专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

11. 发明授权

US06185506B2 Method for selecting an optimally diverse library of small molecules based on validated molecular structural descriptors 失效
标题翻译：基于经验证的分子结构描述符选择小分子的最佳多样文库的方法
公开(公告)号：US06185506B2
公开(公告)日：2001-02-06
申请号：US08592132
申请日：1996-01-26
申请人： Richard D. Cramer , David E. Patterson , Robert D. Clark , Allan M. Ferguson
发明人： Richard D. Cramer , David E. Patterson , Robert D. Clark , Allan M. Ferguson
IPC分类号： G06F1700
CPC分类号： C40B50/02 , B01J2219/007 , C40B30/02 , G06F19/704 , Y10S707/99943
摘要： The use of biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets. By the appropriate application of validated metrics, the method of this invention selects a subset of a combinatorial accessible chemical universe such that the molecules of the subset are representative of all the diversity present in the universe and yet do not contain multiple members which represent the same diversity (oversample). The use of the neighborhood definition of a validated metric may also be used to combine (without oversampling the same diversity) any number of combinatorial screening libraries.
摘要翻译：只有当子集包含代表宇宙总体多样性的成员时，才能使用大型组合可访问化学宇宙的子集（库）的生物筛选目的来提高筛选过程的效率。为了确保包含在表示所考虑的宇宙总体多样性的分子子集中，需要定量反映宇宙中分子多样性的有效分子描述符。一种独特的验证方法用于检查新的三维空间度量和一些现有技术的度量。使用这种方法，可以从其应用于随机选择的文献数据集中确定各个度量的相对有用性/有效性。通过适当应用经验证的度量，本发明的方法选择组合可访问化学宇宙的子集，使得该子集的分子代表存在于宇宙中的所有分集，但不包含表示相同的多个成员多样性（过度抽样）。使用验证度量的邻域定义也可以用于组合（不过采样相同的多样性）任意数量的组合筛选库。

12. 发明授权

US5307287A Comparative molecular field analysis (COMFA) 失效
标题翻译：比较分子场分析（COMFA）
公开(公告)号：US5307287A
公开(公告)日：1994-04-26
申请号：US716824
申请日：1991-06-17
申请人： Richard D. Cramer, III , Svante B. Wold
发明人： Richard D. Cramer, III , Svante B. Wold
IPC分类号： C07K1/00 , G06F17/17 , G06F17/30 , G06F17/50 , G06F19/00 , G06F15/46
CPC分类号： C07K1/00 , G06F17/50 , G06F19/704 , G06F19/708 , G06F2217/10
摘要： Comparative Molecular Field Analysis (CoMFA) is an effective computer implemented methodology of 3D-QSAR employing both interactive graphics and statistical techniques for correlating shapes of molecules with their observed biological properties. For each molecule of a series of known substrates the steric and electrostatic interaction energies with a test probe atom are calculated at spatial coordinates around the molecule. Subsequent analysis of the data table by a partial least squares (PLS) cross-validation technique yields a set of coefficients which reflect the relative contribution of the shape elements of the molecular series to differences in biological activities. Display in three dimensions in an interactive graphics environment of the spatial volumes highly associated with biological activity, and comparison with molecular structures yields an understanding of intermolecular associations. CoMFA will also predict the biological activity of new molecular species.
摘要翻译：比较分子场分析（CoMFA）是3D-QSAR的有效计算机实现方法，采用交互式图形和统计技术将分子形状与其观察到的生物学特性相关联。对于一系列已知底物的每个分子，在分子周围的空间坐标处计算与测试探针原子的空间和静电相互作用能量。通过偏最小二乘法（PLS）交叉验证技术对数据表的后续分析产生一组系数，其反映了分子序列的形状元素对生物活性差异的相对贡献。在与生物活性高度相关的空间体积的交互式图形环境中显示三维，并与分子结构进行比较，可以了解分子间的关联。 CoMFA还将预测新分子物种的生物活性。

13. 发明授权

US5025388A Comparative molecular field analysis (CoMFA) 失效
标题翻译：比较分子场分析（CoMFA）
公开(公告)号：US5025388A
公开(公告)日：1991-06-18
申请号：US237491
申请日：1988-08-26
申请人： Richard D. Cramer, III , Svante B. Wold
发明人： Richard D. Cramer, III , Svante B. Wold
IPC分类号： C07K1/00 , G06F17/17 , G06F17/30 , G06F17/50 , G06F19/00
CPC分类号： C07K1/00 , G06F17/50 , G06F19/704 , G06F19/708 , G06F2217/10
摘要： Comparative Molecular Field Analysis (CoMFA) is an effective computer implemented methodology of 3D-QSAR employing both interactive graphics and statistical techniques for correlating shapes of molecules with their observed biological properties. For each molecule of a series of known substrates the steric and electrostatic interaction energies with a test probe atom are calculated at spatial coordinates around the molecule. Subsequent analysis of the data table by a partial least squares (PLS) cross-validation technique yields a set of coefficients which reflect the relative contribution of the shape elements of the molecular series to differences in biological activities. Display in three dimensions in an interactive graphics environment of the spatial volumes highly associated with biological activity, and comparison with molecular structures yields an understanding of intermolecular associations. CoMFA will also predict the biological activity of new molecular species.
摘要翻译：比较分子场分析（CoMFA）是3D-QSAR的有效计算机实现方法，采用交互式图形和统计技术将分子形状与其观察到的生物学特性相关联。对于一系列已知底物的每个分子，在分子周围的空间坐标处计算与测试探针原子的空间和静电相互作用能。通过偏最小二乘法（PLS）交叉验证技术对数据表的后续分析产生一组系数，其反映了分子序列的形状元素对生物活性差异的相对贡献。在与生物活性高度相关的空间体积的交互式图形环境中显示三维，并与分子结构进行比较，可以了解分子间的关联。 CoMFA还将预测新分子物种的生物活性。

14. 发明申请

US20110282910A1 Template Constrained Fragment Alignment Used To Identify Fragments Of Similar Shape and Activity In Drug Development 有权
标题翻译：用于识别药物开发中类似形状和活性的片段的模板约束片段比对
公开(公告)号：US20110282910A1
公开(公告)日：2011-11-17
申请号：US13018195
申请日：2011-01-31
申请人： Richard D. Cramer
发明人： Richard D. Cramer
IPC分类号： G06F17/30
CPC分类号： G06F19/706
摘要： The computational drug discovery method disclosed herein permits a user to specify a three dimensional representation of a molecular fragment derived from a query molecule involved in a drug interaction that then serves as a template to which fragments derived from molecules in database libraries may be aligned. The likely activity of the substitution of the fragment from the database library for the fragment from the query molecule may then be predicted by appropriate shape characterization and CoMFA analysis. The spatial three dimensional representation of the query fragment may be developed from binding data, crystallographic data, modeling data, or any other biophysical or biochemical technique. The alignment method of the present invention supplants the topomeric alignment taught in U.S. Pat. No. 7,329,222 and U.S. application Ser. No. 12/045,511 for use in computing a CoMFA 3D QSAR.
摘要翻译：本文公开的计算药物发现方法允许用户指定衍生自参与药物相互作用的查询分子的分子片段的三维表示，其然后用作模板，来自数据库文库中的分子的片段可以与其对齐。然后可以通过适当的形状表征和CoMFA分析来预测来自查询分子的来自数据库库的片段的可能活性。查询片段的空间三维表示可以从结合数据，晶体学数据，建模数据或任何其他生物物理或生物化学技术开发。本发明的取向方法取代了美国专利No. 美国专利申请第7,329,222号， No. 12 / 045,511，用于计算CoMFA 3D QSAR。

15. 发明授权

US07096162B2 Computer-implemented method of merging libraries of molecules using validated molecular structural descriptors and neighborhood distances to maximize diversity and minimize redundancy 失效
标题翻译：使用验证的分子结构描述符和邻域距离合并分子库的计算机实现的方法，以最大化分集和最小化冗余
公开(公告)号：US07096162B2
公开(公告)日：2006-08-22
申请号：US09776711
申请日：2001-02-05
申请人： Richard D. Cramer , David E. Patterson
发明人： Richard D. Cramer , David E. Patterson
IPC分类号： G06G7/48 , G01N33/48 , G06F7/00
CPC分类号： C40B50/02 , B01J2219/007 , C40B30/02 , G06F19/704 , Y10S707/99943
摘要： The use for biological screening purposes of a subset (library) of a large combinatorially accessible chemical universe increases the efficiency of the screening process only if the subset contains members representative of the total diversity of the universe. In order to insure inclusion in the subset of molecules representing the total diversity of the universe under consideration, valid molecular descriptors which quantitatively reflect the diversity of the molecules in the universe are required. A unique validation method is used to examine both a new three dimensional steric metric and some prior art metrics. With this method, the relative usefulness/validity of individual metrics can be ascertained from their application to randomly selected literature data sets. By the appropriate application of validated metrics, the method of this invention selects a subset of a combinatorial accessible chemical universe such that the molecules of the subset are representative of all the diversity present in the universe and yet do not contain multiple members which represent the same diversity (oversample). The use of the neighborhood definition of a validated metric may also be used to combine (without oversampling the same diversity) any number of combinatorial screening libraries.
摘要翻译：用于大型组合可访问化学宇宙的子集（库）的生物筛选目的仅在子集包含代表宇宙总体多样性的成员时提高筛选过程的效率。为了确保包含在表示所考虑的宇宙总体多样性的分子子集中，需要定量反映宇宙中分子多样性的有效分子描述符。一种独特的验证方法用于检查新的三维空间度量和一些现有技术的度量。使用这种方法，可以从其应用于随机选择的文献数据集中确定各个度量的相对有用性/有效性。通过适当应用经验证的度量，本发明的方法选择组合可访问化学宇宙的子集，使得该子集的分子代表存在于宇宙中的所有分集，但不包含表示相同的多个成员多样性（过度抽样）。使用验证度量的邻域定义也可以用于组合（不过采样相同的多样性）任意数量的组合筛选库。

16. 发明授权

US4161609A Synthesis of carboxylic acid esters 失效
标题翻译：羧酸酯的合成
公开(公告)号：US4161609A
公开(公告)日：1979-07-17
申请号：US833371
申请日：1977-09-14
申请人： Richard D. Cramer
发明人： Richard D. Cramer
IPC分类号： C07C67/20
CPC分类号： C07C67/20
摘要： A method is provided for converting a carboxylic acid amide to a carboxylic acid ester by reacting a vaporized mixture of the amide and an aliphatic alcohol or a phenol in the presence of a suitable catalyst at temperatures of from 100.degree. C. to 400.degree. C. The process is especially useful for the conversion of methacrylamide to methyl methacrylate.
摘要翻译：提供了一种通过在合适的催化剂存在下，在100℃至400℃的温度下使酰胺和脂族醇或酚的汽化混合物反应将羧酸酰胺转化为羧酸酯的方法。该方法对甲基丙烯酰胺转化成甲基丙烯酸甲酯是特别有用的。

17. 发明申请

US20150025871A1 Method for Aligning Molecules in Three Dimensions Based Upon Their Correspondence To An Exemplary Template Molecule for Use In Performing 3D QSAR Analyses 有权
标题翻译：基于与对应于用于执行3D QSAR分析的示例性模板分子的对应关系的三个维度中的分子对准的方法
公开(公告)号：US20150025871A1
公开(公告)日：2015-01-22
申请号：US14337832
申请日：2014-07-22
申请人： Richard D. Cramer
发明人： Richard D. Cramer
IPC分类号： G06F19/00
摘要： A computerized procedure for aligning molecules for use in CoMFA or other 3D QSAR methodologies does not rely on fragmentation of the molecules instead, aligning molecules based upon comparison to identified template molecules.Initially an anchor bond is identified in the candidate and template molecule that have similar atoms at each end of the bonds. Unlike prior art methods, the anchor bond need not be an acyclic bond. The candidate molecule is overlaid onto the template molecule by aligning the anchor bonds. Starting and working away from the anchor bond, matching atoms or atom types between the candidate and template molecule are identified. Multiple layers of atomic connections are evaluated for matches. The atoms may or may not be contained within ring structures. Once all matching atoms have been identified, the 3D coordinates of the template atoms are assigned to the corresponding atoms in the candidate molecule to place the candidate molecule into alignment.Automation of the method sequentially uses every bond in the template and candidate molecule structures as an anchor bond to identify the best alignment. The total number of combinatorial possibilities for the automated process may be reduced by use of several criteria. Subsequently, following the usual CoMFA analytical procedure, the aligned molecules can be placed into a three dimensional grid, their shapes characterized by electrostatic and steric interaction energies, and the resulting shape characterizations along with their structure activity relationship data used to populate the CoMFA data table. Resulting CoMFA analyses yield superior 3D QSARs.
摘要翻译：用于对齐用于CoMFA或其他3D QSAR方法学的分子的计算机程序不依赖于分子的碎裂，而是基于与鉴定的模板分子的比较来对齐分子。最初在候选和模板分子中识别出锚键在每个末端具有相似的原子。不同于现有技术的方法，锚键不一定是非环键。将候选分子通过对准锚定键重叠在模板分子上。开始和离开锚点，确定候选和模板分子之间匹配的原子或原子类型。评估多层原子连接的匹配。原子可以包含或不包含在环结构内。一旦所有匹配的原子已被鉴定，模板原子的3D坐标被分配给候选分子中的相应原子，以使候选分子对齐。该方法的自动化顺序地使用模板中的每个键和候选分子结构作为锚键以确定最佳对准。可以通过使用几个标准来减少自动化过程的组合可能性的总数。随后，按照通常的CoMFA分析程序，对准的分子可以放置在三维网格中，其形状以静电和空间相互作用能为特征，并且所得到的形状特征以及用于填充CoMFA数据表的结构活动关系数据。所得到的CoMFA分析产生优异的3D QSAR。

18. 发明授权

US06240374B1 Further method of creating and rapidly searching a virtual library of potential molecules using validated molecular structural descriptors 失效
标题翻译：使用验证的分子结构描述符创建和快速搜索潜在分子的虚拟文库的进一步方法
公开(公告)号：US06240374B1
公开(公告)日：2001-05-29
申请号：US08903217
申请日：1997-07-20
申请人： Richard D. Cramer , David E. Patterson
发明人： Richard D. Cramer , David E. Patterson
IPC分类号： G06F100
CPC分类号： C40B30/02 , B01J2219/007 , C40B50/02 , G06F19/704 , Y10S707/99943
摘要： The problem of how to select out of a large chemically accessible universe molecules representative of the diversity of that universe is resolved by the discovery of a method to validate molecular structural descriptors. Using the validated descriptors, optimally diverse subsets can be selected. In addition, from the universe, molecules with characteristics similar to a selected molecule can be identified. The validated descriptors also enable the generation of a huge virtual library of potential product molecules which could be formed by combinatorial arrangement of structural variations and cores. In this virtual library it is possible to search billions of possible product compounds in relatively short time frames.
摘要翻译：通过发现一种验证分子结构描述符的方法来解决如何选择代表宇宙多样性的大型化学可及性宇宙分子的问题。使用经过验证的描述符，可以选择最佳多样化的子集。此外，从宇宙中，可以鉴定具有与选定分子相似的特征的分子。经验证的描述符还可以生成潜在产品分子的巨大虚拟库，这些潜在的产品分子可以通过结构变化和核心的组合排列来形成。在这个虚拟库中，可以在相对较短的时间范围内搜索数十亿种可能的产品化合物。

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式