专利号:US-5977301-A 优先权日:1992-09-24 标题 :Synthesis of N-substituted oligomers 发明人:ZUCKERMAN RONALD N; KERR JANICE M; KENT STEPHEN B H; MOOS WALTER H; SIMON REYNA J; GOFF DANE A 权利人:CHIRON CORP 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 -NH2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound alpha -haloacetamide) with a sufficient amount of a second sub-monomer comprising an -NH2 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.
专利号:EP-0671928-B1 优先权日:1992-09-24 标题 :Synthesis of n-substituted oligomers 发明人:ZUCKERMANN RONALD N; KERR JANICE M; KENT STEPHEN BRIAN HENRY; MOOS WALTER H; SIMON REYNA J; GOFF DANE A 权利人:CHIRON CORP 摘要:Poly N-substituted Glycines (poly NSGs), wherein the substituents bear purine or pyrimidine bases (R<9>) every second glycine: In addition, a solid phase method for the synthesis of N-substituted oligomers of more general structures is disclosed.The poly NSGs obtainable by this method 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 -NH2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound alpha -haloacetamide) with a sufficient amount of a second sub-monomer comprising an -NH2 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 the 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.
专利号:US-5877278-A 优先权日:1992-09-24 标题:Synthesis of N-substituted oligomers 发明人:ZUCKERMANN RONALD N; GOFF DANE A; NG SIMON; SPEAR KERRY; SCOTT BARBARA O; SIGMUND AARON C; GOLDSMITH RICHARD A; MARLOWE CHARLES K; PEI YAZHONG; RICHTER LUTZ; SIMON REYNA 权利人:CHIRON CORP 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 -NH2, 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 -NH2 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.
专利号:WO-0140193-A1 优先权日:1999-12-03 标题:Method for the synthesis of pyrazolines 发明人:BOLDI ARMEN M 权利人:CHEMRX ADVANCED TECHNOLOGIES I; BOLDI ARMEN M 摘要:The present invention provides a method for the synthesis of compounds of Formula (I). Also claimed are novel intermediates and their methods of synthesis.
专利号:US-2002103381-A1 优先权日:2000-11-30 标 题 :Method for the synthesis of pyrazolines 发明人:BOLDI ARMEN M 摘要:The present invention provides a method for the synthesis of compounds of Formula I: n n n Also claimed are novel intermediates and their methods of synthesis.
专利号:US-8278440-B2 优先权日:2010-02-17 标 题:Process for the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid 发明人:PEGLION JEAN-LOUIS; CAIGNARD PASCAL 权利人:PEGLION JEAN-LOUIS; CAIGNARD PASCAL; SERVIER LAB 摘要:Process for the synthesis of ivabradine of formula (I): n nand addition salts thereof with a pharmaceutically acceptable acid.
摘要:Pilgrim, B. S.; Tucker, M. J., Science of Synthesis Knowledge Updates, (2019) 1, 237. 摘要:Bagal, D. B.; Bhanage, B. M., Science of Synthesis: Catalytic Reduction in Organic Synthesis, (2018) 2, 387. 摘要:U.S. Army Armament Research & Development Command, Chemical Systems Laboratory, NIOSH Exchange Chemicals., NX#04483 摘要:Tang, R.-Y., Science of Synthesis: Knowledge Updates, (2024) 1, 426.