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    INDUCTION OF GATA2 BY HDAC1 AND HDAC2 INHIBITORS
    41.
    发明申请
    INDUCTION OF GATA2 BY HDAC1 AND HDAC2 INHIBITORS 审中-公开
    HDAC1和HDAC2抑制剂诱导GATA2的研究

    公开(公告)号：WO2016057779A2

    公开(公告)日：2016-04-14

    申请号：PCT/US2015/054666

    申请日：2015-10-08

    Applicant: ACETYLON PHARMACEUTICALS, INC.

    Inventor： SHEARSTONE, Jeffrey, R. ,  JARPE, Matthew, B.

    CPC classification number: C07D409/14 ,  A61K31/404 ,  A61K31/47 ,  A61K31/496 ,  A61K31/5377 ,  C07D295/155 ,  C07D333/24 ,  C07D409/12

    Abstract: Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with Gata2 deficiency, particularly diseases or disorders that involve any type of HDAC1 and/or HDAC2 expression. Such diseases include acute myeloid leukemia (AML); familial myelodysplastic syndrome (MDS); leukemia; sickle-cell anemia; beta-thalassemia; monocytopenia and mycobacterial infections; dendritic cell, nonocyte, B, and natural killer lymphoid deficiency; Emberger syndrome; asymptomatic neurocognitive impairment; mild neurocognitive disorder; and HIV- associated dementia.

    Abstract translation: 本文提供化合物，包含此类化合物的药物组合物以及使用此类化合物治疗与Gata2缺陷相关的疾病或病症，特别是涉及任何类型的HDAC1和/或HDAC2表达的疾病或病症的方法 。 这些疾病包括急性骨髓性白血病（AML）; 家族性骨髓增生异常综合征（MDS）; 白血病; 镰状细胞性贫血; β-地中海贫血; 单核细胞减少症和分枝杆菌感染; 树突细胞，非细胞，B和天然杀伤性淋巴样缺陷; Emberger综合征; 无症状的神经认知障碍; 轻度神经认知障碍; 和艾滋病相关的痴呆。

    TREATMENT OF DISEASES CAUSED BY ABNORMAL LYMPHOCYTE FUNCTION WITH AN HDAC6 INHIBITOR
    44.
    发明申请
    TREATMENT OF DISEASES CAUSED BY ABNORMAL LYMPHOCYTE FUNCTION WITH AN HDAC6 INHIBITOR 审中-公开
    用HDAC6抑制剂治疗由异常淋巴细胞功能引起的疾病

    公开(公告)号：WO2015042418A1

    公开(公告)日：2015-03-26

    申请号：PCT/US2014/056584

    申请日：2014-09-19

    Applicant: ACETYLON PHARMACEUTICALS, INC. ,  EDWARD VIA COLLEGE OF OSTEOPATHIC MEDICINE ,  VIRGINIA TECH INTELLECTUAL PROPERTIES, INC.

    Inventor： REILLY, Christopher, M. ,  GAFOOR, Abdul ,  CAUDELL, David, L. ,  REGNA, Nicole L. ,  JARPE, Matthew

    IPC: A61K31/495 ,  A61P37/00 ,  A61P7/00

    CPC classification number: A61K31/505

    Abstract: An HDAC6 inhibitor (a compound of Formula I) is shown to reduce the pathogenesis associated with the B cell mediated autoimmune disease, systemic lupus erythematosus (SLE). Administration of a compound of Formula I attenuated many of the symptoms characteristic of SLE including splenomegaly, abnormal B cell differentiation, an increase in the number double-negative thymic T cells, an increase in the level of auto-antibodies such as anti-dsDNA, immune complex -mediated glomerulonephritis and an increase in inflammatory cytokine production. Treatment with a compound of Formula I also increased the number of the subject's splenic Treg cells while removing circulating auto-antibodies. Inhibition of HDAC6 altered bone marrow B cell differentiation by increasing the percentage of cells in the early-stage developmental fractions of both pro-and pre-B cells. These results demonstrate HDAC6 inhibition with a compound of Formula I can treat SLE disease by altering aberrant T and B cell differentiation.

    Abstract translation: 显示HDAC6抑制剂（式I的化合物）可以减少与B细胞介导的自身免疫性疾病，系统性红斑狼疮（SLE）有关的发病机制。 式I化合物的给药减轻了SLE特征性症状的许多症状，包括脾肿大，异常B细胞分化，双阴性胸腺T细胞数量的增加，自身抗体水平的提高，如抗dsDNA， 免疫复合物介导的肾小球肾炎和炎症细胞因子产生的增加。 使用式I化合物的治疗也增加受试者的脾Treg细胞的数量，同时除去循环自身抗体。 HDAC6的抑制通过增加前和后B细胞的早期发育部分中细胞的百分比来改变骨髓B细胞分化。 这些结果表明，用式I化合物的HDAC6抑制可以通过改变异常的T和B细胞分化来治疗SLE疾病。

    IMPROVED SYNTHESIS OF CAPURAMYCIN AND ITS ANALOGUES
    45.
    发明申请
    IMPROVED SYNTHESIS OF CAPURAMYCIN AND ITS ANALOGUES 审中-公开

    公开(公告)号：WO2015027137A8

    公开(公告)日：2015-02-26

    申请号：PCT/US2014/052246

    申请日：2014-08-22

    Applicant: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION

    Inventor： KUROSU, Michio

    IPC: C07H19/06 ,  C07H19/067 ,  A61K31/7042 ,  A61P31/04

    Abstract: Provided herein are compounds of Formula I, Formula II, and Formula X, which are useful for the treatment of infectious diseases. Also provided herein are processes for preparing 1-[5-0-[4,6-Dideoxy-6-oxo-6-[[[(3S)-hexahydro-2-oxo-1H-azepine]-3-y1]amino]-Pβ-L-erythro-4- hexenopyranosyl]-3-0-methyl 6-deoxy-6-amino-α-L-talofuranuronosyl]-1,2,3,4-tetrahydro-2,4- dioxopyrimidine (capuramycin), analogues thereof, and intermediates useful therefore. Also provided herein are III, IIIa, and IX, which are useful in the process for preparing capuramycin and/or a certain compound of Formula I.

    INHIBITING THE TRANSIENT RECEPTOR POTENTIAL A1 ION CHANNEL
    48.
    发明申请
    INHIBITING THE TRANSIENT RECEPTOR POTENTIAL A1 ION CHANNEL 审中-公开
    抑制瞬态受体电位A1离子通道

    公开(公告)号：WO2014113671A1

    公开(公告)日：2014-07-24

    申请号：PCT/US2014/012049

    申请日：2014-01-17

    Applicant: CUBIST PHARMACEUTICALS, INC.

    Inventor： LI, Qingyi ,  CHENG, Lily ,  LIU, Christopher ,  WRONA, Iwona ,  LIPPA, Blaise, S. ,  METCALF, Chester, A. III ,  JACKSON, Andrew, J.

    IPC: C07D473/08

    CPC classification number: C07D473/08 ,  C07F9/092

    Abstract: Provided herein are pharmaceutical compositions and methods for the treatment of pain, respiratory conditions, including chronic or inflammatory pain, asthma or COPD as well as inhibiting the Transient Receptor Potential Al (TRPA1 ) ion channel. The compounds include tetrahydropurinyl alpha-methyl amide derivatives containing heterocyclic moieties such as pyridinyl, pyrimidinyl, pyrazinyl, and pyrrolidinyl. One such example includes (S)-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(6-(2-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-yl)propanamide.

    Abstract translation: 本文提供了用于治疗疼痛，呼吸病症（包括慢性或炎性疼痛，哮喘或COPD）以及抑制瞬时受体电位Al（TRPA1）离子通道的药物组合物和方法。 所述化合物包括含有杂环部分的四氢嘌呤基α-甲基酰胺衍生物，例如吡啶基，嘧啶基，吡嗪基和吡咯烷基。 一个这样的实例包括（S）-2-（1,3-二甲基-2,6-二氧代-1,2,3,6-四氢-7H-嘌呤-7-基）-N-（6-（2- （（S）-2-（三氟甲基）吡咯烷-1-基）嘧啶-5-基）吡嗪-2-基）丙酰胺。

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