114737-99-4Relevant academic research and scientific papers
Targeting Mobilization of Ferrous Iron in Pseudomonas aeruginosa Infection with an Iron(II)-Caged LpxC Inhibitor
Blank, Brian R.,Talukder, Poulami,Muir, Ryan K.,Green, Erin R.,Skaar, Eric P.,Renslo, Adam R.
, p. 1366 - 1375 (2019)
Iron is essential to all life, and competition for this vital nutrient is central to host-pathogen interactions during infection. The opportunistic Gram-negative pathogen Pseudomonas aeruginosa utilizes a diverse array of iron-acquisition strategies, including those enabling import of extracellular ferrous iron. We hypothesize that soluble and redox-active ferrous iron can be employed to activate caged antibiotics at sites of infection in vivo. Here we describe new chemistry that expands the application of our laboratory's Fe2+-activated-prodrug chemistry to cage hydroxamic acids, a class of drugs that present manifold development challenges. We synthesize the caged form of a known LpxC inhibitor and show that it is efficacious in an acute P. aeruginosa mouse-lung infection model, despite showing little activity in cell-culture experiments. Overall, our results are consistent with the Fe2+-promoted uncaging of an antibacterial payload at sites of infection in an animal and lend support to recent reports indicating that extracellular pools of ferrous iron can be utilized by bacterial pathogens like P. aeruginosa during infection.
CYCLOHEXANE ANALOGUES AS GPR119 AGONISTS
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Page/Page column 37, (2012/03/12)
This invention relates to a series of substituted cyclohexane containing analogues which are agonists of GPR119 intended to treat metabolic diseases mediated by GPR119 including Type I & II diabetes mellitus. Diabetes mellitus is an ever-increasing threat to human health causing various complications (blindness, kidney failure, neuropathy, heart attack, stroke, etc.). Recently it was found that activation of GPR119 which is highly expressed in pancreatic beta cells causes glucose dependent insulin secretion and GLP-1 release. Many pharmaceuticals are currently developing GPR119 agonists and herein we disclose alternative GPR119 agonists. Our invention describes GPR119 agonists having structural Formula (I), pharmaceutically acceptable salt or solvate of Formula (I), isomer or prodrug of Formula (I), and combination therapy of Formula (I) with other anti-diabetic drugs like DPP-IV inhibitors and/or insulin sensitizers.
Process for preparing the enantiomeric forms of cis-configured 1,3-cyclohexanediol derivatives
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Page 17, (2010/02/08)
Process for preparing the enantiomeric forms of cis-configured 1,3-cyclohexanediol derivatives A process is described for preparing chiral, nonracemic, cis-configured 1,3-disubstituted cyclohexanols of the formula (I) where the radicals are as defined, by
Synthesis and catalytic activity of rhodium diene complexes bearing indenyl-type fullerene η5-ligand
Toganoh, Motoki,Matsuo, Yutaka,Nakamura, Eiichi
, p. 295 - 300 (2007/10/03)
Rhodium η5-complexes bearing an indenyl-type fullerene ligand, Rh[C60(PhCH2)2Ph](cod) (2), Rh[C60(PhCH2)2Ph](nbd) (3) and Rh(C70Ph3)(cod) (4), have been synthesized from the corresponding fullerene tri-adducts in 93-96% yields. X-ray crystallographic analysis of 4 indicated that the structure of 4 is similar to that of Rh(Ind)(cod). The rhodium complex 2 catalyzes alkyne trimerization reactions and hydroboration reactions.
Trifluoromethyl-substituted indenyl rhodium and iridium complexes are highly selective catalysts for directed hydroboration reactions
Brinkman, John A.,Nguyen, Tam T.,Sowa Jr., John R.
, p. 981 - 983 (2007/10/03)
(equation presented) Rhodium and iridium catalysts containing trifluoromethyl-substituted indenyl ligands (Ind′MCod, Ind′ = C9H7, (1-CF3)C9H6, (2-CF3)C9H6, (1,3-CFsub
Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. Part 14: Regioselectivity of the opening reactions with MeOH of remote O-substituted 1,2-epoxycyclohexanes under gas-phase operating conditions
Crotti, Paolo,Di Bussolo, Valeria,Favero, Lucilla,Pineschi, Mauro,Marianucci, Francesco,Renzi, Gabriele,Amici, Giuseppina,Roselli, Graziella
, p. 7513 - 7524 (2007/10/03)
The regiochemical behavior of cyclohexene oxides bearing a remote O-functionality was determined in the gas-phase in opening reactions with MeOH, using a gaseous acid (D3/+, C(n)H5/+, Me2F+
Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. 8. Synthesis and ring opening reactions of cis- and trans-oxides derived from 3-benzyloxycyclohexene and 2-benzyloxy-5,6-dihydro-2H-pyran
Calvani, Federico,Crotti, Paolo,Gardelli, Cristina,Pineschi, Mauro
, p. 12999 - 13022 (2007/10/02)
The regiochemical outcome of the ring opening of 1,2-epoxides bearing polar remote functionalization through chelation processes assisted by metal ions, was verified in cyclic oxirane systems having the polar functionality in an allylic position to the oxirane ring. The diastereoisomeric cis/trans epoxide pairs 5,6 and 7,8 derived from 3-benzyloxycyclohexene, and 2-benzyloxy-5,6-dihydro-2H-pyran, respectively, were prepared and several of their opening reactions were studied. The regioselectivity observed largely depends on the reaction conditions (standard or metal-assisted) and, interestingly, on the nature of the nucleophile used.
Regiochemical Control of the Ring-Opening of 1,2-Epoxides by Means of Chelating Processes. Synthesis and Reactions of the cis- and trans-Oxides Derived from 4-(Benzyloxy)cyclohexene
Chini, Marco,Crotti, Paolo,Flippin, Lee A.,Macchia, Franco
, p. 4265 - 4272 (2007/10/02)
The synthesis and reactions of diastereomeric epoxides cis-1 and trans-2 with heteronucleophiles were carried out in order to probe the effect of remote polar functionality on the regioselectivity of nucleophilic addition to the epoxide ring.The reaction
