:it present a better case for radicd effect, but :tlso for other niolecular configurations containing C--1-1 bonds adjacent to functions 1i:Lving high r:idic:il st:ibilizirig :bbilitj-. Rccent ly, f u r t h w t~vidc~iictc~ tor the t osophoric cliais:tctrr of thc betizj.lic H i l l chlor:t.niplieriicol comw from :in elegant study b!. I\utter : i t i d (;:trrett.4’i Tho d e u t e r o a n d o g of ch1oranipht:nicol \v:ts synthesized in Kutter’s laboratory, :d then its atitib:tcterial wtivity tested bj. tlir niicrohi:d liitirtic niethocl~ i i i (2arrett’s laborLitoi~j.. .{ti isotope' vffect of 1.1 \v:ts found; that isj t l i r s 1) :tti:ilog i v w coiisic1cr:ibly I t w :icti\e th:iti tht. p t i * t l t i t H-coilt:iiiiiiig (Iriig. 7‘1iis ost:Lblislitls t h y iiivolvvnirtiit of t l i r ~ a-11 :itotn i t i t l i ( t toxicity of thew conipouitcls t o 1;. ~ ~:is ii)i.t:clictcd.4 i (’t’nig : t i i d ~\Ic.\l:~lioti h:tv(> ~ ( I I I o ~ Y Y up I tlirir studiw on tht. microsom:il oxitlatioti of cu-tlt~ritct~ot~tliylbc~ti~eii~~ arid h:ivc s h o w t P that t h t J i . i I i h :iii isotopcl c$t’ect i i i this process of 1 .X. I t is t~sti.c~mt~l>interestiiig that the size of the isotope eft’tvt is roinpar:tblt~ i i i the two similar systems. Evc~tiif icIciitic:11 n i z ~ ~ i n rwere s it)v o l v c ~ l(this is most likrlj. tiot t hr. c:tw). oiii’ \vuulcl clspt’c*t :t smallt.1. isotopt. c>ft’t.rt n i t l i tlie niorc3 highl>ac8tiv:rted CY positioii of cliloi,:tmphPiiicol. Tht, isotopi. t+ft:ct found for chlorampliriiicol a i d tlie coniparablt~ effect, in the I’hEt system strotigly support the ture-activity concept deduced f i w n (’(1 1 :is w ~ l l :ts the special ch:ir:tctcr ( ~ fbt,iiz\.l :itid :illy1 nioietiw in medicinal chemistry. Another large c h s of c(JI1ipOUiith (!oiit~titiitigbt.11z>.lichydrogens is thrl psychotomimetic aniitit’s in Ivhich there is presently g i w t intewst i l l striicturt.-:tctivity (40) Personal communication frorn E . I i u t t e r . l ) r . Karl Thuniae C i i r r l ~ l l C:ompany. Biherarh, Germany.
Notes The Use of u + i n Structure-Activity Correlations’
-1,he u s e of substituent, constaiits :tiid coniputeriztd rogrwsion nnalysis for corre1:tting chemical struct,urr \vith bio1ogic:il :ictivi is bcgitining to \+Id fascinating rtmlts.2 H o w v t sine(. oiir knowledge, of rcwptor sites and enzymic mechanisms is so very limited, we are still in the embryonic st’agesof developing systemat’icprocedures for disentangling substituent effects in structure-activit~- relationships. In the present ~
(1) T l i i a I Y C J ~ \\a? L b i i i ) i , u r t y < l Ili. ( : i i i i i i C.1 11 110 froiii ( l i e l a t i u i i a l Institiites of tIealtli. (2) (a) C . Hansch. . 1 c c o i ~ i 1 bCIieir‘, IL‘cs., 2 , 232 ( l Y ( i $ i ) : 1 l i 1 C. Ilan.rli, J . Oru. Chrm., 36, 620 (lY70).
log RS = 1.6107r 1.831g 1.729
+
)1
7.
9 0.936 0.282
(
1)
Journal sf dledicinol Cheitiistry, 1970, Vol. 13, ,Vo. 5 965
NOTES T.\ULK
1l.\T.\ FOlt
I
1- tlitiit~tliylhesyl)dodecahy~lro methyl-lH-belie / e ]indt~~ic~-(i-i~~eth;\-lamir~e]bis(et~hylrnt~t1iamiiie)cobalt ( 3 ) trichloride (111). T h e ir spectruni tcnt with thc. :issigntd structure. I r masinxi to btl charact,eristic of ( ' 0 -S b o d s we1.t) p r e s e ~ i t . ~l;in:illJ,, 111, which is complt~tel\. witei, soluble. gavc :I 1 I):itticlt. tie1 ion of thr. f r t w i i i g Ovei- t'lit. last dec:idr, niuch ~vorl; has beeii done coilpoint i n aqu eou z soI u t i 011,sti I i d i:tm:ignc>t ic. 'I'lius . wrning t8hesyrithe of steroid :in:tlog systems wherein :dl the data coilfirm thc~ struc :~ssigritdfor I I ;ind v:irious ring carbon atoms have been ieplaced with S. 111. 0 , or S. Some of the a z a , us:^. m d thia steriods 1he 1)repar:ition of ot'hei-inc>talchelute sttiwid a i i a 1 1 1 p possess biological activit!.. u-ondered if it might bc. is unc1erw:ty. :ind the completr coiiformatiorial ch:tixcpossible to synthesize 21 molecule which cont'ained :I terization of I1 :inti I11 by X-ray difTraction niet'hocls m e t d chelate ring within :I misoniible facsimile of :I will soon bt> iiiiti:itcd. Tt is interehng to notch thiit steroid ring system. Scheme I s h o w s t h e resctioii m o d e l s of I11 stlo\\- t1Mt the IloI~malshape of the ("1'' chiiiployed t'o prepare thc rcquisitr lig:iiid3 7-:imino-:
