▁The ▁M AT ▁binding ▁pocket ▁analog ous ▁to ▁the ▁lip oph il ic ▁place ▁on ▁c oca ine - like ▁comp ounds , ▁inclus ive ▁of ▁the ▁ben z ene ▁ring , ▁is ▁approximate ▁to ▁ 9 ▁Å ▁in ▁length . ▁Which ▁is ▁only ▁slightly ▁larger ▁than ▁a ▁phen yl ▁ring ▁by ▁itself . ▁ ▁meta - subst it uted ▁ben zo yl m eth yle c gon ines ▁▁ ɑ IC 5 0 ▁value ▁for ▁disp lacement ▁of ▁[ 3 H ] c oca ine ▁ ▁orth o - subst it uted ▁ben zo yl m eth yle c gon ines ▁ ▁The ▁hydro x yl ated ▁ 2 ′ - OH ▁analog ue ▁exhib ited ▁a ▁ten fold ▁increase ▁in ▁pot ency ▁over ▁c oca ine . ▁▁ ɑ IC 5 0 ▁value ▁for ▁disp lacement ▁of ▁[ 3 H ] c oca ine ▁ ▁manifold ▁ben zo y lo xy ▁phen yl - subst itution s ▁ ▁Multi - subst itution s ▁( subst itution s ▁of ▁substitution s ; ▁e . g . ▁meta - ▁& ▁para -) ▁or ▁manifold ▁(" many - fold ") ▁subst it uted ▁analog ues ▁are ▁analog ues ▁where ▁more ▁than ▁one ▁modification ▁from ▁the ▁parent ▁mole c ule ▁takes ▁place ▁( h aving ▁numerous ▁inter medi ary ▁constitu ents ). ▁These ▁are ▁created ▁with ▁often ▁surprising ▁structure – activity ▁relationship ▁results ▁ext rap ol ated ▁there from . ▁It ▁is ▁even ▁a ▁common ▁case ▁where ▁two ▁separate ▁substitution s ▁can ▁each ▁yield ▁a