Several analogs of the a-tropanyl esters of 2-(4-chlorophenoxy)butyric acid (SM21) and 2-phenylthiobutyric acid (SM32), endowed with potent antinociceptive and cognition enhancing activity, were synthesized, aimed at obtaining more potent and safe drug candidates. Variation of the acyl moiety (4–11), as well as the conformational restriction of atropine to give the a-tropanyl ester of 2,3-dihydrobenzofurane-3-carboxylic acid (18), practically abolished activity. In the case of 18, the antimuscarinic activity was also severely affected by the conformation restrain. On the contrary, conformational restriction of phenoxybutyric and phenylthiobutyric acid derivatives to give the a-tropanyl ester of 2,3-dihydro-benzofurane-2-carboxylic acid and 2,3-dihydro-benzothiophene- 2-carboxylic acid (12–17), afforded potent analgesic drugs that unfortunately were too toxic to be reliable drug candidates. A series of related esters of benzofurane-3-carboxylic acid (20–27) and benzothiophene-3-carboxylic acid (28) were also studied and found to be potent but toxic analgesics.

FURTHER STRUCTURE-ACTIVITY RELATIONSHIPS IN THE SERIES OF TROPANYL ESTERS ENDOWED WITH POTENT ANTINOCICEPTIVE ACTIVITY / S. SCAPECCHI; A. GIORGI; C. BELLUCCI; S. DEI; C. GHELARDINI; D. MANETTI; M. ROMANELLI; E. TEODORI. - In: IL FARMACO. - ISSN 0014-827X. - STAMPA. - 53(1998), pp. 764-772.

FURTHER STRUCTURE-ACTIVITY RELATIONSHIPS IN THE SERIES OF TROPANYL ESTERS ENDOWED WITH POTENT ANTINOCICEPTIVE ACTIVITY

SCAPECCHI, SERENA;BELLUCCI, CRISTINA;DEI, SILVIA;GHELARDINI, CARLA;MANETTI, DINA;ROMANELLI, MARIA NOVELLA;TEODORI, ELISABETTA
1998

Abstract

Several analogs of the a-tropanyl esters of 2-(4-chlorophenoxy)butyric acid (SM21) and 2-phenylthiobutyric acid (SM32), endowed with potent antinociceptive and cognition enhancing activity, were synthesized, aimed at obtaining more potent and safe drug candidates. Variation of the acyl moiety (4–11), as well as the conformational restriction of atropine to give the a-tropanyl ester of 2,3-dihydrobenzofurane-3-carboxylic acid (18), practically abolished activity. In the case of 18, the antimuscarinic activity was also severely affected by the conformation restrain. On the contrary, conformational restriction of phenoxybutyric and phenylthiobutyric acid derivatives to give the a-tropanyl ester of 2,3-dihydro-benzofurane-2-carboxylic acid and 2,3-dihydro-benzothiophene- 2-carboxylic acid (12–17), afforded potent analgesic drugs that unfortunately were too toxic to be reliable drug candidates. A series of related esters of benzofurane-3-carboxylic acid (20–27) and benzothiophene-3-carboxylic acid (28) were also studied and found to be potent but toxic analgesics.
53
764
772
S. SCAPECCHI; A. GIORGI; C. BELLUCCI; S. DEI; C. GHELARDINI; D. MANETTI; M. ROMANELLI; E. TEODORI
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1878
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact