WOOL AS AN INDICATOR OF NEUROPHARMACOLOGICAL ACTIVITY 75 



Affinity for 1 gm. 



of wool in mMoles Compounds Mol. Weight 



x 10 2 



5.1 N,N-Diisopropyl l-(3-indolylmethyl) iso- C21H32CIN3O 



nipecotamide hydrochloride Mol. Wt. 377.9 



CH S 



V\ , 



NH 



CH 



/ 1 

 CH; 



CH— CH 3 

 CH 3 



active 



It is interesting to note that the first compound, which resembles most the 

 LSD structure, displays a high affinity, namely 5.3 mMoles X 10 -2 /gm. of wool 

 and is a potent adrenergic blocking agent. The second compound is also an 

 active one but with single — instead of two — "LSD-tails" due to the absence 

 of the indole ring; its affinity for wool is, therefore, lower than that of the first 

 compound. The third compound is inactive apparently because of its lack of 

 the dialkylated "LSD-tail", causing, among others, a difference in basicity. 

 The fourth compound seems to be inactive for the same reason as the third one. 

 The fifth compound has the highest affinity for wool because of its large molec- 

 ular weight (the largest in this series); the benzyl-group on the primary amino 

 nitrogen, however, does not conform with that finer structure apparently needed 

 for such compounds to display biological activity. The meaning of the "finer 

 structure" is similar to that of Ehrlich's "key-hole" concept. The sixth com- 

 pound has a high affinity for wool and is pharmacologically active; the dialkyl- 

 ated "LSD-tail," the indole nucleus with its N — C — C — CN-grouping are 

 features fitting the requirements set up previously. 



These results again illustrate our contention that affinity for wool of a com- 

 pound does not imply a specific neuropharmacological activity if the finer struc- 

 tural configuration necessary for that activity is absent. 



VI 



Interlude: Affinity for a-keratin, a Clarification of Terms 



There are two types of bonds which might build cross-linkages between pro- 

 tein chains: (1) covalent bonds like disulfide, peptide, ester and ether bonds, or 

 (2) the most common secondary bonds, e.g. hydrogen-van der YYaals or salt- 

 bonds. Affinity of a substance to protein results in a binding by the aid of one 

 or more bonds. A substance bound to protein by secondary bonds will display 



