NUCLEOSIDES AS ANTI-ORTHOPOXVIRUS AGENTS
核苷作为抗正痘病毒剂
基本信息
- 批准号:6532839
- 负责人:
- 金额:$ 26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-08-15 至 2004-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (adapted from applicant's abstract): We are proposing a study to
further develop two compound classes as potential antipoxvirus agents. The
leads for our study are carbocyclic 3-deazaadenosine, which has reproducible
and potent in vitro and in vivo anti-vaccinia virus activities, and N1-
aralkyloxyadenosines, which have reproducible and potent in vitro anti-
vaccinia virus activity, but have not yet been examined in vivo. The in vitro
activities for both lead compounds groups were previously discovered in a
USAMRIID compound screen against viruses of interest to the Army, while the in
vivo anti-vaccinia activity has been recently seen in a USAMRIID study of
compounds as potential antipoxvirus agents.
Our efforts toward the proposed carbocyclic 3-deazaadenosine analogues will be
directed toward optimizing both their antipoxvirus activities as well as their
S-adenosylhomocysteine (SAH) hydrolase inhibition. A close relationship has
been noted between these two properties in our lead compound and in a number
of other nucleoside analogues reported in the literature. We will be
targeting new carbocyclic 3-deazaadenosine analogues and other nucleoside
analogues that have a modified 5-prime side chain that can interact with the
hydrophobic and hydrophilic groups in the hydrolase pocket that normally
interact with the homocysteine of S-adenosylhomocysteine. Our pursuit of new
analogues of our N1-aralkyloxyadenosines lacks a mechanistic rationale, and
thus, we will be preparing new analogues with aralkyl (both heterocyclic and
benzylic) and cycloalkyl groups that can help in both the optimization of
their anti-vaccinia activities and the elucidation of the mechanism of action
will be joint focuses.
The synthesis of all of our target compounds will be pursued in SRI. Larger
quantities of any promising leads can also be synthesized in our Prep
laboratories. The design of future targets will be a joint effort between SRI
and our group of collaborators. Dr. John Huggins of USAMRIID, Dr. Ronald T.
Borchardt of the University of Kansas, and Dr. Erik De Clercq of the Rega
Institute in Belgium will be evaluating our compounds for their antipoxvirus
activities and their SAH hydrolase inhibition. Dr. Stewart Shuman of the
Sloan Kettering Research Institute will be helping us by concentrating on the
mechanism of action of the N1-aralkyloxyadenosine analogs.
描述(改编自申请人摘要):我们正在提出一项研究
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN A SECRIST其他文献
JOHN A SECRIST的其他文献
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{{ truncateString('JOHN A SECRIST', 18)}}的其他基金
4'-Substituted nucleoside analogs as anticancer drugs
4-取代核苷类似物作为抗癌药物
- 批准号:
8212510 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
Drug Design and Synthesis for Orthopoxvirus Infections
正痘病毒感染的药物设计与合成
- 批准号:
7652108 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
4'-Substituted nucleoside analogs as anticancer drugs
4-取代核苷类似物作为抗癌药物
- 批准号:
7464122 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
4'-Substituted nucleoside analogs as anticancer drugs
4-取代核苷类似物作为抗癌药物
- 批准号:
8018541 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
4'-Substituted nucleoside analogs as anticancer drugs
4-取代核苷类似物作为抗癌药物
- 批准号:
7758375 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
4'-Substituted nucleoside analogs as anticancer drugs
4-取代核苷类似物作为抗癌药物
- 批准号:
7585807 - 财政年份:2008
- 资助金额:
$ 26万 - 项目类别:
DESIGN OF NEW NUCLEOSIDES BASED ON ENZYME SPECIFICITIES
基于酶特异性的新核苷设计
- 批准号:
6563806 - 财政年份:2002
- 资助金额:
$ 26万 - 项目类别:
DESIGN OF NEW NUCLEOSIDES BASED ON ENZYME SPECIFICITIES
基于酶特异性的新核苷设计
- 批准号:
6300244 - 财政年份:2000
- 资助金额:
$ 26万 - 项目类别:
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