Sovember, 1963
CHEMOTHERAPEUTIC ~ I T R O F U R A S S .
Ix
Chemotherapeutic Nitrofurans. 1X.l 2-[l-Acyl-2-(5-nitrofurfurylidene)hydrazino]acetamides I:R.~NK F. EBETINO, WAKKESF. CARET,ASI)HEXJAMISF. STEVESSOA Eaton Laboratories Dicision, The .Vorwich Pharnzacal (‘ompany, *Yorwich, ‘Yezo York Received M a y 6, 1963
A serieE of 2- [ l-acy1-2-( 5-nitrofurfurylidene)hydrazino]acetariiideshits been syntliesi/;ed and tested for antibacterial activity in mice. Structure-artivity relationships are developed. 111a continuing program on the synthesis of potential chemotherapeutic nitrofurans, it was of interest to prepare 2-(S-nitrofurfurylidenehydrazino)acetamide (1) and some derivatives of this compound. 111ethyl hydrazinoacetate hydrochloride was readily converted to the corresponding amide in coilcentrated aiiimoiiium hydroxide solution, and the amide was reacted without isolation with 5-nitro-2-furaldehyde to give a 720 921 1
>280/>20 82/3 210/1
16b/L'O
>280/%0 >280/> 20 >1020/10 >210/6
Dialkylattiino
S (C~HO):!
13615
>s40/>20
COCH3
3G7/3
>840/>20
H
COCH3
sT / 3
H
COCHI
H H
0
H
0
H
SCHz( CH2)aCHz E.
.ir>latiiino
d.
.icylarnino
e.
Hydroxyl
COCH3
"CsH6
COCH3
168/3
>840/-
NHCOCH,
H COCHi
100yo mortality in 2 to 3 days in the control groups. Varying amounts of each compound (limited by toxic considerations) were suspended in 0.757, carboxy-
OH OH
113/0 6
>
120/>20 >1020/>20
>840/>20 >600/>1O
>840/-
>1320/5 >l20/>20 >1020/>20
methylcellulose and administered orally 30 min. after infection. The criteria for activity adopted here includes graded dose-survival relationships. The
ring and cooling until just basiv. wished with benzene and water.
The solid w s filtered and
Acknowledgment.-The authors are indebted to Mr. \YArren 0. Smith for assistance in the synthetic work. to
Dr. John C. Ho1val-d for preparilig (aonlpoulid 31, to the Microbiology and Physical and A\iialytical sections for supplying the biological, aiiulytic~al.and ultraviolet absorption data.
N - M o n o - and N,N-Dialliyl-N'-1-naphthylalkylenediamines
Research Laboratories, Parke, Davis and Company, Ann .4rbor, Jlichigan
Rtcriced March 12, 1963 Aiseries of S-mono- and S,N-di:illi~~l-S'-l-~iaphthylalk~lrnedianiirles were prepared by: ( 1 ) alk!.lation of 1-naphthylamine lyitli an alkylaniinoalkyl halide : ( 2 ) reducstive alkylation of 1-naphthylamine with an amino with an amine: ( 4 ) reaction of 1aldehyde or ketone; ( 3 ) treatnwnt of a S-(o-haloaI~yl)-I-naphthylamine naphthol Fith an slkylenediamine: ( 5 ) tlie action of ethylene oxide, aldehydes, or alkyl halides on a X-(lnaphthy1)ethylenediamine. The use o f sodium hydrosulfite in the Bucherer reartion with l-naphth,)l is descrihrd. 1-(1-Saphthy1)aziridine was prrparcd l)y t i l e action of strong base on S-(~-hromorthyl~-l-na~~hth~laniitir,
During the course of coiitiiiuiiig effort.; ill thede Laboratories to develop nen- schistosoinicidal agents, it was discovered that various 4-(aminoalkj lainiiio)-lnaphthylazo heterocyclic compound5 ot I (1957). (10). J. P. Mason and H. W.Block, ibid., 62, 1443 (lS401. (11) S.Gabriel and J. Colman, Ber., 39, 2879 (1906). (12) 0. Magidson and I. T h . Strukor, d r c h . Pharm.. 271, 569 (1938). (13) S.-T. Lu, C.-K. Liu, C.-S. Yang, T.-H. Chu, and C.-C. Cliaiie, Hua Hsueh Hsueh Pao, 22, 589 (1956); Chem. Abstr., 62, 12866a (19%1. Kaye, .I. d m . Chem. S o r , . . 70, 128:3 (19481.
TH-Y-NH2
X
