Photochemical synthesis of N-arylbenzophenanthridine selective estrogen receptor modulators (serms).
Selective estrogen receptor modulators are an emerging class of pharmaceutically important molecules. Many compounds in this class contain an aminoethoxyaryl moiety attached to a polycyclic framework at an asymmetric carbon atom. To assess whether this carbon atom can be replaced by nitrogen, we have employed a Ninomiya enamide photocyclization for the rapid synthesis of a novel N-arylbenzophenanthridine framework, 4. Further elaboration of 4 into a new structural class of achiral, nonsteroidal estrogen receptor modulators is described.
Grese
T A
TA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. grese@lilly.com
Adrian
M D
MD
Phillips
D L
DL
Shetler
P K
PK
Short
L L
LL
Glasebrook
A L
AL
Bryant
H U
HU
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D001667:Binding, Competitive; D003500:Cyclization; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010777:Photochemistry; D011869:Radioligand Assay; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D010617:Phenanthridines; D011960:Receptors, Estrogen