- ERK INHIBITORS
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The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are ERK2 inhibitors. The invention also provides a method of inhibiting ERK2 in a patient in need of such treatment comprising administering to said patient an effective amount of at least one compound of Formula (I). The invention also provides a method for treating cancer in a patient in need of such treatment, said method comprising administering to said patient an effective amount of at least one compound of Formula (I).
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Page/Page column 76
(2016/07/05)
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- A rapid and efficient one-pot method for the reduction of N-protected α-amino acids to chiral α-amino aldehydes using CDI/DIBAL-H
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N-Protected amino acids can be easily converted into chiral α-amino aldehydes in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H. This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from proteinogenic amino acids in very good isolated yields and complete stereointegrity.
- Ivkovic, Jakov,Lembacher-Fadum, Christian,Breinbauer, Rolf
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supporting information
p. 10456 - 10460
(2015/11/10)
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- Synthesis of tetrasubstituted symmetrical pyrazines from β-keto γ-amino esters: A mild strategy for self-dimerization of peptides
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A facile synthesis of highly symmetrical tetrasubstituted pyrazines through simple aerial oxidation of β-keto γ-amino esters is reported. The scope of the reaction was examined by use of various amino acid side-chain functional groups andpeptides. The mil
- Kumar, Mothukuri Ganesh,Thombare, Varsha J.,Bhaisare, Rupal D.,Adak, Anindita,Gopi, Hosahudya N.
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p. 135 - 141
(2015/02/02)
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- New routes towards reutericyclin analogues
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A range of N-acylpyrrolo[3,4-c]isoxazoles and derived N-acyltetramides has been prepared via a nitrile oxide dipolar cycloaddition approach, as analogues of the acyltetramic acid metabolite reutericyclin, of interest for its antibiotic potential against G
- Jones, Raymond C. F.,Bullous, James P.,Law, Carole C. M.,Elsegood, Mark R. J.
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p. 1588 - 1590
(2014/02/14)
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- Hypervalent iodine/TEMPO-mediated oxidation in flow systems: A fast and efficient protocol for alcohol oxidation
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Hypervalent iodine(III)/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times.
- Ambreen, Nida,Kumar, Ravi,Wirth, Thomas
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p. 1437 - 1442
(2013/08/23)
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- Allylation of aldehydes and imines: Promoted by reuseable polymer-supported sulfonamide of N-glycine
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A allylation of aldehydes and imines (generated in situ from aldehydes and amines) with allyltributyltin promoted by recoverable and reusable the polymer-supported sulfonamide of N-glycine has been developed. Good to high yields were obtained in various cases. Most of the SnBu3 residue can be recovered as Bu3SnCl. Highly stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine 7 was achieved by using the P4a-mediated allylation of Boc-L-phenylglycinal as a key step.
- Li, Gui-Long,Zhao, Gang
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p. 633 - 636
(2007/10/03)
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- Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl
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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.
- 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.
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p. 1486 - 1490
(2007/10/03)
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- Enantiospecific formation of 3,6-dihydro-1H-pyridin-2-ones: Low-pressure palladium-catalysed decarboxylative carbonylation of 3-tosyl-5-vinyloxazolidin- 2-ones
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Palladium-catalysed decarboxylative carbonylation of 3-tosyl-5- vinyloxazolidin-2-ones 5 occurs at atmospheric pressure to give 1-tosyl-3,6-dihydro-1H-pyridin-2-ones 6. The reaction proceeds with no loss of enantiopurity and detosylation with sodium napht
- Knight, Julian G.,Lawson, Iain M.,Johnson, Christopher N.
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p. 227 - 230
(2007/10/03)
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- PROCESS FOR PREPARING OXAZOLIDINE DERIVATIVES
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A process for preparing (4S,5R)-5-carboxymethyl-2,2-dimethyl-4-phenyl-oxazolidine-3-carboxylic acid t-butyl ester, an intermediate in the preparation of anticancer compounds having a taxane skeleton, such as paclitaxel, docetaxol, etc.
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Page/Page column 10-11
(2008/06/13)
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- Novel cell-penetrating α-keto-amide calpain inhibitors as potential treatment for muscular dystrophy
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Dipeptide-derived α-keto-amide compounds with potent calpain inhibitory activity have been identified. These reversible covalent inhibitors have IC50 values down to 25 nM and exhibit greatly improved activity in muscle cells compared to the reference compound MDL28170. Several novel calpain inhibitors have shown positive effects on histological parameters in an animal model of Duchenne muscular dystrophy demonstrating their potential as a treatment option for this fatal disease.
- Lescop, Cyrille,Herzner, Holger,Siendt, Herve,Bolliger, Reto,Henneboehle, Marco,Weyermann, Philipp,Briguet, Alexandre,Courdier-Fruh, Isabelle,Erb, Michael,Foster, Mark,Meier, Thomas,Magyar, Josef P.,Von Sprecher, Andreas
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p. 5176 - 5181
(2007/10/03)
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- A direct and efficient stereoconservative procedure for the selective oxidation of N-protected β-amino alcohols
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An efficient, very simple and eco-friendly procedure has been developed for the synthesis of highly enantioenriched α-amino aldehydes by IBX-mediated oxidation of the corresponding β-amino alcohols. The procedure has been applied to a wide range of substr
- Ocejo, Marta,Vicario, Jose L.,Badía, Dolores,Carrillo, Luisa,Reyes, Efraim
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p. 2110 - 2112
(2007/10/03)
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- Enantioselective synthesis of primary 1-(aryl)alkylamines by nucleophilic 1,2-addition of organolithium reagents to hydroxyoxime ethers and application to asymmetric synthesis of G-protein-coupled receptor ligands
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(E)-Arylaldehyde oxime ethers bearing a (1S)-2-hydroxy-1-phenylethyl or (2R)-1-hydroxy-2-phenylethyl group as a chiral auxiliary, both derived from a single precursor, methyl (R)-mandelate, underwent nucleophilic addition with organolithium reagents via six-membered chelates to give the diastereomerically enriched (R)- and (S)-adducts, respectively, which, after chiral auxiliary removal by reductive N-O bond cleavage, led to the corresponding (R)- and (S)-1-(aryl)ethylamines. This organolithium addition protocol using methyllithium was applied in an enantiodivergent fashion to the preparation of both enantiomers of 1-(2-hydroxyphenyl)ethylamine, which has been previously used as an efficient chiral auxiliary for the synthesis of natural products in this laboratory. The synthetic utility of this methodology involving diastereoselective methyl addition was demonstrated by further application to the asymmetric synthesis of a new type of calcium receptor agonist (calcimimetics), (R)-(+)-NPS R-568 and its thio analogue. Furthermore, diastereoselective vinylation was accomplished by application of the hydroxy oxime ether-based protocol using vinyllithium, which allowed the development of the enantioselective synthesis of the NK-1 receptor antagonists, (+)-CP-99,994 and (+)-CP-122,721.
- Atobe, Masakazu,Yamazaki, Naoki,Kibayashi, Chihiro
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p. 5595 - 5607
(2007/10/03)
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- Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
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The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
- Catalano, John G,Deaton, David N,Furfine, Eric S,Hassell, Annie M,McFadyen, Robert B,Miller, Aaron B,Miller, Larry R,Shewchuk, Lisa M,Willard Jr., Derril H,Wright, Lois L
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p. 275 - 278
(2007/10/03)
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- Stereoselective synthesis of L-733,060
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Enantioselective synthesis of non-peptidic neurokinin NK1 receptor antagonist L-733,060 is described using ring-closing metathesis as a key step, starting from L-phenylglycine.
- Bhaskar,Rao, B. Venkateswara
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p. 915 - 917
(2007/10/03)
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- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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Page/Page column 45-46
(2010/02/03)
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- Enantioselective synthesis of NK-1 receptor antagonists (+)-CP-99,994 and (+)-CP-122,721
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An enantioselective total synthesis of NK-1 receptor antagonists, (+)-CP-99,994 and (+)-CP-122,721, is described. The key steps are diastereoselective addition of vinyllithium to a chiral benzaldehyde oxime ether and diastereoselective borane reduction of
- Yamazaki, Naoki,Atobe, Masakazu,Kibayashi, Chihiro
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p. 7979 - 7982
(2007/10/03)
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- Enantiomerically pure N-Boc- and N-benzoyl-(S)-phenylglycinals
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Enantiomerically pure N-Boc- and N-benzoyl-(S)-phenylglycinals were prepared by oxidation of the respective alcohols with Dess-Martin periodinane. The glycinals were phosphonylated with lithium O,O-dimethyl phosphonate at -70°C or (MeO)2POTMS a
- Wroblewski, Andrzej E.,Piotrowska, Dorota G.
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p. 2509 - 2512
(2007/10/03)
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- Versatile synthons for optically pure alpha-amino aldehydes and alpha-amino acids: (+)- and (-)-4,5-dialkoxy-2-oxazolidinones.
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Both enantiomers of trans-5-benzyloxy-4-methoxy- (BMOx) and trans-4,5-dimethoxy-2-oxazolidinones (DMOx), which are readily accessible from simple 2-oxazolone heterocycles, represent good candidates for a new class of chiral synthons for use in the preparation of optically pure alpha-amino aldehydes and alpha-amino acids, respectively.
- Morita,Nagasawa,Yahiro,Matsunaga,Kunieda
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p. 897 - 899
(2007/10/03)
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- Stereoselective intramolecular cyclization of allyl and homoallyl benzamide via π-allylpalladium complex catalyzed by Pd(0)
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The transformation of acyclic allylic benzamides 4 and homoallylic benzamides 12 to vinyl oxazolines 3 is achieved in the presence of base by the catalysis and Pd(0) in high yield and with high diastereoselectivity. Especially, in the case of homoallylic benzamides 12, trans-oxazolines 3 are formed exclusively or predominantly over cis-oxazolines 8, irrespective of the composition of their stereoisomers. The reaction is believed to proceed via the same π-allylpalladium complex that arises from either primary or secondary allylic acetates. We applied this method to the syntheses of β- amino-α-hydroxy acids 1 and γ-amino-β-hydroxy acids 2, conveniently protected as oxazoline.
- Lee, Kee-Young,Kim, Yong-Hyun,Park, Min-Sung,Oh, Chang-Young,Ham, Won-Hun
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p. 9450 - 9458
(2007/10/03)
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- A highly stereocontrolled asymmetric synthesis of the Taxol C-13 side chain; (4S, 5R)-2,4-Diphenyloxazoline-5 carboxylic acid
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A stereoselective synthesis of (4S, 5R)-2,4-diphenyloxaline-5-carboxylic acid, a precursor of the Taxol C-13 side chain was achieved using palladium- catalyzed oxazoline formation reaction from commercially available amino acid.
- Lee, Kee-Young,Kim, Yong-Hyun,Park, Min-Sung,Ham, Won-Hun
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p. 8129 - 8132
(2007/10/03)
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- Stereoselective synthesis of anti-β-amino-α-hydroxy acid derivatives using nucleophilic epoxidation of 1-arylthio-1-nitroalkenes
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Reaction of lithium t-butylperoxide with 1-arylthio-1-nitroalkenes 5, prepared by condensation of (4-tolylthio)nitromethane with N-(Boc)-protected α-amino aldehydes, leads to the formation of oxazolidinones rather than the expected oxitranes. Initially, a mixture of cis 8 and trans 9 diastereoisomers is formed, but upon exposure to silica gel complete conversion to the cis-diastereoisomers 8 takes place.
- Ambroise, Lydia,Jackson, Richard F.W.
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p. 2311 - 2314
(2007/10/03)
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- Synthesis of taxol and taxotere side chains by 2-(trimethylsilyl)thiazole based homologation of L-phenylglycine
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L-Phenylglycine is homologated by the use of 2-(trimethylsilyl)thiazole into (2R,3S)-N-benzoyl- and N-tert-butoxycarbonyl-3-phenylisoserine, which are isolated as acetonide derivatives in 47 and 35% overall yields and with 84 and 90% ee, respectively.
- Dondoni,Perrone,Semola
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p. 181 - 186
(2007/10/02)
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- Structure-activity studies of antitumor taxanes: Synthesis of novel C-13 side chain homologated taxol and taxotere analogs
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Taxol and taxotere analogs with one carbon homologated side chains were synthesized from 10-deacetylbaccatin III and a key oxazolidineacetic acid intermediate, which was synthesized in four steps from (S)-(+)-2- phenylglycine. 10-Deacetyl-1a'-homotaxol and 1a'-homotaxotere were at least 27 times less active than taxol in the microtubule assembly assay. The inability of these homologs to induce microtubule formation may be due to unfavorable solution conformations, preventing productive interactions with the taxol binding site on microtubules.
- Jayasinghe,Datta,Ali,Zygmunt,Vander Velde,Georg
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p. 2981 - 2984
(2007/10/02)
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