Joiirnd of Jlcdicind Chemistry, 1.970, Vol. 1.3, A\vo.5 977
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15, arid bemegride had EDSOlb of 10 mg/kg sc or lehs, 1, 3, 7, 10, 11, 12, 14, and 16 had EDjOfs of 11 to 3.5 mg/kg sc, and 4 was inactive. Further testing in the rat of the 4 most active compounds by the tail flick method6 and the AgSOo inflamed joint test7 indicated that none of these compounds possessed significant analgetic properties. The results of analeptic screening show that 8 and 13 compare favorably Ivith bemegride as analeptics, and warrant further evaluation in the CSS area. Experimental Section
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1-Formimidoy1indolines.-A solution of eqiiimolar amounts of indoline and appropriate amide i n I ,2-dichloroethane [250 ml (0.1 m)] \Tab treated dropni5e n i t h an equimolar solation of POC1, in 1,2-dichloroethane [50 ml (0.1 m)] over a period of 0.5-1 hr. The mixture, after being stirred for 15 hr, was poured onto crushed ice, and made qtrongly basic with 20% KaOH with stirring. The organic layer ?I as separated and extracted with dilute HC1. The acid solution mas made basic with 2070 NaOH and extracted again (EtnO). The extract was concentrated to obtain the crude product. The HC1 salt nas prepared in the usual manner and recrystallized from appropriate solvent as shown in Table I.
Acknowledgment.--We wish to thank Nessrs. L. E. Allen, T. J. Eaton, T. C. JIays, Jr., J . F. Purcell, Jr., T. F. Williams, Jr., and R. A. Winnecke for their technical assistance. (6) IT. R. Bass and .\I. J. Vander Brook. J . d m e r P h n r m A b s Scz. Ed., 41, 569 (1952). (7) A. LrtDrPle and H . Tisloir, J . Pharmncol. E r p . Ther.. 98, 19 (1950).
Synthesis of Some Local Anesthetics P. K. SRIVASTAVA AND P. S . SRIVMTAVA Department of Chemistry, University of Roorkee, Roorkee, India E
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Received April 22, 1970
It has been found by many workerslV2 that the ebsential structure requirements for a local anesthetic are a lipolytic end containing an aromatic nucleus, a hydropilic end consisting of a tertiary amino group, and an intermediate alkyl or substituted alkyl chain. Compounds having a dialkylamino alkylamino group connected to an aromatic or heterocyclic nucleus as a lipolytic moiety confer greater activity and less toxicity. Therefore, it was thought worthwhile to synthesize some pyridine-2-aminoacetyl-2-aminobenzothiazoleand N , N-diethylanilino-p-aminoacetyl- 2 - aminobenzothiazole derivatives, by condensation of chloroacetyl chloride with different 2-aminobenzothiazole~ followed by treatment with 2-aminopyridine and p-amino-N,N-die thylaniline, respectively. Experimental Section Different 2-aminobenzothiazoles were prepared according to Hugershoff . g Chloroacetyl-2-aminobenzothiazoles were prepared by known methods.' Pyridine-2-aminoacetyl-2-aminobenzothiazole.-2-Chloroacetylaminobenzothiazole (5g) dissolved in EtOH (30 ml) was added t o 2-aminopyridine (3 g) dissolved in EtOH (20 ml) and the reac( 1 ) F. F. Rlicke and H. C'. Park, J . A m e r . Chenr. Soc., 61, I200 (1939). (2) A. .\I. XIattocks and 0. 9. IIutcliinson, i h i d . , 70, 34i4 (1048). ( 3 ) .i. Hugerslioff. Chem. B m . . 34, 3130 (1901); 36, 3121 (1903). (4) P. N.Bliarya\-a and G . C. Sinrli, J . Irtdtirn Chsm. SOC.,98, i i (1YB1).
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w~1brefluxed f u r ti fir. lixcess EtOH was distilled arid the residue was washed (Ir;aHC03, H20). The product \vas crystallized from EtOH, m p go", yield 4.9 g. 2-Amino:icetyl pyridine dei,ivatives of other 2-arniiirjt)erizothiazoles wcrc ~)tvp:iretl ~ i i i i i l d ~ T~ l.l r i l , h~
