Study of the Mannich reaction: beta-amino-methylation of N-aryl and N-azaheteroaryl-substituted 2,5-dimethylpyrroles, compounds with potential biological activity.
Owing to the increasing need of drugs for the treatment of a variety of fungal and bacterial opportunistic infections, a study has been started with the aim of synthesizing structures amenable to a number of easily-to-perform structural modifications in order to meet the requirement of bypassing resistance phenomena. This paper reports on the synthesis of several N-(alpha-azaheteroaryl)-substituted 2,5-dimethyl-pyrroles bearing in one beta-position (or in both beta-positions) aminomethyl groups, introduced via a Mannich reaction. Electronic and steric effects by the N-(azaheteroaryl) substituents and the 2- and 5-methyl groups on the course of the Mannich reaction are discussed along with the results of in vitro tests against many Candida species, some bacteria, and several pathogenic plant fungi.
Biava
M
M
Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, Roma, Italy.
Fioravanti
R
R
Porretta
G C
GC
Frachey
G
G
Mencarelli
P
P
Sleiter
G
G
Perazzi
M E
ME
Simonetti
N
N
Villa
A
A
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002175:Candida / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005658:Fungi / Q000187:drug effects*; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D008352:Mannich Bases; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013844:Thiazoles