- SMALL-MOLECULE PI5P4K ALPHA/BETA INHIBITORS AND METHODS OF TREATMENT USING SAME
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The present invention relates to the discovery of novel 2-amino-dihydropteridinone compounds and analogues thereof capable of inhibiting phosphatidylinositol phosphate kinases. In certain embodiments, the compounds of the invention can be used to treat p5
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Page/Page column 43; 44; 46
(2020/03/02)
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- Chiral Pyridoxal-Catalyzed Asymmetric Biomimetic Transamination of α-Keto Acids
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A series of chiral pyridoxals 8 and 9 have been developed from commercially available pyridoxine and (S)-α,α-diarylprolinols. The pyridoxals exhibited good catalytic activity in an asymmetric transamination of α-keto acids with 2,2-diphenylglycine (7f) as the amine source to give various α-amino acids in 29-85% yields with 53-80% ee's. The current asymmetric transamination has successfully mimicked a complete biological transamination process characterized by two half-transaminations, a small chiral pyridoxal molecule acting as the catalyst, and enantioselective control.
- Shi, Limin,Tao, Chuangan,Yang, Qin,Liu, Yong Ethan,Chen, Jing,Chen, Jianfeng,Tian, Jiaxin,Liu, Feng,Li, Bo,Du, Yongling,Zhao, Baoguo
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p. 5784 - 5787
(2015/12/11)
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- Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist
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Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, 1, which selectively inhibited neutrophil elastase release induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve pharmacological activity, a series of tryptophan-containing dipeptides were synthesized and their pharmacological activities were investigated in human neutrophils. Of these, five compounds 3, 6, 19a, 24a, and 24b exhibited potent and dual inhibitory effects on FMLP-induced superoxide anion (O2-) generation and neutrophil elastase release in neutrophils with IC50 values of 0.23/0.60, 1.88/2.47, 1.87/3.60, 0.12/0.37, and 1.32/1.03 μM, respectively. Further studies indicated that inhibition of superoxide production in human neutrophils by these dipeptides was associated with the selective inhibition of formyl peptide receptor 1 (FPR1). Furthermore, the results of structure-activity relationship studies concluded that the fragment N-benzoyl-Trp-Phe-OMe (3) was most suitable as a core structure for interaction with FPR1, and may be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases. As some of the synthesized compounds exhibited separable conformational isomers, and showed diverse bioactivities, the conformation analysis of these compounds is also discussed herein. The Royal Society of Chemistry 2013.
- Hwang, Tsong-Long,Hung, Chih-Hao,Hsu, Ching-Yun,Huang, Yin-Ting,Tsai, Yu-Chi,Hsieh, Pei-Wen
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p. 3742 - 3755
(2013/06/27)
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- Rhodium/graphite-catalyzed hydrogenation of carbocyclic and heterocyclic aromatic compounds
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Rhodium on graphite (Rh/Gr, C24Rh) was prepared by reaction of anhydrous rhodium trichloride with potassium graphite (C8K, 3 equivalents) and used as a heterogeneous catalyst for the hydrogenation of carbocyclic and heterocyclic aromatic compounds at room temperature and 1 atm of hydrogen pressure. The effect of substitution on the benzene ring was examined in a variety of derivatives, including those with alkyl, hydroxy, alkoxy, aryloxy, carboxy, amino, nitro, acyl, chloro, or functionalized alkyl groups. Reduction of carbonyl functions of aromatic aldehydes and ketones occurred with complete or partial cleavage of the benzylic C-O bond; this cleavage also occurred in the hydrogenation of benzylic alcohols and esters. Georg Thieme Verlag Stuttgart.
- Falini, Giuseppe,Gualandi, Andrea,Savoia, Diego
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experimental part
p. 2440 - 2446
(2010/02/27)
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- Conjugate additions of organocuprates to a 3-methylene-6-isopropyldiketopiperazine acceptor for the asymmetric synthesis of homochiral α-amino acids
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Addition of a range of organocuprates to (S)-N,N′-bis(p-methoxybenzyl)-3-methylene-6-isopropylpiperazine-2, 5-dione 8 affords cis-3-isopropyl-6-alkyldiketopiperazines in excellent yield and >95% de. Subsequent deprotection and hydrolysis of these cis-3-isopropyl-6-alkyldiketopiperazines affords homochiral (S)-α-amino acids in excellent yield.
- Bull,Davies,Garner,O'Shea
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p. 3281 - 3287
(2007/10/03)
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- Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
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The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.
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- Novel acylguanidine containing thrombin inhibitors with reduced basicity at the P1 moiety
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Replacement of the noragmatine group in thrombin inhibitors with a β- alanyl-guanidine group resulted in a nearly equipotent and more selective compound 8 despite the fact that the pK(a) of this P1 moiety is five orders of magnitude lower. Furt
- Adang, Anton E.P.,Lucas, Hans,De Man, Adrianus P.A.,Engh, Richard A.,Grootenhuis, Peter D.J.
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p. 3603 - 3608
(2007/10/03)
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- The stereospecific preparation of a hydroxyethylene isostere precursor via a novel piperidine-2,5-dione template
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Hydroxyethylene isostere precursor 2 was synthesized by stereochemical manipulation of a novel ketolactam 'template'. The final product was prepared in very high enantiomeric purity, in 23% overall yield from L-phenylalanine.
- Plata,Leanna,Morton
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p. 3623 - 3626
(2007/10/02)
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