Cyclopropanecarboxylic Acid Esters as Potential Prodrugs with Enhanced Hydrolytic Stability
Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 °C and pH 6 the half-life of 14 is >300 h while the va...
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| Veröffentlicht in: | Organic letters 2008-02, Vol.10 (3), p.509-511 |
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| creator | Bender, David M Peterson, Jeffrey A McCarthy, James R Gunaydin, Hakan Takano, Yu Houk, K. N |
| description | Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 °C and pH 6 the half-life of 14 is >300 h while the value for 13 is 69.7 h. CBS-QB3 calculations on isodesmic reactions for transfer of groups from an alkane to an ester show that a cyclopropyl group provides hyperconjugative stabilization. |
| doi_str_mv | 10.1021/ol702892e |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 2008-02, Vol.10 (3), p.509-511 |
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| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Acyclovir - analogs & derivatives Acyclovir - chemistry Acyclovir - pharmacology Antiviral Agents - chemistry Antiviral Agents - pharmacology Cyclopropanes - chemistry Cyclopropanes - pharmacology Esters Hydrolysis Molecular Structure Prodrugs - chemistry Prodrugs - pharmacology Valine - analogs & derivatives Valine - chemistry Valine - pharmacology |
| title | Cyclopropanecarboxylic Acid Esters as Potential Prodrugs with Enhanced Hydrolytic Stability |
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