[SCA 40 and derivatives: new bronchodilators in an imidazo(1,2-a)pyrazine series].
Asthma is a complex disease characterised by bronchoconstriction and airways inflammation. Recent advances in medicinal chemistry will surely lead to a better reappraisal of therapeutic strategies. 8-(Methylamino)imidazo(1,2-a)pyrazines with substitution either on position 2 or 3 powerful relaxing agents in vitro as well as in vivo in animals. 6-Bromo-8-(methylamino)imidazo[1,2-a]pyrazine- 2-carbonitrile, SCA40, is a new and potent bronchodilator. Chemical synthesis of such a series of derivatives involves a condensation reaction with formation of the imidazole ring and/or diverse electrophilic substitutions. Chemical reactivity of the heterocycle can be modulated by introduction on position 8 of electrodonating groups that highly favor electrophilic substitution on position 3. Interestingly, lithiation studies on the heterocycle exhibit regioselectivity, leading either to an halogen exchange when position 3 is occupied by a bromine atom or an ortho-directed metalation in accord with the presence of an halogen on position 6.
Laboratoire de Chimie Organique Pharmaceutique, Faculté de Pharmacie, Montpellier.
P A
PA
Bonnet
O
O
Vitse
V
V
Bénezech
G
G
Subra
J R
JR
Fabréguettes
L
L
Zanik
F
F
Laurent
A
A
Michel
J
J
Bompart
J P
JP
Chapat
D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001993:Bronchodilator Agents; D007093:Imidazoles; D011719:Pyrazines; C080660:6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile
SCA40 et dérivés: nouveaux bronchodilatateurs en série imidazo[1,2-a]pyrazinique.