- Me3SI-promoted chemoselective deacetylation: a general and mild protocol
-
A Me3SI-mediated simple and efficient protocol for the chemoselective deprotection of acetyl groups has been developedviaemploying KMnO4as an additive. This chemoselective deacetylation is amenable to a wide range of substrates, tolerating diverse and sensitive functional groups in carbohydrates, amino acids, natural products, heterocycles, and general scaffolds. The protocol is attractive because it uses an environmentally benign reagent system to perform quantitative and clean transformations under ambient conditions.
- Gurawa, Aakanksha,Kashyap, Sudhir,Kumar, Manoj
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p. 19310 - 19315
(2021/06/03)
-
- Production of oxygen-containing alicyclic compounds (by machine translation)
-
[Problem] to provide, in a one-step reaction synthesizes an alicyclic compound containing oxygen, high yield production of oxygen-containing compound is a cycloaliphatic. [Solution] one or more hydroxy or carbonyl group 2, or a hydroxyl group having the carbon number of 5 or more aliphatic carbonyl group 2 in accordance with one or more oxygen-containing compound, a basic catalyst is brought into contact with an oxygen-containing alicyclic compound by cyclodehydration reaction, oxygen-containing alicyclic compound. [Drawing] no (by machine translation)
- -
-
Paragraph 0035; 0036; 0038
(2020/04/24)
-
- Vicinal, Double C-H Functionalization of Alcohols via an Imidate Radical-Polar Crossover Cascade
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A double functionalization of vicinal sp3 C-H bonds has been developed, wherein a β amine and γiodide are incorporated onto an aliphatic alcohol in a single operation. This approach is enabled by an imidate radical chaperone, which selectively affords a transient β alkene that is amino-iodinated in situ. Overall, the radical-polar-crossover cascade entails the following key steps: (i) β C-H iodination via 1,5-hydrogen atom transfer (HAT), (ii) desaturation via I2 complexation, and (iii) vicinal amino-iodination of an in situ generated allyl imidate. The synthetic utility of this double C-H functionalization is illustrated by conversion of aliphatic alcohols to a diverse collection of α,β,γsubstituted products bearing heteroatoms on three adjacent carbons. The radical-polar crossover mechanism is supported by various experimental probes, including isotopic labeling, intermediate validation, and kinetic studies.
- Nagib, David A.,Prusinowski, Allen F.,Twumasi, Raymond K.,Wappes, Ethan A.
-
supporting information
(2020/03/16)
-
- COMBINATION TREATMENTS COMPRISING IMIDAZOPYRAZINONES FOR THE TREATMENT OF PSYCHIATRIC AND/OR COGNITIVE DISORDERS
-
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of psychiatric and/or cognitive disorders such as for example Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, narcolepsy, schizophrenia, cognitive impairment or cognitive impairment associated with schizophrenia (CIAS). Separate aspects of the invention are directed to the combined use of said compounds for the treatment of psychiatric and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of psychiatric and/or cognitive disorders.
- -
-
Page/Page column 103-104
(2018/05/24)
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- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF IMIDAZOPYRAZINONES
-
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of neurodegenerative disorders such as for example Alzheimer's Disease, Parkinson's Disease or Huntington's Disease. Separate aspects of the invention are directed to the combined use of said compounds for the treatment of neurodegenerative and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of neurodegenerative disorders.
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Page/Page column 106-107
(2018/05/24)
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- BIARYL PYRAZOLES AS NRF2 REGULATORS
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The present invention relates to biaryl pyrazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators.
- -
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Page/Page column 539
(2017/08/01)
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- Efficient carbon-supported heterogeneous molybdenum-dioxo catalyst for chemoselective reductive carbonyl coupling
-
Reductive coupling of various carbonyl compounds to the corresponding symmetric ethers with dimethylphenylsilane is reported using a carbon-supported dioxo-molybdenum catalyst. The catalyst is air- and moisture-stable and can be easily separated from the reaction mixture for recycling. In addition, the catalyst is chemoselective, thus enabling the synthesis of functionalized ethers without requiring sacrificial ligands or protecting groups.
- Liu, Shengsi,Li, Jiaqi,Jurca, Titel,Stair, Peter C.,Lohr, Tracy L.,Marks, Tobin J.
-
p. 2165 - 2169
(2017/07/22)
-
- Chemoselective continuous-flow hydrogenation of aldehydes catalyzed by platinum nanoparticles dispersed in an amphiphilic resin
-
A chemoselective continuous-flow hydrogenation of aldehydes catalyzed by a dispersion of platinum nanoparticles in an amphiphilic polymer (ARP-Pt) has been developed. Aromatic and aliphatic aldehydes bearing various reducible functional groups, such as keto, ester, or amide groups, readily underwent flow hydrogenation in aqueous solutions within 22 s in a continuous-flow system containing ARP-Pt to give the corresponding primary benzylic or aliphatic alcohols in ≤99% yield with excellent chemoselectivity. Moreover, the long-term continuous-flow hydrogenation of benzaldehyde for 8 days was realized, and the total turnover number of the catalyst reached 997. The flow hydrogenation system provides an efficient and practical method for the chemoselective hydrogenation of aldehydes bearing reducible functional groups.
- Osako, Takao,Torii, Kaoru,Hirata, Shuichi,Uozumi, Yasuhiro
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p. 7371 - 7377
(2017/11/09)
-
- AMINE DERIVATIVE COMPOUNDS FOR TREATING OPHTHALMIC DISEASES AND DISORDERS
-
Provided are amine derivative compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.
- -
-
Paragraph 1895-1896
(2016/08/07)
-
- IMIDAZOPYRAZINONES AS PDE1 INHIBITORS
-
The present invention provides imidazopyrazinones as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Page/Page column 107
(2016/11/17)
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- TRIAZOLOPYRAZINONES AS PDE1 INHIBITORS
-
The present invention provides triazolopyrazinones as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Page/Page column 41; 42
(2016/05/02)
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- Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors
-
ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.
- Bamborough, Paul,Chung, Chun-Wa,Furze, Rebecca C.,Grandi, Paola,Michon, Anne-Marie,Sheppard, Robert J.,Barnett, Heather,Diallo, Hawa,Dixon, David P.,Douault, Clement,Jones, Emma J.,Karamshi, Bhumika,Mitchell, Darren J.,Prinjha, Rab K.,Rau, Christina,Watson, Robert J.,Werner, Thilo,Demont, Emmanuel H.
-
p. 6151 - 6178
(2015/08/24)
-
- An Organocatalytic Access to Spiro[45]decanes and Spiro[4.6]undecanes Containing Aminolactones and 3-Aminopyrrolidines
-
The organocatalyzed Mannich coupling of cyclic carboxaldehydes allowed the concise and simple preparation of spirocyclic aminolactones. Their conversion into pharmaceutically relevant spiro[4.5]cyclic and spiro[4.6]cyclic 3-aminopyrrolidines is also described.
- Cormier, Morgan,Chardon, Aurélien,Blanchet, Jér?me,Rouden, Jacques,Maddaluno, Jacques,De Paolis, Micha?l
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p. 2549 - 2553
(2015/09/01)
-
- LiAlH4-induced reductive dephosphonylation of αα-dialkyl triethyl β-phosphonyl esters: Mechanistic study and synthetic application
-
Treatment of αα-dialkyl triethyl β-phosphonyl esters with LiAlHin CHlTHF caused the one-pot dephosphonylation and reduction to yield the corresponding primary alcohols bearing a controllable β secondary carbon center. Mechanistic study has revealed that the LiAlHinduced dephosphonylation should occur first with the assistance of the carboxylate group, and the hydrogen source of the resultant new C-H bond is LiAlH. Georg Thieme Verlag Stuttgart . New York.
- Zhu, Jia-Liang,Bau, Jr-Sheng,Shih, You-Cheng
-
experimental part
p. 863 - 866
(2012/05/20)
-
- Cell-permeable and plasma-stable peptidomimetic inhibitors of the postsynaptic density-95/N-methyl-D-aspartate receptor interaction
-
The protein-protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETASV (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.
- Bach, Anders,Eildal, Jonas N. N.,Stuhr-Hansen, Nicolai,Deeskamp, Rasmus,Gottschalk, Marie,Pedersen, S?ren W.,Kristensen, Anders S.,Str?mgaard, Kristian
-
supporting information; experimental part
p. 1333 - 1346
(2011/05/07)
-
- HERBICIDALLY ACTIVE 2-(SUBSTITUTED-PHENYL)-CYCLOPENTANE-1,3-DIONE DERIVATIVES
-
Compounds of formula (I) are suitable for use as herbicides: wherein R is methyl, ethyl, vinyl, ethynyl or cyclopropyl, R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C7cycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, vinyl, propenyl, ethynyl, propynyl, halogen, or optionally substituted phenyl, R2 is methyl, ethyl, vinyl, ethynyl or methoxy, R3 and R4 are hydrogen or together form a double bond, A is C3-C7cycloalkyl which is unsubstituted or substituted once or twice by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6alkylcarbonyloxy, C2-C6alkenyl, =0 or =N-R10, or A is cyclohexyl substituted once, at the 4-position, by one (C3-C6cycloalkyl)methoxy, C3-C6cycloalkyloxy, C2-C5alkenyl-CH2-oxy, or benzyloxy substituent, or A is decahydro-1-naphthyl or decahydro-2-naphthyl, or A is optionally substituted phenyl, and G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or a latentiating group.
- -
-
Page/Page column 70
(2011/02/24)
-
- Electron transfer reduction of unactivated esters using SmI 2-H2O
-
The reduction of unactivated esters using samarium diiodide is reported for the first time. The optimised protocol allows for the reduction of primary, secondary and tertiary alkyl esters in excellent yields and is competitive with reductions mediated by metal hydrides and alkali metals.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
-
supporting information; experimental part
p. 10254 - 10256
(2011/10/31)
-
- Hydroformylation of alkenes using heterogeneous catalyst prepared by intercalation of HRh(CO)(TPPTS)3 complex in hydrotalcite
-
Intercalation of HRh(CO)(TPPTS)3 complex into the interlayer space of hydrotalcite was carried out to prepare an eco-friendly heterogeneous hydroformylation catalyst. Intercalated catalyst was characterized by 31P NMR, P-XRD, FT-IR, SEM and surface area measurements. Catalytic activity of intercalated catalyst [HT(3.5)-INT] was evaluated for hydroformylation of linear alkenes of varied carbon number from C5 to C13 as well as cyclic alkenes. Selectivity of the aldehydes was observed to decrease with increase in the carbon chain length of linear alkenes. Effect of reaction parameters on catalytic activity of intercalated catalyst was studied by varying the catalyst amount, 1-hexene concentration, reaction temperature, partial pressure of carbon monoxide and hydrogen for hydroformylation of 1-hexene. The catalyst was re-cycled up to five times without significant loss in the alkene conversion and selectivity of aldehydes.
- Sharma, Sumeet K.,Parikh, Parimal A.,Jasra, Raksh V.
-
experimental part
p. 153 - 162
(2010/05/01)
-
- ALKYNYL PHENYL DERIVATIVE COMPOUNDS FOR TREATING OPHTHALMIC DISEASES AND DISORDERS
-
Provided are alkynyl phenyl derivative compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.
- -
-
Page/Page column 181
(2009/03/07)
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- ALKOXY COMPOUNDS FOR DISEASE TREATMENT
-
The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are alkoxyl derivative compounds and pharmaceutical compositions comprising these compounds. The subject compositions are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.
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Page/Page column 155
(2009/05/29)
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- The use of Nafion-H as an efficient catalyst for the deprotection of trimethylsilyl ethers to their corresponding alcohols under mild and heterogeneous conditions
-
Trimethylsilyl ethers were converted to their corresponding alcohols in the presence Nafion-H and wet SiO2 with good-to-excellent yields under mild and heterogeneous conditions.
- Zolfigol, Mohammad Ali,Mohammadpoor-Baltork, Iraj,Habibi, Davood,Mirjalili, Bibi Fatemeh,Bamoniri, Abdolhamid
-
p. 2189 - 2193
(2007/10/03)
-
- (2-hydroxy)ethyl-thioureas useful as modulators of alpha2B adrenergic receptors
-
Compounds of formula (i) and of formula (ii) wherein the symbols have the meaning disclosed in the specification, specifically or selectively modulate α2B and/or α2C adrenergic receptors in preference over α2A adrenergic receptors, and as such are useful for alleviating chronic pain and allodynia and have no or only minimal cardivascular and/or sedatory activity.
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-
-
- Silica Gel-supported Zinc Borohydride. Part 3. Regioselective Reductive Cleavage of Methylenecycloalkane Oxides to the Less-substituted Alcohols
-
Highly selective reductive cleavage of methylenecycloalkane oxides to less-substituted alcohols has been achieved by a simple procedure using silica gel supported zinc borohydride in tetrahydrofuran.
- Ranu, Brindaban C.,Das, Asish R.
-
p. 1881 - 1882
(2007/10/02)
-
- Catalytic procedure for the synthesis of cycloalkanemethanols from cycloalkenes and aqueous methyl formate
-
Cycloalkanemethanols are synthesized via hydrocarbonylation (hydroformylation) of the corresponding cycloalkenes in the presence of aqueous methyl formate. Methyl formate is the source of carbon monoxide and hydrogen is generated by the water gas shift reaction. The selectivity is affected by the concomitant hydrogenation process.
- Jenner
-
p. 505 - 508
(2007/10/02)
-
- Substituent and Ring Size Dependence of the 4J(Me-C-C-H) Coupling Constant
-
The magnitude of the 4J proton-proton coupling constant across the fragment CH3-C-C-H (a probe of the bond order between the central sp2-sp2 hybridized carbon atoms) has been found to be essentially independent of substitution on a toluene fragment and the size of the ring containing the ortho-allylic fragment.The coupling constant is sensitive to direct substitution on the ortho-allilyc fragment, especially where the substituent is placed α to methyl group.KEY WORDS - 4J proton-proton coupling constant ortho-benzylic coupling constant ring size dependence substituent dependence
- Collins, M. J.,Hatton, P. M.,Sternbell, S.,Tansey, C. W.
-
p. 824 - 828
(2007/10/02)
-
- Synthetic Methods and Reactions. 112. Synthetic Transformations with Trichloromethylsilane/Sodium Iodide Reagent
-
A new, convenient, and inexpensive alternative to the in situ equivalent of iodotrimethylsilane was developed.A mixture of trichloromethylsilane/sodium iodide in dry acetonitrile is found to be a more selective reagent than chlorotrimethylsilane/sodium iodide for the cleavage of ethers, esters, and lactones.Ethers are cleaved regioselectively by this reagent.Cleavage of esters and lactones also occured more readily with the present system.Conversion of alcohols, particularly tertiary and benzylic alcohols, to corresponding iodides is achieved in very short times at ambient temperatures.Deoxygenation of sulfoxides to sulfides is found to be instantaneous.Reductive dehalogenation of alicyclic α-halo ketones to the corresponding ketones has also been studied.The reagent is also used for the deprotection of acetals to carbonyl compounds.
- Olah, George A.,Husain, Altaf,Singh, Brij P.,Mehrotra, Ashok K.
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p. 3667 - 3672
(2007/10/02)
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- Importance of the Aromatic Ring in Andrenergic Amines. 5. Nonaromatic Analogues of Phenylethanolamine as Inhibitors of Phenylethanolamine N-Methyltransferase: Role of Hydrophobic and Steric Interactions
-
The synthesis of five classes of nonaromatic analogues of β-phenylethanolamine and an evaluation of their inhibitory potency (IC50) for phenylethanolamine N-methyltransferase (PNMT) are described.The key intermediates for the synthesis of the ethanolamines were the appropriate aldehydes or ketones.The aldehydes 11a (cyclobutyl) and 13a (cycloheptyl) of type A were prepared from the correspondingacids by reduction of the acid to the alcohol with lithium aluminum hydride and oxidation of the alcohol to the aldehyde with pyridinium chlorochromate (PCC).The aldehydes 15a (cycloundecyl) and 41a (adamantyl) of type A were prepared by oxidation of the corresponding alcohols with PCC.The first reported synthesis of cyclononanecarboxaldehyde (type A, 14a) is described.This aldehyde was prepared via a multistep route beginning with a Favorskii rearrangement of 2-bromocyclodecanone to cyclononanecarboxylic acid.The acid was reduced with lithium aluminum hydride to the corresponding alcohol, which was subsequently oxidized to the aldehyde with PCC.The aldehydes or ketones were converted (with trimethylsilyl cyanide) into their cyanohydrin ethers, which were subsequently reduced to the desired ethanolamine with lithium aluminum hydride.The ethanolamines were tested as inhibitors (LCEC assay) of PNMT.The most potent inhibitors were the type A compounds 8 (cyclooctyl), 13c (cycloheptyl), 14c (cyclononyl), and 15c (cycloundecyl) and the type D compounds 26c (cyclononyl) and 27c (cycloundecyl) with IC50 values from 6 to 17 μM.It isconcluded that the binding site of PNMT accepts hydrophobic groups of an optimal length (ca. 6.4 Angstroem) and width (ca. 2.5 Angstroem) and has a significant height restriction for the hydrophobic group.The ethanolamine side chain prefers to lie away from and in the longitudinal axis of the hydrophobic group.An ethanolamine side chain attached to a cycloalkyl ring of n carbon atoms (types A and D) is almost always considerably more potent at inhibiting PNMT than the open-chain compounds of n total carbon atoms (types B, C, and E).
- Vincek, William C.,Aldrich, Constance S.,Borchardt, Ronald T.,Grunewald, Gary L.
-
-