A new synthesis of 3-arylthioindoles as selective COX-2 inhibitors using PIFA |
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Authors: | Jeffrey A Campbell Chris A Broka Leyi Gong Keith AM Walker Jin-Hai Wang |
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Institution: | Department of Medicinal Chemistry, Roche Palo Alto., 3431 Hillview Ave, Palo Alto, CA 94304, USA |
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Abstract: | The direct 3-arylthiolation of 2-substituted indoles using phenyliodine(III)bis trifluoroacetate (PIFA) in (CF3)2CHOH with a wide variety of benzenethiols has been accomplished. In particular, indoles bearing a 6-MeSO2 and either a 2-methyl or 2-carboxymethyl substituent could be 3-arylthiolated in good to excellent yields to afford the corresponding 3-arylthioindoles as selective COX-2 inhibitors. In a study varying the electronic nature of the 5-substituent of 2-CO2Et indoles, it was discovered that the yield of the reaction improved as the substituent became more electron withdrawing. This result was consistent with a proposed mechanism involving benzenethiol displacement of an intermediate 3-IPh indole complex. |
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Keywords: | PIFA 3-Arylthioindole Selective COX-2 inhibitors Benzenethiol |
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