Diazo, Bromo, and Mesyloxy Ketones as Biological Alkylating Agents

September 1965. Biological Alkylating Agents. 657. Table I. Indole Derivatives. Kt^x. No. K. X. M.p., "C. Formula. I. H. 3-COCOCHN,. 148-150 dec. CnH7...
1 downloads 0 Views 478KB Size
Uiazo, Bronio, and Jlesyloxy Ketones

ab

Biological _~lkylatiiig iigentsiCL

657

BIOLOGICAL ALKYLATIXG AGENTS

September 1965

T.4BLE

1

INDOLE DERIVATIVES

I

H hI.p., "e.

x

H.

Nu.

yo calcd.

Formula,

54 found

-----

Infrared, f i - - - SEN C=O ROS02CH3

NH

I I1

H H

5-COCOCHNZ 3-COCOCH2Br

148-150 dec. CllH;N302 N : 19.71 148-149 Cl1HsBr?jO2 Br : 30.04

19.52 3 . 0 8 s 30.29 3 . 0 7 5

4.70s

I11

H

3-COCOCHzOSO&Ha

197-198

Ci2HllN068

11 40

11.163.06s

...

11T

CHaO 3-COCOCHKS CHaO 3-COCOCH2Br

150 dec. 177-178

C12HgN303 E: 17.3.5 C12H10BrN03Br: 26.99

17.54 3 . 1 0 s 27.20 3 . 0 5 s

4.72s

TI

CHBO 3-COCOCHzOS02CH3

205-206 dec. CI3H13N0& S:

10.31

10.703.10s

... ...

TI1 VI11 IX

H H H

166-167 dec. C10H7~30 N : 22 69 130-131 CloH6BrN0 Br: 33.56 148-150 C ~ I H ~ ~ N O IS: S 12.66

22.51 3 . 0 7 s 33.36 3 . 0 2 s 12.62 2 . 9 8 s

4.77s

8-COCHK;, 2-COCH2Br 2-COCH20S02CH3

S:

,

..

,

..

...

,

..

...

6.30s 5 . 8 0 ~ 6.25 s 5.78m 6.29s 6.42s 5.82~6 . 3 0 s? 5,80w 6 . 3 7 s? 6.05, 6.09s 5.98s

... ... 7.38s

8.58s ... ... , , . 7.39s 8.60s ,.. ...

7.45s 8.55 s

TABLE I1 MCCICACIDDERIVATIVES RO H H OK.

I I

I

I i I 1

Xco-c--c-c-c-cox

RO OR

H R

X

X XI XI1

CHIC0 CH3C0 CHSCO

CHK2 CH2Br CHzOSOzCHa

180-181 dec. 164-1 66 193-194

XI11

H

CHNz

163-165 dec.

NO.

mp.,

%

C'

calcd.

found

NZX

c=o

C16H&4010 s: 13.14 C1QH20Br2010Br : 30.04 Ci6H26O1&2 s: 11.41

12.95 30.08 11.31

4.72 s

...

5.72 s 5.75 s 5.75s

C ~ H I O S ~ O , N : 21.72

21.30

4.72 s

6.20 s

Formula

oc.

cedures.'g I n addition compounds 1-111 were screened for in vitro cytostatic activity on He-La cell cultures. Results for the indoles are shown in Table 111. All compounds were inactive in vivo at near-toxic doses. In v i t ~ ocytostatic activity was shown only by the bronio ketone I1 a t 1 g./nil. TABLE 111 In Vivo

AND

in Vitro

h C T I V l T Y O F I N D O L E L)XRIVATIVES

50%

No.

I I1

I11 IV V VI VI1 \TI1 IX

Tumor inhib. T/C

He-La inhib., y/ml.

0 0

10

0 0 0 0 0 0 0

1

10

ka,o X 10-4 hf sec.-l ("C.)

2.3(20) 8.9(20) 9.0(50)

.. .. .. .. .. ..

kg,os X 10-4 M sec.-1 ("(2.)

410 (20) KO reaction 3.3(50)

T

with nitrobenzylpyridine, 10-4 .Tf

0.07 0.01 1.10