公开(公告)号：US5958792A

公开(公告)日：1999-09-28

申请号：US485006

申请日：1995-06-07

申请人： Manoi C. Desai ,  John M. Nuss ,  Kerry L. Spear ,  Rajinder Singh ,  Paul A. Renhowe ,  Edward G. Brown ,  Lutz Richter ,  Barbara O. Scott

发明人： Manoi C. Desai ,  John M. Nuss ,  Kerry L. Spear ,  Rajinder Singh ,  Paul A. Renhowe ,  Edward G. Brown ,  Lutz Richter ,  Barbara O. Scott

IPC分类号： C07D239/42 ,  C07B61/00 ,  C07C235/84 ,  C07D207/16 ,  C07D211/76 ,  C07D211/86 ,  C07D213/85 ,  C07D223/16 ,  C07D307/46 ,  C07D309/32 ,  C07D491/052 ,  C07D493/04 ,  C07K1/04 ,  C40B40/04 ,  C40B50/00 ,  G01N33/543 ,  A61K38/06 ,  G01N33/53 ,  G01N33/545

CPC分类号： C40B50/14 ,  C07C231/12 ,  C07K1/047 ,  C40B40/04 ,  C07B2200/11

摘要： The invention relates to libraries of cyclic organic compounds and method of producing and assaying such libraries. According to the invention, each cyclic organic compound is constructed from a starting material in the form of a solid surface derivatized with a starting resin. Compounds are reacted with the resin to add or to form a cyclic group. The reactions are preferable carried out using a split resin procedure so that different compounds can be reacted with a plurality of subamounts so as to increase the size of the library. For example, compounds are reacted with a solid support bound starting resin to obtain a compound which includes an aldehyde functional group wherein the aldehyde compound or compounds reacted with it have substituents which are varied such that a mixture of products is obtained. The invention further relates to methods of producing combinatorial libraries of cyclic organic compounds from substrate bound compounds by cleaving the compounds from the support after synthesizing is completed and to assaying libraries of such compounds.

摘要翻译： 本发明涉及循环有机化合物的文库以及生产和测定这些文库的方法。 根据本发明，每种环状有机化合物由起始树脂衍生化的固体表面形式的原料构成。 化合物与树脂反应以加成或形成环状基团。 反应优选使用裂解树脂方法进行，使得不同的化合物可以与多个次级基团反应，从而增加文库的大小。 例如，使化合物与固体支持体结合的起始树脂反应，得到包含醛官能团的化合物，其中醛化合物或与其反应的化合物具有变化的取代基，从而得到产物的混合物。 本发明还涉及通过在合成完成后从载体上切割化合物和测定这些化合物的文库，从底物结合的化合物生产环状有机化合物的组合文库的方法。

公开(公告)号：US5877278A

公开(公告)日：1999-03-02

申请号：US487282

申请日：1995-06-07

申请人： Ronald N. Zuckermann ,  Dane A. Goff ,  Simon Ng ,  Kerry Spear ,  Barbara O. Scott ,  Aaron C. Sigmund ,  Richard A. Goldsmith ,  Charles K. Marlowe ,  Yazhong Pei ,  Lutz Richter ,  Reyna Simon

发明人： Ronald N. Zuckermann ,  Dane A. Goff ,  Simon Ng ,  Kerry Spear ,  Barbara O. Scott ,  Aaron C. Sigmund ,  Richard A. Goldsmith ,  Charles K. Marlowe ,  Yazhong Pei ,  Lutz Richter ,  Reyna Simon

IPC分类号： C07D243/14 ,  A61K38/00 ,  C07B61/00 ,  C07D217/24 ,  C07D221/12 ,  C07D487/04 ,  C07K1/04 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C08G69/10

CPC分类号： C40B40/04 ,  C07K1/04 ,  C07K1/047 ,  C07K14/001 ,  C07K7/06 ,  C07K7/08 ,  C08G69/10 ,  C40B50/14 ,  A61K38/00 ,  B01J2219/00497 ,  B01J2219/00596 ,  B01J2219/0072 ,  C07B2200/11 ,  C40B40/10

摘要： A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a solid support-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology of the present method makes these oligomers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of the invention, such as N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of peptide-like compounds not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability.Combinatorial libraries of cyclic compounds are disclosed wherein the cyclic compounds are comprised of at least one ring structure derived from cyclization of a peptoid backbone. The diversity of product compounds is generated by the sequential addition of substituted submonomers. The combinatorial library includes 10 or more, preferably 100 or more, and more preferably 1,000 or more distinct and different compounds. The library includes each of the product compounds in retrievable and analyzable amounts and preferably includes at least one biologically active compound. Methods of synthesizing the combinatorial libraries and assay devices produced using the libraries are disclosed as is methodology for screening for and obtaining biologically active cyclic organic compounds.