compound are shown in column /I67 of Table 1.

Examples include M-(j-[(i,y-penzodioxane-coylmethyl)aminocopropyl)-N-methyl-3-1 medelenedioxyanilincohydrochloride N-(i-(w-benzyl(t , a-penzodioxane-ylmethyl)benzylamino]globil) -J
, 9t-methylenedioxyanilinco, or after dissolving in 1011 acetonitrile,! 7 arrogant formalin 8 will
and sodium cyanoborohydride were added, and the mixture was stirred at room temperature for 11 minutes. Thereafter, the mixture was stirred for 1 hour while being neutralized with glacial acetic acid. Thereafter, the reaction solution was dried under reduced pressure, ethyl acetate and water were added to the residue, and the layers were separated. Ethyl acetate II
After washing the mixture with water and saturated brine sequentially and drying over anhydrous sodium sulfate, hydrogen chloride-ethyl acetate was added under ice-cooling. After collecting the precipitated crystal t-F, it is dried to obtain the methyl form. (1111)/Det-3C) Next, this product is dissolved in co-O-water-too much ethanol, and then reduced with hydrogen for 5 hours under stirring at room temperature and pressure in the presence of palladium black. Before and after the catalyst door, the P solution was dried under reduced pressure, and the residue was crystallized from acetate/M-(J-((/, bait-penzodioxane-choylmethyl)ano]propyl) -N
-Methyl-3, cimethelenedioxyaniline chloride lI
Obtain 2f of I salt. (Yield: ≦-) The physical properties of this compound are shown in the column labeled "Scrap A" in Shishi-1.

Example j ii -(J-[(i, Bait-penzodioxane-choylmether)amino]propyl]-N-carbamoyl-3
,9t-methylenedioxyaniline-[i-[N-pe/dyl(/,bait-benzodioxane-ylmethyl)ano]propyl]-3. After dissolving Hiro-methylene/dioxyanilinco in 10 d of glacial acetic acid, add 1 μt of sodium isocyanate while cooling with water, and at room temperature! Stir for an hour.

Thereafter, the mixture was neutralized with an aqueous sodium hydroxide solution, and ethyl acetate was added to separate the layers. acetic acid nibble layer.

Wash sequentially with water and saturated brine, dry with anhydrous sulfuric acid (V) ram, and dry under reduced pressure. Ethyl ether is added to the residue, and the precipitated crystals are dried to obtain a carbamoyl compound. (mpz co-o-1c) Next, add this material to ethanol t
00dK, dissolved firefly.

After adding 0 Ls of hydrogen chloride and ethyl acetate under ice-cooling to form a hydrochloride salt, reduction with hydrogen is carried out under stirring at room temperature and pressure for 4 hours in the presence of palladium black. Catalyst - front and back, P
The liquid was dried under reduced pressure, and the residue was made alkaline by adding an aqueous N-sodium hydroxide solution, followed by extraction with ethyl acetate.

After separating the layers, the mixture is washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and then dried under reduced pressure. The residue is crystallized from ether to obtain N-(J-((/, Hiro-benzodioxane-choylmether)amino]propyl]-N-carbamoyl-31 μm methylenedioxyanilinpana V.
Yield/%, JH) The physical properties of this compound are shown in the A6r column of Table 2.

Examples ≦ y-(3-(: (t, bait-benzodioquinan-choylmethyl)aminocopropylthio) -t,r-benzodioxebine/hydrochloride 7-(J-bromopropylthio) -/, Narpenzodioxepinco, Of 1kN, After dissolving in 10d of N-dimethylformamide, add Coannometheru/111L-Hinzodiomeisan 8jf and triethylamine Co-, and stir at roC under nitrogen atmosphere for 2 hours. After cooling, water was added, and the precipitated oil was extracted with ethyl acetate. After separation, water,
Wash sequentially with saturated saline and dry with anhydrous sodium sulfate.

Ethyl acetate was dried under reduced pressure, ethyl ether was added to the residue, and after dissolving, hydrogen chloride-ethyl acetate was added under ice cooling. The precipitated crystals tF were collected and recrystallized in ethanol to give 7-(J-[(1,-1penzodioxane-choylmethyl)aminocopropylthio)-/, napenzodioxepin l hydrochloride. Get 2f. (yield y r,
7-) The physical properties of this compound are shown in column 716/f of Table 1.

Example 7 7-[J-((/,9t-benzodioxan-ylmethyl)aminocopropylsulfinyl) -1,1-
After dissolving penzodioxepin l hydrochloride 2-(J-bromopropylthio)-i,t-penzodioxepin J, Of in 10@water-acetic acid tyd,
While cooling with water, add 10% hydrogen peroxide solution. Thereafter, the mixture was stirred for 30 minutes under water cooling and for 1 hour at room temperature. Then reaction 11
Cooled with water for 1 hour, neutralized with saturated aqueous sodium hydrogen carbonate solution,
Precipitated oil.

Extract with benzene, separate for 1 minute, wash sequentially with water and saturated brine, and dry over anhydrous sodium sulfate.

Dry the benzene under reduced pressure to obtain a syrup. Next, 1. After dissolving this syrup in N,N-dimethylformamide/ld, co-aminomethyl/,%-benzodioxanco, Of and triethylamine J- were added, and 9! , in the basic atmosphere under ROC? Stir for an hour. After cooling, water was added, and the precipitated oil was extracted with ethyl acetate. After 1 separation, the mixture was washed successively with water and saturated brine, and dried over anhydrous sulfuric acid. Ethyl acetate was dried to dryness under pressure in an upper region, and the remaining residue was added with ether and ether. After dissolution, 20% hydrogen chloride-ethyl acetate was added under ice cooling. The precipitated crystals were collected, recrystallized from acetone, and
-(3-((/, Bait-penzodioxane-choylmethyl)annocopropylsulfinyl) -t,t-benzodioxebine/hydrochloride 3.3f is obtained. (Yield 7
j, I%) The physical properties of this compound are shown in column A/6 of Table 1.

Compounds were produced in the same manner below, and the physical properties of the obtained compounds are shown in Table 1 together with the above compounds.

Continuation of page 1 [Phase] Inventor: Kenichi Nakao 4-18 Soshigaya, Setagaya-ku, Tokyo No. 24 0 shots clear by Kanno Mamoru 5-3 Komazawa, Setagaya-ku, Tokyo ground 7

Claims (1)

[Claims] (11 General formula (1) [In the formula, ma and n represent integers of 1 to 3, or a hydrogen atom, a lower alkyl group, an acyl group, or (R' represents a lower alkyl group) ) or -NHOO-] and acid addition salts thereof.