17136-45-7Relevant articles and documents
Selenoimidazolium Salts as Supramolecular Reagents for Protein Alkylation
Lim, David,Wen, Xiaojin,Seebeck, Florian P.
, p. 3515 - 3520 (2020/09/21)
Se-benzyl selenoimidazolium salts are characterized by remarkable alkyl-transfer potential under physiological conditions. Structure-activity relationship studies show that selective monoalkylation of primary amines depends on supramolecular interactions
A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor
Borsari, Chiara,Rageot, Denise,Dall'Asen, Alix,Bohnacker, Thomas,Melone, Anna,Sele, Alexander M.,Jackson, Eileen,Langlois, Jean-Baptiste,Beaufils, Florent,Hebeisen, Paul,Fabbro, Doriano,Hillmann, Petra,Wymann, Matthias P.
, p. 8609 - 8630 (2019/10/16)
The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure-activity relationship (SAR) studies led to the identification of compound 12b with a ～450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.
Controlling the self-assembly of homochiral coordination architectures of CuII by substitution in amino acid based ligands: Synthesis, crystal structures and physicochemical properties
Kumar, Navnita,Khullar, Sadhika,Mandal, Sanjay K.
supporting information, p. 5672 - 5687 (2015/03/30)
Through the strategic design of ligands based on amino acids, structural diversity in chiral coordination architectures of CuII is demonstrated with six new examples: {[Cu(l-HTyrbenz)2]·CH3OH·H2O}n (1), {[Cu(l-HSerbenz)2]·3H2O}n (2), {[Cu(l-HTyrthio)2]·H2O}n (3), [Cu(l-HTyr4-pyr)2(H2O)]·2H2O (4), [Cu(l-HSerthio)2(H2O)] (5), and [Cu(l-Phethio)2(H2O)]·3H2O (6) [where l-H2Tyrbenz = l-N-(benzyl)-tyrosine, l-H2Serbenz = l-N-(benzyl)-serine, l-H2Tyrthio = l-N-(methyl-2-thiophenyl)-tyrosine, l-H2Tyr4-pyr = l-N-(methyl-4-pyridyl)-tyrosine, l-H2Serthio = l-N-(methyl-2-thiophenyl)-serine and l-HPhethio = l-N-(methyl-2-thiophenyl)-phenylalanine]. For these 1:2 metal-ligand complexes, the availability of a donor atom (either from the phenolic OH group or the carboxylate group of one of the ligands) for bridging between the CuII centers results in the formation of coordination polymers (1-3), while no such availability allows a water molecule to occupy the fifth site around the CuII center to generate hydrogen bonded supramolecular assemblies (4-6). In 1, a coordination polymer is formed via a syn-anti bridging carboxylate, and the phenolic group has no role in its formation. To further emphasize this point, l-tyrosine in 1 is replaced with l-serine to form 2, in which an anti-anti bridging by the carboxylate group is observed. On the other hand, the formation of {[Cu(l-HTyrthio)2]·H2O}n (3) results from the growth of a spiral polymer via the unique phenolic bridging with a distance of 10.806(9) ? between two CuII centers. On changing from the l-H2Tyrbenz ligand to the l-H2Tyr4-pyr ligand (1vs.4), the strong hydrogen bonding of the pyridyl nitrogen with the phenolic group does not allow the latter to bind to CuII. Similarly, on changing from l-H2Tyrthio to l-H2Serthio (3vs.5), the length of the -CH2OH group in the latter is much less than the distance between the two CuII centers, therefore this group cannot occupy the fifth site and thus a water molecule is coordinated. This is further confirmed by reacting 5 with 2 eq. of l-H2Tyrthio in methanol to form 3, while the reverse is not possible. All these compounds are characterized by a number of analytical methods, such as elemental analysis, FTIR, UV-Vis and circular dichroism spectroscopy, polarimetry, powder and single crystal X-ray diffraction and thermogravimetric analysis. Photoluminescence properties of all ligands containing the l-tyrosine group and their metal complexes (1, 3 and 4) are compared in solution at room temperature. This journal is
Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H- indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epide
Gavai, Ashvinikumar V.,Fink, Brian E.,Fairfax, David J.,Martin, Gregory S.,Rossiter, Lana M.,Holst, Christian L.,Kim, Soong-Hoon,Leavitt, Kenneth J.,Mastalerz, Harold,Han, Wen-Ching,Norris, Derek,Goyal, Bindu,Swaminathan, Shankar,Patel, Bharat,Mathur, Arvind,Vyas, Dolatrai M.,Tokarski, John S.,Chiang, Yu,Oppenheimer, Simone,Hongjian, Zhang,Marathe, Punit,Fargnoli, Joseph,Lee, Francis Y.,Wong, Tai W.,Vite, Gregory D.
supporting information; experimental part, p. 6527 - 6530 (2010/03/26)
Structure-activity relationships in a series of 4-[1H-indazol-5-ylamino] pyrrolo[2,1-f][1,2,4]triazine-6-carbamates identified dual human epidermal growth factor receptor (HER)1/HER2 kinase inhibitors with excellent biochemical potency and kinase selectiv
Resolution of racemic N-benzyl α-amino acids by liquid-liquid extraction: A practical method using a lipophilic chiral cobalt(III) salen complex and mechanistic studies
Dzygiel, Pawel,Reeve, Toby B.,Piarulli, Umberto,Krupicka, Martin,Tvaroska, Igor,Gennari, Cesare
supporting information; experimental part, p. 1253 - 1264 (2009/04/07)
The efficient resolution of racemic N-benzyl α-amino acids (N-Bn-AA) has been achieved by a liquid-liquid extraction process using the lipophilic chiral salen-cobalt(III) complex [CoIII(3)(OAc)]. As a result of the resolution by extraction, one enantiomer (S) of the N-benzyl α-amino acid predominated in the aqueous phase, while the other enantiomer (R) was driven into the organic phase by complexation to cobalt. The complexed amino acid (R) was then quantitatively released by a reductive (CoIII→Co II) counter-extraction with aqueous sodium dithionite or L-ascorbic acid in methanol. The reductive cleavage allowed to recover the [Co II(3)] complex in good yield, which could be easily re-oxidized to [CoIII(3)(OAc)] with air/AcOH and reused with essentially no loss of reactivity and selectivity. Investigation on the nitrogen substitution indicates that the presence of a single benzyl group on the amino acid nitrogen is important to obtain high enantioselectivity in the extraction process. The kinetic vs. thermodynamic nature of the resolution process was also investigated with an enantiomeric exchange experiment, which shows that the liquid-liquid extraction with [CoIII(3)-(OAc)] is an equilibrium process operating under thermodynamic control. In the absence of a suitable crystal structure of the [CoIII(3)(N-Bn-AA)] complexes, computational and spectroscopic studies were used to investigate how the N-benzyl α-amino acids are accommodated in the "binding pocket" of the chiral cobalt complex. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
SYNTHETIC PROCESS
-
, (2008/06/13)
The present invention provides a process for preparing compounds of formula (I) ["insert chemical structure here"](I)or a pharmaceutically acceptable salt thereof. The compounds prepared by the process of the invention inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
A highly practical method for monobenzylation of amino acids
Shao, Hua-Wu,Wu, Yikang,Li, Rongxiu
, p. 1911 - 1915 (2007/10/03)
Amino acids are cleanly monobenzylated at ambient temperature using benzyl chloride in water containing potassium carbonate.
Chiral Synthesis of 3-Substituted Morpholines via Serine Enantiomers and Reductions of 5-Oxomorpholine-3-carboxylates
Brown, George R.,Foubister, Alan J.,Wright, Brian
, p. 2577 - 2580 (2007/10/02)
The chiral synthesis of 3-hydroxymethyl- and 3-carboxy-morpholines from serine enantiomers is described.Chemoselective and total reductions of 5-oxomorpholine-3-carboxylates are key synthetic steps.
AN EFFICIENT ONE-STEP REDUCTIVE N-MONOALKYLATION OF α-AMINO ACIDS
Ohfune, Yasufumi,Kurokawa, Natsuko,Higuchi, Naoki,Saito, Masayuki,Hashimoto, Masaki,et al.
, p. 441 - 444 (2007/10/02)
Reactions of protection-free α-amino acids with aldehydes or ketones in the presence of sodium cyanoborohydride afforded the N-monoalkylated amino acids in inorganic salt-free form.Application of this method to synthesis of N-alkyl derivatives of biologic
