- Substituted aza five-membered ring derivative and application thereof in medicine
-
The invention discloses a substituted aza-five-membered ring derivative and application thereof to medicines. , The invention provides a substituted aza five-membered ring compound or a stereoisomer, a tautomer, an oxynitride, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutical composition containing the compound of the present invention. The invention also discloses application of the compound or the pharmaceutical composition of the compound in preparation of a medicament for treating PDE4 related diseases such as atopic dermatitis (AD) or chronic obstructive pulmonary disease (COPD).
- -
-
Paragraph 0466-0470
(2021/10/30)
-
- Discovery of 3-Quinazolin-4(3 H)-on-3-yl-2, N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors
-
Phosphoinositide 3-kinases (PI3Ks) mediate a series of events related to cell growth, proliferation, survival, and differentiation. Overexpression of PI3Ks can lead to the dysregulation of cell homeostasis and cause tumorigenesis. In this study, rationally designed compounds were investigated as PI3Kα-selective inhibitors. Our efforts culminated in the discovery of a series of quinazolin-4(3H)-one derivatives with 2-substituted-N-methylpropanamide substitutions as PI3Kα-selective inhibitors. The best compound, 10, has PI3Kα enzymatic and cellular IC50 values of 1.8 and 12.1 nM, respectively. It exhibits biochemical selectivities for PI3Kα over PI3Kβ/δ/γof 150/7.72/7.67-fold and cellular selectivities of 115/15.1/>826-fold, respectively. Compound 10 is 59% orally bioavailable with a dose-normalized AUC of 3090 nM. These effects translated into in vivo conditions, as 10 significantly time- and dose-dependently inhibited phosphorylation of Akt in BT-474 subcutaneous xenograft mice and inhibited tumor growth.
- Dong, Jiaqiang,Huang, Jingjie,Zhou, Ji,Tan, Ye,Jin, Jing,Tan, Xi,Wang, Bei,Yu, Tao,Wu, Chengde,Chen, Shuhui,Wang, Tie-Lin
-
supporting information
p. 1463 - 1469
(2020/08/14)
-
- Tert-Butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a green and chemoselective N-tert-butoxycarbonylation reagent
-
The use of tert-butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a chemoselective tert-butoxycarbonylation reagent for aromatic and aliphatic amines has been demonstrated. To gain insight into this reaction, in situ React IR technology was used to confirm the effectivity and chemoselectivity of this novel Boc reagent. The reaction was carried out chemoselectively in high yield under mild, environment-friendly conditions and was completed quickly within 1 hour. Simultaneously, the Boc carrier was easily recyclable, and has great application prospects for industrial production.
- Du, Fangyu,Zhou, Qifan,Fu, Yang,Zhao, Hanqi,Chen, Yuanguang,Chen, Guoliang
-
p. 6549 - 6554
(2019/05/04)
-
- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound useful in the treatment of a neurodegenerative disorder and their combined use as a medicament, in particular for the treatment of neurodegenerative and/or cognitive disorders.
- -
-
Page/Page column 111
(2019/07/19)
-
- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
-
The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Paragraph 0524-0525
(2019/07/10)
-
- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound which compound is useful in the treatment of a psychiatric disorder and their combined use as a medicament, in particular for the treatment of psychiatric and/or cognitive disorders.
- -
-
Page/Page column 108
(2019/07/19)
-
- Progress toward the total synthesis of mirabalin isomers
-
Key fragments of the cytotoxic marine macrolide mirabalin have been synthesized, by using a flexible strategy based on asymmetric reductions to control the hydroxy- and carbamate-bearing stereocenters. In particular, ruthenium or rhodium-mediated asymmetric hydrogenation and transfer hydrogenation were used in combination with a dynamic kinetic resolution to control two contiguous stereocenters in a single step.
- Echeverria, Pierre-Georges,Pons, Amandine,Prévost, Sébastien,Férard, Charlène,Cornil, Johan,Guérinot, Amandine,Cossy, Janine,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie
-
-
- Method for selective removal of t-butyloxycarboryl from nitrogen
-
The invention discloses a method for selective removal of t-butyloxycarboryl from nitrogen. According to the synthesis method, directed at a reaction substrate having t-butyloxycarboryl and another acyl protecting group on a molecular nitrogen atom, in the presence of a selectfluor reagent, reaction is carried out in a solution for selective removal of t-butyloxycarboryl and retention of another acyl protecting group. The synthesis method provided by the invention is novel and efficient, is not reported in literature, and can be widely used in total synthesis and drug intermediate synthesis.
- -
-
Paragraph 0024-0025; 0026-0028; 0038-0040
(2018/03/26)
-
- Synthesis, biological evaluation, and molecular modeling studies of chiral chloroquine analogues as antimalarial agents
-
In a focused exploration, we designed, synthesized, and biologically evaluated chiral conjugated new chloroquine (CQ) analogues with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity (in vitro 50% inhibitory concentration, 56.98 nM for strain 3D7 and 97.76 nM for strain K1; selectivity index in vivo [up to at a dose of 12.5 mg/kg of body weight], 3,510) as a new lead antimalarial agent. Other compounds (compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c) also showed moderate activity against a CQ-sensitive strain (3D7) and superior activity against a CQ-resistant strain (K1) of Plasmodium falciparum. Furthermore, we carried out docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to explain the structure-activity relationships (SAR). Our new findings specify the significance of the H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the favorable and unfavorable sites of CQ analogues for incorporating steric, hydrophobic, and electropositive groups to improve the antimalarial activity.
- Kondaparla, Srinivasarao,Debnath, Utsab,Dola, Vasantha Rao,Sinha, Manish,Katti, Seturam B.,Soni, Awakash,Srivastava, Kumkum,Puri, Sunil K.
-
-
- 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
-
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Page/Page column 102; 103
(2018/09/25)
-
- New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
-
A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
- Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
-
supporting information
p. 2127 - 2132
(2017/10/31)
-
- RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles
-
The established cytotoxic agent RITA contains a thiophene-furan-thiophene backbone and two terminal alcohol groups. Herein we investigate the effect of using thiazoles as the backbone in RITA-like molecules and modifying the terminal groups of these trithiazoles, thereby generating 41 unique structures. Incorporating side chains with varied steric bulk allowed us to investigate how size and a stereocenter impacted biological activity. Subjecting compounds to growth inhibition assays on HCT-116 cells showed that the most potent compounds 7d, 7e, and 7h had GI50 values of 4.4, 4.4, and 3.4 μM, respectively, versus RITA (GI50 of 800 nM). Analysis of these compounds in apoptosis assays proved that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated that it acts via a different mechanism of action to that of RITA. RITA suppressed Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an alternative mechanism independent of p53.
- Pietkiewicz, Adrian L.,Zhang, Yuqi,Rahimi, Marwa N.,Stramandinoli, Michael,Teusner, Matthew,McAlpine, Shelli R.
-
supporting information
p. 401 - 406
(2017/04/21)
-
- Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
-
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
- Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
-
p. 1326 - 1337
(2017/06/23)
-
- Consecutive hydrazino-Ugi-azide reactions: Synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles
-
Isocyanide-based multicomponent reactions (IMCRs) allow the construction of relatively complex molecules through a one-pot synthesis. The combination of IMCRs in a consecutive or sequential fashion further extends the complexity of the molecules obtained. Herein, we report the efficient application of this approach to the synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles. Our strategy was accomplished in only three steps: first, a one-pot hydrazino-Ugi-azide four-component reaction; second a hydrazinolysis and finally an additional hydrazino-Ugi-azide reaction. This sequence provides the title compounds in moderate to excellent yields. The products synthesized herein contain functional groups within their structures that can be easily modified to obtain new acylhydrazino 1,5-disubstituted tetrazoles.
- De Fátima Barreto, Angélica S.,Dos Santos, Veronica Alves,Zandrade, Carlos Kleber
-
p. 2596 - 2602
(2018/01/17)
-
- Synthesis of trans-Configured Enol Ethers by a Sequence of syn-Selective Glycolate Aldol Addition, Hydrolysis, and Grob Fragmentation
-
A trans-selective access to enol ethers with a disubstituted C=C bond was developed. It consists of a diastereoselective glycolate aldol addition, a hydrolysis, and a Grob fragmentation. Aldol additions of N-[(benzyloxy)acetyl]oxazolidinones furnished syn-aldols selectively. Hydrolytic removal of the auxiliaries gave α-benzyloxy-β-hydroxycarboxylic acids. Exposure to DMF dineopentylacetal induced Grob fragmentations, which delivered trans-configured enol ethers. Applying our 3-step sequence in a bidirectional synthesis led to bis(enol ethers) trans,trans-selectively, i.e., to a motif rarely encountered in the literature. A modified precursor synthesis allowed for the first time to access both the E- and the Z-isomer of an enol ether with a trisubstituted C=C bond stereoselectively using a Grob fragmentation route. The Ar–Br and C≡C–SiMe2tBu motifs of appropriate enol ethers engaged in follow-up reactions via organometallics. These provided more elaborated enol ethers.
- Engesser, Tobias,Brückner, Reinhard
-
supporting information
p. 5789 - 5794
(2017/10/23)
-
- SUBSTITUTED AMINOPYRIMIDINE COMPOUNDS AND METHODS OF USE
-
The invention relates to the preparation and use of new aminopyrimidine derivatives as drug candidates in free form or in pharmaceutically acceptable salt form and formulations thereof for the modulation of a disorder or disease which is mediated by the activity of the PI3K enzymes. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of disorders or diseases, such as disorders of immunity and inflammation in which PI3K enzymes play a role in leukocyte function, and hyperproliferative disorders associated with PI3K activity, including but not restricted to leukemias and solid tumors, in mammals, especially humans.
- -
-
Paragraph 407
(2016/10/04)
-
- Propargyl-Assisted Selective Amidation Applied in C-terminal Glycine Peptide Conjugation
-
Alkyl esters, such as propargyl esters, typically lack the electron-withdrawing inductive effects needed to participate in nucleophilic acyl substitution reactions. Herein, we report an unusual observation in which glycine propargyl ester derivatives displayed selective, base-independent reactivity towards linear alkylamines under mild, metal-free conditions. Through global reaction route mapping (GRRM) modeling calculations, it is predicted that these observations may be governed by factors related to hydrogen-bonding and intermolecular interactions, rather than electron-withdrawing inductive effects. Based on this concept of propargyl-assisted selective amidation, a direct application was made to develop a novel site-specific C-terminal glycine peptide bioconjugation technique as a proof-of-concept, which relies upon the selective reactivity of glycine propargyl esters over that of aspartate and glutamate side-chain-linked propargyl esters.
- Vong, Kenward King Ho,Maeda, Satoshi,Tanaka, Katsunori
-
supporting information
p. 18865 - 18872
(2016/12/26)
-
- NOVEL COMPOUNDS
-
A compound of formula (I) or a pharmaceutically acceptable derivative thereof, (formula 1) wherein R1,R2, R3, R4, R5, X, m and n are defined in the specification; a process for preparing such compounds; a pharmaceutical composition comprising such compounds; and the use of such compounds in medicine.
- -
-
Page/Page column 82
(2016/02/26)
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- Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions
-
Herein we describe a versatile approach for the synthesis of acylhydrazino-peptomers, a new class of peptidomimetics. The key idea in this approach is based on a simple route using a one-pot hydrazino-Ugi four-component reaction followed by a hydrazinolysis or hydrolysis reaction and subsequent hydrazino-Ugi reaction or classical Ugi reaction for the construction of acyclic acylhydrazino-peptomers. The consecutive multicomponent reactions produced a variety of acylhydrazino-peptomers in moderate to excellent yields (47-90%). These compounds are multifunctional intermediates that can be further functionalized to obtain new peptidomimetics with potential biological activity.
- Barreto, Angélica De Fátima S.,Dos Santos, Veronica Alves,Andrade, Carlos Kleber Z.
-
supporting information
p. 2865 - 2872
(2017/01/09)
-
- Efficient and Flexible Synthesis of Highly Functionalised 4-Aminooxazoles by a Gold-Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition
-
Oxazoles are important motifs within bioactive and functional materials. Complex, fully substituted and functionalised 4-aminooxazoles are accessed by an efficient intermolecular reaction between an ynamide and an N-acylpyridinium N-aminide in the presence of a gold catalyst. The formal [3+2] dipolar cycloaddition employs a nucleophilic nitrenoid approach to access the 1,3-N,O-dipole character in a controllable fashion. The selectivity for a cycloaddition pathway provides a stark contrast against the indiscriminate reactivity of electrophilic acyl nitrenes. Protocols for the formation of acyl-functionalised aminides are reported from accessible precursors including carboxylic esters and acids. The function of these aminides in the oxazole-forming reaction has been explored and it is shown that substantial elaboration is accommodated despite proximity to the reactive centre. As a result functional oxazole-based motifs, such as chiral oxazoles with biologically pertinent substitution patterns, are readily accessible. The use of ynamide types that are unexplored or little used in gold catalysis has been evaluated. Unusual all-heteroatom substitution patterns around the oxazole are shown to be accessible using thio-ynamides. The study shows that a close stoichiometry of reactants is suitable alongside relatively low loadings of the bench-stable precatalysts in practically straightforward multi-mmol scale reactions. The efficiency and flexibility of this regioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.
- Gillie, Andrew D.,Jannapu Reddy, Raju,Davies, Paul W.
-
supporting information
p. 226 - 239
(2016/02/14)
-
- Ultrasound-Assisted Methyl Esterification of Carboxylic Acids ACatalyzed by Polymer-Supported Triphenylphosphine
-
A convenient and efficient sonochemical method for methyl esterification of carboxylic acids catalyzed by polymer-supported triAphenylphosphine (PS-Ph3P) is reported. In the presence of 1:0.1:2 molar ratio of 2,4,6-trichloro-1,3,5-triazine/PS-Ph3P/Na2CO3, methyl esters of various carboxylic acids bearing reactive hydroxyl groups as well as acid-or base-labile functionalities could be rapidly prepared (within 10-20 min) in good to excellent yields without necessity to pre-activate the acids. Using the polymer-bound phosphine also allows easy isolation of the products which, in most of the cases, were obtained in high purities without column chromatography.
- Jaita, Subin,Phakhodee, Wong,Pattarawarapan, Mookda
-
p. 2006 - 2008
(2015/09/01)
-
- Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-Catalyzed Atroposelective Bromination
-
We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other atropisomerically defined products of interest. For example, (1) a dehalogenation Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.
- Diener, Matthew E.,Metrano, Anthony J.,Kusano, Shuhei,Miller, Scott J.
-
supporting information
p. 12369 - 12377
(2015/10/12)
-
- A simple, rapid, and efficient N-Boc protection of amines under ultrasound irradiation and catalyst-free conditions
-
A green and simple approach for the N-Boc protection on structurally diverse amines under ultrasound irradiation is described. Selective N-Boc protection was achieved in excellent isolated yield in a short reaction time at room temperature. Mild conditions, inexpensive and an easily available reagent, and absence of any auxiliary substances are the main advantages of this procedure. Graphical abstract: [Figure not available: see fulltext.]
- Amira, Aicha,K'Tir, Hacene,Berredjem, Malika,Aouf, Nour-Eddine
-
p. 509 - 515
(2014/03/21)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMD A receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 00136
(2014/08/19)
-
- Catalytic methyl transfer from dimethylcarbonate to carboxylic acids
-
Although methylation reactions are commonplace, currently used reagents are hazardous, toxic, and/or unstable. Dimethylcarbonate has been put forth as an inexpensive, nontoxic, and green potential methylating reagent. Herein we report a general, base-catalyzed methyl transfer from dimethylcarbonate to carboxylic acids. High selectivity for esterification is observed even in the presence of unprotected phenols, and the mild reaction conditions enable conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling studies suggest a mechanism proceeding by direct methyl transfer from dimethylcarbonate to the substrate.
- Ji, Yuan,Sweeney, Jessica,Zoglio, Jillian,Gorin, David J.
-
p. 11606 - 11611
(2013/12/04)
-
- Oligomeric epoxide-amine adducts based on 2-amino-N-isopropylacetamide and a-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties
-
2-Amino-N-isopropylacetamide and α-amino-ε-caprolactam were reacted with glycerol diglycidyl ether to give novel oligomeric thermoresponsive epoxide-amine adducts. These oligomers exhibit a lower critical solution temperature (LCST) behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD) and the curing properties of the amine-epoxide mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed.
- Fischer, Julian,Ritter, Helmut
-
p. 2803 - 2811
(2014/01/06)
-
- One-pot synthesis of α-amino acids from CO2 using a bismetal reagent with Si-B bond
-
In the presence of 1.1 equiv of PhMe2Si-Bpin, 5 equiv of CsF, and 20 mol % of TsOH·H2O, precursors of N-Boc-imines can be converted into the corresponding α-aryl or α-alkenyl glycine derivatives under gaseous CO2 in moderate-to-high yields with a single operation. α-Isobutenyl glycine thus obtained can be further derivatized into various types of α-amino acids including N-Boc-leucine, serine, and glycine derivatives in short steps.
- Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
-
p. 6202 - 6205
(2013/02/23)
-
- Development of an efficient solvent free one-pot Heck reaction catalyzed by novel palladium (II) complex-via green approach
-
A novel 1-glycyl-3-methyl imidazolium chloride-palladium (II) complex [[Gmim]Cl-Pd (II)] was found to be a heterogeneous catalyst for an efficient Heck reaction with good to excellent yield under solvent free condition. Tetra-coordinated palladium complex was prepared by reacting PdCl2 with 1-glycyl-3-methyl imidazolium chloride and its catalytic function invented for the CC bond formation. Spectroscopic evidence of complex has been proved by powder XRD, SEM, FT-IR and AFM. This protocol provides a simple strategy for the generation of a variety of new CC bonds under environmentally benign condition.
- Karthikeyan, Parasuraman,Muskawar, Prashant Narayan,Aswar, Sachin Arunrao,Bhagat, Pundlik Rambhau,Sythana, Suresh Kumar
-
experimental part
p. 112 - 120
(2012/06/01)
-
- Novel 1-glycyl-3-methyl imidazolium chloride-iron(III) complex for synthesis of propargylamines
-
The development of a highly efficient, 1-glycyl-3-methyl imidazolium chloride-iron(III) [Gmim-Fe(III)] complex, catalyst for the threecomponent coupling reaction of aldehydes, alkyne and amine (A3-coupling) was described. In the presence of [Gmim-Fe(III)] (0.05 mmol), the A 3-coupling reaction were carried out at room temperature under solvent-free reaction condition and the corresponding propargylamines were generated in good to excellent yields. Both aliphatic and aromatic aldehydes were used in the reaction. Furthermore, the catalyst could be reused several times without a significant loss of its catalytic activity.
- Karthikeyan, Parasuraman,Arunrao, Aswar Sachin,Narayan, Muskawar Prashant,Senthil Kumar,Kumar, Sythana Suresh,Bhagat, Pundlik Rambhu
-
experimental part
p. 4285 - 4289
(2012/07/27)
-
- Universal peptidomimetics
-
This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.
- Ko, Eunhwa,Liu, Jing,Perez, Lisa M.,Lu, Genliang,Schaefer, Amber,Burgess, Kevin
-
supporting information; scheme or table
p. 462 - 477
(2011/04/16)
-
- Chemoselective esterification and amidation of carboxylic acids with imidazole carbamates and ureas
-
Imidazole carbamates and ureas were found to be chemoselective esterification and amidation reagents. A wide variety of carboxylic acids were converted to their ester or amide analogues by a simple synthetic procedure in high yields.
- Heller, Stephen T.,Sarpong, Richmond
-
supporting information; experimental part
p. 4572 - 4575
(2010/12/25)
-
- Parallel synthesis of an oligomeric imidazole-4, 5-dicarboxamide library
-
A library of oligomeric compounds was synthesized based on the imidazole-4, 5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.
- Xu, Zhigang,DiCesare, John C.,Baures, Paul W.
-
supporting information; experimental part
p. 248 - 254
(2010/08/19)
-
- A highly efficient flow reactor process for the synthesis of N-Boc-3,4-dehydro-l-proline methyl ester
-
The multi-step preparation of N-Boc-3,4-dehydro-l-proline methyl ester using a modular flow reactor is reported. The use of immobilised reagents and scavengers in pre-packed glass tubes allows us to obtain the pure product in 87% overall yield, 97% purity, and >98% enantiomeric excess without any additional purification step. Our flow-based protocol enables the rapid multi-gram synthesis (about 9 g/12 h) of the desired product.
- Tamborini, Lucia,Conti, Paola,Pinto, Andrea,Micheli, Carlo De
-
experimental part
p. 222 - 225
(2010/05/02)
-
- A facile access to pyrroles from amino acids via an aza-Wacker cyclization
-
(Chemical Equation Presented) A facile and efficient synthesis of pyrroles from readily available amino acids is described. The key step in the method is an aza-Wacker oxidative cyclization catalyzed by palladium(II)/Cu(OTf) 2. A series of pyrroles were obtained by this method under mild conditions.
- Zhang, Zuhui,Zhang, Jintang,Tan, Jiajing,Wang, Zhiyong
-
p. 5180 - 5182
(2008/12/20)
-
- Enzymatic synthesis of ω-carboxy-β-hydroxy-(l)-α-amino acids
-
Commercially available ω-carboxy-aldehydes and glycine have been subjected to the catalytic action of an l-threonine aldolase from Escherichia coli to give the corresponding β-hydroxy-α-(l)-amino acids as a mixture of erythro/threo epimers. Specifically, the reaction with glyoxylic acid (2) gave the epimeric β-hydroxy-(l)-aspartates (t,e)-9 that could be isolated by ion-exchange chromatography in 67% yield. Following esterification and N-Boc protection, the two epimers could be isolated as pure compounds. Similarly, the aldolase-catalyzed addition of glycine to succinic semialdehyde (4) gave the expected mixture of β-hydroxy-l-α-aminoadipic acids (t)-12 and (e)-12 in 34% yield.
- Sagui, Francesca,Conti, Paola,Roda, Gabriella,Contestabile, Roberto,Riva, Sergio
-
p. 5079 - 5084
(2008/09/21)
-
- 6-Hydrazinopurine 2′-methyl ribonucleosides and their 5′-monophosphate prodrugs as potent hepatitis C virus inhibitors
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A series of 6-hydrazinopurine 2′-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5′-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC50 of 24 nM vs 92 μM for the parent).
- Gunic, Esmir,Chow, Suetying,Rong, Frank,Ramasamy, Kanda,Raney, Anneke,Yunzhi Li, David,Huang, Jingfan,Hamatake, Robert K.,Hong, Zhi,Girardet, Jean-Luc
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p. 2456 - 2458
(2008/02/03)
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- AMINO-ALKYL-AMIDE DERIVATIVES AS CCR3 RECEPTOR LIGANDS
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The present invention relates to the CCR3 receptor ligands of the general formula (I), within them favourably to antagonists and to the salts, solvates and isomers thereof, to the pharmaceutical compositions containing them, to the use of the compounds of the general formula (I) and their salts, solvates and isomers and to the preparation of the compounds of the general formula (I) and their salts, solvates and isomers and to the new intermediates of the general formula (XX) and (XXI).
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Page/Page column 27-28
(2010/11/26)
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- Synthesis and evaluation of a novel samarium-153 bifunctional chelating agent for radioimmunotargeting applications
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A new bifunctional chelating agent (BCA), 3-(4-isothiocyanatobenzyl) triethylenetetraaminehexaacetic acid (9), has been synthesized in fast and easy conditions. An improved synthesis of its position isomer 1-(4- isothiocyanatobenzyl)triethylenetetraaminehexaacetic acid (19) is also described. Stability in serum media of the two corresponding aminobenzyl derivatives-samarium-153 complexes, respectively, 3-(4-aminobenzyl) triethylenetetraaminehexaacetic acid-samarium-153 and 1-(4-aminobenzyl) triethylenetetraaminehexaacetic acid-samarium-153, have been evaluated. The 3-(4-aminobenzyl)triethylenetetraaminehexaacetic acid complex revealed excellent stability in serum media, and therefore 3-(4-isothiocyanatobenzyl) triethylenetetraaminehexaacetic acid (9) appears useful for future in vivo radioimmunotherapy investigations. Copyright
- Morandeau, Laurence,Remaud-Le Saec, Patricia,Ouadi, Ali,Bultel-Riviere, Karine,Mougin-Degraef, Marie,De France-Robert, Agnes,Faivre-Chauvet, Alain,Gestin, Jean-Francois
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p. 109 - 123
(2007/10/03)
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- Ceric ammonium nitrate (CAN) mediated esterification of N-Boc amino acids allows either retention or removal of the N-Boc group
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Reaction of N-Boc amino acids with ceric ammonium nitrate in an alcohol as the solvent at room temperature resulted in the esterification of N-Boc amino acids with Boc group retention. When the reaction was conducted at reflux temperature, esterification was accompanied with simultaneous removal of the Boc group. Both reactions gave the desired products in good yields.
- Kuttan, Ashani,Nowshudin, Shiek,Rao
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p. 2663 - 2665
(2007/10/03)
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- Solution phase synthesis of esters within a micro reactor
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A range of techniques are demonstrated for the solution phase synthesis of esters within an EOF-based borosilicate glass micro reactor, including the use of mixed anhydrides and the in situ preparation of acyl halides.
- Wiles, Charlotte,Watts, Paul,Haswell, Stephen J.,Pombo-Villar, Esteban
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p. 10173 - 10179
(2007/10/03)
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- Development of a temporary marker for peptides
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3-[(N,N-Dimethylaminophenyl)-4′-diazenyl]benzoic acid was coupled with several amino acid esters and the product acylated further with Boc. The material thus obtained was then submitted to cleavage by electrolysis and nucleophilic attack in order to evaluate the possibility of using this chromophore as a temporary marker.
- Sameiro,Goncalves,Maia, Hernani L.S.
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p. 1480 - 1485
(2007/10/03)
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- Synthesis of chiral 3,4-disubstituted pyrroles from L-amino acids
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A general methodology for the conversion of naturally occurring amino acids to 3,4-disubstituted pyrroles is described. A suitably protected amino acid (1) was first converted to the corresponding aldehyde (2). Homer-Emmons olefination afforded a facile entry to the corresponding α,β-unsaturated ester (3). The construction of the pyrrole ring system was accomplished in a single step, using an intramolecular cyclization reaction with tosylmethyl isocyanide (TOSMIC).
- Hover, Jocelyn A.,Bock, Charles W.,Bhat, Krishna L.
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p. 791 - 798
(2007/10/03)
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- METHOD FOR STORING QUATERNARY AMMONIUM SALT
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A method of improving the stability of a quaternary ammonium salt and a method of efficiently preparing the quaternary ammonium salt having improved stability.
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- A temporary marker for biological applications
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Having in mind the development of new colour labelled amino acid derivatives, a carboxyl azo dye was coupled to amino acid esters to give the corresponding orange N-acyl derivatives, which were in turn further acylated at their N-terminus with Boc for investigation of the conditions of possible cleavage of the chromophore by electrolysis or with nucleophiles. While difficulties were met with electrolysis owing to competitive reduction of the azo group, cleavage with N,N-diethylaminoethylamine (DEAEA) gave satisfactory results. This allows the use of the chromophore as a temporary marker.
- Sameiro, M,Gon?alves, T,Maia, Hernani L.S
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p. 7775 - 7777
(2007/10/03)
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- Direct conversion of azides and benzyl carbamates to t-butyl carbamates using polymethylhydrosiloxane and Pd-C
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One step direct conversion of azides and benzyl carbamates to t-butyl carbamales is achieved using inexpensive and safe hydride source namely polymethylhydrosiloxane (PMHS) under Pd-C catalysis.
- Chandrasekhar,Chandraiah,Raji Reddy,Venkat Reddy
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p. 780 - 781
(2007/10/03)
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- An efficient conversion of allyl esters to urethanes with Pd catalyst
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Reaction of allyl esters in a proper alcohol with Pd catalyst in the presence of (PhO)2P(O)N3 and NaN3 at 80 °C directly gave urethanes. The reactions in t-BuOH afforded amines protected with Boc.
- Okumoto, Hiroshi,Nishihara, Satoshi,Yamamoto, Sinya,Hino, Hirokazu,Nozawa, Akihiro,Suzuki, Akira
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p. 991 - 992
(2007/10/03)
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- N-acyl-5,5-dimethyl-oxazolidin-2-ones as latent aldehyde equivalents
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N-acyl-5,5-dimethyl-oxazolidin-2-ones can function as versatile latent aldehyde equivalents - reductive cleavage with DIBAL-H affords aldehydes in good yield, while tandem DIBAL-H/Wittig methodology affords α,β-unsaturated esters.
- Bach, Jordi,Bull, Steven D.,Davies, Stephen G.,Nicholson, Rebecca L.,Sanganee, Hitesh J.,Smith, Andrew D.
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p. 6677 - 6680
(2007/10/03)
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- Asymmetric alkylations using SuperQuat auxiliaries - An investigation into the synthesis and stability of enolates derived from 5,5-disubstituted oxazolidin-2-ones
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Studies on the alkylation of enolates derived from a range of N-acyl-5,5-dimethyloxazolidin-2-ones and N-acyl-5,5-diphenyloxazolidin-2-ones reveal that high yields and high diastereoselectivities are best obtained when homochiral 4-isopropyl-5,5-dimethyloxazolidin-2-one is employed as a chiral auxiliary.
- Bull, Steven D.,Davies, Stephen G.,Jones, Simon,Sanganee, Hitesh J.
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p. 387 - 398
(2007/10/03)
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