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Studies on the Synthesis and Antitubercular Activity of Acyl Derivatives of Isonicotinic Acid Hydrazide

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(1)

I

Journal of Pharmacentical Society of Korea

13, 43^46(1969)

Isonicotinic a c id h y d r a z id e A cyl 룔 흠 텔

슘델 해한

(Received March 30. 1969)

I

H yun Kee K oh: Studies on the Synthesis and A n titu b e rc u la r A ctivity of A cyl D erivatives of Isonicotinic A cid H ydrazide

Five new acyl derivatives of isonicotinic acid hydrazide such as N- (2,4-dichlorophenoxyacetyl)-isoniotinic acid hydrazideCI), N-(p-nitroben- zoyl)-isonicotinic acid hydrazide (II), N-benzoylisonicotinic acid hydrazide (III), N-furoylisonicotinic acid hydrazide (IV) and N-Cp-aminobenzoyl)- isonicotinic acid hydrazide (V) were synthesized. They were obtained by the action of 2,4-dichlorophenylacetyI chloride, p-nitrobenzoyl chloride, benzoyl chloride, furoyl chloride and p-aminobenzoyl chloride with isonico­

tinic acid hydrazide in pyridine solution.

Evaluated for their in vitro antitubercular activity against Mycobaterium tuberculosis Har Rv N-furoylisonicotinic acid hydra2ide (IV) showed antitube­

rcular activity at ir/ml.

i

1921 부 에 31 텔의

그찰 1952:

« 하여 거외 1 0 S : 3~5

H. Meyer**

isonicotinic acid hydrazide (IN A H )

했하였으며

Hoffmann La Roche, Squibb

St

Bayer j|t

(히^에

INAH

®콩 ^ ® ? 늙Sffll 라는

15

* 되

.

니>

IN AH

mg/kg

하고

I t i

1 0 1

8~12mg/kg

계하면 혈:#하게

I t

®되

)

해육혹? 외 긴다

. '**

IS S

pyridoxal

IN AH

iS

|

Schiff

텔*

g!:*

Vitamin

7J

때문이라고 한다

.

이러한

10 eOMNNNt

쏘 척 " ^ " ] ^ \ "■ ^ ^

CH»OM CHO OOMMH-

P y r iio x in e l^rfdcw al

t

♦ College of Pharmacy, Seoul N ational University

**— 4 3

(2)

4 4

^ ;

Isonicotinic acid iiydrazide의

Asyl

Mftl*

^

S l S f P

'®^시 ;^,하

IN AH

Schiff s

«볼를 하는

-NHNH2

체 에

B

횟»를

schiff m m .

;었

i ^ i t

하는

s i£ 이

이러한

e

&

s

ft

t i

sodium isonicotinic acid hydrazicle methanesulfonate(IHMS), D-glucuronoIatone isonicotinyl hydrazone I I

있으며

^

;5

1

보^되고 있다

.

이런것은

IN AH

fci^

월씬 럼하고

Vitamin Bg

4~5 fg fi

잠류가 학 하 다

.

풀흠는

SBS

IN A H

5 S

acyl HP 2 ,4-dichlorophenoxyacetyl chloride, p-nitrobenzoyl chloride, benzoylchloride, furoyl chloride

p-aminobenzoyl chloride

f f

5 8

N-(2, 4-dichloropenoxyacetyl)-isonicotinic acid hydra2ide( \ ), N-(p-nitrobenzoy 1)-isonicotinic acid hydrazide( J ), N-benzoylisonicotinic acid hydrazide (U ), N-furoylisonicotinic acid hydra­

zide (IV)

N-(p-aminobenzoyl)-isonicotinic acid hydrazide (V

) 를 *닭하고

W

N-Furoyl isonicotinic acid hydrazide (IV )

H37RV

화하여 _ 블뾰한

e t

훨* 울 알았옴으로 펄송하는

.

* 홈가 ®한

® SS S

다옴과 같다

CONHMHt CON

0

1 ) R=

a

£}!?■

ffl 0 iy R-

y ) R*

n m

N-acylisonicotinic acid hydrazide

텔의

gt

IN A H 2g(0.015 mole)

pyridine 10m

/ 가

50m

/ 외

=

혁후라스크에 현탁시커고 이것에

종로 겠한

S

acyl chloride (2, 4-dichlorophenoxyacetyl chloride, p-nitrobenzoyl chlo~

ride, benzoyl chloride, furoyl chloride, p-aminobeiuoyl chloride) 0.015 mole

?

5 HF

하면서 천천히 넣는다

.

이때

S flS r t

13온

하며 효 해

이된다

.

30

;&참

^ S J g

의IN AH 률

a * 하고 S J iiK a i

:외물

( I , I , r&BiE

)

또는etherClL

Y

(3)

March. 1969 m m n m 4 5 —

숨축) 에 부으면

g l l

된다

.

초겠

t l

물로

EtOH

S i g l l

하였으며

ijg *

Table 1

같다

.

펠했

®

**

_hlB 5 ffi

isonicotinic acid hydrzide (IN A H

) 를 혈하여

0. Ir/rnl,. Ir/m l., lOr/mL, lOOr/ml•

도록 만든

Ogawa medium

mycobacterium tuberculosis HjyRti

a

37°C

28 S r^

f f

다옴 별후

t i K

IN AH

i t t

한바

N- furoylisonicotinic acid hydrazide (IV )

l^/m l

®

i

K

IN A H

[ 황한

형을 나타냈으며

lOOr/ml

에서도

Sn^iJfF

없었다

.

Table.

1

. Acyl Derivatives of Isonicotinic Acid Hydrazides

Compd.

No. R m .p .C O Appearance Yield(%) Formula Analysis(%)

Calcd.

of N Found

I 1

168-170

White Plate

85 C14H11N3O3CI2 12.35 12.60

S I

224—225 Pale yellow

Powder 87 C13H10N4O4 19.57 19.36

1 9

21 8-219 White Powder 75 C13H11N3O2 17.42 17.69

IV

214—215 white powder 63

CnHftNsOa

18.17 1 8.5a

V

J ?

7

176-178 yellow

powder

78

C

15

H

12

N

4

O

2 2 1 .8 6 22.13

T - O ^

IS

SI m tsi

1 . IN AH

5

헬의

acyl S fb

청을

S ®

시켜

isonicotinic acid hydrazide

5 ®

acyl

N-(2, 4-<iichlorophenoxyacetyl)-isonicotinic acid hydrazide(I), N-(p-nitrobenzoyl) isonicotinic acid hydrazide(II), N-benzoylisonicotink acid hydrazide (H I), N-furoylisonicotinic acid hydra- zide(IV)

N-Cp^andnobenzoyl)-isonicotinic acid hydrazide(V

) 률

하였다

.

2. IN AH

acyl S

IS

N-furoylisonicotinic acid hydrazide

N-(p-aminobenzoyl) isonicotinic acid hydrazide

pyridine

^ 표울

U S

t

부었울때

@6

항^율 릎으로 얻기가

H I®

하였으나

.

pyridine

첸 울

i i S

ether

붙흡울 다옴 물로 씻고

E tO H

jStfp

얻었다

.

3. 5

^- C2,4-dichlorophenoxyacetyl)-isonicotin^^

N- (p-ammobenzoyl)-i3onicotmic acid hydrazide(V

)의

m.p.

INAH(171®C), IHMS(166~168*"C)

m.p.

2 ©

하였으며

Kftfe C I J L i y V

) 는 모두

210°C U

창였다

,

(4)

4 6 —

M '

Isonicotinic acid hydrazide

Asyl

황휴텔숭]몇

^

f

ffi

4.

'S

"&J

^ N-furoylisonicotinic acid hydrazide (IV

) 는

A S

® ® HjyRt;

을 한 된을 나타냈다

.

W5E

2T5g

주신 숲혔

g

® » t

드러며 ?£흑숭환울 하여주

^

렸활을 하며주신

S

M S a R

K

W

론를

*

한다

.

References

1) Meyer.. Mally, Monatsch, 33, 400 (1912) 2) H.H. Fox, J. Org. Chem., 17. 555 (1952) 3) C.A. '47 2358d, 3929 ab (1953)

4) / N l, m m 10, 198 (1959)

o) U.S. Public Health Rep., 63. 1305(1948), 팬, 후 : 서 울;*:뽑 * 19 « 162, (1968)

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