- Construction and activity evaluation of novel dual-target (SE/CYP51) anti-fungal agents containing amide naphthyl structure
-
With the increase of fungal infection and drug resistance, it is becoming an urgent task to discover the highly effective antifungal drugs. In the study, we selected the key ergosterol bio-synthetic enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) as dual-target receptors to guide the construction of novel antifungal compounds, which could achieve the purpose of improving drug efficacy and reducing drug-resistance. Three different series of amide naphthyl compounds were generated through the method of skeleton growth, and their corresponding target products were synthesized. Most of compounds displayed the obvious biological activity against different Candida spp. and Aspergillus fumigatus. Among of them, target compounds 14a-2 and 20b-2 not only possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2 μg/mL), but also maintained the anti-drug-resistant fungal activity (MIC50, 1–4 μg/mL). Preliminary mechanism study revealed the compounds (14a-2, 20b-2) could block the bio-synthetic pathway of ergosterol by inhibiting the dual-target (SE/CYP51) activity, and this finally caused the cleavage and death of fungal cells. In addition, we also discovered that compounds 14a-2 and 20b-2 with low toxic and side effects could exert the excellent therapeutic effect in mice model of fungal infection, which was worthy for further in-depth study.
- An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Liu, Yating,Sun, Bin,Sun, Zhuang
-
-
- Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers
-
Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide 1 stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple in vivo studies of PAM pathway-driven tumors.
- Chen, Xiaoling,Clark, Anderson,Crowley, Lindsey,Deselm, Lizbeth,Georgi, Katrin,Goutopoulos, Andreas,Haxell, Thomas,Heasley, Brian H.,Huck, Bayard,Jackson, Jennifer,Johnson, Theresa,Jones, Reinaldo,Lan, Ruoxi,Lin, Jing,Machl, Andreas,Mochalkin, Igor,Moore, Joseph,Neagu, Constantin,Potnick, Justin,Richardson, Thomas E.,Rohdich, Felix,Sherer, Brian,Sutton, Amanda,Tian, Hui,Wilker, Erik,Xiao, Yufang
-
supporting information
p. 14603 - 14619
(2021/10/20)
-
- Visible-Light-Induced Intermolecular Oxyimination of Alkenes
-
An intermolecular vicinal O-N difunctionalization reaction of olefins with oxime esters through energy transfer catalysis has been developed.
- Li, Jun,Yuan, Yong,Bao, Xiazhen,Sang, Tongzhi,Yang, Jie,Huo, Congde
-
supporting information
p. 3712 - 3717
(2021/05/10)
-
- Organoiodine-Catalyzed Enantioselective Intermolecular Oxyamination of Alkenes
-
Metal-free, catalytic enantioselective intermolecular oxyamination of alkenes is realized by use of organoiodine(I/III) chemistry. The protocol is applicable toward aryl- and alkyl-substituted alkenes with high enantioselectivity and electronically controlled regioselectivity. The oxyaminated products can be easily deprotected in one step to reveal free amino alcohols in high yields without loss of enantioselectivity. A key to our success is the discovery of a virtually unexplored chemical entity, N-(fluorosulfonyl)carbamate, as a bifunctional N,O-nucleophile.
- Wata, Chisato,Hashimoto, Takuya
-
supporting information
p. 1745 - 1751
(2021/02/05)
-
- COMPLEMENT MODULATORS AND RELATED METHODS
-
The present disclosure presents compounds and compositions that interact with complement components. Some compounds inhibit complement activity. Included are small molecule compounds and compositions that function as C5 inhibitor compounds. Methods for inhibiting complement activity and methods of treating complement-related indications with the C5 inhibitor compounds and compositions are provided.
- -
-
Paragraph 0378
(2020/10/20)
-
- Aryl olefin azole derivative as well as preparation method and application thereof
-
The invention belongs to the technical field of medicines, and relates to an aryl olefin azole derivative shown in a general formula I, stereoisomers thereof and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and substituent groups Ar, R and X have definitions given in the specification. The invention also relates to a method for preparing the compound as shown in the general formula I, a medicinal composition containing the compound and application of the compound and the medicinal composition in preparation of medicines for treating and preventing superficial fungal and deep fungal diseases.
- -
-
Paragraph 0065; 0070-0071
(2021/01/15)
-
- Late-Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2
-
A robust, click-chemistry-inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (11C, 13C, 14C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.
- Del Vecchio, Antonio,Caillé, Fabien,Chevalier, Arnaud,Loreau, Olivier,Horkka, Kaisa,Halldin, Christer,Schou, Magnus,Camus, Nathalie,Kessler, Pascal,Kuhnast, Bertrand,Taran, Frédéric,Audisio, Davide
-
supporting information
p. 9744 - 9748
(2018/07/31)
-
- Method for preparing beta arylamine
-
The invention discloses a method for preparing beta arylamine. The method includes mixing an aziridine compound, halogenated aromatic hydrocarbon, an oxidizing agent, a reducing agent and an organic solvent to obtain a mixed solution and obtaining the beta arylamine after reaction. The oxidizing agent is at least one of a mixture of nickel iodide and bipyridine, a mixture of nickel chloride dimethoxyethane and bipyridine and 2,2'-bipyridinium nickel iodide. The reducing agent is at least one of zinc powder, manganese powder, iron powder, cobalt powder, titanium powder, calcium powder and tetrakis(dimethylamino)ethylene. The halogenated aromatic hydrocarbon is at least one of the chlorinated aromatic hydrocarbon, the brominated aromatic hydrocarbon and aryl iodide. An organometallic reagentis not required, the preparation process is simple and reliable and high in yield, and the aziridine compound is wide in selection range.
- -
-
Paragraph 0047
(2019/01/14)
-
- Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water
-
A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring-opening of enantiopure styryl and pyridyl (S)-epoxides by N3- in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2-azido ethanols with up to 99% enantio- and regioselectivity, while the (S)-adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives.
- Wang, Hai-Yang,Huang, Kun,De Jesús, Melvin,Espinosa, Sandraliz,Pi?ero-Santiago, Luis E.,Barnes, Charles L.,Ortiz-Marciales, Margarita
-
-
- Efficient Routes to a Diverse Array of Amino Alcohol-Derived Chiral Fragments
-
Efficient syntheses of chiral fragments derived from chiral amino alcohols are described. Several unique scaffolds were readily accessed in 1-5 synthetic steps leading to 45 chiral fragments, including oxazolidinones, morpholinones, lactams, and sultams. These fragments have molecular weights ranging from 100 to 255 Da and are soluble in water (0.085 to >15 mM).
- Haftchenary, Sina,Nelson, Shawn D.,Furst, Laura,Dandapani, Sivaraman,Ferrara, Steven J.,Bo?kovi?, ?arko V.,Figueroa Lazú, Samuel,Guerrero, Adrian M.,Serrano, Juan C.,Crews, Demarcus K.,Brackeen, Cristina,Mowat, Jeffrey,Brumby, Thomas,Bauser, Marcus,Schreiber, Stuart L.,Phillips, Andrew J.
-
supporting information
p. 569 - 574
(2016/10/06)
-
- Selective amidation of unprotected amino alcohols using surfactant-in-water technology: A highly desirable alternative to reprotoxic polar aprotic solvents
-
A general selective and environmentally friendly method for the formation of amide bonds using a surfactant in water as medium is described. The use of readily available 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide (EDC) and hydroxybenzotriazol (HOBt)
- Parmentier, Michael,Wagner, Mona K.,Magra, Kevin,Gallou, Fabrice
-
supporting information
p. 1104 - 1107
(2017/01/16)
-
- Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors
-
Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50 = 1.0 μM, cell IC50 = 1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50 = 120 nM and cell potency to IC50 = 230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine.
- Dinges, Jurgen,Harris, Christopher M.,Wallace, Grier A.,Argiriadi, Maria A.,Queeney, Kara L.,Perron, Denise C.,Dominguez, Eric,Kebede, Tegest,Desino, Kelly E.,Patel, Hetal,Vasudevan, Anil
-
p. 2297 - 2302
(2016/04/20)
-
- Iridium-catalyzed asymmetric allylic substitutions with bulky amines/oxidative double bond cleavage - Entry into the reetz synthesis of amino alcohols
-
Branched allylic amines were prepared by Ir-catalyzed enantioselective allylic aminations with the bulky N-nucleophiles HN(Boc)2 and HNBn2. The products were transformed into N-protected amino aldehydes, which were either reduced or coupled diastereoselectively with organometallic compounds to give vicinal amino alcohols. A formal synthesis of the neurokinin receptor antagonist (+)-L-733060 was carried out as an application. Ir-catalyzed enantioselective allylic aminations with bulky N-nucleophiles HN(Boc)2 and HNBn2 gave N-protected allylic amines, which were transformed into N-protected chiral amino aldehydes. These are useful chiral building blocks as previously demonstrated by Reetz et al. A formal synthesis of the neurokinin receptor antagonist (+)-L-733060 was carried out as an application.
- Seehafer, Kai,Malakar, Chandi C.,Bender, Markus,Qu, Jianping,Liang, Chen,Helmchen, Günter
-
p. 493 - 501
(2016/02/18)
-
- Docking model of the nicotinic acetylcholine receptor and nitromethylene neonicotinoid derivatives with a longer chiral substituent and their biological activities
-
In the present study, nitromethylene neonicotinoid derivatives possessing substituents that contain a sulfur atom, oxygen atom or aromatic ring at position 5 on the imidazolidine ring were synthesized to evaluate their affinity for the nicotinic acetylcholine receptor (nAChR) and their insecticidal activity against adult female houseflies. Comparing the receptor affinity of the alkylated derivative with the receptor affinity of compounds possessing either ether or thioether groups revealed that conversion of the carbon atom to a sulfur atom did not influence the receptor affinity, whereas conversion to an oxygen atom was disadvantageous for the receptor affinity. The receptor affinity of compounds possessing a benzyl or phenyl group was lower than that of the unsubstituted compound. Analysis of the three-dimensional quantitative structure-activity relationship using comparative molecular field analysis demonstrated that steric hindrance of the receptor should exist around the C3 of an n-butyl group attached at position 5 on the imidazolidine ring. A docking study of the nAChR-ligand model suggested that the ligand-binding region expands as the length of the substituent increases by brushing against the amino acids that form the binding region. The insecticidal activity of the compounds was positively correlated with the receptor affinity by considering log P and the number of heteroatoms, including sulfur and oxygen atoms, in the substituents, suggesting that the insecticidal activity is influenced by the receptor affinity, hydrophobicity, and metabolic stability of the compounds.
- Nagaoka, Hikaru,Nishiwaki, Hisashi,Kubo, Takuya,Akamatsu, Miki,Yamauchi, Satoshi,Shuto, Yoshihiro
-
p. 759 - 769
(2015/02/19)
-
- SONIC HEDGEHOG MODULATORS
-
Sonic Hedgehog modulators and methods of use thereof are provided for.
- -
-
Paragraph 0960
(2014/04/17)
-
- Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: Potent inhibitors of R5 HIV-1 replication
-
The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.
- Skerlj, Renato,Bridger, Gary,Zhou, Yuanxi,Bourque, Elyse,McEachern, Ernest,Metz, Markus,Harwig, Curtis,Li, Tong-Shuang,Yang, Wen,Bogucki, David,Zhu, Yongbao,Langille, Jonathan,Veale, Duane,Ba, Tuya,Bey, Michael,Baird, Ian,Kaller, Alan,Krumpak, Maria,Leitch, David,Satori, Michael,Vocadlo, Krystyna,Guay, Danielle,Nan, Susan,Yee, Helen,Crawford, Jason,Chen, Gang,Wilson, Trevor,Carpenter, Bryon,Gauthier, David,MacFarland, Ron,Mosi, Renee,Bodart, Veronique,Wong, Rebecca,Fricker, Simon,Schols, Dominique
-
supporting information
p. 8049 - 8065
(2013/11/06)
-
- BRANCHED OXATHIAZINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, USE THEREOF AS MEDICINE AND DRUG CONTAINING SAID DERIVATIVES AND USE THEREOF
-
The invention relates to compounds of formula (I) and to the physiologically compatible salts thereof. Said compounds are suitable, for example, for treating hyperglycemia.
- -
-
Paragraph 0361-0362
(2014/02/15)
-
- Magnetic nanoparticles catalyzed N-tert-butoxycarbonylation of Amines and amine derivatives
-
A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using magnetically recoverable γ-Fe2O3@SiO 2 nanoparticles is reported. The catalyst can be easily recovered and recycled without a significant loss in the catalytic activity. No competitive side reactions, such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were obsereved.
- Akbari, Jafar,Sajirani, Soghra B.,Nezhad, Jafar M.,Heydari, Akbar
-
experimental part
p. 165 - 168
(2012/07/14)
-
- Platinum nanoparticles supported on zirconia mediated synthesis of N-acyl and N-(tert-butoxycarbonyl)amines from nitroarenes and azides
-
A convenient and useful protocol has been designed for the synthesis of N-aryl acetamides from the corresponding nitro compounds via a reductive N-acylation process using bi-functional, recyclable heterogeneous platinum nanoparticles supported on zirconia [Pt(0)/ZrO2] catalyst, employing molecular hydrogen as the environmentally benign reductant and the corresponding anhydrides as acylating agents. N-Boc protected amines were also synthesized in similar lines, from the corresponding azides. The reaction is successfully performed under mild conditions to afford good to excellent yields of the products. The solid bifunctional-catalyst, Pt(0)/ZrO2 is quantitatively recovered by simple centrifugation and reused for multiple cycles with consistent activity and selectivity.
- Kantam, M. Lakshmi,Reddy, R. Sudarshan,Srinivas,Chakravarti,Sreedhar,Figueras,Venkat Reddy, Ch.
-
experimental part
p. 96 - 101
(2012/03/09)
-
- High performance of N -alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition
-
Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl- imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.
- Yamada, Ken-Ichi,Konishi, Takehito,Nakano, Mayu,Fujii, Shintaro,Cadou, Romain,Yamamoto, Yasutomo,Tomioka, Kiyoshi
-
p. 1547 - 1553
(2012/03/26)
-
- ZnO nanorods as an efficient and heterogeneous catalyst for N-Boc protection of amines and amine derivatives
-
An efficient ZnO nano catalyst, which was readily prepared from Zn(CH3CO2)2, 2H2O and PVP by a chemical solution approach has successfully catalyzed N-tertbutoxy carbonylation of amines. The ZnO nanorods were successful and gave promising results for highly active and chemoselective as well as easily recyclable catalyst for the NBoc protection reaction of a wide variety of amines. The catalyst could be easily recycled for five times without noticeable decrease in catalytic activity. The ZnO nanocatalyst was characterized with XRD and SEM.
- Nouria, Azita,Akbari, Jafar,Heydaric, Akbar,Nouri, Arezu
-
experimental part
p. 38 - 42
(2012/05/04)
-
- Acid-promoted aza-cyclization versus -cyclization of N -acyliminium species into fused pyrrolo[1,2-a]imidazolones and pyrrolo[2,1- a ]isoquinolinones
-
A new approach for the synthesis of fused imidazolones and isoquinolinones is presented. The key step of this sequence was the interception of an N-acyliminium species with nitrogen or -aromatic nucleophiles under kinetic vs. thermodynamic control. In add
- Fleury, Jean-Fran?ois,Netchita?lo, Pierre,Da?ch, Adam
-
scheme or table
p. 1821 - 1826
(2011/09/19)
-
- Discovery of a novel series of cyclic urea as potent CCR5 antagonists
-
A novel series of cyclic urea-based CCR5 antagonists was designed aiming to resolve instability issue in the fasted simulated intestinal fluid (FSIF) associated with the acyclic urea moiety in 1. This class of CCR5 compounds demonstrated high antiviral ac
- Duan, Maosheng,Kazmierski, Wieslaw M.,Tallant, Matt,Jun, Jung Ho,Edelstein, Mark,Ferris, Rob,Todd, Dan,Wheelan, Pat,Xiong, Zhiping
-
scheme or table
p. 6381 - 6385
(2011/12/02)
-
- Protic ionic liquid [TMG][Ac] as an efficient, homogeneous and recyclable catalyst for Boc protection of amines
-
An efficient and practical protocol for the chemoselective N-Boc protection of various structurally different aryl, aliphatic and heterocyclic amines was carried out with (Boc)2O using protic 1, 1, 3, 3-tetra-methylguanidinium acetate (10 mol%) as recyclable catalyst under solvent free condition at ambient temperature. No competitive side reactions (isocyanate, urea and N, N-di-Boc) were observed. α-Amino alcohols afforded the N-Boc-derivative without oxazolidinone formation.
- Akbari, Jafar,Heydari, Akbar,Ma'mani, Leila,Hassan Hosseini, Seyed
-
experimental part
p. 544 - 547
(2010/11/05)
-
- Synthesis, SAR and evaluation of [1,4′]-bipiperidinyl-4-yl-imidazolidin-2-one derivatives as novel CCR5 antagonists
-
Elaboration of our previously disclosed spiropiperidine template led to the development of a series of novel CCR5 antagonists. Results of SAR exploration and preliminary lead characterization are described.
- Rotstein, David M.,Gabriel, Stephen D.,Manser, Nicole,Filonova, Lubov,Padilla, Fernando,Sankuratri, Surya,Ji, Changhua,deRosier, Andre,Dioszegi, Marianna,Heilek, Gabrielle,Jekle, Andreas,Weller, Paul,Berry, Pamela
-
scheme or table
p. 3219 - 3222
(2010/09/18)
-
- Thioglycoluril as a highly efficient, recyclable and novel organocatalyst for N-Boc protection of amines
-
A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using thioglycoluril as the catalyst is described. The catalyst can be readily separated from the reaction products by simple filtration and recovered for reuse. No competitive side reactions, such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were observed.
- Khaksar, Samad,Vahdat, Seyed Mohammad,Tajbakhsh, Mahmood,Jahani, Fatemeh,Heydari, Akbar
-
experimental part
p. 6388 - 6391
(2011/01/03)
-
- DUAL-ACTION INHIBITORS AND METHODS OF USING SAME
-
Provided are compounds, compositions, and methods for treating diseases and conditions wherein an inhibitor of a kinase, such as rho kinase (ROCK), and an inhibitor of one or more of the monoamine transporters, such as NET or SERT, act in concert to improve the condition.
- -
-
Page/Page column 121
(2010/11/17)
-
- Hydrogen bond catalyzed chemoselective N-tert-butoxycarbonylation of amines
-
A novel, chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butoxypyrocarbonate (Boc)2O is described that relies on selective carbonyl activation by hydrogen bond formation. This mild, acid- and metal-free process requires only catalytic amounts of thiourea as hydrogen bond donor.
- Khaksar, Samad,Heydari, Akbar,Tajbakhsh, Mahmood,Vahdat, Seyed Mohammad
-
p. 3527 - 3529
(2008/09/21)
-
- 1,1,1,3,3,3-Hexafluoroisopropanol: A recyclable organocatalyst for N-Boc protection of amines
-
A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent and catalyst is described. The catalyst can be readily separated from the reaction products and recovered for direct reuse. No competitive side reactions such as formation of isocyanate, urea, and N,N-di-Boc were observed. α-Amino alcohols afforded the N-Boc derivatives without oxazolidinone formation. Georg Thieme Verlag Stuttgart.
- Heydari, Akbar,Khaksar, Samad,Tajbakhsh, Mahmood
-
experimental part
p. 3126 - 3130
(2009/04/06)
-
- Selenium promoted synthesis of enantiopure pyrrolidines starting from chiral aminoalcohols
-
Starting from commercially available enantiomerically pure aminoalcohols and using simple conversions promoted by organoselenium reagents, several enantiomerically pure substituted pyrrolidines were prepared. After double protections (R)- or (S)-2-phenylg
- Tiecco, Marcello,Testaferri, Lorenzo,Bagnoli, Luana,Scarponi, Catalina,Temperini, Andrea,Marini, Francesca,Santi, Claudio
-
p. 2758 - 2767
(2008/03/28)
-
- CHEMOKINE RECEPTOR BINDING COMPOUNDS
-
The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
- -
-
Page/Page column 28
(2010/11/26)
-
- N-tert-Butoxycarbonylation of amines using H3PW12O40 as an efficient heterogeneous and recyclable catalyst
-
The commercially available heteropoly acid H3PW12O40 (0.5 mol %) is a very efficient and environmentally benign catalyst for N-tert-butoxycarbonylation of amines (primary, secondary) with di-tert-butyl dicarbonate at room temperature in short reaction times (10 min). No competitive side products such as isocyanates, ureas, N,N-di-tert-butoxycarbonyls, O-Boc and oxazolidinones were observed. Chiral α-amino alcohols and esters afforded the corresponding N-Boc derivatives chemoselectively in excellent yields.
- Heydari, Akbar,Shiroodi, Roohollah Kazem,Hamadi, Hossein,Esfandyari, Maryam,Pourayoubi, Mehrdad
-
p. 5865 - 5868
(2008/02/09)
-
- Highly diastereoselective and enantioselective direct organocatalytic anti-selective Mannich reactions employing N-tosylimines
-
Organocatalytic direct anti-selective Mannich reactions of O-TBS-hydroxyacetone with various N-tosylimines derived from aromatic aldehydes in the presence of L-threonine-derived catalyst afforded 1,2-amino alcohols in good yields and with enantioselectivi
- Cheng, Lili,Han, Xiao,Huang, Huiming,Wong, Ming Wah,Lu, Yixin
-
p. 4143 - 4145
(2008/03/18)
-
- Synthesis of new pyrrolidine derivatives as inhibitors of α-mannosidase and of the growth of human glioblastoma cells
-
New 2-benzylamino-3,4-dihydroxypyrrolidines bearing aromatic and aliphatic amido side chains have been prepared. The influence of the amido substituents on the inhibitory activity of these diamines toward 24 commercially available glycosidases was determi
- Favre, Sylvain,Fiaux, Hele,Schuetz, Catherine,Vogel, Pierre,Juillerat-Jeanneret, Lucienne,Gerber-Lemaire, Sandrine
-
p. 179 - 192
(2008/02/10)
-
- Asymmetric allylic substitution catalyzed by C1-symmetrical complexes of molybdenum: Structural requirements of the ligand and the stereochemical course of the reaction
-
Application of new chiral ligands (R)-(-)-12a and (S)-(+)-12c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 → 6), led to excellent regio- and enantioselectivities (>30:1, ≤98% ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements of the ligand and the mechanism are discussed. The application of single enantiomers of deuterium-labeled substrates (both linear 38c and branched 37c) and analysis of the products (41-43) by 2{ 1H) NMR spectroscopy in a chiral liquid crystal matrix allowed the stereochemical pathways of the reaction to be distinguished. With ligand (S)-(+)-12c, the matched enantiomer of branched substrate was found to be (S)-5, which was converted into (R)-6 with very high regio- and stereoselectivity via a process that involves net retention of stereochemistry. The mismatched enantiomer of the branched substrate was found to be (R)-5, which was also converted into (R)-6, that is, with apparent net inversion, but at a lower rate and with lower overall enantioselectivity. This latter feature, which may be termed a "memory effect", reduced the global enantioselectivity in the reaction of the racemic substrate (±)-5. The stereochemical pathway of the mismatched manifold has been shown also to be one of net retention, the apparent inversion occurring through equilibration via an Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration leads to the memory effect and thus to lower enantioselectivity. Analysis of the mismatched manifold over the course of the reaction revealed that the memory effect is progressively attenuated with the nascent global selectivity increasing substantially as the reaction proceeds. The origin of this effect is suggested to be the depletion of CO sources in the reaction mixture, which attenuates turnover rate and thus facilitates greater equilibrium. The linear substrate was also converted into the branched product with net syn stereochemistry, as shown by isotopic labeling. An analogous process operates in the generation of small quantities of linear product from branched substrate.
- Malkov, Andrei V.,Gouriou, Laure,Lloyd-Jones, Guy C.,Stary, Ivo,Langer, Vratislav,Spoor, Paul,Vinader, Victoria,Kocovsky, Pavel
-
p. 6910 - 6929
(2007/10/03)
-
- CETP INHIBITORS
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Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalky substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalky substituent connected directly to the ring or attached to the ring through a -CH2-.
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Page/Page column 56
(2010/10/19)
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- Kinetic resolution of 2-oxazolidinones via catalytic, enantioselective N-acylation
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Kinetic resolution of racemic 2-oxazolidinones via catalytic, enantioselective N-acylation has been achieved for the first time and with outstanding selectivities. Copyright
- Birman, Vladimir B.,Jiang, Hui,Li, Ximin,Guo, Lei,Uffman, Eric W.
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p. 6536 - 6537
(2007/10/03)
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- A stereoselective route to cis-2-phenyl-3-piperidinol
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Enantiopure cis-2-phenyl-3-piperidinol is a commonly used synthon for the obtention of a potent class of neurokinin substance P receptor antagonists. Starting from (R)-phenylglycine, the present report describes an efficient route for the stereoselective
- Liang, Ningning,Srinivas, Pusuluri,Datta, Apurba
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p. 7221 - 7223
(2007/10/03)
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- Functionalized pyrrolidines inhibit α-mannosidase activity and growth of human glioblastoma and melanoma cells
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New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases we
- Fiaux, Hélène,Popowycz, Florence,Favre, Sylvain,Schütz, Catherine,Vogel, Pierre,Gerber-Lemaire, Sandrine,Juillerat-Jeanneret, Lucienne
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p. 4237 - 4246
(2007/10/03)
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- Lithium perchlorate-catalyzed Boc protection of amines and amine derivatives
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A new mild and chemoselective method for mono-N-protection of amines and amine derivatives as tert-butoxycarbonyl derivatives is reported. The reaction proceeds with lithium perchlorate (20 mol %) and pyrocarbonates, and shows general applicability. The catalytic action of LiClO4 is specific for the activation of Boc2O, thus acid-sensitive functionalities of the starting materials remain unchanged in the protection process. This procedure works well for sterically hindered primary amine as well as electron-deficient primary arylamines, primary and secondary amino alcohols, α-amino acid esters, hydroxylamines, hydrazines and sulfonamides.
- Heydari, Akbar,Hosseini, Seyed Esmaeil
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p. 1929 - 1932
(2007/10/03)
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- Lewis base-catalyzed additions of alkynes using trialkoxysilylalkynes
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(Chemical Equation Presented) The Lewis base-catalyzed additions of alkynyl nucleophiles to aldehydes, ketones, and imines is described. Mechanistic studies strongly indicate that the use of new triethoxysilylalkynes facilitates access of a reactive hyper
- Lettan II, Robert B.,Scheidt, Karl A.
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p. 3227 - 3230
(2007/10/03)
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- Asymmetric synthesis of 1,2-amino alcohols using tert-butanesulfinimines as chiral auxiliary
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Facile and highly stereoselective synthesis of 1,2-amino alcohols has been achieved by the addition of [(dimethylphenyl-silyl)methyl] magnesium chloride to the tert-butanesulfinimines, followed by Fleming-Tamao oxidation of the silicon moiety.
- Ko, Chang Hong,Jung, Doo Young,Kim, Min Kyun,Kim, Yong Hae
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p. 304 - 308
(2007/10/03)
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- General and facile synthesis of 1,2-amino alcohols
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Facile preparation of 1,2-amino alcohols has been achieved by the reaction of benzyloxymethyl lithium with imines, which are generated from α-amido sulfones and benzyloxymethyl lithium in situ at -78°C in THF.
- Jung, Doo Young,Ko, Chang Hong,Kim, Yong Hae
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p. 1315 - 1317
(2007/10/03)
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- Selenium-promoted synthesis of enantiomerically pure substituted morpholines starting from alkenes and chiral aminoalcohols
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Enantiomerically pure 2,3,5-trisubstituted morpholines with two newly created stereocenters have been prepared by a short synthetic sequence having as the key step the selenium-promoted addition of (R)-phenylglycinol to a substituted alkene.
- Tiecco, Marcello,Testaferri, Lorenzo,Marini, Francesca,Sternativo, Silvia,Santi, Claudio,Bagnoli, Luana,Temperini, Andrea
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p. 2651 - 2657
(2007/10/03)
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- The Lindlar Catalyst Revitalized: A Highly Chemoselective Method for the Direct Conversion of Azides to N-(tert-Butoxycarbonyl)amines
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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
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p. 3740 - 3744
(2007/10/03)
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- Chemoselective conversion of azides to t-butyl carbamates and amines
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Azides were converted to the corresponding carbamates using a system of 20 mol% of decaborane (B10H14) and 20 weight% of 10% Pd/C in methanol in the presence of di-tert-butyl dicarbonate at rt in high yields and to the corresponding amines using a system of 10 mol% of decaborane and 20 weight% of 10% Pd/C in methanol in the absence of di-tert-butyl dicarbonate at rt in high yields.
- Jung, Yeon Joo,Chang, Yu Mi,Lee, Ji Hee,Yoon, Cheol Min
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p. 8735 - 8739
(2007/10/03)
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- Drugs containing phosphoric acid derivatives as the active ingredient
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The present invention relates to phosphoric acid derivatives represented by general formula (I), wherein each symbol is as defined in the description and nontoxic salts thereof. Because of having a TNFα production inhibitory effect, the compounds represented by general formula (I) are useful as preventives and/or remedies for rheumatoid arthritis, ulcerative colitis, Crohn's disease, hepatitis, sepsis, hemorrhagic shock, multiple sclerosis, cerebral infarction, diabetes, interstitial pneumonia, uveitis, pain, glomerulonephritis, HIV-associated diseases, cachexia, myocardial infarction, chronic heart failure, oral aphtha, Hansen's disease, infection, etc.
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- The proline-catalyzed direct asymmetric three-component Mannich reaction: Scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols
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We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide β-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, an
- List, Benjamin,Pojarliev, Peter,Biller, William T.,Martin, Harry J.
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p. 827 - 833
(2007/10/03)
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- Synthesis of chiral α-amino acids
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A novel method for the synthesis of chiral α-amino acids has been developed where the acid functionality was constructed by oxidizing a hydroxymethyl group introduced by Evans' method in the α-position of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.
- Chakraborty, Tushar K.,Ghosh, Animesh
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p. 9691 - 9693
(2007/10/03)
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- A new scaffold for amide ligation
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Highly chemoselective amide forming ligation reactions have facilitated the synthetic access to proteins and other amide-linked bioconjugates. In order to generalize this approach, a Nα-2-phenyl ethanethiol scaffold has been developed to promote S to N acyl transfer in a manner analogous to native chemical ligation with N-terminal cysteine residues. Analysis of scaffold-mediated ligation reactions in aqueous solution indicate that the ligation rate at Xaa-Gly junctions is sufficient for the synthesis of large polypeptides. In addition, it was found that the ligation rate is independent of the stereo center in the scaffold and S-to N-acyl transfer is rate limiting. These studies indicate that the Nα -2-phenyl ethanethiol scaffold is a good candidate for the development of a ligation chemistry for the formation of Xaa-Gly peptides and other unhindered amides. Copyright
- Marinzi, Chiara,Bark, Steven J.,Offer, John,Dawson, Philip E.
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p. 2323 - 2328
(2007/10/03)
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