Synthesis and Biological Evaluation of Thieno[3,2-d]- pyrimidinones, Thieno[3,2-d]pyrimidines and Quinazolinones: Conformationally Restricted 17b-Hydroxysteroid Dehydrogenase Type 2 (17b-HSD2) Inhibitors
Abstract
:1. Introduction
Cmpd | R1 | R2 | Percentage of inhibition at 1µM a | |
---|---|---|---|---|
17β-HSD2 b | 17β-HSD1 c | |||
A | OMe | OMe | 63% | 0% |
B | OH | OH | 70% | 21% |
2. Results and Discussion
Compound | Percentage of inhibition at 1 µM a | |
---|---|---|
17β-HSD2 b | 17β-HSD1 c | |
1a | n.i. | n.i. |
1b | n.i. | n.i. |
2a | n.i. | n.i. |
2b | 11% | n.i. |
3a | n.i. | n.i. |
3b | 36% | 50% |
3c | n.i. | n.i. |
3d | 25% | 48% |
4a | n.i. | n.i. |
4b | n.i. | n.i. |
5a | n.i. | n.i. |
5b | n.i. | n.i. |
5c | n.i. | n.i. |
5d | n.i. | n.i. |
13 | n.i. | n.i. |
12 | n.i. | n.i. |
3. Experimental
3.1. General Procedure for Suzuki — Miyaura Coupling (2a, 17) — Method A
3.2. General Procedure for Cleavage of Ethers 1b–4b — Method B
3.3. General Procedure for the Preparation of Compounds 18a–b — Method C
3.4. General Procedure for the Preparation of Compounds 19a–b — Method D
3.5. General Procedure for the Preparation of Compounds 5a–b – Method E
3.6. General Procedure for the Preparation of Compounds 5c–d – Method F
4. Conclusions
Acknowledgments
References
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Perspicace, E.; Marchais-Oberwinkler, S.; Hartmann, R.W. Synthesis and Biological Evaluation of Thieno[3,2-d]- pyrimidinones, Thieno[3,2-d]pyrimidines and Quinazolinones: Conformationally Restricted 17b-Hydroxysteroid Dehydrogenase Type 2 (17b-HSD2) Inhibitors. Molecules 2013, 18, 4487-4509. https://doi.org/10.3390/molecules18044487
Perspicace E, Marchais-Oberwinkler S, Hartmann RW. Synthesis and Biological Evaluation of Thieno[3,2-d]- pyrimidinones, Thieno[3,2-d]pyrimidines and Quinazolinones: Conformationally Restricted 17b-Hydroxysteroid Dehydrogenase Type 2 (17b-HSD2) Inhibitors. Molecules. 2013; 18(4):4487-4509. https://doi.org/10.3390/molecules18044487
Chicago/Turabian StylePerspicace, Enrico, Sandrine Marchais-Oberwinkler, and Rolf W. Hartmann. 2013. "Synthesis and Biological Evaluation of Thieno[3,2-d]- pyrimidinones, Thieno[3,2-d]pyrimidines and Quinazolinones: Conformationally Restricted 17b-Hydroxysteroid Dehydrogenase Type 2 (17b-HSD2) Inhibitors" Molecules 18, no. 4: 4487-4509. https://doi.org/10.3390/molecules18044487