Details for Patent: 4,996,206
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Title: | N-(pyrrolo[2,3-d]pyrimidin-3-ylacyl)-glutamic acid derivatives |
Abstract: | N-(Acyl)glutamic acid derivatives in which the acyl group is substituted with 4-hydroxypyrrolo[2,3-d]pyrimidin-3-yl group are antineoplastic agents. A typical embodiment is N-[4-(2-{4-hydroxypyrrolo[2,3-d]pyrimidin-3-yl}ethyl)benzoyl]-L-glutamic acid. |
Inventor(s): | Taylor; Edward C. (Princeton, NJ), Kuhnt; Dietmar G. (Leverkusen, DE), Shih; Chuan (Indianapolis, IN), Grindey; Gerald B. (Indianapolis, IN) |
Assignee: | The Trustees of Princeton University (Princeton, NJ) |
Filing Date: | May 24, 1990 |
Application Number: | 07/528,805 |
Claims: | 1. A compound of the formula: ##STR16## in which: R.sup.1 is -OH or -NH.sub.2 ; R.sup.3 is 1,4-phenylene or 1,3-phenylene unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl; thienediyl or furanediyl unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl; cyclohexadiyl; and alkanediyl of two to four carbon atoms; R.sup.4 is hydrogen, methyl, or hydroxymethyl; and R.sup.5 is hydrogen or alkyl of 1 to 6 carbon atoms; the configuration about the carbon atom designated * is S; and the pharmaceutically acceptable salts thereof. 2. A compound according to claim 1 wherein R.sup.1 is -OH; R.sup.3 is 1,4-phenylene; and R.sup.4 is hydrogen. 3. A compound according to claim 2 wherein R.sup.5 is hydrogen. 4. A compound according to claim 2 wherein R.sup.5 is methyl. 5. A compound according to claim 1 wherein R.sup.1 is -OH; R.sup.3 is 1,4-phenylene, and R.sup.4 is hydroxymethyl. 6. A compound according to claim 5 wherein R.sup.5 is hydrogen. 7. A compound according to claim 5 wherein R.sup.5 is methyl. 8. A compound according to claim 1 wherein R.sup.1 is -OH; R.sup.3 is thienediyl, and R.sup.4 is hydrogen. 9. A compound according to claim 8 wherein R.sup.5 is hydrogen. 10. A compound according to claim 8 wherein R.sup.5 is methyl. 11. The compound according to claim 1 which is N-{4-[2-(4-hydroxypyrrolo[2,3-d]pyrimidin-3-yl)ethyl]benzoyl}-L-glutamic acid. 12. The compound according to claim 1 which is N-{4-[2-(4-hydroxy-6-methylpyrrolo[2,3-d]pyrimidin-3-yl)ethyl]benzoyl}-L-g lutamic acid. 13. The method of combatting neoplastic growth in a mammal which comprises administering to the mammal in a single or multiple dose regimen an effective amount of a compound according to claim 1. 14. A pharmaceutical composition for combatting neoplastic growth in a mammal which comprises an amount of a compound according to claim 1 which upon administration to the mammal in a single or multiple dose regimen is effective to combat said growth, in combination with a pharmaceutically acceptable carrier. 15. A compound of the formula: ##STR17## in which: R.sup.1 is -OH or -NH.sub.2 ; R.sup.2 ' is hydrogen, or a carboxy protecting group; R.sup.3 is 1,4-phenylene or 1,3-phenylene unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl, thienediyl or furanediyl unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl, cyclohexadiyl, or alkanediyl of two to four carbon atoms; R.sup.4 ' is hydrogen, methyl, hydroxymethyl, or hydroxymethyl substituted with a hydroxy protecting group; and R.sup.5 40 is hydrogen or alkyl of 1 to 6 carbon atoms, at least one of R.sup.2 ' and R.sup.4 ', being a carboxy protecting group or a hydroxy protecting group, respectively. |