公开(公告)号：US06730783B2

公开(公告)日：2004-05-04

申请号：US10419972

申请日：2003-04-22

申请人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan

发明人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan

IPC分类号： A61K31255

CPC分类号： C07C309/73 ,  C07C309/75 ,  C07C309/76 ,  C07C309/77 ,  C07C311/16 ,  C07C311/17 ,  C07C311/18 ,  C07C311/19 ,  C07C311/21 ,  C07C317/14 ,  C07C323/66 ,  C07C2601/02 ,  C07C2601/14 ,  C07D211/96 ,  C07D213/42 ,  C07D213/74 ,  C07D215/36 ,  C07D217/02 ,  C07D217/22 ,  C07D239/42 ,  C07D295/13 ,  C07D295/26 ,  C07D307/66

摘要： Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR9 and R1-R4, R6-R9, R11, R12, Ra, Rb, Rc, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents.

摘要翻译： 氨基胍和烷氧基胍化合物，包括下式的化合物：其中X是O或NR 9和R 1 -R 4，R 6 -R 9，R 11，R 12， 说明书中列出的R a，R b，R c，Y，Z，n和m以及抑制蛋白水解酶如凝血酶的水合物，溶剂合物或其药学上可接受的盐是 描述。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，凝血酶，纤溶酶和因子Xa。 某些化合物通过直接，选择性抑制凝血酶表现出抗血栓形成活性，或者是用于形成具有抗血栓形成活性的化合物的中间体。 本发明包括用于抑制血小板损失，抑制血小板聚集体形成，抑制纤维蛋白形成，抑制血栓形成和抑制哺乳动物栓塞形成的组合物，其包含本发明化合物在药学上可接受的载体中。 本发明化合物的其它用途是作为凝血剂或者物理上连接于用于血液收集，血液循环和血液储存（例如导管，血液透析机，采血注射器和管）中使用的装置的制造中使用的材料的抗凝剂， 血线和支架。

公开(公告)号：US06706765B2

公开(公告)日：2004-03-16

申请号：US10359078

申请日：2003-02-06

申请人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

发明人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

IPC分类号： A61K3118

CPC分类号： C07C309/73 ,  C07C309/75 ,  C07C309/76 ,  C07C309/77 ,  C07C311/16 ,  C07C311/17 ,  C07C311/18 ,  C07C311/19 ,  C07C311/21 ,  C07C317/14 ,  C07C323/66 ,  C07C2601/02 ,  C07C2601/14 ,  C07D211/96 ,  C07D213/42 ,  C07D213/74 ,  C07D215/36 ,  C07D217/02 ,  C07D217/22 ,  C07D239/42 ,  C07D295/13 ,  C07D295/26 ,  C07D307/66

摘要： Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR9 and R1-R4, R6-R9, R11, R12, Ra, Rb, Rc, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents.

摘要翻译： 氨基胍和烷氧基胍化合物，包括下式的化合物：其中X是O或NR 9和R 1 -R 4，R 6 -R 9，R 11，R 12， 说明书中列出的R a，R b，R c，Y，Z，n和m以及抑制蛋白水解酶如凝血酶的水合物，溶剂合物或其药学上可接受的盐是 描述。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，凝血酶，纤溶酶和因子Xa。 某些化合物通过直接，选择性抑制凝血酶表现出抗血栓形成活性，或者是用于形成具有抗血栓形成活性的化合物的中间体。 本发明包括用于抑制血小板损失，抑制血小板聚集体形成，抑制纤维蛋白形成，抑制血栓形成和抑制哺乳动物栓塞形成的组合物，其包含本发明化合物在药学上可接受的载体中。 本发明化合物的其它用途是作为凝血剂或者物理上连接于用于血液收集，血液循环和血液储存（例如导管，血液透析机，采血注射器和管）中使用的装置的制造中使用的材料的抗凝剂， 血线和支架。

公开(公告)号：US6127191A

公开(公告)日：2000-10-03

申请号：US980062

申请日：1997-11-26

申请人： Todd L. Graybill ,  Zhengdong Wu ,  Nalin Subasinghe ,  Cynthia L. Fedde ,  Joseph M. Salvino

发明人： Todd L. Graybill ,  Zhengdong Wu ,  Nalin Subasinghe ,  Cynthia L. Fedde ,  Joseph M. Salvino

IPC分类号： C07B61/00 ,  C07C237/42 ,  C07C271/28 ,  C07C275/42 ,  C07C279/14 ,  C07C311/08 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C335/22 ,  C07D295/13 ,  C07D295/15 ,  C07J41/00 ,  C07C69/76 ,  C07C63/04 ,  C07C211/00

CPC分类号： C07D295/13 ,  C07C237/42 ,  C07C271/28 ,  C07C275/42 ,  C07C279/14 ,  C07C311/08 ,  C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C335/22 ,  C07D295/15 ,  C07J41/0055 ,  C40B40/04 ,  C40B50/14 ,  C07B2200/11 ,  C07C2101/02 ,  C07C2101/04 ,  C07C2101/08 ,  C07C2101/14 ,  C07C2103/74

摘要： The present invention provides a library of compounds, each comprised of a common aminobenzenedicarboxylic acid core structure (scaffold) that serves as a template for synthesizing approximately 10.sup.1 -10.sup.6 compounds which are analogs of the scaffold. The library is employed to study ligand binding by biological receptors, such as enzymes, G-protein coupled receptors and membrane channels. For example, certain individual compounds within the library selectively bind and inhibit the action of trypsin-like serine proteases. The present invention also relates to combinatorial synthetic methods for making such libraries of compounds. Additionally, the present invention relates to novel scaffold-modified solid supports, particularly scaffold-modified polymer resins and methods for preparing said resins. Further, the present invention is directed to methods for screening a compound or plurality of compounds made according to the synthetic methods disclosed herein, which comprise using the compounds in suitable assays developed for detecting the compounds' utility as pharmaceutical agents.

摘要翻译： 本发明提供了一种化合物文库，每一种化合物均由常用的氨基苯二甲酸核心结构（支架）组成，其用作合成大约101-106个作为支架类似物的化合物的模板。 该文库用于研究配体结合生物受体，如酶，G蛋白偶联受体和膜通道。 例如，文库中的某些单个化合物选择性地结合并抑制胰蛋白酶样丝氨酸蛋白酶的作用。 本发明还涉及制备这种化合物文库的组合合成方法。 另外，本发明涉及新的支架改性固体支持物，特别是支架改性的聚合物树脂以及制备所述树脂的方法。 此外，本发明涉及用于筛选根据本文公开的合成方法制备的化合物或多种化合物的方法，其包括在合适的测定中使用该化合物，其用于检测化合物作为药剂的效用。

公开(公告)号：US06235778B1

公开(公告)日：2001-05-22

申请号：US08979234

申请日：1997-11-26

申请人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

发明人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

IPC分类号： A61K31255

CPC分类号： C07C309/73 ,  C07C309/75 ,  C07C309/76 ,  C07C309/77 ,  C07C311/16 ,  C07C311/17 ,  C07C311/18 ,  C07C311/19 ,  C07C311/21 ,  C07C317/14 ,  C07C323/66 ,  C07C2601/02 ,  C07C2601/14 ,  C07D211/96 ,  C07D213/42 ,  C07D213/74 ,  C07D215/36 ,  C07D217/02 ,  C07D217/22 ,  C07D239/42 ,  C07D295/13 ,  C07D295/26 ,  C07D307/66

摘要： Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR9 and R114 R4, R6-R9, R11, R12, Ra, Rb, Rc, Y, Z, n and mare set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents.

摘要翻译： 氨基胍和烷氧基胍化合物，包括下式的化合物：其中X是O或NR9，R114R4，R6-R9，R11，R12，Ra，Rb，Rc，Y，Z，n和母本也在说明书中列出 描述了抑制蛋白水解酶如凝血酶的水合物，溶剂合物或其药学上可接受的盐。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，凝血酶，纤溶酶和因子Xa。 某些化合物通过直接，选择性抑制凝血酶表现出抗血栓形成活性，或者是用于形成具有抗血栓形成活性的化合物的中间体。 本发明包括用于抑制血小板损失，抑制血小板聚集体形成，抑制纤维蛋白形成，抑制血栓形成和抑制哺乳动物栓塞形成的组合物，其包含本发明化合物在药学上可接受的载体中。 本发明化合物的其它用途是作为凝血剂或者物理连接于制造用于血液收集，血液循环和血液储存中的装置的材料的抗凝剂，例如导管，血液透析机，采血注射器和管， 血线和支架。

公开(公告)号：US06638931B1

公开(公告)日：2003-10-28

申请号：US09722363

申请日：2000-11-28

申请人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

发明人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Carl R. Illig ,  Thomas P. Markotan ,  Thomas P. Stagnaro

IPC分类号： A61K31255

CPC分类号： C07C309/73 ,  C07C309/75 ,  C07C309/76 ,  C07C309/77 ,  C07C311/16 ,  C07C311/17 ,  C07C311/18 ,  C07C311/19 ,  C07C311/21 ,  C07C317/14 ,  C07C323/66 ,  C07C2601/02 ,  C07C2601/14 ,  C07D211/96 ,  C07D213/42 ,  C07D213/74 ,  C07D215/36 ,  C07D217/02 ,  C07D217/22 ,  C07D239/42 ,  C07D295/13 ,  C07D295/26 ,  C07D307/66

摘要： Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR9 and R1-R4, R6-R9, R11, R12, Ra, Rb, Rc, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents.

摘要翻译： 氨基胍和烷氧基胍化合物，包括下式的化合物：其中X是O或NR 9和R 1 -R 4，R 6 -R 9，R 11，R 12， 说明书中列出的R a，R b，R c，Y，Z，n和m以及抑制蛋白水解酶如凝血酶的水合物，溶剂合物或其药学上可接受的盐是 描述。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，凝血酶，纤溶酶和因子Xa。 某些化合物通过直接，选择性抑制凝血酶表现出抗血栓形成活性，或者是用于形成具有抗血栓形成活性的化合物的中间体。 本发明包括用于抑制血小板损失，抑制血小板聚集体形成，抑制纤维蛋白形成，抑制血栓形成和抑制哺乳动物栓塞形成的组合物，其包含本发明化合物在药学上可接受的载体中。 本发明化合物的其它用途是作为凝血剂或者物理上连接于用于血液收集，血液循环和血液储存（例如导管，血液透析机，采血注射器和管）中使用的装置的制造中使用的材料的抗凝剂， 血线和支架。

公开(公告)号：US06518310B2

公开(公告)日：2003-02-11

申请号：US09809293

申请日：2001-03-16

申请人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L Fedde ,  Carl R Illig ,  Thomas P. Markotan ,  Thomas P Stagnaro

发明人： Bruce E. Tomczuk ,  Richard M. Soll ,  Tianbao Lu ,  Cynthia L Fedde ,  Carl R Illig ,  Thomas P. Markotan ,  Thomas P Stagnaro

IPC分类号： A61K31255

CPC分类号： C07C309/73 ,  C07C309/75 ,  C07C309/76 ,  C07C309/77 ,  C07C311/16 ,  C07C311/17 ,  C07C311/18 ,  C07C311/19 ,  C07C311/21 ,  C07C317/14 ,  C07C323/66 ,  C07C2601/02 ,  C07C2601/14 ,  C07D211/96 ,  C07D213/42 ,  C07D213/74 ,  C07D215/36 ,  C07D217/02 ,  C07D217/22 ,  C07D239/42 ,  C07D295/13 ,  C07D295/26 ,  C07D307/66

摘要： Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR9 and R1-R4, R6-R9, R11, R12, Ra, Rb, Rc, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents.

摘要翻译： 氨基胍和烷氧基胍化合物，包括下式的化合物：其中X为O或NR 9，R 1 -R 4，R 6 -R 9，R 11，R 12，R a，R b，R c，Y，Z，n和m在说明书中阐述， 以及抑制蛋白水解酶如凝血酶的水合物，溶剂合物或其药学上可接受的盐。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，凝血酶，纤溶酶和因子Xa。 某些化合物通过直接，选择性抑制凝血酶表现出抗血栓形成活性，或者是用于形成具有抗血栓形成活性的化合物的中间体。 本发明包括用于抑制血小板损失，抑制血小板聚集体形成，抑制纤维蛋白形成，抑制血栓形成和抑制哺乳动物栓塞形成的组合物，其包含本发明化合物在药学上可接受的载体中。 本发明化合物的其它用途是作为凝血剂或者物理上连接于用于血液收集，血液循环和血液储存（例如导管，血液透析机，采血注射器和管）中使用的装置的制造中使用的材料的抗凝剂， 血线和支架。

公开(公告)号：US5891909A

公开(公告)日：1999-04-06

申请号：US828160

申请日：1997-03-27

申请人： Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Bruce E. Tomczuk ,  Carl Illig

发明人： Richard M. Soll ,  Tianbao Lu ,  Cynthia L. Fedde ,  Bruce E. Tomczuk ,  Carl Illig

IPC分类号： A61K31/00 ,  A61K31/165 ,  A61K31/18 ,  A61K31/275 ,  A61K31/277 ,  A61K31/41 ,  A61K31/415 ,  A61K31/433 ,  A61K31/44 ,  A61K31/4406 ,  A61K31/47 ,  A61K31/472 ,  A61P1/00 ,  A61P1/18 ,  A61P7/00 ,  A61P7/02 ,  A61P43/00 ,  C07C45/29 ,  C07C45/71 ,  C07C47/277 ,  C07C281/18 ,  C07C309/67 ,  C07C309/73 ,  C07C309/74 ,  C07C309/75 ,  C07C309/77 ,  C07C311/21 ,  C07C323/66 ,  C07D213/70 ,  C07D213/71 ,  C07D215/36 ,  C07D217/02 ,  C07D231/14 ,  C07D231/18 ,  C07D233/52 ,  C07D285/14 ,  C07D317/40 ,  C07D333/34 ,  A61K31/155 ,  A61K31/255

CPC分类号： C07D285/14 ,  C07C281/18 ,  C07C309/73 ,  C07C309/74 ,  C07C309/75 ,  C07C309/77 ,  C07C311/21 ,  C07C323/66 ,  C07C45/29 ,  C07C45/71 ,  C07C47/277 ,  C07D213/71 ,  C07D215/36 ,  C07D217/02 ,  C07D231/18 ,  C07D233/52 ,  C07D317/40 ,  C07D333/34 ,  C07C2101/02

摘要： Amidino and benzamidino compounds, including compounds of the formula: ##STR1## wherein R.sup.1 -R.sup.4, R.sup.6 -R.sup.9, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I.

摘要翻译： 脒基和苯甲脒基化合物，包括下式的化合物：其中R 1 -R 4，R 6 -R 9，Y，Z，n和m在说明书中列出，以及其水合物，溶剂合物或其药学上可接受的盐， 描述抑制蛋白水解酶如凝血酶的方法。 还描述了制备式I化合物的方法。

公开(公告)号：US5258525A

公开(公告)日：1993-11-02

申请号：US675786

申请日：1991-03-27

申请人： Cynthia A. Maryanoff ,  Cynthia L. Fedde ,  Robin C. Stanzione ,  Frank J. Villani, Jr.

发明人： Cynthia A. Maryanoff ,  Cynthia L. Fedde ,  Robin C. Stanzione ,  Frank J. Villani, Jr.

IPC分类号： C07D209/42 ,  C07D209/04

CPC分类号： C07D209/42

摘要： The processes provide for the preparation of a [2S-(2.alpha., 3a.beta., 7a.beta.)]-octahydro-lH-indole-2-carboxylic ester from an ester precursor by a stereospecific hydrogenation at a pressure below about 400 psi. In addition, the processes provide for the preparation of [2S-(2.alpha.m 3a.beta., 7a.beta.)]-octahydro-lH-indole-2-carboxylic acid or a ester thereof by the hydrogenation of a (2S)-2-carboxyindoline acid precursor.

摘要翻译： 该方法提供了在低于约400psi的压力下通过立体特异性氢化从酯前体制备[2S-（2α，3aβ，7aβ）] - 八氢-1H-吲哚-2-羧酸酯。 此外，该方法通过氢化（2S）-2-甲氧基 - 吲哚-2-羧酸或其酯来制备[2S-（2α，3aβ，7aβ）] - 八氢-1H-吲哚-2-羧酸或其酯。 羧基吲哚啉酸前体。