26-10-2017 дата публикации
Номер: US20170305924A1
Автор:
Apgar James M.,
Dang Qun,
Mandal Mihir,
Meng Dongfang,
Olsen David B.,
Painter Ronald E.,
Parker Dann,
Singh Sheo B.,
Su Jing,
Suzuki Takao,
Wilkening Robert R.,
Yang Lihu,
Young Katherine
The present invention relates to novel nargenicin related compounds which can inhibit DnaE and have antibacterial, particularly antimycobacterial activity against Mycobacterium tuberculosis. The present invention also relates to method for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by by administering an antimycobacterially effective amount of nargenicin or a nargenicin-related compound and/or their pharmaceutically acceptable salts. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is O.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', 'A, 'sub': 1-6', '2-6', '3', '3', '3', '3', '3', '1-6, 'Ris H, Calkyl, Calkenyl, —CH(CH)NH-cyclopropyl, —CH(CH)═NOH, —CH(CH)OR, —CH(CH)-1H-indene-1,3(2H)-dione, —CH(CH)-isoindoline-1,3-dione, —C(═O)Calkyl, or AryA;'}{'sup': '1b', 'Ris H;'}{'sup': A', 'g', 'g', 'g', 'g, 'sub': 1-6', '1-6', '2, 'claim-text': {'sub': '3', 'wherein the alkyl is optionally substituted with one or two substituents independently selected from halogen, —SCH, AryA, and HetA; and'}, 'Ris H, Calkyl, —C(═O)Calkyl, C(═O)NHR, —C(═O)OR, —C(═O)C(═O)NHR, —C(═O)C(═O)OR, —C(═O)-AryA, —C(═O)-HetA, —C(═O)C(═O)-HetA, —SOOH, or tert-butyl dimethylsilyl;'}{'sup': g', 'x', 'y', 'x', 'y, 'sub': 1-8', '3-6', '3', '3, 'Ris H, Calkyl, Ccycloalkyl, —C(═O)CCl, NRR, —NHC(═O)NRR, —NHC(═O)OCH;'}and{'sub': 2', '2', '2', '2', '2', '1-6, 'sup': x', 'y', 'x', 'y, 'AryA or —CH(CH-AryA)C(═O)NHCH(CHCHCHNHC(═NH)NH)C(═O)NH-AryA, wherein the alkyl is optionally substituted by 1 to 3 NRRor —OH substituents or 1 sub stituent selected from Calkoxy, —COOH, —C(═O)NRR, AryA, and HetA.'}6. The compound of claim 5 , wherein [{'sub': 1', '6', '1', '6', '2', '0-1', '1-6', '1-6', '2', '1-6', '1-6', '2', '0-1', '2, 'sup': x', 'y, '1) a monocyclic ring selected from furanyl, imidazolyl, pyrazolyl, pyrrolyl, phenyl, pyridinyl, tetrazolyl, thiazolyl, or ...
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