公开(公告)号：US06781000B1

公开(公告)日：2004-08-24

申请号：US09356842

申请日：1999-07-19

申请人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

发明人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

IPC分类号： C07D20912

CPC分类号： C07K5/0202 ,  A61K38/00 ,  C07K5/0205 ,  C07K5/0207 ,  C07K5/06043 ,  C07K5/0808

摘要： &agr;-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X2 is Ar or Ar—X3 wherein X3 is is —C═O, or —CH2CO—, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R1, and R2 are each individually selected from the side chains of the known natural &agr;-amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and wherein X4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R3 is selected from the known natural &agr;-amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.

摘要翻译： 用于治疗由20S蛋白酶体介导的疾病的α-酮酰胺化合物，其具有下式：其中X 2是Ar或Ar-X 3，其中X 3是-C = O或-CH 2 CO-，并且其中Ar是苯基，取代的苯基， 吲哚，取代的吲哚和任何其它杂芳基; R1和R2分别选自已知天然α-氨基酸和非天然氨基酸的侧链，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代芳基 ，1-10碳直链，支链取代的芳基，烷氧基芳基，3-8碳环烷基，杂环取代的杂环，杂芳基和取代的杂芳基; X1选自氢氧化物，一烷基氨基，二烷基氨基，醇盐，芳基氧化物，其中X4为氢氧化物，芳基氨基，单烷基氨基，二烷基氨基，醇盐或芳基醇盐; R 3选自已知的天然α-氨基酸，非天然氨基酸，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代的芳基，1-10碳直链和支链 取代的芳基，烷氧基芳基，3-8碳环烷基，杂环，取代的杂环，杂芳基和取代的杂芳基。

公开(公告)号：US6075150A

公开(公告)日：2000-06-13

申请号：US13365

申请日：1998-01-26

申请人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

发明人： Lisa Wang ,  Robert T. Lum ,  Steven R. Schow ,  Alison Joly ,  Suresh Kerwar ,  Michael M Wick

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61P37/00 ,  C07K5/02 ,  C07K5/023 ,  C07K5/027 ,  C07K5/03 ,  C07K5/06 ,  C07K5/062 ,  C07K5/083 ,  C07D209/12 ,  A01N43/38

CPC分类号： C07K5/0202 ,  C07K5/0205 ,  C07K5/0207 ,  C07K5/06043 ,  C07K5/0808 ,  A61K38/00

摘要： .alpha.-ketoamide compounds useful for treating disorders mediated by 20S proteasome in mammals having the following formula: wherein X.sub.2 is Ar or Ar--X.sub.3 wherein X.sub.3 is --C.dbd.O, or --CH.sub.2 CO--, and wherein Ar is phenyl, substituted phenyl, indole, substituted indoles, and any other heteroaryls; R.sub.1, and R.sub.2 are each individually selected from the side chains of the known natural .alpha.-amino acids and unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear, branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle substituted heterocycle, heteroaryl and substituted heteroaryl; X.sub.1 is selected from hydroxide, monoalkylamino, dialkylamino, alkoxide, arylkoxide and ##STR1## wherein X.sub.4 is hydroxide, arylamino, monoalkylamino, dialkylamino, alkoxide, or arylalkoxide; and R.sub.3 is selected from the known natural .alpha.-amino acids, unnatural amino acids, hydrogen, 1-10 carbon linear and branched alkyl, 1-10 carbon linear and branched substituted alkyl, aryl, substituted aryl, 1-10 carbon linear and branched substituted aryl, alkoxyaryl, 3-8 carbon cycloalkyl, heterocycle, substituted heterocycle, heteroaryl and substituted heteroaryl.

摘要翻译： 用于治疗由20S蛋白酶体介导的疾病的α-酮酰胺化合物，其具有下式：其中X2是Ar或Ar-X3，其中X3是-C = O或-CH2CO-，其中Ar是苯基，取代的苯基，吲哚 取代的吲哚和任何其它杂芳基; R1和R2分别选自已知天然α-氨基酸和非天然氨基酸的侧链，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代的芳基 ，1-10碳直链，支链取代的芳基，烷氧基芳基，3-8碳环烷基，杂环取代的杂环，杂芳基和取代的杂芳基; X1选自氢氧化物，单烷基氨基，二烷基氨基，醇盐，芳基醇盐，其中X4是氢氧根，芳基氨基，单烷基氨基，二烷基氨基，醇盐或芳基醇盐; R 3选自已知的天然α-氨基酸，非天然氨基酸，氢，1-10碳直链和支链烷基，1-10碳直链和支链取代的烷基，芳基，取代芳基，1-10碳直链和支链 取代的芳基，烷氧基芳基，3-8碳环烷基，杂环，取代的杂环，杂芳基和取代的杂芳基。

公开(公告)号：US5516929A

公开(公告)日：1996-05-14

申请号：US17960

申请日：1993-02-12

申请人： K. Barry Sharpless ,  Matthias Beller ,  Brent Blackburn ,  Yasuhiro Kawanami ,  Hoi-Lun Kwong ,  Yasukazu Ogino ,  Tomoyuki Shibata ,  Tatsuzo Ukita ,  Lisa Wang

发明人： K. Barry Sharpless ,  Matthias Beller ,  Brent Blackburn ,  Yasuhiro Kawanami ,  Hoi-Lun Kwong ,  Yasukazu Ogino ,  Tomoyuki Shibata ,  Tatsuzo Ukita ,  Lisa Wang

IPC分类号： C07C29/48 ,  C07C67/31 ,  C07D453/02 ,  C07D453/04 ,  C07C29/04

CPC分类号： C07C67/31 ,  C07C29/48 ,  C07D453/02 ,  C07D453/04 ,  C07B2200/07 ,  C07C2101/14 ,  C07C2101/18 ,  C07C2102/10

摘要： Osmium-catalyzed methods of addition to an olefin are discussed. In the method of asymmetric dihydroxylation of the present invention, an olefin, a chiral ligand, an organic solvent, water, an oxidant and an osmium-containing compound are combined. In the method of asymmetric oxyamination of the present invention, an olefin, a chiral ligand, an organic solvent, water, a metallochloramine derivative, an osmium-containing compound and, optionally, a tetraalkyl ammonium compound are combined. In the method of asymmetric diamination of the present invention, an olefin, a chiral ligand, an organic solvent, a metallo-chloramine derivative, an amine and an osmium-containing compound are combined. In one embodiment, an olefin, a chiral ligand which is a polymeric dihydroquinidine derivative or a dihydroquinine derivative, acetone, water, a base, an oxidant and osmium tetroxide are combined to effect asymmetric dihydroxylation of the olefin.

摘要翻译： 讨论了添加到烯烃中的锇催化方法。 在本发明的不对称二羟基化方法中，合并烯烃，手性配体，有机溶剂，水，氧化剂和含锇化合物。 在本发明的不对称氧化法的方法中，合并烯烃，手性配体，有机溶剂，水，金属氯胺衍生物，含锇化合物和任选的四烷基铵化合物。 在本发明的不对称二氨基化方法中，合并烯烃，手性配体，有机溶剂，金属氯胺衍生物，胺和含锇化合物。 在一个实施方案中，将烯烃，作为聚合二氢奎尼丁衍生物或二氢喹啉衍生物的手性配体，丙酮，水，碱，氧化剂和四氧化锇组合以实现烯烃的不对称二羟基化。

公开(公告)号：US06576619B2

公开(公告)日：2003-06-10

申请号：US09317523

申请日：1999-05-24

申请人： Brent K. Blackburn ,  Chris Melville ,  Jeff A. Zablocki ,  Venkata P. Palle ,  Elfaith O. Elzein ,  Lisa Wang

发明人： Brent K. Blackburn ,  Chris Melville ,  Jeff A. Zablocki ,  Venkata P. Palle ,  Elfaith O. Elzein ,  Lisa Wang

IPC分类号： A61K3170

CPC分类号： C07H19/16

摘要： Esters of N6-oxa, thia, thioxa and azacycloalkyl substituted adenosine derivatives having the following formula; wherein the compounds are selective adenosine type 1 receptor agonists that are useful for the treatment cardiovascular diseases and central nervous system disorders.

摘要翻译： 具有下式的N6-氧杂，硫杂，噻吩和氮杂环烷基取代的腺苷衍生物的酯;其中所述化合物是可用于治疗心血管疾病和中枢神经系统疾病的选择性腺苷1型受体激动剂。