18202-13-6Relevant articles and documents
Synthesis of novel symmetrical, single-chain, diacetylene-modified bolaamphiphiles with different alkyl chain lengths
Drescher, Simon,Helmis, Katrin,Langner, Andreas,Dobner, Bodo
, p. 339 - 349 (2010)
General syntheses of novel symmetrical, single-chain, diacetylene-modified bolaphospholipids have been carried out in five steps. For the ω-alkynols, which have an important role as key intermediates, three different synthetic approaches were comprehensively investigated. For the final synthesis it is suggested that (1) alkylation of lithium (trimethylsilyl)acetylide with tetrahydropyranyl-protected ω-bromoalcohols, followed by (2) cleavage of the trimethylsilyl moiety and the tetrahydropyranyl protecting group, and (3) copper(II)-catalyzed Eglinton coupling is the best strategy for obtaining diacetylene-modified alkane-1,ω-diols, because higher yields were obtained while avoiding the formation of by-products. Moreover, conversion of the diols into bipolar phospholipids was achieved by bis-phosphorylation with β-bromoethylphosphoric acid dichloride and subsequent quaternization with trimethylamine or dimethylamine. Finally, spectral data are presented for novel single-chain, diacetylene-modified bolaphospholipids with promising potential as starting molecules in the formation of polymerizable and, thus, thermostable nanofibers.
NUCLEOSIDE PRODRUGS AND USES RELATED THERETO
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Page/Page column 131; 133; 134, (2021/02/26)
Disclosed are acyclic nucleoside prodrugs with improved metabolic stability and oral bioavailability. In general, the prodrugs are derivatives of acyclic nucleoside phosphonates containing a lipid-like moiety that can increase oral absorption and subsequent stability in the liver and plasma. Preferably, the lipid-like moiety can resist enzyme-mediated ω-oxidation, such as ω -oxidation catalyzed by cytochrome P450 enzymes. Also disclosed are pharmaceutical formulations of the acyclic nucleoside prodrugs. The acyclic nucleoside prodrugs and pharmaceutical formulations thereof can be used to treat viral infections, such as HIV infections, and/or viral-associated cancer, such as HPV-associated cancers.
ω-Functionalized Lipid Prodrugs of HIV NtRTI Tenofovir with Enhanced Pharmacokinetic Properties
Bartsch, Perry W.,Basson, Adriaan E.,Burton, Samantha L.,Bushnev, Anatoliy,D'Erasmo, Michael,Dasari, Madhuri,Derdeyn, Cynthia A.,Giesler, Kyle E.,Hwang, Soyon S.,Iskandar, Sabrina,Liotta, Dennis C.,Miller, Eric J.,Pribut, Nicole,Raghuram, Akshay,Sharma, Savita K.
, p. 12917 - 12937 (2021/09/13)
Tenofovir (TFV) is the cornerstone nucleotide reverse transcriptase inhibitor (NtRTI) in many combination antiretroviral therapies prescribed to patients living with HIV/AIDS. Due to poor cell permeability and oral bioavailability, TFV is administered as one of two FDA-approved prodrugs, both of which metabolize prematurely in the liver and/or plasma. This premature prodrug processing depletes significant fractions of each oral dose and causes toxicity in kidney, bone, and liver with chronic administration. Although TFV exalidex (TXL), a phospholipid-derived prodrug of TFV, was designed to address this issue, clinical pharmacokinetic studies indicated substantial hepatic extraction, redirecting clinical development of TXL toward HBV. To circumvent this metabolic liability, we synthesized and evaluated ω-functionalized TXL analogues with dramatically improved hepatic stability. This effort led to the identification of compounds 21 and 23, which exhibited substantially longer t1/2 values than TXL in human liver microsomes, potent anti-HIV activity in vitro, and enhanced pharmacokinetic properties in vivo.
Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization
Ganss, Stephanie,Breit, Bernhard
supporting information, p. 9738 - 9742 (2016/08/10)
A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of ω-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including α,β-unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity.
Total synthesis and reassignment of the structures of the antimicrobial lipodepsipeptides circulocin γ and δ
Cochrane, James R.,Exner, Claudia J.,Jolliffe, Katrina A.
, p. 4491 - 4500 (2015/05/13)
The structures of the naturally occurring antimicrobial lipodepsipeptides circulocin γ and circulocin δ have been reported to comprise a common cyclic depsipeptide core attached to 3-hydroxy,ω-guanidino fatty acid chains differing in length by two methyle
Ultralow adhesion and friction of fluoro-hydro alkyne-derived self-assembled monolayers on H-terminated Si(111)
Pujari, Sidharam P.,Spruijt, Evan,Cohen Stuart, Martien A.,Van Rijn, Cees J. M.,Paulusse, Jos M. J.,Zuilhof, Han
, p. 17690 - 17700 (2013/03/13)
New fluorine-containing terminal alkynes were synthesized and self-assembled onto Si(111) substrates to obtain fluorine-containing organic monolayers. The monolayers were analyzed in detail by ellipsometry, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), static water contact angle measurements (CA), and atomic force microscopy (AFM). The SAMs exhibit excellent hydrophobicity, with static water contact angles of up to 119 and low critical surface tensions of 5-20 mN/m depending on the number of F atoms per molecule. IRRAS confirmed the formation of highly ordered monolayers, as indicated by the antisymmetric and symmetric stretching vibrations of the CH2 moieties at 2918-2920 and 2850-2851 cm-1, respectively. Upon increasing the number of fluorine atoms in the alkyne chains from 0 to 17, the adhesion of bare silica probes to the SAMs in air decreases from 11.6 ± 0.20 mJ/m 2 for fluorine-free (F0) alkyne monolayers to as low as 3.2 ± 0.03 mJ/m2 for a heptadecafluoro-hexadecyne (F17)-based monolayer. Likewise, the friction coefficient decreases from 5.7 × 10-2 to 1.2 × 10-2. The combination of high ordering, excellent hydrophobicity, low adhesion, and low friction makes these fluoro-hydro alkyne-derived monolayers highly promising candidates for use in high-performance microelectronic devices.
17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues
Falck, John R.,Wallukat, Gerd,Puli, Narender,Goli, Mohan,Arnold, Cosima,Konkel, Anne,Rothe, Michael,Fischer, Robert,Müller, Dominik N.,Schunck, Wolf-Hagen
supporting information; experimental part, p. 4109 - 4118 (2011/08/05)
17(R),18(S)-Epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca 2+-overload with EC50 ≈ 1-2 nM. Structure-activity studies revealed that a cis-Δ11,12- or Δ14,15- olefin and a 17(R),18(S)-epoxide are minimal structural elements for antiarrhythmic activity whereas antagonist activity was often associated with the combination of a Δ14,15-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates.
HETEROCYCLIC DERIVATIVES THAT ARE USED IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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Page/Page column 14, (2011/06/10)
The present invention relates to compounds of Formula (I) below, to their pharmaceutically acceptable salts and to their isomers or mixtures of isomers: HetAr—X—CHR1R2 (I) in which: -HetAr represents a group chosen from: —X represents a linear, saturated or unsaturated, hydrocarbon-based chain comprising from 8 to 22 carbon atoms, optionally interrupted by an —NH— or —NH—CO— group, —R1 represents a hydrogen atom or an —OH, —O(C1-C6)alkyl, —OCO((C1-C6)alkyl), —OSO2((C1-C6)alkyl) or —OSO3H group, and —R2 represents a hydrogen atom or a (C2-C6)alkynyl, (C2-C6)alkenyl or (C3-C6)cycloalkyl group. The present invention also relates to a process for preparing the compounds of Formula (I), and also to the use thereof, especially in the treatment of neurodegenerative diseases.
Novel eicosanoid derivatives
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Page/Page column 41-42, (2010/08/07)
The present invention provides compounds (n-3 PUFA derivatives) of formula (I): that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.
Synthesis of natural polyacetylenes bearing furan rings
Barancelli, Daniela A.,Mantovani, Anderson C.,Jesse, Cristiano,Nogueira, Cristina W.,Zeni, Gilson
supporting information; experimental part, p. 857 - 860 (2009/12/26)
The first total syntheses of four new polyacetylene compounds have been achieved using convergent routes, which involved Cadiot-Chodkiewicz copper-catalyzed cross-coupling reactions to sp-sp centers as the key steps. 19-Furan-2-ylnonadeca-5,7-diynoic acid (1), 19-furan-2-ylnonadeca-5,7-diynoic acid methyl ester (2), 2-pentacosa-7,9-diynylfuran (3), and 21-furan-2- ylhenicosa-14,16-diyn-1-ol (4) were stable and could be readily identified, isolated, and purified in high overall yields.
