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Aza Analogs of the TRPML1 Inhibitor Estradiol Methyl Ether (EDME).
- Source :
-
Molecules . Nov2023, Vol. 28 Issue 21, p7428. 18p. - Publication Year :
- 2023
-
Abstract
- Estradiol methyl ether (EDME) has recently been described by us as a very potent and subtype-specific inhibitor of the lysosomal cation channel TRPML1. Following the principle of bioisosteres, we worked out efficient synthetic approaches to ring-A aza-analogs of EDME, namely a methoxypyridine and a methoxypyrimidine analog. Both target compounds were obtained in good overall yields in six and eight steps starting from 19-nortestosterone via the oxidative cleavage of ring A followed over several intermediates and with the use of well-selected protective groups by re-cyclization to provide the desired hetero-analogs. The methoxypyridine analog largely retained its TRPML1-inhibitory activity, whereas the methoxypyrimidine analog significantly lost activity. [ABSTRACT FROM AUTHOR]
- Subjects :
- *METHYL ether
*ESTRADIOL
*BIOISOSTERES
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 28
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 173565854
- Full Text :
- https://doi.org/10.3390/molecules28217428