77449-94-6Relevant articles and documents
A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors
Tian, Yinping,Jin, Jin,Wang, Congying,Lv, Wenhui,Li, Xuewei,Che, Xiaona,Gong, Yanchao,Li, Yanjun,Li, Quanli,Hou, Jingli,Wang, Peng G.,Shen, Jie
supporting information, p. 2434 - 2437 (2016/07/07)
This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.
PHENYL AMINO PYRIMIDINE BICYCLIC COMPOUNDS AND USES THEREOF
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, (2014/01/17)
The present invention relates to phenyl amino pyrimidine bicyclic compounds formula (I) which are inhibitors of protein kinases including JAK kinases. In particular the compounds are active against JAK1, JAK2, JAK3 and TYK2 kinases. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.
Proline editing: A general and practical approach to the synthesis of functionally and structurally diverse peptides. Analysis of steric versus stereoelectronic effects of 4-substituted prolines on conformation within peptides
Pandey, Anil K.,Naduthambi, Devan,Thomas, Krista M.,Zondlo, Neal J.
supporting information, p. 4333 - 4363 (2013/05/08)
Functionalized proline residues have diverse applications. Herein we describe a practical approach, proline editing, for the synthesis of peptides with stereospecifically modified proline residues. Peptides are synthesized by standard solid-phase peptide synthesis to incorporate Fmoc-hydroxyproline (4R-Hyp). In an automated manner, the Hyp hydroxyl is protected and the remainder of the peptide synthesized. After peptide synthesis, the Hyp protecting group is orthogonally removed and Hyp selectively modified to generate substituted proline amino acids, with the peptide main chain functioning to "protect" the proline amino and carboxyl groups. In a model tetrapeptide (Ac-TYPN-NH2), 4R-Hyp was stereospecifically converted to 122 different 4-substituted prolyl amino acids, with 4R or 4S stereochemistry, via Mitsunobu, oxidation, reduction, acylation, and substitution reactions. 4-Substituted prolines synthesized via proline editing include incorporated structured amino acid mimetics (Cys, Asp/Glu, Phe, Lys, Arg, pSer/pThr), recognition motifs (biotin, RGD), electron-withdrawing groups to induce stereoelectronic effects (fluoro, nitrobenzoate), handles for heteronuclear NMR (19F:fluoro; pentafluorophenyl or perfluoro-tert-butyl ether; 4,4-difluoro; 77SePh) and other spectroscopies (fluorescence, IR: cyanophenyl ether), leaving groups (sulfonate, halide, NHS, bromoacetate), and other reactive handles (amine, thiol, thioester, ketone, hydroxylamine, maleimide, acrylate, azide, alkene, alkyne, aryl halide, tetrazine, 1,2-aminothiol). Proline editing provides access to these proline derivatives with no solution-phase synthesis. All peptides were analyzed by NMR to identify stereoelectronic and steric effects on conformation. Proline derivatives were synthesized to permit bioorthogonal conjugation reactions, including azide-alkyne, tetrazine-trans-cyclooctene, oxime, reductive amination, native chemical ligation, Suzuki, Sonogashira, cross-metathesis, and Diels-Alder reactions. These proline derivatives allowed three parallel bioorthogonal reactions to be conducted in one solution.
Design and stereoselective synthesis of four peptide nucleic acid monomers with cyclic structures in backbone
Watanabe, Akiko,Kiyota, Naotoshi,Yamasaki, Tetsuo,Tanda, Kazuhiro,Miyagoe, Tatsunori,Sakamoto, Masanori,Otsuka, Masami
experimental part, p. 1132 - 1139 (2011/11/05)
Four isomers of the monomer of peptide nucleic acid (PNA) were derived from (2S,4R)-4-hydroxyproline; they had different stereochemistries at the C 2 and C4 positions in the pyrrolidine ring. These different backbone conformations corresponding to four different stereochemistries were realized through a combination of inversions at the C2 and the C4 positions in pyrrolidine ring. The obtained backbone frameworks were reacted with N-benzoyl thymine to give the corresponding PNA monomers. Spectroscopic comparison of the resultant monomers confirmed their stereochemistries.
A general approach for preparation of polymer-supported chiral organocatalysts via acrylic copolymerization
Kristensen, Tor E.,Vestli, Kristian,Jakobsen, Martin G.,Hansen, Finn K.,Hansen, Tore
supporting information; experimental part, p. 1620 - 1629 (2010/04/29)
(Figure Presented) Polymer-supported chiral organocatalysts, as well as most other forms of immobilized catalysts, are traditionally prepared by a postmodification approach where modified catalyst precursors are anchored onto prefabricated polymer beads. Herein, we report an alternative and more scalable approach where polymer-supported chiral enamine and iminium organocatalysts are prepared in a bottom-up fashion where methacrylic functional monomers are prepared in an entirely nonchromatographic manner and subsequently copolymerized with suitable comonomers to give cross-linked polymer beads. All syntheses have been conducted on multigram scale for all intermediates and finished polymer products, and the catalysts have proven successful in reactions taking place in solvents spanning a wide range of solvent polarity. While polymer-supported proline and prolineamides generally demonstrated excellent results and recycling robustness in asymmetric aldol reactions of ketones and benzaldehydes, the simplest type of Joargensen/Hayashi diarylprolinol TMS-ether showed excellent selectivity, but rather sluggish reactivity in the Enders-type asymmetric cascade. The polymer-supported version of the first-generation MacMillan imidazoHdinone had a pattern of reactivity very similar to that of the monomeric catalyst, but is too unstable to allow recycling.
MINERALOCORTICOID RECEPTOR ANTAGONIST AND METHODS OF USE
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Page/Page column 21, (2010/10/03)
The present invention provides a compound of the formula: Compound (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising Compound (I) in combination with a suitable carrier, diluent, or excipient; and methods for treati
Asymmetric synthesis of the ABC-ring system of the antitumor antibiotic MPC1001
Peng, Jianbiao,Clive, Derrick L. J.
supporting information; experimental part, p. 513 - 519 (2009/06/06)
trans-4-Hydroxy-L-proline was converted into a tricyclic compound representing three contiguous rings of the anticancer antibiotic MPC1001. The tricyclic model contains the dihydrooxepin and diketopiperazine subunits, as well as one of the sulfur atoms of the natural product. The diketopiperazine unit was formed by a new method that involves cyclization of an enolate onto the carbonyl of a phenyl carbamate, and the dihydrooxepin ring was generated by using an acid-induced cyclization of an alcohol onto the β-carbon of a vinylogous amide.
MINERALOCORTICOID RECEPTOR ANTAGONISTS AND METHODS OF USE
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Page/Page column 21, (2009/07/10)
The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly congestive heart failure, hypertension, diabetic nephropathy, or chronic kidney disease, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors
Stevens, Kirk L.,Alligood, Krystal J.,Alberti, Jennifer G. Badiang,Caferro, Thomas R.,Chamberlain, Stanley D.,Dickerson, Scott H.,Dickson, Hamilton D.,Emerson, Holly K.,Griffin, Robert J.,Hubbard, Robert D.,Keith, Barry R.,Mullin, Robert J.,Petrov, Kimberly G.,Gerding, Roseanne M.,Reno, Michael J.,Rheault, Tara R.,Rusnak, David W.,Sammond, Douglas M.,Smith, Stephon C.,Uehling, David E.,Waterson, Alex G.,Wood, Edgar R.
scheme or table, p. 21 - 26 (2009/04/10)
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Azadideoxyadenosine: Synthesis, enzymology, and anti-HIV activity
Nishonov, Abdumalik A.,Ma, Xiaohui,Nair, Vasu
, p. 4099 - 4101 (2007/10/03)
Synthesis of an azanucleoside, a new analogue of dideoxyadenosine, is described. This compound is only slowly deaminated by mammalian adenosine deaminase and it is a substrate for adenosine kinase. It exhibits in vitro anti-HIV activity.
