Journal of Medicinal Cheniisirii, l W 1 , Vol. 14, iYo. 10 1005
NOTES
-Aminch---1%1,
I
Yield,"
n
KO.
____ Hydrochlorides----
(rnrri),
%
A1 I > ,
'
nip, o
"(
c
110- 11I
14M-144 ( 2 . 0 ) 134-1:3*i ( 0 .1.7) 130-131 ( 1 . 0 ) 150-1?52 ( 0 . 2 ) 16S-169(0.3)
104-10.5 82-8:3 82-44 2 rT 123-126 XO 89-90 3 11 130- 131 71 109-110 4 I1 127-128 7.i 107-108 .i II 133- 134 76h 106-107 6 TI 117-1 18 80* 82-83 7 1% 134-136 (0.3) 126-127 113-114 90 '3 CIT3 l,52-lfi3 ( 0 . 3 ) 102-103 93 96-98 9 cIf3 127-128 131-132(0.4) 95 109-111 IO crr3 132-133 162-164 (0.3) s4 120-121 11 CTI3 120-121 8 .i 177-179(0.4) 12 CHS 92-93 143-144(0.6) 131-132 93 118-119 13 C1 15.5-1.56 (0.4) 10.5-106 84 96-97 14 C1 173-17.5 (0.3) 13.5- 136 76 132-133 15 C1 195-197 ( 0 . 6 ) 122-123 71 146-147 16 C1 16 3- 166 86* 108-109 17 '2113 Purified bases. * Unpiirified bases. c Oxalates were arialysed for C, H, N and hydrochlorides for N, S, C1. obtained for those elements were within &0.4% of the theoret value. Calcd for total C1. x7 X2
I1
1
TIELF: PI1I.LIMIN IRY PH.LRM.lCOLOGIC
Major overt effect
Motor deficit, ataxia, CXS depression Motor deficit, ataxia, CNS depression Motor deficit, ataxia, CNS depression Motor deficit. ataxia, CNS depression Motor deficit, ataxia, CNS depression, decreased muscle tone CNS depression, decreased locomotion CNS depression, decreased locomotion CNS depression, ataxia CNS depression, ataxia CNS depression, ataxia CNS depression, ataxia CNS depresqion, motor deficit Ilecreased locomotion Decreased muscle tone Low carriage, ataxia CNS depression, motor deficit Decreased locomotion
..i 6
4 5
> 100 > 100
6 7 8 9
> 100
> 10
>loo > 100 > 100 89.1 > 100 > 100
>10 >.i.6 >17.6 50.1 >10 >17.8 >.i.6 >3.2 >d.6 >17.8 >5.6
79.4
10 10 17.8 5 .6 10 1.8 11 10 5 .6 12 13 17.X 14 > 100 31.6 > 100 1.8 1.5 16 > 100 .i .6 > 100 17.8 17 ]lose levels are in mg/kg of body wt.
>\lOUSl: SCREKiX'
>17.8 > 10 2A.1 > 10 >5.6
nIEDso
> 100 > 100
10.0 3.2 10.0 17.8
I1
ACTIVITY. PItIMARY
L Dso/l\l E Dsa
LDso
1 2 3
NO.
FormulaC
CizH&lN02S CiaHv2ClNOzS Ci3HzoClNOzS CijH,zClNO,S CiaHzoClN03S CizHi sClN20S Ci4Hz3ClNzOS Ci3HzoClNOzS Cr5H24ClNOzS CI4Hz2CINOzS C~~HZ~C~NO~S CijHzzClN03S Ci3HigClzN02Sd Ci,HziClzNOzSd CijH2iC12N0zSd C14Hi9Cl N03Sd C13HziClN20S The anal results
Duration of effect, min
60 60 60 60 30 60 60 30 30 30 60 60 60 60 60 60 60
was employed to calc the minimal effective dose (MEI)50). The ratio of the median lethal dose ( L 1 ) j O ) to the lfEl)~o was detd for each cvmpd. Preliminary pharmacologic evaluations are listed i n Table 11.
we were attracted by published data's2 on certain 1-azaphenothiazine derivative^.^ In particular 2-(diisopropy1amino)ethyl I-azaphenothiazine-lO-thiolcarboxylate (1, Table I) was reported to have an anticholinergic activity 8 t'imes that of atropine and a spasmolytic activity 9 times that^ of p a p a ~ e r i n e . ~ Neuropharmacological Profile of In addition to establishing a pharmacological profile 1-Azaphenothiazine-10-thiolcarboxylates of 1 we studied the compds 2-6, which were derived ";DW.ZRD R . ATKINSON, * P,\MI.:L.\ L. ItLTSS, ?Vl.\RG.\RET A. TUCIWR, from other a,minothiols, and also 4 substitution products (7-10) of 1. The substituent groups in 7-9 were Arthur D. Little, Znc., Cambridge, ,llassachusetts .\ND FR.\NI
