Recent developments in the chemistry and in the biological applications of amidoximes.
Amidoximes are compounds bearing both a hydroxyimino and an amino group at the same carbon atom which makes them versatile building blocks for the synthesis of various heterocycles. Their importance in chemistry along with their rich biology, make amidoximes an attractive target for medicinal chemists, biochemists and biologists. Amidoximes and simple O-substituted derivatives possess very important biological activities functioning as antituberculotic, antibacterial, bacteriostatic, insecticidal, elminthicidal, antiviral, herbicidal, fungicidal, antineoplastic, antiarrythmic, antihypertensive, antihistaminic, anxiolytic-antidepressant, anti-inflammatory/antioxidant, antiaggregatory (NO donors) or plant growth regulatory agents. A number of amidoximes has already been used as drugs, or currently being in clinical trials. Their numerous pharmaceutical applications have been recently enriched, due to the fact that some mechanistic pathways, concerning their conversion to amidines, as well as their ability to release NO were clarified, giving a new insight to their mode of action and allowing the design of new therapeutic agents. The main subject of the present review paper is to highlight aspects concerning chemical and biological questions on this interesting class of compounds. Some new synthetic methodologies as well as improvements of previously reported general reactions involving amidoximes, acylated amidoximes, and amidines are presented. The biological applications of amidoximes over the end of 2006 are also extensively reviewed.
Fylaktakidou
K C
KC
Molecular Biology and Genetics Department, Democritus University of Thrace, Alexandroupolis 68100, Greece. kfylakta@mbg.duth.gr
Hadjipavlou-Litina
D J
DJ
Litinas
K E
KE
Varella
E A
EA
Nicolaides
D N
DN
D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010575:Pesticides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D018926:Anti-Allergic Agents; D000889:Anti-Arrhythmia Agents; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D002491:Central Nervous System Agents; D020030:Nitric Oxide Donors; D010091:Oximes; D010575:Pesticides; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs