33234-48-9Relevant academic research and scientific papers
GRP94 SELECTIVE INHIBITORS AND USES THEREOF
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Paragraph 0129; 0130, (2018/05/24)
The present technology provides compounds according to Formula I or Formula III as well as compositions including such compounds useful for the treatment of metastatic cancer and/or glaucoma.
Transformation of the non-selective aminocyclohexanol-based Hsp90 inhibitor into a Grp94-seletive scaffold
Mishra, Sanket J.,Ghosh, Suman,Stothert, Andrew R.,Dickey, Chad A.,Blagg, Brian S. J.
, p. 244 - 253 (2017/12/30)
Glucose regulated protein 94 kDa, Grp94, is the endoplasmic reticulum (ER) localized isoform of heat shock protein 90 (Hsp90) that is responsible for the trafficking and maturation of toll-like receptors, immunoglobulins, and integrins. As a result, Grp94 has emerged as a therapeutic target to disrupt cellular communication, adhesion, and tumor proliferation, potentially with fewer side effects compared to pan-inhibitors of all Hsp90 isoforms. Although, the N-terminal ATP binding site is highly conserved among all four Hsp90 isoforms, recent cocrystal structures of Grp94 have revealed subtle differences between Grp94 and other Hsp90 isoforms that has been exploited for the development of Grp94-selective inhibitors. In the current study, a structure-based approach has been applied to a Grp94 nonselective compound, SNX 2112, which led to the development of 8j (ACO1), a Grp94-selective inhibitor that manifests -440 nM affinity and ≥200-fold selectivity against cytosolic Hsp90 isoforms.
An efficient one-pot synthesis of 2-benzylpyrroles and 3-benzylindoles
Sharma, Ratnesh,Chouhan, Mangilal,Sood, Divya,Nair, Vipin A.
experimental part, p. 305 - 309 (2012/01/03)
One-pot regioselective benzylation of pyrroles and indoles using zirconium tetrachloride is discussed. This has been achieved by in-situ generation of di(1H-pyrrol-1-yl)zirconium(IV) chloride and di(1H-indol-1-yl)zirconium(IV) chloride. It was observed th
In Situ vinylpyrrole synthesis. Diels-alder reactions with maleimides to give tetrahydroindoles
Noland, Wayland E.,Lanzatella, Nicholas P.,Sizova, Elena P.,Venkatraman, Lakshmanan,Afanasyev, Oleg V.
scheme or table, p. 503 - 534 (2009/09/05)
(Chemical Equation Presented) A series of 108 tetrahydroindoles has been prepared by a one-pot synthesis from 2-alkylpyrroles, cyclic ketones, maleimides, and an acid catalyst. A 5-vinylpyrrole is formed by an acid-catalyzed condensation of a 2-alkyl-substituted pyrrole with a ketone, which is subsequently trapped in situ by a maleimide in a predominantly endo-addition Diels-Alder reaction. Isomerization of the double bond into the pyrrole ring gives a tetrahydroindole with predominant cis-fusion of the cycloalkane ring.
Mono- and dialkylations of pyrrole at C2 and C5 positions by nucleophilic substitution reaction in ionic liquid
Jorapur, Yogesh R.,Lee, Chang-Hee,Chi, Dae Yoon
, p. 1231 - 1234 (2007/10/03)
(Chemical Equation Presented) A novel ionic liquid methodology for pyrrole C-alkylation is described. The pyrrole alkylation is achieved with various simple alkyl halides and mesylates selectively at C2 and C5 positions in good yields with minimal byproducts under relatively mild conditions in various ionic liquids. 2-(3-Phenylpropyl)pyrrole (2a) was synthesized from pyrrole and 1-bromo-3-phenylpropane in a mixture solvent system, [bmim][SbF6] and CH3CN, in 81% yield at 115°C for 44 h with 5% yield of dialkylated compound 3a.
The Direct Alkylation of π-Rich, Acid-Sensitive Heterocyclic Compounds via Essentially Free Carbocations
Darbeau, Ron W.,White, Emil H.
, p. 8091 - 8094 (2007/10/03)
Alkylation of π-rich heteroaromatics such as pyrroles and furans by the standard Friedel-Crafts approach is impractical because the acid catalysts employed (Bronsted or Lewis) induce polyalkylation, ring opening, and polymerization. The present study describes the facile benzylation of π-excessive heteroaromatics using the nitrosoamide approach, which generates nitrogen-separated carbocation-counterion ion-pairs as the alkylating agent with no catalyst being required. N-Nitrosoamides are favorable sources of carbocations because of the following variables: mildness of the conditions required to generate cations, high reactivity of the unsolvated carbocations formed, solubility of the precursors in a wide range of solvents, homogeneity of the reactions, wide range of decomposition temperatures possible, straightforward chemistry, and excellent product balance. The majority of the cations that are generated in pyrrole (80%) are intercepted by the solvent, and only 20% are intercepted by the counterion; this result provides support for the intermediacy of nitrogen-separated ion-pairs in deamination. A nucleophilicity scale is presented for reactions of selected nucleophiles with essentially free carbocations.
N-(Triisopropylsilyl)pyrrole. A Progenitor "Par Excellence" of 3-Substituted Pyrroles
Bray, Brian L.,Mathies, Peter H.,Naef, Reto,Solas, Dennis R.,Tidwell, Thomas T.,et al.
, p. 6317 - 6328 (2007/10/02)
A very effective strategy has been devised for the synthesis of 3-substituted pyrroles based on the use of the triisopropylsilyl (TIPS) moiety as a sterically demanding nitrogen substituent to obstruct the attack of electrophilic reagents at the α positions. 1-(Triisopropylsilyl)pyrrole (1) undergoes highly preferential kinetic electrophilic substitution at the β position with a variety of electrophiles (Br+, I+, NO2+, RCO+, etc.) and fluoride ion induced desilylation of the products provides the corresponding 3-substituted pyrroles in good overall yields.Competitive trifluoroacetylation experiments demonstrate that substitution of TIPS-pyrrole at the α positions is decelerated by a factor of >104, vs pyrrole at the same sites, without affecting reactivity at the β positions. 1-(Triisopropylsilyl)-3-bromopyrrole (2) is readily converted into the 3-lithio compound 44 by bromine-lithium interchange with alkyllithium reagents.This previously unavailable, formal equivalent of 3-lithiopyrrole is itself an excellent source of a wide range of β-substituted pyrroles, many of which would not be directly preparable from 1.TIPS-pyrrole can be 3,4-dihalogenated and these compounds undergo sequential halogen-metal interchange trapping reactions.This process is exemplified by an efficient, three-step synthesis of the antibiotic verrucarin E (63) from the dibromo compound (5).
Synthesis of Alkylpyrroles by the Sodium Borohydride Reduction of Acylpyrroles
Greenhouse, Robert,Ramirez, Coral,Muchowski, Joseph M.
, p. 2961 - 2965 (2007/10/02)
N-Unsubstituted alkylpyrroles are obtained by the reduction of the corresponding acylpyrroles with sodium borohydride in boiling 2-propanol.This reaction was demonstrated to proceed via the pyrrolylalkylcarbinol and was extended to the synthesis of a branched chain alkylpyrrole 25 from the tertiary alcohol 24.
Catalytic Hydrogenation of Pyrroles at Atmospheric Pressure
Kaiser, Hans-Peter,Muchowski, Joseph M.
, p. 4203 - 4209 (2007/10/02)
N-(tert-Butoxycarbonyl)pyrroles are catalytically hydrogenated to the corresponding pyrrolidines, over 5percent platinum on carbon catalyst, at room temperature and atmospheric pressure.Under these conditions O-benzyl groups are retained and 2,5-disubstit
A General Method for the Preparation of 2-Benzylpyrroles by Modified Borohydride Reduction of Azafulvenium Salts
McGillivray, George,Smal, Elma
, p. 633 - 636 (2007/10/02)
2-Benzylpyrroles (5a-h) can be prepared in high yield from pyrroles by reduction, with modified borohydride reagents, of the corresponding 1-azafulvenium salts (3a-h) generated in situ in the presence of excess of phosphoryl trichloride.The procedure is compatible with ester groups.
