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:US-8017323-B2 优先权日:2003-03-26 标 题 :Free reactant use in nucleic acid-templated synthesis 发明人:LIU DAVID R; SAKURAI KAORI 权利人:HARVARD COLLEGE 摘要:The present invention provides methods and compositions for expanding the scope of chemical reactions that can be performed during nucleic acid-templated organic syntheses. In particular, nucleic acid-templated chemistries are used to produce reaction intermediates attached to an oligonucleotide that can be used to identify the reaction intermediates and/or the resulting reaction products. The reaction intermediates then are reacted with free reactants (for example, reactants that are difficult or impractical to couple to an oligonucleotide) to produce a reaction product. This approach expands the scope of reagents useful in nucleic acid-templated syntheses to reagents that do not need to be or cannot be tethered to an oligonucleotide. The reagents, however, still permit the synthesis of reaction products attached to oligonucleotides that can be used to identify the reaction products.
专利号:WO-2013035102-A1 优先权日:2011-09-05 标 题 :Processes for the preparation of imatinib base and intermediates thereof 发明人:KOMPELLA AMALA KISHAN; RACHAKONDA SREENIVAS; GAMPA VENU GOPALA KRISHNA; ADIBHATLA KALI SATYA BHUJANGA RAO; NANNAPANENI VENKAIAH CHOWDARY 权利人:NATCO PHARMA LTD; KOMPELLA AMALA KISHAN; RACHAKONDA SREENIVAS; GAMPA VENU GOPALA KRISHNA; ADIBHATLA KALI SATYA BHUJANGA RAO; NANNAPANENI VENKAIAH CHOWDARY 摘要:The invention relates to an improved process for the preparation of highly pure imatinib base (99.99% HPLC purity) of formula (I) and the pharmaceutically acceptable acid addition salts thereof. This invention also relates to processes for the preparation of the intermediates in the synthesis of imatinib base.
专利号:US-4719053-A 优先权日:1980-08-01 标题 :Beta-chloroethylsulfonylmethyl-benzoic halides as intermediates 发明人:SCHLAEFER LUDWIG; HAEHNLE REINHARD 权利人:HOECHST AG 摘要:New beta -chloroethylsuflonylmethyl-benzoic acid halides which can serve as fibre-reactive anchors for thesynthesis of novel organic, water-soluble compounds, preferably dyestuffs, having fibre-reactive and fibre-finishing properties, such as preferably dyestuff properties, and containing, as a fibre-reactive group, one or two beta -chloroethylsufonylmethylbenzoic acid amide groups. For the synthesis of these novel fibre-finishing compounds, said new beta -chloroethylsulfonylmethyl-benzoic acid halide compounds are reacted with an organic, water-soluble compound having fibre-finishing properties and continuing one or two amino groups. Also precursors of the fibre-finishing, fibre-reactive compounds, containing said beta -chloroethylsulfonylmethyl-benzxoic acid amid grouping, can be employed for their synthesis. The novel fibre-finishing compounds can be applied onto suitable fibre materials, such as especially cellulose fibre material and natural or synthetic polyamide fibre materials, and fixed on these fibre materials in a manner similar to application and fixation methods usual in the technique for fibre-reactive compounds. The fibre-finished material, such as dyed material, shows very good wet fastnesses.
[参考文献]: Mankil Jung, Et Al. Design, Synthesis, And Discovery Of Stilbene Derivatives Based On Lithospermic Acid B As Potent Protein Tyrosine Phosphatase 1B Inhibitors. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4481-6. [参考文献]: Yasuo Yoshimi, Et Al. Improved Gate Effect Enantioselectivity Of Phenylalanine-Imprinted Polymers In Water By Blending Crosslinkers. Anal Chim Acta. 2015 Mar 3:862:77-85.
合成参考文献
摘要:Subramanian, L. R., Science of Synthesis, (2004) 19, 173.