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    Aminopyrimidine derivatives as antiviral agents for respiratory syncytial virus
    1.
    发明授权
    Aminopyrimidine derivatives as antiviral agents for respiratory syncytial virus 失效
    氨基嘧啶衍生物作为呼吸道合胞病毒的抗病毒剂

    公开(公告)号：US5256668A

    公开(公告)日：1993-10-26

    申请号：US032065

    申请日：1993-03-17

    申请人： Kuo-Hom L. Hsu ,  Daniel M. Teller ,  Alan R. Davis ,  Michael D. Lubeck ,  Jehan F. Bagli

    发明人： Kuo-Hom L. Hsu ,  Daniel M. Teller ,  Alan R. Davis ,  Michael D. Lubeck ,  Jehan F. Bagli

    IPC分类号： A61K31/505

    CPC分类号： A61K31/505

    摘要： Antiviral activity against respiratory syncytial virus has been found in some substituted 6-aminopyrimidines having the formula: ##STR1## wherein R.sup.1 is lower alkyl, preferably methyl or t-butyl, R.sup.2 is halogen or cyano, and R.sup.3 is C.sub.1 -C.sub.6 alkyl or --(CH.sub.2).sub.n R.sup.4 where n is 1 or 2 and R.sup.4 is phenyl, phenyl substituted by lower alkoxy, lower alkyleneoxy, bromo, or 3,4-methylenedioxy; 3 or 4-pyridinyl, pyridinyl substituted by cyano or bromo, thienyl, or di-(C.sub.1 -C.sub.6 alkyl)amino.

    摘要翻译： 已经在一些具有下式的取代的6-氨基嘧啶中发现抗呼吸道合胞病毒的抗病毒活性：其中R1是低级烷基，优选甲基或叔丁基，R2是卤素或氰基，R3是C1-C6烷基或 - （CH2）nR4，其中n是1或2，R4是苯基，被低级烷氧基取代的苯基，低级亚烷基氧基，溴代或3,4-亚甲基二氧基; 3或4-吡啶基，被氰基或溴取代的吡啶基，噻吩基或二 - （C1-C6烷基）氨基。

    Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants
    6.
    发明授权
    Immunogenic compositions comprising cold-adapted attenuated respiratory syncytial virus mutants 失效
    包含冷适应性减毒呼吸道合胞病毒突变体的免疫原性组合物

    公开(公告)号：US06284254B1

    公开(公告)日：2001-09-04

    申请号：US08453304

    申请日：1995-05-30

    申请人： Brian R. Murphy ,  Robert M. Chanock ,  James E. Crowe, Jr. ,  Mark Connors ,  Kuo-Hom Lee Hsu ,  Alan R. Davis ,  Michael D. Lubeck ,  Bernard H. Selling

    发明人： Brian R. Murphy ,  Robert M. Chanock ,  James E. Crowe, Jr. ,  Mark Connors ,  Kuo-Hom Lee Hsu ,  Alan R. Davis ,  Michael D. Lubeck ,  Bernard H. Selling

    IPC分类号： A61K39155

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K39/155 ,  A61K2039/5254 ,  A61K2039/543 ,  C12N2760/18534 ,  C12N2760/18561

    摘要： The respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and children throughout the world. RSV is a major cause of pneumonia and bronchiolitis in infants under one year of age, and is a major cause of fatal respiratory tract disease in these infants. The treatment and prevention of RSV infection has been problematic. However, the present invention addresses some of these concerns by providing attenuated RSV strains that are suitable for inclusion in immunizing compositions. Specifically, the present invention is directed toward the introduction of growth restriction mutations into incompletely attenuated host range-restricted cold-passaged respiratory syncytial virus (cpRSV) strains by further passage of the strains at increasingly reduced temperatures to produce derivative strains which are more satisfactorily attenuated. These cold-adaptation (ca) approaches were used to introduce further attenuation in the parental RSV virus cpRSV-3131, which is incompletely attenuated in seronegative children. Mutants of the parental strain were obtained by selecting for large plaque production at reduced temperatures. An RSV cp-3131 derivative, designated D1, was isolated that produces large plaques at 25° C. Biologically cloned virus D1 produces distinctly and uniformly larger plaques at 25° C. as compared to the parental attenuated strain cpRSV-3131 or wild-type strain A2. Thus, D1 is an attenuated cold-adapted, but not temperature-sensitive, RSV mutant. The invention also provides methods for stimulating RSV-specific immune responses in an individual through the administration of said mutants.

    摘要翻译： 呼吸道合胞病毒（RSV）是全世界婴幼儿下呼吸道疾病的主要原因。 RSV是一岁以下婴儿肺炎和细支气管炎的主要原因，是这些婴儿致命性呼吸道疾病的主要原因。 RSV感染的治疗和预防是有问题的。 然而，本发明通过提供适于包含在免疫组合物中的减毒RSV菌株来解决其中的一些问题。 具体而言，本发明涉及通过在越来越多的降低的温度下进一步通过菌株，将生长限制性突变引入不完全减毒的宿主范围限制的冷传代呼吸道合胞病毒（cpRSV）菌株，以产生更令人满意地减毒的衍生菌株 。 这些冷适应（ca）方法用于在父母RSV病毒cpRSV-3131中引入进一步的衰减，其在血清阴性儿童中不完全减毒。 通过在降低的温度下选择大的斑块产生来获得亲本菌株的突变体。 分离出标记为D1的RSV cp-3131衍生物，其在25℃下产生大噬菌斑。与亲本减毒株cpRSV-3131或野生型相比，生物克隆病毒D1在25℃下产生明显均匀的大斑块 菌株A2。 因此，D1是减毒的冷适应但不是温度敏感的RSV突变体。 本发明还提供了通过施用所述突变体来刺激个体中RSV特异性免疫应答的方法。