3575-31-3Relevant academic research and scientific papers
Potentiation of the fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida
Stephens, Matthew D.,Yodsanit, Nisakorn,Melander, Christian
supporting information, p. 1952 - 1956 (2016/10/22)
A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-species F. novicida and F. philomiragia.
SELECTIVE INHIBITORS AND ALLOSTERIC ACTIVATORS OF SPHINGOSINE KINASE
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, (2014/08/19)
Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases, such as cancer and vascular remodeling in pulmonary arterial hypertension. Inhibitors of sphingosine kinase 1 and 2 (SK1 and SK2), which catalyze the synthesis of S1P, may be useful anti- proliferative agents. We have synthesized a series of sphingosine-based inhibitors of SK and SK2. Also provided in this invention are compounds that activate SK1 which can be used in diseases such as fibrosis, where intracellular S1P is anti-fibrotic.
Structure-Activity relationships and molecular modeling of sphingosine kinase inhibitors
Baek, Dong Jae,MacRitchie, Neil,Anthony, Nahoum G.,MacKay, Simon P.,Pyne, Susan,Pyne, Nigel J.,Bittman, Robert
, p. 9310 - 9327 (2014/01/06)
The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases 1 and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of d-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SK1. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention.
METHOD OF REGIOSELECTIVE SYNTHESIS OF SUBSTITUTED BENZOATES
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Page/Page column 11; 12; 16; 18; 19; 20, (2013/03/26)
A method of synthesis of para-substituted benzoate esters and acids is provided, wherein the para-substituted regioisomer is obtained substantially free of the meta-substituted impurity, the method comprising contacting a coumalate ester or acid and an un activated alkene at elevated temperature in the presence of a metal oxidation catalyst and an oxidant. The metal oxidation catalyst can be palladium, such as palladium on carbon, and the oxidant can be the oxygen gas in ambient air. The reaction can be carlied out without solvent or in high boiling hydrocarbon solvents such as mesitylene. When the un activated alkene is a monosubstituted alkene, yields of at least about 50 or 60% of para-substituted ester and acid products, respectively, are obtained, substantially free of the regioisomelic meta-substituted impurity.
Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthemamide derivatives formed by an EDCI/HOBt condensation
Yu, Peng,Hu, Jun,Zhou, Tao-Yu,Wang, Peng,Xu, Yan-Hua
, p. 703 - 706 (2012/03/10)
A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, 1H NMR and elemental analyses. Their insecticidal activity was also evaluated.
Aromatics from pyrones: Para-substituted alkyl benzoates from alkenes, coumalic acid and methyl coumalate
Kraus, George A.,Riley, Sean,Cordes, Travis
experimental part, p. 2734 - 2736 (2011/11/06)
The Diels-Alder reaction of coumalic acid and methyl coumalate with unactivated alkenes provides only para-substituted adducts in good yield.
Synthesis and biological evaluation of sphingosine kinase substrates as sphingosine-1-phosphate receptor prodrugs
Foss Jr., Frank W.,Mathews, Thomas P.,Kharel, Yugesh,Kennedy, Perry C.,Snyder, Ashley H.,Davis, Michael D.,Lynch, Kevin R.,Macdonald, Timothy L.
experimental part, p. 6123 - 6136 (2009/12/06)
In the search for bioactive sphingosine 1-phosphate (S1P) receptor ligands, a series of 2-amino-2-heterocyclic-propanols were synthesized. These molecules were discovered to be substrates of human-sphingosine kinases 1 and 2 (SPHK1 and SPHK2). When phosphorylated, the resultant phosphates showed varied activities at the five sphingosine-1-phosphate (S1P) receptors (S1P1-5). Agonism at S1P1 was displayed in vivo by induction of lymphopenia. A stereochemical preference of the quaternary carbon was crucial for phosphorylation by the kinases and alters binding affinities at the S1P receptors. Oxazole and oxadiazole compounds are superior kinase substrates to FTY720, the prototypical prodrug immunomodulator, fingolimod (FTY720). The oxazole-derived structure was the most active for human SPHK2. Imidazole analogues were less active substrates for SPHKs, but more potent and selective agonists of the S1P1 receptor; additionally, the imidazole class of compounds rendered mice lymphopenic.
COMPOSITIONS AND METHODS FOR INHIBITING SPHINGOSINE KINASE
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Page/Page column 31; 33, (2009/12/27)
Amidine analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 and SphK2) are provided. The compounds can prevent angiogenesis in tumor cells.
Epimerization of 2- or 4- substituted cyclohexanecarboxylic acids
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, (2008/06/13)
The present invention relates to a new method for obtaining a purity of about 93% to 100% of the trans form of 2- or 4-substituted cyclohexanecarboxylic acid or reactive derivatives thereof from the cis form or a mixture of the cis and trans forms by a single step, particularly, to a method for obtaining a purity of substantially 100% of the trans form of 4-substituted cyclohexanecarboxylic acid.
New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships
Nakai,Konno,Kosuge,Sakuyama,Toda,Arai,Obata,Katsube,Miyamoto,Okegawa,Kawasaki
, p. 84 - 91 (2007/10/02)
(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.
