Synthesis and antispasmodic activity of lidocaine derivatives endowed with reduced local anesthetic action.
The present structure-activity relationship (SAR) study focused on chemical modifications of the structure of the local anesthetic lidocaine, and indicated analogues having reduced anesthetic potency, but with superior potency relative to the prototype in preventing anaphylactic or histamine-evoked ileum contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethyl-phenyl) and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most promising compounds. New insights into the applicability of non-anesthetic lidocaine derivatives as templates in drug discovery for allergic syndromes are provided.
Costa
Jorge C S
JC
Laboratório de Síntese Orgânica, Farmanguinhos, FIOCRUZ, Rio de Janeiro, Brazil.
Neves
Josiane S
JS
de Souza
Marcus V N
MV
Siqueira
Rodrigo A
RA
Romeiro
Nelilma C
NC
Boechat
Nubia
N
e Silva
Patrícia M R
PM
Martins
Marco A
MA
D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000779:Anesthetics, Local; D010276:Parasympatholytics; D006632:Histamine; D008012:Lidocaine