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    Method of promoting cervical and vaginal secretions
    1.
    发明授权
    Method of promoting cervical and vaginal secretions 有权
    促进子宫颈和阴道分泌物的方法

    公开(公告)号：US07432252B1

    公开(公告)日：2008-10-07

    申请号：US09531851

    申请日：2000-03-20

    申请人： William Pendergast ,  Sammy Ray Shaver ,  David J. Drutz ,  Janet L. Rideout ,  Benjamin R. Yerxa

    发明人： William Pendergast ,  Sammy Ray Shaver ,  David J. Drutz ,  Janet L. Rideout ,  Benjamin R. Yerxa

    IPC分类号： A61K31/70

    CPC分类号： C07H21/00

    摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y2 and/or P2Y4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

    摘要翻译： 本发明提供了通过用P2Y2和/或P2Y4N4嘌呤能受体激动剂治疗来刺激哺乳动物的宫颈和阴道分泌物的方法。 讨论了与绝经，化疗和各种疾病状态相关的阴道干燥的治疗以及外阴疼痛的治疗。 公开了合适的激动剂，例如UTP，CTP，ATP，二核苷酸及其类似物。

    Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists
    4.
    发明授权
    Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists 失效
    二核苷多磷酸盐组合物及其治疗用作嘌呤能受体激动剂

    公开(公告)号：US06555675B2

    公开(公告)日：2003-04-29

    申请号：US09817017

    申请日：2001-03-23

    申请人： Janet Rideout ,  Benjamin R. Yerxa ,  Sammy Ray Shaver ,  James G. Douglass, III

    发明人： Janet Rideout ,  Benjamin R. Yerxa ,  Sammy Ray Shaver ,  James G. Douglass, III

    IPC分类号： C07H2100

    CPC分类号： A61K31/7084 ,  C07H19/04 ,  C07H19/20 ,  C07H21/00

    摘要： The present invention relates to certain novel dinucleotide polyphosphates of general Formulae I, II and III, and formulations thereof which are selective agonists of the P2Y purinergic receptors. They are useful in the prevention, management or treatment of diseases and disorders associated with abnormalities of tissue fluid secretion, hydration and clearance, including chronic obstructive pulmonary diseases (chronic bronchitis, PCD, cystic fibrosis, immobility-associated pneumonia), sinusitis, otitis media, nasolacrimal duct obstruction, dry eye disease, glaucoma, retinal degeneration, and edematous retinal disorders, including retinal detachment, vaginal dryness, and gastrointestinal tract disease. Finally, these novel dinucleotides may be useful for diagnostic purposes, such as the facilitation of sputum induction and expectoration for the analysis of respiratory tract secretions.

    摘要翻译： 本发明涉及通式I，II和III的某些新型二核苷酸多磷酸酯及其制剂，它们是P2Y嘌呤能受体的选择性激动剂。 它们可用于预防，管理或治疗与组织液分泌异常，水合和清除相关的疾病和病症，包括慢性阻塞性肺疾病（慢性支气管炎，PCD，囊性纤维化，不动性相关性肺炎），鼻窦炎，中耳炎 ，鼻泪管阻塞，干性眼病，青光眼，视网膜变性和水肿性视网膜病变，包括视网膜脱离，阴道干燥和胃肠道疾病。 最后，这些新型二核苷酸可用于诊断目的，例如促进痰诱导和咳痰分析呼吸道分泌物。

    Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof
    5.
    发明授权
    Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof 有权
    用尿苷5'-二磷酸治疗肺部疾病的方法及其类似物

    公开(公告)号：US06451288B1

    公开(公告)日：2002-09-17

    申请号：US09645161

    申请日：2000-08-24

    申请人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    发明人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    IPC分类号： A61K912

    CPC分类号： A61K31/7068 ,  A61K9/0073 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/10 ,  Y10S514/826 ,  Y10S514/851 ,  A61K2300/00

    摘要： Compounds of Formula I: wherein: X1, and X2 are each independently either O− or S−; X3 and X4 are each independently either —H or —OH, with the proviso that X3 and X4 are not simultaneously —H; R1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R4 is selected from the group consisting of —OR′, —SR′, —NR′, and —NR′R″, wherein R′ and R″ are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R′ is absent when R4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

    摘要翻译： 式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地为-H或-OH，条件是X 3和X 4不同时为-H; R 1为选自 由O，亚氨基，亚甲基和二卤代亚甲基组成的组; R 2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R 3选自H，烷基，酰基， 芳基和芳基烷基; 和R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基， 芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4位上的碳时，R'不存在，用于水合 肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。 还描述了含有式I化合物和式I的新化合物的药物组合物。

    Uridine 5'-diphosphate and analogs useful for treating lung diseases
    8.
    发明授权
    Uridine 5'-diphosphate and analogs useful for treating lung diseases 有权
    尿苷5'-二磷酸和类似物可用于治疗肺部疾病

    公开(公告)号：US6143279A

    公开(公告)日：2000-11-07

    申请号：US143297

    申请日：1998-08-28

    申请人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    发明人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    IPC分类号： A61K9/00 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  A61P11/00 ,  C07H19/10 ,  A61K9/12

    CPC分类号： A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  A61K9/0073 ,  C07H19/10 ,  Y10S514/826 ,  Y10S514/851

    摘要： Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

    摘要翻译： 式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地是-H或-OH，条件是X 3和X 4不同时为-H; R1选自O，亚氨基，亚甲基和二卤代亚甲基; R2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R3选自H，烷基，酰基，芳基和芳基烷基; 并且R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基 ，芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4-位上的碳时，R'不存在，用于 水分肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。 还描述了含有式I化合物和式I的新化合物的药物组合物。

    Method of treating lung diseases with uridine 5'-diphosphate and analogs thereof
    9.
    发明授权
    Method of treating lung diseases with uridine 5'-diphosphate and analogs thereof 有权
    用尿苷5'-二磷酸治疗肺部疾病的方法及其类似物

    公开(公告)号：US6022527A

    公开(公告)日：2000-02-08

    申请号：US352390

    申请日：1999-07-13

    申请人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    发明人： Richard C. Boucher, Jr. ,  Sammy Ray Shaver ,  William Pendergast ,  Benjamin Yerxa ,  Janet L. Rideout ,  Robert Dougherty ,  Dallas Croom

    IPC分类号： A61K9/00 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  A61P11/00 ,  C07H19/10 ,  A61K9/12

    CPC分类号： A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  A61K9/0073 ,  C07H19/10 ,  Y10S514/826 ,  Y10S514/851

    摘要： Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.

    摘要翻译： 式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地是-H或-OH，条件是X 3和X 4不同时为-H; R1选自O，亚氨基，亚甲基和二卤代亚甲基; R2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R3选自H，烷基，酰基，芳基和芳基烷基; 并且R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基 ，芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4-位上的碳时，R'不存在，用于 水分肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。 还描述了含有式I化合物和式I的新化合物的药物组合物。