SAR and pH Stability of Cyano-Substituted Epothilones
3-Cyano epothilones 15−18 are the only examples of non-hydroxy C-3-substituted analogues. Their tubulin binding affinity and cytotoxicity provide meaningful structure−activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH sta...
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| Veröffentlicht in: | Organic letters 2002-10, Vol.4 (22), p.3815-3818 |
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| container_title | Organic letters |
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| creator | Regueiro-Ren, Alicia Leavitt, Kenneth Kim, Soong-Hoon Höfle, Gerhard Kiffe, Michael Gougoutas, Jack Z DiMarco, John D Lee, Francis Y. F Fairchild, Craig R Long, Byron H Vite, Gregory D |
| description | 3-Cyano epothilones 15−18 are the only examples of non-hydroxy C-3-substituted analogues. Their tubulin binding affinity and cytotoxicity provide meaningful structure−activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH stability over epothilone B, and its activity further supports the hypothesis that C-12 stereochemistry is not critical for tubulin affinity. |
| doi_str_mv | 10.1021/ol026589j |
| format | Article |
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Their tubulin binding affinity and cytotoxicity provide meaningful structure−activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH stability over epothilone B, and its activity further supports the hypothesis that C-12 stereochemistry is not critical for tubulin affinity.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Division - drug effects</subject><subject>Drug Stability</subject><subject>Epothilones - chemical synthesis</subject><subject>Epothilones - chemistry</subject><subject>Epothilones - pharmacology</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Molecular Structure</subject><subject>Structure-Activity Relationship</subject><subject>Tubulin - drug effects</subject><subject>Tubulin - metabolism</subject><subject>Tumor Cells, Cultured</subject><issn>1523-7060</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0MFKw0AQBuBFFFurB19AclHwEJ3ZZDfZYynVCgXB6nmZbDeYkmZjdnPo2zfSUi-eZhg-fpifsVuEJwSOz64GLkWuNmdsjIIncQaCn592CSN25f0GAIeLumQj5EKpVMoxE6vpR0TNOmoX0SpQUdVV2EWujGY7aly86gsfqtAHu47mrQvfVe0a66_ZRUm1tzfHOWFfL_PP2SJevr--zabLmBLEEIuyFJhmBaSUS8pVJiAhY9AokikHZayEXMhU8YyKXGKSEhQEhJxosCKZsIdDbtu5n976oLeVN7auqbGu9zrjucgQ8wE-HqDpnPedLXXbVVvqdhpB_3akTx0N9u4Y2hdbu_6Tx1IGcH8AZLzeuL5rhh__CdoDTytrMw</recordid><startdate>20021031</startdate><enddate>20021031</enddate><creator>Regueiro-Ren, Alicia</creator><creator>Leavitt, Kenneth</creator><creator>Kim, Soong-Hoon</creator><creator>Höfle, Gerhard</creator><creator>Kiffe, Michael</creator><creator>Gougoutas, Jack Z</creator><creator>DiMarco, John D</creator><creator>Lee, Francis Y. 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Their tubulin binding affinity and cytotoxicity provide meaningful structure−activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH stability over epothilone B, and its activity further supports the hypothesis that C-12 stereochemistry is not critical for tubulin affinity.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>12599466</pmid><doi>10.1021/ol026589j</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 2002-10, Vol.4 (22), p.3815-3818 |
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| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Division - drug effects Drug Stability Epothilones - chemical synthesis Epothilones - chemistry Epothilones - pharmacology Humans Hydrogen-Ion Concentration Molecular Structure Structure-Activity Relationship Tubulin - drug effects Tubulin - metabolism Tumor Cells, Cultured |
| title | SAR and pH Stability of Cyano-Substituted Epothilones |
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