606488-94-2Relevant academic research and scientific papers
Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs
Krall, Jacob,Jensen, Claus Hatt,Bavo, Francesco,Falk-Petersen, Christina Birkedahl,Haugaard, Anne St?hr,Vogensen, Stine Byskov,Tian, Yongsong,Nittegaard-Nielsen, Mia,Sigurdardóttir, Sara Bj?rk,Kehler, Jan,Kongstad, Kenneth Thermann,Gloriam, David E.,Clausen, Rasmus Pr?torius,Harps?e, Kasper,Wellendorph, Petrine,Fr?lund, Bente
, p. 9022 - 9039 (2017/11/14)
γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.
IRAK INHIBITORS AND USES THEREOF
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Paragraph 00280-00281, (2014/02/15)
The present invention provides arylo-fused thienopyrimidine compounds, compositions thereof, and methods of using the same.
FLT3 INHIBITORS AND USES THEREOF
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Paragraph 00353-00354, (2014/12/12)
The present invention provides methods of using compounds of formula I: or compositions thereof for the inhibition of FLT3, and the treatment of FLT3-mediated disorders.
DIAZENIUMDIOLATE CYCLOHEXYL DERIVATIVES
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Page/Page column 23, (2011/12/04)
A compound having the structure (I) or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, deuterium, —OH, —OC1-6alkyl, or halogen; R8 is hydrogen, deuterium, or C1-6alkyl; R11 and R12 are independently hydrogen, —C1-6alkyl, —OH, —OC1-6alkyl, or halogen; R13 and R14 are independently —C1-6alkyl, —(CH2)1-2OH, or —OC1-6alkyl, or, together with the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or mono-, di- or tri-substituted with halogen or —C1-6alkyl; R15 is (CR1R2)nC(O)OR16, wherein n is 0, 1 or 2, —C(O)NHCH(R17)OR16, or —C(O)NHCH(R17)C(O)NHCH(R18)C(O)OR16; R16 is hydrogen, C1-6alkyl, or (CH2)1-2N+R19R20R21; R1, R2, R4, R5, R6, R7, R9, R10, R17, R18, R19, R20, and R21 are independently hydrogen or —C1-6alkyl; and stereoisomers thereof, and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of stereoisomers thereof
Degradation of a model naphthenic acid, cyclohexanoic acid, by vacuum UV (172 nm) and UV (254 nm)/H2O2
Drzewicz, Przemyslaw,Afzal, Atefeh,El-Din, Mohamed Gamal,Martin, Jonathan W.
experimental part, p. 12067 - 12074 (2011/02/27)
The mechanism of hydroxyl radical initiated degradation of a typical oil sands process water (OSPW) alicyclic carboxylic acid was studied using cyclohexanoic acid (CHA) as a model compound. By use of vacuum ultraviolet irradiation (VUV, 172 nm) and ultraviolet irradiation in the presence of hydrogen peroxide UV(254 nm)/H2O2, it was established that CHA undergoes degradation through a peroxyl radical. In both processes the decay of the peroxyl radical leads predominantly to the formation of 4-oxo-CHA, and minor amounts of hydroxy-CHA (detected only in UV/H2O 2). In UV/H2O2, additional 4-oxo-CHA may also have been formed by direct reaction of the oxyl radical with H-O 2. The oxyl radical can be formed during decay of the peroxyl-CHA radical or reaction of hydroxy-CHA with hydroxyl radical. Oxo- and hydroxy-CHA further degraded to various dihydroxy-CHAs. Scission of the cyclohexane ring was also observed, on the basis of the observation of acyclic byproducts including heptadioic acid and various short-chain carboxylic acids. Overall, the hydroxyl radical induced degradation of CHA proceeded through several steps, involving more than one hydroxyl radical reaction, thus efficiency of the UV/H 2O2 reaction will depend on the rate of generation of hydroxyl radical throughout the process. In real applications to OSPW, concentrations of H2O2 will need to be carefully optimized and the environmental fate and effects of the various degradation products of naphthenic acids considered.
The vibrational spectra (100-1500 cm-1) of a series of bicyclooctanes assigned by means of scaled 3-21G ab initio harmonic force fields
Eggimann, Thomas,Ibrahim, Nan,Shaw, R. Anthony,Wieser, Hal
, p. 578 - 610 (2007/10/02)
The infrared absorption (vapor phase and solution) and Raman (liquid phase) spectra of bicyclooctane, 8-oxabicyclooctane, 6-oxabicyclooctane, 6,8-dioxabicyclooctane, and the 7,7-dideutero-substituted derivatives of the last two compounds are reported in the region 100-1500 cm-1 for the first time.The vibrational spectra are assigned almost completely with the guidance of ab initio 3-21G geometries and scaled force fields.A total of 14 force-field scale factors are transferred from smaller molecules, predicting the frequencies with an average error of 7.6 cm-1 (1.2percent) for 196 assigned transitions.After optimizing the factors in an overlay refinement involving all six molecules, the frequencies are within 5.7 cm-1 (0.75percent) of experiment.The ab initio absorption and Raman intensities are calculated with the 3-21G basis set and are demonstrated to be of such accuracy as to be useful for the spectral assignments.These intensities are calculated with uniformly and nonuniformly scaled force fields and compared to the experimental spectra.The intensities derived from the latter force fields are superior, meaning that nonuniform scaling is preferable at this level of theory for both vibrational frequencies and normal mode descriptions.
General Syntheses of 6- and 7-Carbomethoxy-trans-1-heteradecalins and 6- and 7-Carbomethoxy-trans-2-heteradecalins
Hirsch, Jerry A.,Truc, Vu Chi
, p. 2218 - 2227 (2007/10/02)
Two routes to all of the title compounds in the oxa and aza series have been studied.The most general path, involving a cyclohexene oxide intermediate, was not successful becauase of difficulty in separating regioisomers.Allylation of 4-carbomethoxycyclohexanone (11) followed by reduction produced the required trans-disubstituted allyl alcohols, which were converted to all of the desired 6-carbomethoxy-trans-1-heteradecalins.The allyl ketones were subjected to a homologation-side chain contraction sequence to produce the 6-carbomethoxy-trans-2-heteradecalins.Allylation of 3-carbomethoxycyclohexanone (12) was not regioselective, but all four product isomers were characterized.The desired 5-carbomethoxy-2-allylcyclohexanone isomers (27 and 28) were converted to the 7-carbomethoxy-trans-decalins by similar series of reactions
