Hantzsch synthesis of pyrazolo[1',2':1,2]pyrazolo[3,4-b]pyridines: partial agonists of the calcitonin receptor.
Small molecule calcitonin receptor agonists are of potential utility in the treatment and prevention of osteoporosis. Bicycloeneamine 1 was a useful intermediate in the synthesis of pyrazolopyridine calcitonin receptor partial agonists 2a-f. Dihydropyridines 10a-c were conveniently prepared by reaction of 1 with Knoevenagel adducts 9a-c, or in the case of 10d, by a three component reaction with 1, beta-ketoester 7b, and aldehyde 8c. Oxidation of 10a-d to pyridines 11a-d and subsequent amide formation afforded the title compounds.
Boros
Eric E
EE
GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA. eric.e.boros@gsk.com
Cowan
David J
DJ
Cox
Richard F
RF
Mebrahtu
Makda M
MM
Rabinowitz
Michael H
MH
Thompson
James B
JB
Wolfe
Lawrence A
LA
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018003:Receptors, Calcitonin / Q000819:agonists*
D011720:Pyrazoles; D011725:Pyridines; D018003:Receptors, Calcitonin; C118531:pyrazolopyridine