- Synthesis of fluorescent dipeptidomimetics and their ribosomal incorporation into green fluorescent protein
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The synthesis and incorporation into position 66 of green fluorescent protein (GFP) by in vitro protein translation of novel oxazole and thiazole based dipeptidomimetics are described. The compounds may be regarded as GFP chromophore analogues, and are strongly fluorescent. An α-amido-β-ketoester intermediate was obtained via bisacylation of a protected glycine. The intermediate underwent dehydrative cyclization to afford the 1,3-oxazole and was treated with Lawesson's reagent to furnish the 1,3-thiazole. When these fluorophores were introduced into position 66 of GFP in place of Tyr66, the resulting GFP analogues exhibited fluorescence emission several-fold greater than wild-type GFP; the emission was also shifted to shorter wavelength. It may be noted that compared to the typical fluorophores formed in the natural and modified fluorescent proteins, the oxazole and thiazole fluorophores are completely stable and do not require activation by posttranslational modification to exhibit fluorescence.
- Roy Chowdhury, Sandipan,Maini, Rumit,Dedkova, Larisa M.,Hecht, Sidney M.
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Read Online
- Synthesis of β-Hydroxy α-Amino Acids through Br?nsted Base-Catalyzed syn-Selective Direct Aldol Reaction of Schiff Bases of Glycine o-Nitroanilide
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Here we report the highly enantio- and syn-selective synthesis of β-hydroxy α-amino acids from glycine imine derivatives under Br?nsted base (BB) catalysis. The key of this approach is the use of benzophenone-derived imine of glycine o-nitroanilide as a pronucleophile, where the o-nitroanilide framework provides an efficient hydrogen-bonding platform that accounts for nucleophile reactivity and diastereoselectivity.
- Vera, Silvia,Vázquez, Ana,Rodriguez, Ricardo,Pozo, Sandra Del,Urruzuno, I?aki,de Cózar, Abel,Mielgo, Antonia,Palomo, Claudio
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p. 7757 - 7772
(2021/06/21)
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- NOVEL OPIOID ANTAGONISTS AND METHODS RELATED THERETO
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Disclosed is a composition and method for a therapeutic treatment that is able to combat certain conditions such as alcohol dependence, opioid abuse treatment, neurological disorders, neuropathic pain, and fibromyalgia. The novel gliotoxin analog compound acts by acting as an antagonist to one or more opioid receptors, which, when present leads to the inhibition of conditions, providing increased performance over known treatments. The disclosed compounds also shows the ability to cross the blood-brain-barrier in a highly efficient manner.
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Paragraph 0046
(2020/05/14)
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- NOVEL SELECTIVE KAPPA OPIOID RECEPTOR ANTAGONISTS AND METHODS RELATED THERETO FOR TREATMENT OF ADDICTION AND NEUROPATHIC PAIN
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Disclosed is a composition and method for a therapeutic treatment that is able to combat certain conditions such as addiction, alcohol dependence, opioid abuse treatment, neurological disorders, neuropathic pain, and combinations thereof. The compounds act by acting as selective antagonist to the kappa (K) opioid receptor, which, when present leads to the inhibition of conditions, providing increased performance over known treatments. The disclosed compounds also shows the ability to cross the blood-brain-barrier in a highly efficient manner. The disclosed compounds are shown to be effective in the nanomolar range.
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Paragraph 00073
(2020/05/28)
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- PROCESSES FOR THE PREPARATION OF 4-{8-AMINO-3-[(2S)-1-(BUT-2-YNOYL)-PYRROLIDIN-2-YL]IMIDAZO[1,5-A]-PYRAZIN-1-YL}N-(PYRIDIN-2-YL)-BENZAMIDE
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The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
- -
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Paragraph 00230
(2020/03/23)
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- Preparation method of 3 -chloro-5-trifluoromethyl-2-pYRidine methylamine salt
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The invention discloses a preparation method of 3 -chloro-5-trifluoromethyl-2-pYRidine methylamine salt, and the compound is mainly used as an intermediate compound for synthesis of bactericide fluopicolide for preventing and treating diseases caused by oomycete pathogenic bacteria. According to the preparation method, intermediate compounds of all the steps are prepared by intermittent step-by-step reaction, the finally obtained 3 -chloro-5-trifluoromethyl-2-pYRidine methylamine salt compound is reacted with 2, 6-dichlorobenzoyl chloride in the presence of an organic amine and a solvent to prepare the final object fluopicolide; and nucleophilic substitution reaction, imine hydrolysis and decarboxylation reaction are performed in the preparation process to obtain the target product, the reaction conditions are mild, the operation is simple, and the method is relatively suitable for industrial production.
- -
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Paragraph 0020; 0021
(2019/04/26)
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- Enantio- and Diastereoselective Synthesis of β-Aryl-β-pyrazolyl α-Amino Acid Esters via Copper-Catalyzed Reaction of Azomethine Ylides with Benzylidenepyrazolones
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A fully stereoselective synthesis of unnatural chiral β-aryl-β-pyrazolyl α-amino acid esters via copper-catalyzed addition reactions of azomethine ylides with benzylidenepyrazolones bearing two contiguous stereogenic centers was developed. A 1H-pyrazol-5-ol was introduced by the aromatization of 3H-pyrazol-3-one in the reaction. The transformation operated at room temperature and afforded β-1H-pyrazol-5-ol-α-amino esters in high yields with good to excellent levels of diastereo- and enantioselectivity.
- Gong, Yan-Chuan,Wang, Yue,Li, Er-Qing,Cui, Hao,Duan, Zheng
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supporting information
(2019/02/07)
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- Enantio- And diastereoselective synthesis of b-Aryl-b-pyrazolyl a-amino acid esters via copper-catalyzed reaction of azomethine ylides with benzylidenepyrazolones
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A fully stereoselective synthesis of unnatural chiral b-aryl-b-pyrazolyl a-amino acid esters via copper-catalyzed addition reactions of azomethine ylides with benzylidenepyrazolones bearing two contiguous stereogenic centers was developed. A 1H-pyrazol-5-ol was introduced by the aromatization of 3H-pyrazol-3-one in the reaction. The transformation operated at room temperature and afforded b-1H-pyrazol-5-ol-a-amino esters in high yields with good to excellent levels of diastereo- and enantioselectivity.
- Gong, Yan-Chuan,Wang, Yue,Li, Er-Qing,Cui, Hao,Duan, Zheng
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supporting information
p. 1389 - 1393
(2019/10/28)
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- Surface-enhanced Raman scattering of alkyne-conjugated MoS2: A comparative study between metallic and semiconductor phases
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Raman enhancement on nonmetallic flat two-dimensional (2D) nanomaterial surfaces has attracted a great deal of attention since the discovery of graphene-enhanced Raman scattering. Molybdenum disulfide (MoS2) is a flat 2D nanomaterial with unique electronic and physical properties that can be applied in surface-enhanced Raman spectroscopy (SERS). Herein, we report a lithium-exfoliated MoS2 (Li-MoS2) has a metallic phase content of about 70%, which is three times higher than the metallic phase content of 20% in thioglycolic acid-exfoliated MoS2 (T-MoS2). Li-MoS2 therefore displays a 2-3 fold increase in the Raman signal for rhodamine 6G (R6G) used as an analyte. Furthermore, the conjugation of a thiol-terminated alkyne with Li-MoS2 also provided a greater SERS signal at 2123 cm-1 than that of T-MoS2. A defect-rich metallic MoS2 monolayer can therefore be used as the perfect substrate for surface-enhanced Raman scattering, although pristine MoS2 hardly exhibits an SERS effect. This study proved that (1) defect-rich metallic MoS2, (2) dipole-dipole interactions, and (3) the enhanced charge transfer effect of MoS2 monolayers are the three primary and essential parameters for enhancing the Raman signals of analytes on MoS2. Key observations include the fact that some alkyne groups were directly coordinated to the edges of Li-MoS2 defect sites, which shifted the alkyne signal to 2153 cm-1 in alkyne spectral mapping. More importantly, to quantify the SERS performance of Li-MoS2, SERS imaging of live cells was demonstrated using the unique alkyne signal at 2123 cm-1.
- Anbazhagan, Rajeshkumar,Vadivelmurugan, Adhisankar,Tsai, Hsieh-Chih,Jeng, Ru-Jong
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p. 1071 - 1082
(2018/02/10)
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- A Manufacturing Process to an Intermediate in the Synthesis of Acalabrutinib
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Optimization and application of the reported synthesis of (3-chloropyrazin-2-yl)methanamine 3 have provided a high yielding, fully telescoped procedure to key intermediate 5 in the synthesis of acalabrutinib.
- Chen, Bo,Golden, Michael,Li, Zhonglian,Xu, Liwen,Xu, Zhaofu,Yao, Xiaolong
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p. 1458 - 1460
(2018/10/15)
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- 2-Hydroxybenzophenone as a Chemical Auxiliary for the Activation of Ketiminoesters for Highly Enantioselective Addition to Nitroalkenes under Bifunctional Catalysis
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An organocatalytic system is presented for the Michael addition of monoactivated glycine ketimine ylides with a bifunctional catalyst. The ketimine bears an ortho hydroxy group, which increases the acidity of the methylene hydrogen atoms and enhances the reactivity, thus allowing the synthesis of a large variety of α,γ-diamino acid derivatives with excellent stereoselectivity.
- Guerrero-Corella, Andrea,Esteban, Francisco,Iniesta, Manuel,Martín-Somer, Ana,Parra, Mario,Díaz-Tendero, Sergio,Fraile, Alberto,Alemán, Jose
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supporting information
p. 5350 - 5354
(2018/04/19)
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- 4,5-Disubstituted N-Methylimidazoles as Versatile Building Blocks for Defined Side-Chain Introduction
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Fungerin is a 1,4,5-trisubstituted imidazole natural product characterised by a broad spectrum of antifungal activities. We planned to develop flexible strategies to access to such compounds. Imidazoles bearing suitable anchor groups at C-4 and C-5 allow the introduction of various substituted side-chains, generating libraries of fungerin derivatives for biological tests. Starting from commercially available reactants, two N-methyl 4,5-substituted imidazole core units were synthesised. Derivatives of type 1 contained two orthogonally protected C-1 anchors. Selective side-chain introduction was achieved through a sequence of Grignard coupling at C-5 to replace a tosylate and a Horner olefination through an aldehyde attached to C-4. Two target fungerin derivatives were synthesised. Since the organometallic substitution of the C-5-CH2-positioned leaving group proved to suffer from limitations concerning potential competing side-reactions, a type 2 imidazole core was built up. These structures had a halogen centre at C-4 and a hydroxyethyl anchor at C-5. Now, selective side-chain introduction allowed us to use Julia olefination to form the allyl side-chain at C-5 and Heck reactions to introduce the C-4 acryl substituents. Eight derivatives, including fungerin, were synthesised by this latter strategy, without producing any regioisomers. The second approach had the advantage that various side-chains could be coupled at C-4 and C-5 in two final steps. Thus, this strategy represents a versatile way to build up libraries of fungerin derivatives for biological testing.
- Przybyla, Daniel,Nubbemeyer, Udo
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supporting information
p. 695 - 703
(2017/02/05)
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- SUBSTITUTED AMINO SIX-MEMBERED SATURATED HETEROCYCLIC FAT USED AS LONG-ACTING DPP-IV INHIBITOR
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The present application relates to a substituted amino six-membered saturated heteroalicycle represented by formula I as a long-acting DPP-IV inhibitor, a method for preparing the same, a pharmaceutical composition comprising the same, and a use of the same in treating and/or preventing diseases and disorders benefitting from DPP-IV inhibition.
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Paragraph 0084; 0085
(2018/01/13)
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- RIBOSOME-MEDIATED INCORPORATION OF PEPTIDES AND PEPTIDOMIMETICS
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Modified ribosomes that were selected using a dipeptidyl-puromycin aminonucleoside are used to mediate site-specific incorporation of one or more peptides and peptidomimetics into protein in a cell free translation system. In addition, new fluorescent dipeptidomimetics have been synthesized and incorporated into proteins, as well as modified proteins containing one or more non-naturally occurring dipeptides.
- -
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Paragraph 0067; 0068
(2016/08/17)
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- Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives
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Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.
- Wang, Tianli,Yu, Zhaoyuan,Hoon, Ding Long,Phee, Claire Yan,Lan, Yu,Lu, Yixin
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supporting information
p. 265 - 271
(2016/01/25)
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- Enantiodivergent Synthesis of Bis-Spiropyrrolidines via Sequential Interrupted and Completed (3 + 2) Cycloadditions
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Both (5R)- and (5S)-1,7-diazaspiro[4.4]nonan-6-ones are obtained via a sequence of interrupted and completed stepwise (3 + 2) cycloadditions between azomethine ylides and π-deficient alkenes. The only source of chirality along the whole process is an enantiopure ferrocenyl pyrrolidine catalytic ligand. When the starting imine incorporates two aryl groups or one aryl group with one electron-releasing substituent, the reaction between the azomethine ylide and the alkene stops at the first step, leading to the corresponding Michael adduct. When imines derived from p-methoxybenzaldehyde are used, the corresponding syn-α-amino-γ-nitro ester is obtained with almost complete enantiocontrol. In contrast, imines derived from benzophenone lead to the corresponding anti analogue. From this interrupted (3 + 2) cycloaddition, cis- and trans-α-amino-γ-lactams can be obtained via hydrogenation of the nitro group followed by in situ cyclization. Imines derived from these latter compounds are the precursors of N-metalated azomethine ylides from which up to four new chiral centers can be generated via completed (3 + 2) cycloaddition reactions with full regio- and diastereocontrol. Cis- and trans-γ-lactams lead to opposite bis-spiropyrrolidine enantiomers. Therefore, both enantiomeric series of spiro compounds can be obtained by means of the same catalytic system. The potential of these rigid, densely substituted homochiral compounds in medicinal chemistry is briefly described.
- Conde, Egoitz,Rivilla, Iván,Larumbe, Amaia,Cossío, Fernando P.
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p. 11755 - 11767
(2015/12/11)
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- Iron-catalyzed oxidative C - H/C - H cross-coupling: An efficient route to α-quaternary α-amino acid derivatives
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Fully loaded: A coordinating activation strategy has been developed to furnish α-quaternary α-amino acids through the iron(III)-catalyzed oxidative functionalization of α-C(sp3) - H bonds of α-tertiary α-amino acid esters. The reaction exhibits a broad substrate scope for both α-amino acids and nucleophiles (Nu) as well as good functional-group tolerance (see scheme, DTBP=di-tert-butyl peroxide, DCE=1,2-dichloroethane). Copyright
- Li, Kaizhi,Tan, Guangying,Huang, Jingsheng,Song, Feijie,You, Jingsong
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supporting information
p. 12942 - 12945
(2014/01/06)
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- Preparation of chiral amino esters by asymmetric phase-transfer catalyzed alkylations of schiff bases in a ball mill
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The asymmetric alkylation of Schiff bases under basic conditions in a ball mill was performed. The starting Schiff bases of glycine were prepared beforehand by milling protected glycine hydrochloride and benzophenone imine, in the absence of solvent. The Schiff base was then reacted with a halogenated derivative in a ball mill in the presence of KOH. By adding a chiral ammonium salt derived from cinchonidine, the reaction proceeded asymmetrically under phase-transfer catalysis conditions, giving excellent yields and enantiomeric excesses up to 75 %. Because an equimolar amount of starting material was used, purification was greatly simplified. Copyright
- Nun, Pierrick,Perez, Violaine,Calmes, Monique,Martinez, Jean,Lamaty, Frederic
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experimental part
p. 3773 - 3779
(2012/04/23)
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- Exploring Leishmania major Inositol Phosphorylceramide Synthase (LmjIPCS): Insights into the ceramide binding domain
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The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C13) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.
- Mina, John G.,Mosely, Jackie A.,Ali, Hayder Z.,Denny, Paul W.,Steel, Patrick G.
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supporting information; experimental part
p. 1823 - 1830
(2011/04/26)
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- PREPARATION OF C-PYRAZINE-METHYLAMINES
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A process for preparing a compound of formula (I) or a salt thereof: (I) wherein R1 is H or optionally substituted aryl or heteroaryl; comprising reacting 2,3- dichloropyrazine with a suitable diaryl imine followed by hydrolysis.
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Page/Page column 11-13
(2010/11/05)
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- Synthesis of novel imidazo[1,5-a]pyridine derivates
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An new, efficient synthesis of imidazo[1,5-a]pyridine derivatives starting from (3-chloro-5-(trifluoromethyl)pyridine-2- yl)methanamine(1) has been developed. A protocol to a 100 g scale synthesis of the amine (1) is given. Good yields are obtained. The structures of two products were confirmed by single crystal X-ray methods.
- Mihorianu, Monica,Mangalagiu, Ionel,Jones, Peter G.,Daniliuc, Constantin-Gabriel,Franz, M. Heiko,Neda, Ion
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experimental part
p. 689 - 695
(2011/10/18)
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- Substrate-controlled diastereoselectivity switch in catalytic asymmetric direct mannich reaction of glycine derivatives with imines: from anti- to syn-α,β-diamino acids
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(Chemical equation Presented) Back and forth: A diastereoselectivity switch has been devised in the Fesulphos-CuI-catalyzed glycine direct Mannich reaction with N-(8-quinolyl)sulfonyl imines by tuning the steric and electronic properties of the glycine component (see scheme). αβ-Diamino acids of syn configuration are produced under high diastereo- and enantiocontrol with glycinate esters derived from electron-deficient benzophenonetype ketimines, in contrast to aldiminederived pronucleophiles that lead to anti-configured products.
- Hernandez-Toribio, Jorge,Array, Ramon Gomez,Carretero, Juan Carlos
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supporting information; experimental part
p. 1153 - 1157
(2010/05/19)
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- Highly enantio- And diastereoselective mannich reactions of glycine schiff bases with in situ generated N-boc-imines catalyzed by a cinchona alkaloid thiourea
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(Figure Presented) Highly ena(Figure Presented)ntlo- and dlastereoselectlve organocatalytlc Mannlch reactions of glycine Schiff bases with N-Boc-protected lmlnes are described. Imlnes were generated In situ from bench-stable a-amldo sulfones. Catalysis mediated by a cinchona alkaloid thiourea provided optically active α,βdlamlno acid derivatives with up to 99% ee and near-perfect dlastereoselection.
- Zhang, Halle,Syed, Salahuddin,Barbas, Carlos F.
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supporting information; scheme or table
p. 708 - 711
(2010/04/02)
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- Diastereo- And enantioselective synthesis of β-Hydroxy-α-amino acids: Application to the synthesis of a key intermediate for lactacystin
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The development of a highly efficient and stereoselective methodology for the preparation of β-hydroxy-α- amino acids is described. Nucleophilic addition of enolates of tricyclic iminolactones 1a and 1b to aldehydes in the presence of 6 equiv of lithium chloride in THF at -78 °C leads to aldol adducts in good yield (63-86%) and high diastereoselectivity (up to >25:1 dr). Subsequently, hydrolysis of the aldol adducts under acidic conditions leads to the corresponding β-hydroxy-a-amino acids in good yields (up to 83%) and excellent enantiomeric excesses (99% ee) with good recovery yields of the chiral auxiliaries 6 and 7. This methodology was applied to the facile synthesis of the key intermediate for lactacystin along with several isomers.
- Li, Qiong,Yang, Shao-Bo,Zhang, Zhihui,Li, Lei,Xu, Peng-Fei
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supporting information; experimental part
p. 1627 - 1631
(2009/09/24)
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- Oxazole cyclopeptides for chirality transfer in C3-symmetric octahedral metal complexes
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A straightforward synthesis of C3-symmetric oxazole-containing macrocyclic peptide scaffolds is presented. This type of macrocycles bears three functional groups on the oxazole rings, which allows fixing of various receptor arms on them in an easy manner. The chiral backbone of the macrocycle proved to be a powerful tool for chirality induction, thus predetermining the configuration of helically coordinated metal centres. The diastereoselective formation of CoII, NiII, CuII and Zn II complexes with tripodal bipyridyl ligand 4 was proved by UV- and CD-absorption spectrophotometric titration experiments. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Pinter, Aron,Haberhauer, Gebhard
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experimental part
p. 2375 - 2387
(2009/04/05)
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- Constraining the amide bond in N-Sulfonylated dipeptide VLA-4 antagonists
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The integrin VLA-4 is implicated in several inflammatory disease states. In search of non-peptidic antagonists of VLA-4, rotational constraints were imposed on the amide bond of prototypical N-sulfonylated dipeptide VLA-4 antagonists. By judicious structural modification of the side chains, trisubstituted imidazoles with moderate binding potencies were obtained, for example, 19, VLA-4 IC50 = 237 nM.
- Chang, Linda L.,Yang, Ginger X.,McCauley, Ermengilda,Mumford, Richard A.,Schmidt, John A.,Hagmann, William K.
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p. 1688 - 1691
(2008/09/20)
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- THE USE OF N-ARYL DIAZASPIRACYCLIC COMPOUNDS IN THE TREATMENT OF ADDICTION
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Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteraryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological "reward" process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, wihout resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).
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Page/Page column 39-40; 65
(2010/10/20)
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- Analogues of thiolactomycin as potential antimalarial agents
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Analogues of the natural antibiotic thiolactomycin (TLM), an inhibitor of the condensing reactions of type II fatty acid synthase, were synthesized and evaluated for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum. Alkylation of the C4 hydroxyl group led to the most significant increase in growth inhibition (over a 100-fold increase in activity compared to TLM). To investigate the mode of action, the P. falciparum KASIII enzyme was produced for inhibitor assay. A number of TLM derivatives were identified that showed improved inhibition of this enzyme compared to TLM. Structure-activity relationships for enzyme inhibition were identified for some series of TLM analogues, and these also showed weak correlation with inhibition of parasite growth, but this did not hold for other series. On the basis of the lack of a clear correlation between inhibition of pfKASIII activity and parasite growth, we conclude that pfKASIII is not the primary target of TLM analogues. Some of the analogues also inhibited the growth of the parasitic protozoa Trypanosoma cruzi, T. brucei, and Leishmania donovani.
- Jones, Simon M.,Urch, Jonathan E.,Kaiser, Marcel,Brun, Reto,Harwood, John L.,Berry, Colin,Gilbert, Ian H.
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p. 5932 - 5941
(2007/10/03)
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- Novel imidazoles
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Novel imidazoles are provided. The compounds are useful as HMGCo-A Reductase Inhibitor. Also provided are pharmaceutical compositions of the compounds. Methods of making and methods of using the compounds are also provided.
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Page/Page column 62
(2010/02/14)
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- The development of new carboxylic acid-based MMP inhibitors derived from a cyclohexylglycine scaffold
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A series of carboxylic acids was prepared based on cyclohexylglycine scaffolds and tested for potency as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for five enzymes within the MMP family, and a number of inhibitors such as compound 18 display low nanomolar potency for MMP-2 and MMP-13, while selectively sparing MMP-1 and MMP-7.
- Tullis, Joshua S.,Laufersweiler, Matthew J.,VanRens, John C.,Natchus, Michael G.,Bookland, Roger G.,Almstead, Neil G.,Pikul, Stanislaw,De, Biswanath,Hsieh, Lily C.,Janusz, Michael J.,Branch, Todd M.,Peng, Sean X.,Jin, Yingkun Y.,Hudlicky, Tomas,Oppong, Kofi
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p. 1975 - 1979
(2007/10/03)
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- Reactions of thioketones with methyl azidoacetate
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The reaction of methyl azidoacetate with several thiocarbonyl compounds at 80°C leads to imine derivatives of methyl glycinate in yields of about 60%. With 2,2,4,4-tetramethyl-3-thioxocyclobutanone, only 19% of the corresponding glycinate 19 is obtained. The main products in this reaction are the symmetrical dispiro-1,2,4-trithiolane 20 and the dispiro-1,4,2-dithiazolidine 21 (Scheme 6). The structure of the latter was established by X-ray crystallography. A reaction mechanism involving an intermediate thiocarbonyl-S-sulfid and a thiocarbonyl-S-imide is proposed in Scheme 7.
- Mloston,Romanski,Linden,Heimgartner
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p. 880 - 890
(2007/10/03)
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- Rhodium(II) Acetate-catalysed Decomposition of 2-Diazo-3-oxobutanamides Derived from L-Phenylalanine
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In order to developed a practical method for alkylating α-amino acids at the α- or β-carbon atom by intramolecular carbene C-H insertion, a series of diazoamides 3a-e was synthesized and subjected to rhodium(II) acetate-catalysed decomposition.The N-benzyl derivative 3a gave mainly the azetidinones 4a and 5a, resulting from a carbene C-H insertion into the N-benzyl group.The N-diphenylmethyl derivative 3c yielded, upon treatment with rhodium(II) acetate, the azetidinone 5c, the imine 6c, the cycloheptapyrrolidinone 7c as well as the desired pyrrolidinone 8c (12percent yield) the latter resulting from an alkylation of the L-phenylalanine framework at the β-carbon atom.
- Zaragoza, Florencio,Zahn, Gernot
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p. 292 - 298
(2007/10/02)
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- SYNTHESE D'ACIDES ω-AMINO-ω-CARBOXY-ALKYLPHOSPHONIQUES
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ω-Amino ω-carboxyalkylphosphonic acids 1 synthesis is reviewed.For n = 4, 5, 6 a general, efficient and inexpensive synthesis is described; acetamido(ω-bromoalkyl)malonates 12 are prepared from commercial dibromoalkanes and acetamidomalonate using the phase transfer catalysis process, then condensed with triethylphosphite through an Arbuzov reaction.An acid hydrolysis followed by purification on Dowex gives aminophosphonic acids 1 (n = 4, 5, 6) with a 70percent overall yield.The lower acid 1 (n = 2) is obtained with an identical overall yield from acetamidomalonate and 2-haloethylphosphonate using also liquid-solid phase transfer catalysis.
- Aboujaoude, E. Elia,Collignon, N.,Savignac, P.,Bensoam, J.
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-