cas 19962-06-2, N-BOC-3-AMINOPHENOL | Articles data

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Copolymers of aniline and 3-aminophenol derivatives with oligo(oxyethylene) side chains as novel water-soluble conducting polymers
A novel water-soluble copolymer of aniline and aminophenol (AP) grafted with oligo(oxyethylene) (PEO) side chains (AP-g-PEO) was synthesized. The AP-g-PEO macromononer was prepared starting from an N-protected 3-aminophenol (protection group: tert-butoxycarbonyl) followed by the substitution of tosylated oligo(oxyethylene) on the hydroxide moiety of the AP and deprotection. Finally, AP-g-PEO was copolymerized with aniline at various feed mole ratios (AP-g-PEO/aniline), The copolymers and various intermediates were characterized by FTIR, MS, NMR, GPC, UV-vis, and chemical elemental analysis. The increase of the aniline content and the decrease of the PEO side chain length generated lower oligo(oxyethylene) grafted concentrations and solubilities in water but longer conjugation lengths and higher conductivities. Four AP-g-PEOs were prepared from four oligo(oxyethylene) methyl ethers with Mn = 164, 350, 750, and 2000. The poly((AP-g-PEO-750)-co-aniline) at a feed mole ratio of 3/1 was water-soluble and possessed a relatively high conductivity (0.12 S/cm). AP-g-PEOs were found to have low reactivities and to generate low homopolymerization degrees because of the torsional effects of the PEO side chains on the backbone of the copolymer. A possible copolymerization mechanism was suggested. Furthermore, the copolymers with high PEO content had lower oxidation and doping levels of their backbones, which were confirmed by X-ray photoelectron spectroscopy.
Hua, Fengjun,Ruckenstein, Eli
p. 6104 - 6112
(2004)
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Synthesis of highly potent anti-inflammatory compounds (ROS inhibitors) from isonicotinic acid
In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro antiinflammatory activity. Remarkably high activities were observed for isonicotinates 5-6 and 8a-8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 μg/mL) with 95.9% inhibition at 25 μg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 μg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.
Yaqoob, Sana,Nasim, Nourina,Khanam, Rahila,Wang, Yan,Jabeen, Almas,Qureshi, Urooj,Ul-Haq, Zaheer,El-Seedi, Hesham R.,Jiang, Zi-Hua,Khan, Farooq-Ahmad
(2021/05/31)

Ultrasound promoted environmentally benign, highly efficient, and chemoselective N-tert-butyloxycarbonylation of amines by reusable sulfated polyborate
The sulfated polyborate catalyzed an efficient and chemoselective N-tert-butyloxycarbonylation of amines under ultrasonic irradiation is developed. A broad substrate scope has been demonstrated for N-Boc protection of various primary/secondary amines. It allows converting several aliphatic/aryl/heteroaryl amines, amino alcohol, aminoester, and chiral amines to their N-Boc-protected derivatives under solvent-free conditions with excellent yields. The protocol has several advantages such as easy catalyst, and product isolation, short reaction time, excellent yields, outstanding chemoselectivity, and catalyst recyclability, among others. This makes the process practicable, economical, and environmentally benign.
Pise, Ashok S.,Ingale, Ajit P.,Dalvi, Navnath R.
supporting information
p. 3768 - 3780
(2021/10/26)

Nanoceria as an efficient and green catalyst for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions
Nanocerium oxide mediated an efficient and green protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at ambient temperature. Various aliphatic, aromatic and heteroaromatic amines were protected using developed protocol and several functional groups such as alcohol, phenol and ester were well tolerated under these conditions. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
Garad, Dnyaneshwar N.,Ingale, Ajit P.,Shinde, Sandeep V.,Ukale, Dattatraya
supporting information
p. 1656 - 1668
(2021/04/05)

Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
supporting information
p. 3791 - 3804
(2021/11/04)

Sulfated tungstate: A highly efficient, recyclable and ecofriendly catalyst for chemoselective N-tert butyloxycarbonylation of amines under the solvent-free conditions
Sulfated tungstate catalyzed an efficient and ecofriendly protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at room temperature. The variety of functionalized aliphatic, aromatic and heteroaromatic amines efficiently undergoes the N-tert-butyloxycarbonylation under the developed protocol. The aminoalcohol, aminophenol, aminoester as well as various chiral amines underwent the chemoselective N-Boc protection under the optimized reaction condition. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
Ingale, Ajit P.,Shinde, Sandeep V.,Thorat, Nitin M.
supporting information
p. 2528 - 2543
(2021/07/02)

KIF18A INHIBITORS
Amide compounds of formula (I): and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of Kinesin Motor Protein KIF18A, such as cancer, psoriasis, atopic dermatitis, an autoimmune disorder, or inflammatory bowel disease, and the like.
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Paragraph 0385; 0386

(2021/02/12)

POLYAROMATIC UREA DERIVATIVES AND THEIR USE IN THE TREATMENT OF MUSCLE DISEASES
The current invention provides urea derivatives, in particular compounds having the core structure heteroaryl-NH-CO-NH-aryl-O- heteroaryl, for use in treating, ameliorating, delaying, curing and/ or preventing a disease or condition associated with muscle cells and/or satellite cells, such as Duchenne muscular dystrophy, Becker muscular dystrophy, cachexia or sarcopenia.
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Page/Page column 120-121

(2021/01/29)

Chemoselective and Site-Selective Lysine-Directed Lysine Modification Enables Single-Site Labeling of Native Proteins
The necessity for precision labeling of proteins emerged during the efforts to understand and regulate their structure and function. It demands selective attachment of tags such as affinity probes, fluorophores, and potent cytotoxins. Here, we report a method that enables single-site labeling of a high-frequency Lys residue in the native proteins. At first, the enabling reagent forms stabilized imines with multiple solvent-accessible Lys residues chemoselectively. These linchpins create the opportunity to regulate the position of a second Lys-selective electrophile connected by a spacer. Consequently, it enables the irreversible single-site labeling of a Lys residue independent of its place in the reactivity order. The user-friendly protocol involves a series of steps to deconvolute and address chemoselectivity, site-selectivity, and modularity. Also, it delivers ordered immobilization and analytically pure probe-tagged proteins. Besides, the methodology provides access to antibody-drug conjugate (ADC), which exhibits highly selective anti-proliferative activity towards HER-2 expressing SKBR-3 breast cancer cells.
Adusumalli, Srinivasa Rao,Kalra, Neetu,Purushottam, Landa,Rai, Vishal,Rawale, Dattatraya Gautam,Reddy, Neelesh C.,Shukla, Sanjeev,Thakur, Kalyani
supporting information
p. 10332 - 10336
(2020/04/27)

FLUOROALLYLAMINE DERIVATIVE AND USE THEREOF
The present invention relates to a fluoroallylamine derivative and use thereof. In particular, the present invention relates to a compound as shown in Formula I, a prodrug, an isomer, an isotope-labeled compound, a solvate or a pharmaceutically acceptable salt thereof, which has VAP-1/SSAO inhibitory activity, and can be used for treating a disease associated with VAP-1/SSAO overactivity.
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Paragraph 0344

(2020/03/17)

Antibody-medicine conjugate targeting EGFR and preparation method and application thereof
The invention relates to an antibody-medicine conjugate targeting an EGFR. The antibody-medicine conjugate targeting the EGFR is characterized in that the antibody-medicine conjugate of a structure shown in a formula I or pharmaceutically-accepted salt or solvate is involved. According to a structural formula of the antibody-medicine conjugate targeting the EGFR, n represents the medicine-antibody proportion and is 3-5; R is O or CONH or NHCO; R is in para-position or meta-position; p is 1-6; m is 0-20. According to the antibody-medicine conjugate targeting the EGFR, based on a bis-ethylene sulfamide connection connexin technology, the antibody-medicine conjugate targeting the EGFR is synthesized for the first time. According to the antibody-medicine conjugate targeting the EGFR, internal sulphur-sulphur bonds of an antibody are broken and then bridged, the conjugate with good uniformity and DAR of about 4 can be obtained, and the antibody is wide in application range.
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Paragraph 0079-0080; 0105-0107

(2019/10/05)

NOVEL METHOD FOR PREPARING THIENOPYRIMIDINE COMPOUND AND INTERMEDIATE
Provided are a novel method of preparing a thienopyrimidine compound having activity of selectively inhibiting tyrosine kinase, particularly, mutant epidermal growth factor receptor tyrosine kinase, and a novel intermediate used for the novel method. According to the method of the present disclosure, a compound of Formula 1 useful as a therapeutic agent for non-small cell lung cancer induced by mutant epidermal growth factor receptor tyrosine kinase can be industrially mass-produced more easily and efficiently than the prior art.
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Paragraph 0127-0128

(2019/11/11)

Indole compound as well as preparation method, pharmaceutical composition and application thereof
The invention discloses an indole compound as well as a preparation method, a pharmaceutical composition and an application thereof. Specifically, the invention relates to an indole derivative as shown in a general formula I and a medicinal salt thereof, a preparation method of the indole derivative, a composition containing one or more compounds, and applications of the compounds in preparation of medicines for preventing and/or treating diseases related to IDO1 and/or TDO.
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Paragraph 1183-1188

(2019/12/02)

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
supporting information
p. 6549 - 6554
(2019/05/04)

Chemoselective: N-tert -butyloxycarbonylation of amines in glycerol
A catalyst-free, efficient and green protocol has been developed for the chemoselective N-Boc protection of amines by using glycerol as a solvent at room temperature. A variety of functionalized amines, such as aliphatic, aromatic as well as heteroaromatic were protected using the developed protocol. N-tert-Butyloxycarbonylation derivatives were formed without the formation of isocyanate, urea, N,N-di-t-Boc, or oxazolidinone as side products. The operational simplicity, cleaner reaction, rapid reaction convergence, functional group tolerance, excellent yield, high selectivity, catalyst-free feature and solvent recyclability are the distinct advantages of this protocol. Owing to these merits, this protocol is feasible, economical and environmentally benign.
Ingale, Ajit P.,More, Vishal K.,Gangarde, Uddhav S.,Shinde, Sandeep V.
supporting information
p. 10142 - 10147
(2018/06/18)

Single-Site Labeling of Native Proteins Enabled by a Chemoselective and Site-Selective Chemical Technology
Chemical biology research often requires precise covalent attachment of labels to the native proteins. Such methods are sought after to probe, design, and regulate the properties of proteins. At present, this demand is largely unmet due to the lack of empowering chemical technology. Here, we report a chemical platform that enables site-selective labeling of native proteins. Initially, a reversible intermolecular reaction places the "chemical linchpins" globally on all the accessible Lys residues. These linchpins have the capability to drive site-selective covalent labeling of proteins. The linchpin detaches within physiological conditions and capacitates the late-stage installation of various tags. The chemical platform is modular, and the reagent design regulates the site of modification. The linchpin is a multitasking group and facilitates purification of the labeled protein eliminating the requirement of additional chromatography tag. The methodology allows the labeling of a single protein in a mixture of proteins. The precise modification of an accessible residue in protein ensures that their structure remains unaltered. The enzymatic activity of myoglobin, cytochrome C, aldolase, and lysozyme C remains conserved after labeling. Also, the cellular uptake of modified insulin and its downstream signaling process remain unperturbed. The linchpin directed modification (LDM) provides a convenient route for the conjugation of a fluorophore and drug to a Fab and monoclonal antibody. It delivers trastuzumab-doxorubicin and trastuzumab-emtansine conjugates with selective antiproliferative activity toward Her-2 positive SKBR-3 breast cancer cells.
Adusumalli, Srinivasa Rao,Rawale, Dattatraya Gautam,Singh, Usha,Tripathi, Prabhanshu,Paul, Rajesh,Kalra, Neetu,Mishra, Ram Kumar,Shukla, Sanjeev,Rai, Vishal
supporting information
p. 15114 - 15123
(2018/11/10)

Synthesis of 7-Azido-3-Formylcoumarin – A Key Precursor in Bioorthogonally Applicable Fluorogenic Dye Synthesis
Coumarins represent an important group of natural products and a common part of various drugs and fluorescent dyestuffs. Herein, we present the synthesis of a coumarin that can serve as a key starting material in the design and synthesis of bioorthogonally applicable fluorogenic dyes. The synthesis of 7-azido-3-formylcoumarin started from 7-diallylaminocoumarin. This allyl protected aminocoumarin is otherwise hard to obtain by conventional methods but was conveniently accessed in good yields by a sequential, Wittig-reaction–UV isomerization process. This sequential approach was studied in more details and applied for the synthesis of a series of substituted coumarins even in one-pot.
Pünk?sti, Zoltán,Kele, Péter,Herner, András
supporting information
p. 1183 - 1188
(2018/03/21)

Nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and manufacture method and application thereof
The invention discloses a nanoprobe for photoacoustic rate bioassay of hydrogen sulfide, and a manufacture method and application thereof. The structural formula of the nanoprobe is shown as the formula I. The manufacture method of the nanoprobe mainly includes subjecting a raw material, Cy7-Cl, to nucleophilic substitution, knoevenagel condensation and amino azide reaction to obtain the nanoprobe. The problems of scattering and tissue absorption of fluorescence signals of fluorescence probes in bioassay are solved; the prepared nanoprobe has the advantages of high photoacoustic-signal penetration depth, imaging of deep tissues, high response speed, high specificity and high rate detection accuracy, and can be applied to bioassay of the hydrogen sulfide, or detection of the hydrogen sulfide in water and food. The formula I is shown in the specification.
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Paragraph 0093-0095

(2018/09/14)

MULTI-FUNCTIONAL CHEMICAL AGENTS, AND THE METHOD FOR PROTEIN MODIFICATION
A multifunctional chemical agents comprising functional agents Fn1, Fn2 and linkers, for the linchpin directed (LDM), protein directed (PDPM) modifications of proteins, and Fn1 accelerated kinetic labeling by Fn2.
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Page/Page column 25

(2017/10/11)

Copper nanoparticles catalyzed N-H functionalization: An efficient solvent-free N-tert-butyloxycarbonylation strategy
A chemoselective transformation of amines to their tert-butyloxycarbonyl (Boc) protected derivatives (NBoc) is described using Cu-NPs under solvent-free conditions. Simple method, rapid reaction rate, mild conditions, tolerance of a wide range of functional groups, excellent yield, ease recovery and high catalytic turnover are the salient features of this approach. tert-Butyloxycarbonylation of chiral amino acid esters and amino alcohols were performed without racemization.
Deb, Barnali,Debnath, Sudipto,Deb, Anindita,Maiti, Dilip K.,Majumdar, Swapan
supporting information
p. 629 - 633
(2017/01/25)

GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF
Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, and methods of using the same, e.g., to treat autoimmune or inflammatory diseases.
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Paragraph 001117

(2018/01/17)

A fluorescent probe for detection of hydrogen peroxide and its preparation method and application
The invention discloses a fluorescent probe for detecting hydrogen peroxide and a preparation method and application thereof. The structural formula of the fluorescent probe for detecting hydrogen peroxide is shown in the description, wherein any one or two of R1-R5 represents electron withdrawing groups. The fluorescent probe is novel in group response, good in selectivity and high in sensitivity; the excitation emission wavelength of the fluorescent probe is located in the range of near infrared waves, damage to tissue is small, the penetrating power is high, and the fluorescent probe can be used for living body imaging. The preparation method comprises the steps that 3-aminophenol and Cy.7.Cl are subjected to a substitution reaction, and Cy-Ph-NH2 is obtained; a retro-Knoevenagel reaction is conducted, and P-NH2 is obtained; P-NH2 and a derivative of phenylglyoxylic acid are subjected to the substitution reaction, and the product P-R is obtained, that is, the fluorescent probe for detecting hydrogen peroxide is obtained. The synthesizing method is simple and suitable for industrial production.
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Paragraph 0068-0069

(2017/10/27)

5-Alkyloxytryptamines are membrane-targeting, broad-spectrum antibiotics
Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6–12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6–10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC)—where mammalian cell toxicity is low—these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs.
Faulkner, Katherine C.,Hurley, Katherine A.,Weibel, Douglas B.
supporting information
p. 5539 - 5544
(2016/11/09)

Construction of a Near-Infrared Fluorescent Turn-On Probe for Selenol and Its Bioimaging Application in Living Animals
As selenocysteine (Sec) carries out the majority of the functions of the various Se-containing species in vivo, it is of high importance to develop reliable and rapid assays with biocompatibility to detect Sec. Herein, an NIR fluorescent turn-on probe for highly selective detection of selenol was designed and synthesized. The probe exhibits large turn-on signal upon treatment with selenocysteine (R-SeH), and it was further demonstrated that the new NIR fluorescent probe can be employed to image selenol in living animals. Simply red: The first near-infrared (NIR) fluorescent turn-on probe for highly selective detection of selenol was designed and synthesized (see figure). The probe exhibits a large turn-on signal upon treatment with selenocysteine (R-SeH), and it has been further demonstrated that the new NIR fluorescent probe can be employed to image selenol in living animals.
Chen, Hua,Dong, Baoli,Tang, Yonghe,Lin, Weiying
supporting information
p. 11696 - 11700
(2015/08/11)

NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 00365

(2015/07/07)

General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as an efficient catalyst
A simple, rapid and solvent-free protocol is described for the chemo-selective transformation of amines to tert-butyloxycarbonyl protected derivatives (NHBoc) using Boc2O and imidazolium trifluoroacetate protic ionic liquid (5-20 mol%). Unwanted side products such as isocyanate, urea or N,N-di-Boc were not detected. The scope of the protection strategy was successfully explored for substrate alcohols, phenols and thiol at elevated temperatures. Optically pure amino acids, amino acid esters and amino alcohols were efficiently converted to the corresponding N-Boc protected derivatives in excellent yields without racemization at the chiral center. The distinct advantages of this method are: operational simplicity, cleaner reaction, high selectivity, excellent yield, rapid reaction convergence, easy preparation and recyclability of the catalyst.
Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Maiti, Dilip K.
p. 24544 - 24550
(2014/07/07)

Synthesis and structure-activity relationship studies of conformationally flexible tetrahydroisoquinolinyl triazole carboxamide and triazole substituted benzamide analogues as σ2 receptor ligands
Two novel classes of compounds targeting the sigma-2 (σ2) receptor were synthesized, and their bioactivities to binding σ1 and σ2 receptors were measured. Four novel triazole carboxamide analogues, 24d, 24e, 24f, and 39c, demonstrated high affinity and selectivity for the σ2 receptor. These data suggest 11C-labeled versions of these compounds may be potential σ2-selective radiotracers for imaging the proliferative status of solid tumors.
Bai, Suping,Li, Shihong,Xu, Jinbin,Peng, Xin,Sai, Kiran,Chu, Wenhua,Tu, Zhude,Zeng, Chenbo,Mach, Robert H.
supporting information
p. 4239 - 4251
(2014/06/09)

PRMT5 INHIBITORS AND USES THEREOF
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described
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Paragraph 00380

(2014/07/08)

Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells
Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC 50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux.
Draoui, Nihed,Schicke, Olivier,Fernandes, Antony,Drozak, Xavier,Nahra, Fady,Dumont, Amélie,Douxfils, Jonathan,Hermans, Emmanuel,Dogné, Jean-Michel,Corbau, Romu,Marchand, Arnaud,Chaltin, Patrick,Sonveaux, Pierre,Feron, Olivier,Riant, Olivier
p. 7107 - 7117
(2013/11/06)

In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures
In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important to develop inhibitors selective for nNOS that do not interfere with other NOS isoforms, especially endothelial NOS (eNOS), which is critical for proper functioning of the cardiovascular system. While we have been successful in developing potent and isoform-selective inhibitors, such as lead compounds 1 and 2, the ease of synthesis and bioavailability have been problematic. Here we describe a new series of compounds including crystal structures of NOS-inhibitor complexes that integrate the advantages of easy synthesis and good biological properties compared to the lead compounds. These results provide the basis for additional structure-activity relationship (SAR) studies to guide further improvement of isozyme selective inhibitors.
Jing, Qing,Li, Huiying,Fang, Jianguo,Roman, Linda J.,Martásek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
supporting information
p. 5323 - 5331
(2013/09/02)

HIGH AFFINITY BETA LACTAMASE INHIBITORS
Inhibitors of beta lactamases and their use in treating bacterial infections are dicslosed
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Page/Page column 54

(2013/04/25)

Simple and efficient method for n-boc protection of amines using PEG-400 as a reaction medium under mild conditions
Simple and efficient method for N-Boc protection of amines using PEG-400 as an ecofriendly reaction medium at room temperature is described. Various aromatic, heteroaromatic, and aliphatic amines were converted to the corresponding N-tert-butyl-carbamates in good to excellent yields in short times.
Zeng, Hongyao,Li, Yongjia,Shao, Huawu
experimental part
p. 25 - 32
(2011/10/19)

Structure-based design of a new series of d-glutamic acid based inhibitors of bacterial UDP-N-acetylmuramoyl-l-alanine: D-glutamate ligase (MurD)
MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of d-glutamic acid-based Escherichia coli MurD inhibitors incorporating the 5-benzylidenethiazolidin-4- one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC50 between 3 and 7 μM). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC 50 values in the low micromolar range, represent the most potent d-Glu-based MurD inhibitors reported to date.
Toma?i?, Tihomir,Zidar, Nace,?ink, Roman,Kova?, Andreja,Blanot, Didier,Contreras-Martel, Carlos,Dessen, Andréa,Müller-Premru, Manica,Zega, Anamarija,Gobec, Stanislav,Kikelj, Danijel,Peterlin Ma?i?, Lucija
supporting information; experimental part
p. 4600 - 4610
(2011/09/14)

Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases
A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (Ki = 880 nM) and significant selectivity against other human related serine proteases like trypsin (Ki = 729 μM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.
Siles, Rogelio,Kawasaki, Yuko,Ross, Patrick,Freire, Ernesto
supporting information; experimental part
p. 5305 - 5309
(2011/10/03)

HETEROCYCLIC COMPOUND AND USE THEREOF
Disclosed is a heterocyclic compound having a strong Raf inhibitory activity. Specifically disclosed is a compound represented by the formula (I), (II) or (III) below, or a salt thereof. (In the formulae, the symbols are as defined in the description.)
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Page/Page column 113

(2010/06/11)

Amination of aryl iodides using a fluorous-tagged ammonia equivalent
A fluorous-tagged ammonia equivalent for the Cu-catalyzed amination of aryl iodides is described in which N-Boc-protected anilines are produced in high overall yield and purity. All purification steps are performed using Fluorous SolidPhase Extraction (F-SPE) greatly simplifying and speeding up the isolation of the desired products.
Nielsen, Simon Dalsgaard,Smith, Garrick,Begtrup, Mikael,Kristensen, Jesper L.
experimental part
p. 3704 - 3710
(2010/09/05)

Unsymmetrical non-adamantyl N,N′-diaryl urea and amide inhibitors of soluble expoxide hydrolase
Incorporation of an adamantyl group in prototypical soluble expoxide hydrolase (sEH) inhibitors afforded improved enzyme potency. We explored replacement of the adamantyl group in unsymmetrical ureas and amides with substituted aryl rings to identify equipotent and metabolically stable sEH inhibitors. We found that aryl rings, especially those substituted in the para position with a strongly electron withdrawing substituent, afforded enzyme IC50 values comparable to the adamantyl compounds in an ether substituted, unsymmetrical N,N′-diaryl urea or amide scaffold.
Anandan, Sampath-Kumar,Webb, Heather K.,Do, Zung N.,Gless, Richard D.
scheme or table
p. 4259 - 4263
(2010/04/26)

BIS-ARYL COMPOUNDS FOR USE AS MEDICAMENTS
There is provided compounds of formula I, wherein ring A, D1, D2a, D2b, D3, L1, Y1, L3 and Y3 have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C4 synthase is desired and/or required, and particularly in the treatment of a respiratory disorder and/or inflammation.
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Page/Page column 107

(2009/12/02)

SOLUBLE EPOXIDE HYDROLASE INHIBITORS
Disclosed are urea and thiourea compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, and diabetic-related diseases.
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Page/Page column 78; 93-94

(2008/12/07)

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature
Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.
Chankeshwara, Sunay V.,Chakraborti, Asit K.
p. 1087 - 1091
(2007/10/03)

Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket
The synthesis of novel coumarins bearing on the lateral side chain in the 3-position an amine or a guanidine group is described. In vitro evaluation highlighted 14d which possesses a meta aniline side chain as a very potent THR inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a decrease in THR inhibiting properties. We, thus, used docking experiments to rationalize the SAR in the series. This study showed the crucial role of a conserved water molecule in the specificity pocket of THR during docking simulation in order to explain the inactivity of guanidine derivatives.
Frederick, Raphael,Charlier, Caroline,Robert, Severine,Wouters, Johan,Masereel, Bernard,Pochet, Lionel
p. 2017 - 2021
(2007/10/03)

BIS-QUINAZOLINE COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
Bis-quinazoline compounds based on the compound (3,4-Dihydro-quinazolin-2-yl)-quinazolin-2-yl-amine, and methods of use of the compounds as inhibitors of bacterial DNA polymerase holoenzymes and in the treatment of bacterial infections are described.
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Page/Page column 35

(2008/06/13)

Fluorescent probe for magnesium ion determination
A fluorescent probe for measuring magnesium ion, which can selectively form a complex with magnesium ion in aqueous system is disclosed. The fluorescent probe for measuring magnesium ion according to the present invention has the structure represented by the following Formula [I]: 1(wherein R1 represents a hydrogen atom, metal atom or an ester-forming group; A represents a group which forms a ring structure together with carbon atom 1 and carbon atom 2; and X is a fluorescent group which may form a condensed ring together with the ring containing the group A).
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(2008/06/13)

PtIV-catalyzed cyclization of arene-alkyne substrates via intramolecular electrophilic hydroarylation
(Figure presented) We herein report that PtCl4 has proven to be a hydroarylation catalyst with an efficiency and substrate scope superior to previously known methods. This catalyst demonstrated consistent performance with arene-yne substrates of diverse structural features, including propargyl ethers, propargylamines, and alkynoate esters, providing good to excellent yields of the 6-endo products (chromenes, dihydroquinolines, and coumarins). In contrast, Pt(II), Pd(II), and Ga(III) salts were shown to be sensitive to the substitution on the alkyne moiety.
Pastine, Stefan J.,Youn, So Won,Sames, Dalibor
p. 1055 - 1058
(2007/10/03)

The Lindlar Catalyst Revitalized: A Highly Chemoselective Method for the Direct Conversion of Azides to N-(tert-Butoxycarbonyl)amines
An exceptionally chemoselective method for the direct conversion of azides to N-(tert-butoxycarbonyl)-protected amines under catalytic transfer-hydrogenation conditions, using the Lindlar catalyst, is reported. The extremely labile functional groups such as N-Cbz, benzyl ester are shown to be inert under the reaction conditions. The present method allows us to synthesize orthogonally protected (N-Cbz and N-Boc) 1,2-diamino systems, which will be immensely useful in organic synthesis.
Reddy, P. Ganapati,Pratap, T. Verabhadra,Kumar, G. D. Kishore,Mohanty, Subhendu K.,Baskaran, Sundarababu
p. 3740 - 3744
(2007/10/03)

Amidino derivatives and their use as thrombin inhibitors
There is provided compounds of formula I, wherein R1, R2, R3, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
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(2008/06/13)

Quinazolines: Combined type 3 and 4 phosphodiesterase inhibitors
A series of quinazolines has been prepared and evaluated for its ability to inhibit cyclic AMP phosphodiesterase type 3, type 4A, 4B and 4D. The most potent inhibitors showed IC50 values in the nanomolar range for type 3 and type 4 isoforms and bind with high affinity to the [3H]rolipram binding site. These quinazolines represent a new family of potent mixed PDE 3 / 4 inhibitors and are expected to have a therapeutic potential.
Charpiot, Brigitte,Brun, Jvan,Donze, Irene,Naef, Reto,Stefani, Monique,Mueller, Thomas
p. 2891 - 2896
(2007/10/03)

Potent and subtype-selective CCK-B/gastrin receptor antagonists: 2,4-dioxo-1,5-benzodiazepines with a plane of symmetry
A series of CCK-B/gastrin receptor antagonists, 2,4-dioxo-1,5-benzodiazepine derivatives with a plane of symmetry, were designed, synthesized, and evaluated for antagonistic activity. Structure-activity relationship studies revealed that carbonylmethyl groups at both N-1 and N-5 positions and hydrophilic groups, such as the carboxyl group on the benzene ring attached to the ureido group at the C-3 position, brought about potent affinity and subtype selectivity for CCK-B/gastrin receptors. Several compounds showed excellent in vivo inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats.
Hagishita, Sanji,Seno, Kaoru,Kamata, Susumu,Haga, Nobuhiro,Ishihara, Yasunobu,Ishikawa, Michio,Shimamura, Mayumi
p. 1433 - 1446
(2007/10/03)