728-80-3Relevant articles and documents
Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand
Isbrandt, Eric S.,Nasim, Amrah,Newman, Stephen G.,Zhao, Karen
supporting information, p. 14646 - 14656 (2021/09/18)
We report a catalytic method to access secondary alcohols by the coupling of aryl iodides. Either aldehydes or alcohols can be used as reaction partners, making the transformation reductive or redox-neutral, respectively. The reaction is mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2ligand, which has previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism is proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alcohol reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcohols, demonstrating control over the oxidation state of both the starting materials and products.
Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase
Winters, Maria,DuHadaway, James B.,Pham, Khoa N.,Lewis-Ballester, Ariel,Badir, Shorouk,Wai, Jenny,Sheikh, Eesha,Yeh, Syun-Ru,Prendergast, George C.,Muller, Alexander J.,Malachowski, William P.
supporting information, p. 455 - 464 (2018/11/25)
Tryptophan (Trp) catabolizing enzymes play an important and complex role in the development of cancer. Significant evidence implicates them in a range of inflammatory and immunosuppressive activities. Whereas inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) have been reported and analyzed in the clinic, fewer inhibitors have been described for tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase-2 (IDO2) which also have been implicated more recently in cancer, inflammation and immune control. Consequently the development of dual or pan inhibitors of these Trp catabolizing enzymes may represent a therapeutically important area of research. This is the first report to describe the development of dual and pan inhibitors of IDO1, TDO and IDO2.
Grignard Reagents on a Tab: Direct Magnesium Insertion under Flow Conditions
Huck, Lena,De La Hoz, Antonio,Díaz-Ortiz, Angel,Alcázar, Jesus
supporting information, p. 3747 - 3750 (2017/07/26)
An on-demand preparation of organomagnesium reagents is presented using a new flow protocol. The risks associated with the activation of magnesium are circumvented by a new on-column initiation procedure. Required amounts of solutions with a precise titration were obtained. Telescoped flow or batch reactions allow access to a diverse set of functional groups.
Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors
Pajouhesh, Hassan,Feng, Zhong-Ping,Ding, Yanbing,Zhang, Lingyun,Pajouhesh, Hossein,Morrison, Jerrie-Lynn,Belardetti, Francesco,Tringham, Elizabeth,Simonson, Eric,Vanderah, Todd W.,Porreca, Frank,Zamponi, Gerald W.,Mitscher, Lester A.,Snutch, Terrance P.
scheme or table, p. 1378 - 1383 (2010/07/06)
A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC50 values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
Glycine transporter-1 inhibitors
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Page/Page column 27, (2008/06/13)
The present invention provides compounds that are glycine transporter 1 (hereinafter referred to as GlyT-1) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of GlyT1 such as cognitive disorders associated with Schizophrenia, ADHD (attention deficit hyperactivity disorder), MCI (mild cognitive impairment), and the like. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Nonracemic diarylmethanols from CuH-catalyzed hydrosilylation of diaryl ketones
Lee, Ching-Tien,Lipshutz, Bruce H.
supporting information; experimental part, p. 4187 - 4190 (2009/05/30)
(Chemical Equation Presented) An efficient method for the synthesis of nonracemic diarylmethanols has been developed. The use of (R)-(-)-(DTBM-SEGPHOS) CuH effects highly enantioselective 1,2-hydrosilylation of prochiral diaryl ketones.
An electrochemical coupling of organic halide with aldehydes, catalytic in chromium and nickel salts. the Nozaki-Hiyama-Kishi reaction.
Durandetti,Nedelec,Perichon
, p. 2073 - 2076 (2007/10/03)
[reaction: see text] Electrochemical arylation of arenecarboxaldehydes using an iron sacrificial anode in the presence of chromium and nickel catalysts afforded the corresponding arylated secondary alcohols in moderate to good yields. The chromium and nickel salts as catalysts are obtained by oxidation of a stainless steel rod during a preelectrolysis in 7% and 3%, respectively. The process was also applied to the addition of vinyl halide, allyl acetate, or alpha-chloroester to aromatic aldehydes.
Nickel- and chromium-catalysed electrochemical coupling of aryl halides with arenecarboxaldehydes
Durandetti, Muriel,Perichon, Jacques,Nedelec, Jean-Yves
, p. 9009 - 9013 (2007/10/03)
Electrochemical arylation of arenecarboxaldehydes using a stainless steel sacrificial anode in the presence of Ni catalysts afforded the corresponding arylated secondary alcohols in good yields.
Solvolysis of benzylic chlorides with extended charge delocalization. α-tert-Butyl(2-naphthyl)methyl, 9-fluorenyl and monosubstituted benzhydryl chlorides
Liu, Kwang-Ting,Lin, Yen-Shyi,Tsao, Meng-Lin
, p. 223 - 229 (2007/10/03)
Rate constants of solvolysis of α-tert-butyl(2-naphthyl)methyl chloride (1), 9-fluorenyl chloride (2) and a series of monosubstituted benzhydryl chlorides (3) in a wide range of solvents were measured. Grunwald-Winstein-type correlation analysis of log k for 2 and 3 against YBnCl, with or without nucleophilicity N, yielded less satisfactory linear correlations than that against log k(l). A new scale of solvent ionizing power, YxBnCl for the correlation of solvolytic reactivities of benzylic chlorides with extended charge delocalization based on log k(1) was developed. Application to the mechanistic study suggested the solvolysis of 2 and 4-nitrobenzhydryl chloride were non-limiting. Hammett plots against α+ constants exhibited more negative ρ values in less nucleophilic solvents. In a benzhydryl chloride containing a strong deactivating substituent, such as 4-nitro, the positive charge delocalizes mainly over the unsubstituted ring in the cationic transition state. The uneven charge distribution was also confirmed by Mulliken population analysis at the level of the RHF/6-31G*//RHF/3-21G(*) basis set for cations. Comparison of the results of correlation analysis using the equation log(k/k0) = mY vs the equation log(k/k0) = mY + hI, and using the equation log(k/k0) = mY +IN vs the equation log(k/ko) = mY + IN + hI indicated the use of YBnCl or YxBncl could give a better understanding of solvolytic mechanisms than the combinatorial use of YCl and I.
3'-Chloro-3α-(diphenylmethoxy)tropane but not 4'-chloro-3α- (diphenylmethoxy)tropane produces a cocaine-like behavioral profile
Kline, Richard H.,Izenwasser, Sari,Katz, Jonathan L.,Joseph, David B.,Bowen, Wayne D.,Newman, Amy Hauck
, p. 851 - 857 (2007/10/03)
A series of 2'- and 3'-substituted and 3',3''-disubstituted 3α- (diphenylmethoxy)tropane analogs were designed and synthesized as novel probes for the dopamine transporter. All the analogs were evaluated for displacement of [3H]WIN 35,428 binding at the dopamine transporter and for inhibition of [3H]dopamine uptake in rat caudate putamen. Compounds were observed to monophasically displace [3H]WIN 35,428 binding to the dopamine transporter with affinities of 21.6-1836 nM (K(i)). Generally, meta- substituted compounds were more potent than benztropine and equipotent to or slightly less potent than their previously reported parasubstituted homologs in inhibiting [3H]WIN 35,428 binding. However, these same metasubstituted analogs were typically less potent than the 4'-substituted analogs in inhibiting [3H]dopamine uptake. Ortho-substituted analogs were generally less potent in both binding and inhibition of uptake at the dopamine transporter than either benztropine or other aryl-substituted homologs. The analogs were also tested for binding at norepinephrine and serotonin transporters as well as muscarinic m1 receptors. None of the compounds in the present study bound with high affinity to either the norepinephrine or serotonin transporters, but all bound to muscarinic m1 receptors with high affinity (K(i) = 0.41-2.52 nM). Interestingly, 3'-chloro-3α- (diphenylmethoxy)tropane (5c) produced effects like cocaine in animals trained to discriminate 10 mg/kg cocaine from saline, unlike its 4'-Cl homolog and all of the previously evaluated benztropine analogs. Further evaluation of compound 5c and the other benztropine analogs will undoubtedly prove useful in the elucidation of the role of the dopamine transporter in the reinforcing effects of cocaine and the ultimate identification of a cocaine-abuse treatment.
