133565-43-2Relevant articles and documents
Discovery of a JAK1/3 Inhibitor and Use of a Prodrug to Demonstrate Efficacy in a Model of Rheumatoid Arthritis
Spergel, Steven H.,Mertzman, Michael E.,Kempson, James,Guo, Junqing,Stachura, Sylwia,Haque, Lauren,Lippy, Jonathan S.,Zhang, Rosemary F.,Galella, Michael,Pitt, Sidney,Shen, Guoxiang,Fura, Aberra,Gillooly, Kathleen,McIntyre, Kim W.,Tang, Vicky,Tokarski, John,Sack, John S.,Khan, Javed,Carter, Percy H.,Barrish, Joel C.,Nadler, Steven G.,Salter-Cid, Luisa M.,Schieven, Gary L.,Wrobleski, Stephen T.,Pitts, William J.
supporting information, p. 306 - 311 (2019/03/19)
The four members of the Janus family of nonreceptor tyrosine kinases play a significant role in immune function. The JAK family kinase inhibitor, tofacitinib 1, has been approved in the United States for use in rheumatoid arthritis (RA) patients. A number
A multifaceted secondary structure mimic based on piperidine-piperidinones
Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
supporting information, p. 3594 - 3598 (2014/04/17)
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
Hydrodehalogenation of alkyl iodides with base-mediated hydrogenation and catalytic transfer hydrogenation: Application to the asymmetric synthesis of N-protected α-methylamines
Mandal, Pijus K.,Birtwistle, J. Sanderson,McMurray, John S.
, p. 8422 - 8427 (2015/03/18)
We report a very mild synthesis of N-protected α-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile protecting groups, such as benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus allowing the conversion of virtually any protected amino acid into the corresponding N-protected α-methylamine.
An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator
Nagendra,Madhu,Vishwanatha,Sureshbabu, Vommina V.
experimental part, p. 5059 - 5063 (2012/09/22)
A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propane phosphonic acid cyclic anhydride (T3P) and subsequent reduction of the intermediate phosphonic anhydride with NaBH4 yield the alcohol in excellent yields with good purity in less duration. Reduction of several alkyl/aryl carboxylic acids and Nα-protected amino acids/peptide acids as well as Nβ-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields and the products characterized. The procedure is mild, safe, simple and the isolation of the products is easy.
Synthesis of threo-β-aminoalcohols from aminoaldehydes via chelation-controlled additions. Total synthesis of l-threo sphingosine and safingol
Jung, Michael E.,Yi, Sung Wook
supporting information; experimental part, p. 4216 - 4220 (2012/08/29)
Chelation-controlled addition of organocuprates to N-carbamoyl aminoaldehydes, prepared from functionalized amino acids, generated predominately the threo-β-amino alcohol derivatives through chelation with the carbamoyl moiety. The carbamate group is a stronger chelating group than other potentially good chelators, for example ethers, esters, thioethers, and gives good diastereoselectivity with cuprates. Thus addition of lithium divinylcuprate to the aldehyde generated from the serine derivative 25 in the presence of extra copper for chelation afforded the threo compound 26 in 83% yield. Cross-metathesis and cleavage of the protecting groups furnished l-threo sphingosine 21. In addition the lyso-sphingolipid protein kinase C inhibitor, safingol, 22, was prepared from commercially available O-benzyl N-BOC serine 28 in six steps and 56% overall yield by this method.
Expedient synthesis of 1,3-substituted benzene peptidomimetics
Bach, Anders,Stromgaard, Kristian
experimental part, p. 807 - 815 (2011/04/25)
A synthetic route for replacing the central amino acid in the tripeptide Thr-Ala-Val (TAV) with a 1,3-substituted benzene ring was developed. l-Threonine was introduced into the benzene ring by a Grignard reaction with protected l-threoninal, where the na
Simple and efficient synthesis of Fmoc/Boc/Cbz-protected-β-amino alcohols and peptidyl alcohols employing Boc2O
Lalithamba,Sureshbabu, Vommina V.
experimental part, p. 1372 - 1378 (2011/01/13)
An efficient method for the activation of Fmoc/Boc/Cbz-protected amino acids using Boc2O and the reduction of the in situ generated carbonic-carbonic anhydride to their corresponding 1β-amino alcohols using sodium borohydride has been described. The method is simple, rapid and free from racemization. Besides, the protocol is also extended for the conversion of N-urethane protected peptide acids to their corresponding alcohols. Copyright
Synthesis of N-urethane protected β-amino alcohols employing N-(protected-α-aminoacyl)benzotriazoles
Sureshbabu, Vommina V.,Sudarshan,Muralidhar,Narendra
, p. 683 - 685 (2008/09/20)
A simple and racemisation-free synthesis of N-urethane protected α-amino/peptidyl alcohols by the reduction of the corresponding easily accessible N-acylbenzotriazoles is described. The method is practical, straightforward, fast and efficient for the synt
Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl
Alper, Phillip B.,Liu, Hong,Chatterjee, Arnab K.,Nguyen, Khanhlinh T.,Tully, David C.,Tumanut, Christine,Li, Jun,Harris, Jennifer L.,Tuntland, Tove,Chang, Jonathan,Gordon, Perry,Hollenbeck, Thomas,Karanewsky, Donald S.
, p. 1486 - 1490 (2007/10/03)
A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the P1 pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S.
Dehydrooligopeptides. XVII. Practical syntheses of all of the diastereomers of N,N-protected 2,3-diaminobutanoic acids from L- and D-threonine derivatives
Nakamura,Hirai,Tamotsu,Yonezawa,Shin
, p. 1369 - 1377 (2007/10/02)
Syntheses of all of the dioctereomers of 2,3-diaminobutanoic acids, found in some pedtide antibiotics and toxins, were accomplished. The four isomers were derived mainly through two pathways including S(N)2 inversions of the β-substituent of L- or D-threonine derivatives. The various protecting groups and effective nucleophiles for the S(N)2 inversion were examined.
