cas 170491-63-1, 2-HYDROXYMETHYL-PYRROLIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

Articles about 170491-63-1Total 28 be found

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Discovery of Arylsulfonamide Nav1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile
The voltage-gated sodium channel Nav1.7 continues to be a high-profile target for the treatment of various pain afflictions due to its strong human genetic validation. While isoform selective molecules have been discovered and advanced into the clinic, to date, this target has yet to bear fruit in the form of marketed therapeutics for the treatment of pain. Lead optimization efforts over the past decade have focused on selectivity over Nav1.5 due to its link to cardiac side effects as well as the translation of preclinical efficacy to man. Inhibition of Nav1.6 was recently reported to yield potential respiratory side effects preclinically, and this finding necessitated a modified target selectivity profile. Herein, we report the continued optimization of a novel series of arylsulfonamide Nav1.7 inhibitors to afford improved selectivity over Nav1.6 while maintaining rodent oral bioavailability through the use of a novel multiparameter optimization (MPO) paradigm. We also report in vitro-in vivo correlations from Nav1.7 electrophysiology protocols to preclinical models of efficacy to assist in projecting clinical doses. These efforts produced inhibitors such as compound 19 with potency against Nav1.7, selectivity over Nav1.5 and Nav1.6, and efficacy in behavioral models of pain in rodents as well as inhibition of rhesus olfactory response indicative of target modulation.
Ballard, Jeanine E.,Brunskill, Andrew P. J.,Burgey, Christopher S.,Clements, Michelle,Daley, Christopher,Greshock, Thomas J.,Houghton, Andrea K.,Jovanovska, Aneta,Kelly, Michael J.,Klein, Rebecca,Kraus, Richard L.,Layton, Mark E.,Li, Yuxing,Peng, Xuanjia,Pero, Joseph E.,Roecker, Anthony J.,Sun, Haiyan,Wang, Deping,Wang, Xiu,Zhao, Fuqiang
supporting information
p. 1038 - 1049
(2021/06/28)

Oxidative Deprotection of p-Methoxybenzyl Ethers via Metal-Free Photoredox Catalysis
An efficient and greener deprotection method for p-methoxybenzyl (PMB) ethers using a metal-free visible light photoredox catalyst and air and ammonium persulfate as the terminal oxidants is presented. Various functional groups and protecting groups were tolerated in the developed method to achieve good to excellent yields in short reaction times. Significantly, the developed method was compatible with PMB ethers derived from primary, secondary, and tertiary alcohols and a gram-scale reaction. Mechanistic studies support a proposed reaction mechanism that involves single electron oxidation of the PMB ether.
Ahn, Deok Kyun,Kang, Young Woo,Woo, Sang Kook
p. 3612 - 3623
(2019/03/11)

Inexpensive multigram-scale synthesis of cyclic enamines and 3-N spirocyclopropyl systems
Cyclic enamines are important synthons for many synthetic and pharmacological targets. Here, we report an inexpensive, catalyst-free, multigram-scale synthesis for cyclic enamines with exocyclic double bonds and four- to seven-membered rings. This strategy is more conducive to scale up, permissive of functionalization around the cyclic system, and less sensitive to the nature of the N-protecting group than previously-described methods for cyclic enamine synthesis. Further, we explore application of these enamines to the synthesis of highly-strained spirocyclic 3N-cyclopropyl scaffolds.
Kumar, Pratik,Zainul, Omar,Laughlin, Scott T.
supporting information
p. 652 - 656
(2018/02/07)

Stereocontrolled Total Synthesis of (?)-Stemaphylline
Homologation of readily available α-boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl?) are employed. By performing a solvent switch from Et2O to CHCl3, efficient 1,2-metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (?)-stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11 % overall yield. The synthesis also features a late-stage lithiation–borylation reaction with a tertiary amine containing carbenoid.
Varela, Ana,Garve, Lennart K. B.,Leonori, Daniele,Aggarwal, Varinder K.
p. 2127 - 2131
(2017/02/15)

As hepatitis c inhibitor spiro compound and its use in medicine
The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
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Paragraph 0814; 1804; 1805

(2017/12/28)

THIAZOLIDINONE COMPOUNDS AND USE THEREOF
A pharmaceutical composition containing a compound of Formula (I) for treating an opioid receptor-associated condition. Also disclosed is a method for treating an opioid receptor-associated condition using such a compound. Further disclosed are two sets of thiazolidinone compounds of formula (I): (i) compounds each having an enantiomeric excess greater than 90% and (ii) compounds each being substituted with deuterium.
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Paragraph 0994-0995

(2017/09/21)

NOVEL INDOLE DERIVATIVES AND THEIR USE IN NEURODEGENERATIVE DISEASES
The present invention relates to indole compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of P2X7, and for the treatment of P2X7-related disorders.
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Paragraph 0823-0824

(2016/11/24)

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone-catalyzed aerobic oxidation reactions via multistep electron transfers with iron(II) phthalocyanine as an electron-transfer mediator
A new biomimetic catalytic oxidation system which employs 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the catalyst, molecular oxygen as the terminal oxidant and iron(ii) phthalocyanine (FeIIPc) as the electron-transfer mediator has been developed. This system can be applied for oxidative deprotection of PMB ethers, alcohol oxidation, aromatization and α,β-unsaturated aldehyde formation. After immobilizing FeIIPc on multi-walled carbon nanotubes, it can be reused without loss of activity.
Hong, Yiming,Fang, Tiantian,Li, Meichao,Shen, Zhenlu,Hu, Xinquan,Mo, Weimin,Hu, Baoxiang,Sun, Nan,Jin, Liqun
p. 51908 - 51913
(2016/06/13)

A rapid and efficient one-pot method for the reduction of N-protected α-amino acids to chiral α-amino aldehydes using CDI/DIBAL-H
N-Protected amino acids can be easily converted into chiral α-amino aldehydes in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H. This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from proteinogenic amino acids in very good isolated yields and complete stereointegrity.
Ivkovic, Jakov,Lembacher-Fadum, Christian,Breinbauer, Rolf
supporting information
p. 10456 - 10460
(2015/11/10)

Synthesis of (+)-Ipalbidine Based on 6-exo-trig Radical Cyclization of a β-Amino Radical
N-Boc (S)-proline was converted into (2S)-2-[(phenylselanyl)methyl]pyrrolidine, which was alkylated on nitrogen with 2-bromo-1-(4-methoxyphenyl)ethan-1-one. Reaction with vinyllithium, 6-exo-trig radical cyclization (Bu3SnH, AIBN, PhMe, 110 °C), dehydration (P2O5, H3PO4), and demethylation (BBr3) gave (+)-ipalbidine with ee >99%.
Chea, JongMyoung,Clive, Derrick L. J.
p. 10294 - 10298
(2015/11/03)

FUSED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X', Y, Y', A, A',Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.
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Paragraph 00314; 00328; 00649; 00650; 00654

(2014/06/23)

BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
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Page/Page column 195; 196

(2014/09/16)

Encapsulation of a catalytic imidazolium salt into avidin: Towards the development of a biohybrid catalyst active in ionic liquids
Herein, we report the development of biohybrid catalysts that are capable of catalyzing the aldol reaction. The use of biotinylated imidazolium salts in combination with racemic or enantiomerically pure catalytic anions allowed us to study the adaptive and cooperative positioning of the anionic catalyst inside the protein. Supramolecular encapsulation of the biotinylated catalyst into avidin resulted in good selectivity for the aldol reaction performed in ionic liquid/water mixtures. Biohybrid catalysts capable of catalyzing the aldol reaction are prepared from avidin and biotinylated imidazolium salts with either racemic or enantiomerically pure catalytic anions. Supramolecular encapsulation (see figure) of the biotinylated catalyst in avidin resulted in good selectivities for the aldol reaction when performed in ionic liquid/water mixtures and the adaptive and cooperative positioning of the anionic catalyst inside the avidin protein is discussed. Copyright
Gauchot, Vincent,Branca, Mathieu,Schmitzer, Andreea
p. 1530 - 1538
(2014/03/21)

Ruthenium-catalyzed hydroformylation/reduction of olefins to alcohols: Extending the scope to internal alkenes
In the presence of 2-phosphino-substituted imidazole ligands and Ru 3(CO)12 or Ru(methylallyl)2(COD) direct hydroformylation and hydrogenation of alkenes to alcohols takes place. In addition to terminal alkenes, also more challenging internal olefins are converted preferentially to industrially important linear alcohols in high yield (up to 88%) and regioselectivity (n:iso up to 99:1).
Wu, Lipeng,Fleischer, Ivana,Jackstell, Ralf,Profir, Irina,Franke, Robert,Beller, Matthias
supporting information
p. 14306 - 14312
(2013/10/21)

Gold-catalyzed oxycyclization of allenic carbamates: Expeditious synthesis of 1,3-oxazin-2-ones
A combined experimental and computational study on regioselective gold-catalyzed synthetic routes to 1,3-oxazinan-2-ones (kinetically controlled products) and 1,3-oxazin-2-one derivatives (thermodynamically favored) from easily accessible allenic carbamates has been carried out.
Alcaide, Benito,Almendros, Pedro,Quiros, M. Teresa,Fernandez, Israel
p. 818 - 826
(2013/06/05)

SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS
Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, infectious disease, inflammatory disorder, graft rejection, and graft-verses-host disease.
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(2011/04/13)

Enantioselective hydroformylation of N-vinyl carboxamides, allyl carbamates, and allyl ethers using chiral diazaphospholane ligands
Rhodium complexes of diazaphospholane ligands catalyze the asymmetric hydroformylation of N-vinyl carboxamides, allyl ethers, and allyl carbamates; products include 1,2- and 1,3-aminoaldehydes and 1,3-alkoxyaldehydes. Using glass pressure bottles, short reaction times (generally less than 6 h), and low catalyst loading (commonly 0.5 mol %), 20 substrates are successfully converted to chiral aldehydes with useful regioselectivity and high enantioselectivity (up to 99% ee). Chiral Roche aldehyde is obtained with 97% ee from the hydroformylation of allyl silyl ethers. Commonly difficult substrates such as 1,1- and 1,2-disubstituted alkenes undergo effective hydroformylation with 89-97% ee and complete conversion for six examples. Palladium-catalyzed aerobic oxidative amination of allyl benzyl ether followed by enantioselective hydroformylation yields the β3-aminoaldehyde with 74% ee.
McDonald, Richard I.,Wong, Gene W.,Neupane, Ram P.,Stahl, Shannon S.,Landis, Clark R.
supporting information; body text
p. 14027 - 14029
(2011/01/04)

Synthesis of 6- and 7-membered cyclic enaminones: Scope and mechanism
Six- and seven-membered cyclic enaminones can be prepared using common, environmentally benign reagents. Amino acids are used as synthetic precursors allowing diversification and the incorporation of chirality. The key reaction in this multistep process involves deprotection of Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A β-amino elimination side reaction was identified in a few labile substrates that led to either loss of stereochemical purity or degradation. This process can be mitigated in specific cases using mild deprotection conditions. NMR and deuterium-labeling experiments provided valuable insight into the workings and limitations of this reaction. Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking, thus changing the mode of addition to a 6-endo-trig cyclization. This method can be used to construct an array of monocyclic and bicyclic scaffolds, many of which are found in well-known natural products (e.g., indolizidine, quinolizidine, and Stemona alkaloids).
Niphakis, Micah J.,Turunen, Brandon J.,Georg, Gunda I.
supporting information; scheme or table
p. 6793 - 6805
(2010/12/20)

HETEROCYCLIC COMPOUND
The present invention relates to wherein each symbol is as defined in the specification. The compound of the present invention has a superior RBP4-lowering action, and is useful as a medicament for the prophylaxis or treatment of disease and condition mediated by increased RBP4.
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Page/Page column 72-73

(2010/07/08)

ALKYNYL ALCOHOLS AS KINASE INHIBITORS
Selected compounds are effective for prophylaxis and treatment of inflammation and inflammatory disorders, such as NIK-mediated disorders. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, inflammation and the like.
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Page/Page column 96-97

(2010/01/30)

Investigations concerning the organolanthanide and group 3 metallocene-catalyzed cyclization-functionalization of nitrogen-containing dienes
Organolanthanide catalyzed cyclization-silylation of nitrogen-containing polyunsaturated systems allows access to core structures commonly found in naturally occurring alkaloids. Nitrogen-containing dienes with various substitution patterns were investigated. The method was most successful for substrates with terminal alkenes. Cyclization upon pendant 1,1-disubstituted olefins was not realized under various conditions. Interestingly, sterically hindered sulfonamides, which were previously believed to render the catalyst inactive, were actually compatible with the catalyst, thus affording the cyclized products after prolonged reaction times. Variations using fused ring systems were also investigated.
Molander, Gary A.,Romero, Jan Antoinette C.
p. 2631 - 2643
(2007/10/03)

INHIBITORS OF HUMAN TUMOR-EXPRESSED CCXCKR2
Pharmaceutical compositions containing organic compounds or salts thereof that serve as modulators for the SDF-1 or I-TAC chemokines are disclosed. The compounds and compositions are useful in the treatment of cancer, especially in the inhibition of cancer proliferation, growth, and metastasis. Methods of interfering with SDF-1 and/or I-TAC binding to the CCXCKR2 receptor and treating cancer using the compounds and pharmaceutical compositions of the present invention are also disclosed.
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Page 38;39

(2008/06/13)

Cathepsin cysteine protease inhibitors
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of Cathepsins K and L. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
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Page 12-13

(2010/02/06)

2-(arylalkenyl)azacycloalkane derivatives as ligands for sigma receptors
New 2-(arylalkenyl)azacycloalkane derivatives which are ligands for sigma receptors, of the formula (I) STR1 in which: Ar is aryl or heteroaryl, optionally mono- to trisubstituted, m has the value 1 or 2, n has the value 1 to 3, R is phenyl, or cycloalkyl containing 3 to 7 carbon atoms, their isomers and their addition salts. Medicinal drugs which are antipsychotic agents and are useful in gastroenterology.
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(2008/06/13)

2-Oxopropanal, Hydroxy-2-propanone, and 1-Pyrroline - Important Intermediates in the Generation of the Roast-Smelling Food Flavor Compounds 2-Acetyl-1-pyrroline and 2-Acetyltetrahydropyridine
On the basis of labeling experiments with [13C]6-glucose/unlabeled proline as well as quantitative data obtained in model studies using stable isotope dilution assays, 1-pyrroline and hydroxy-2-propanone were identified as effective intermediates in generating the roast-smelling food odorant 2-acetyltetrahydropyridine (ATHP; two tautomers). Synthesis of the key precursor compound, 2-(1-hydroxy-2-oxo-propyl)pyrrolidine, and studies on its degradation confirmed the important role of this intermediate in ATHP formation. Boiling of the intermediate for 30 min in aqueous solution generated >30% of ATHP on a molar basis. 1-Pyrroline and 2-oxopropanal were confirmed as important intermediates in the generation of the further roast food odorant, 2-acetyl-1-pyrroline (AP). On the basis of results of labeling experiments with [13C]6-glucose/unlabeled proline, two different mechanisms could be proposed. One leads to AP via 2-(1,2-dioxopropyl)pyrrolidine as the precursor with elimination of the aldehyde group in 2-oxopropanal as carbon dioxide. The other one suggests elimination of carbon-2 of the pyrroline ring. The latter mechanism was further established by a result showing that from the reaction of 2-methyl- 1-pyrroline with 2-oxopropanal AP was also generated.
Hofmann, Thomas,Schieberle, Peter
p. 2270 - 2277
(2007/10/03)

Heterocyclic acetylenic amines having central nervous system activity
Heterocyclic acetylenic amine compounds having the following structural formula STR1 having cholinergic agonist or antagonist activity useful in the treatment of mental disorders, extrapyramidal motor disorders, disorders of the parasympathetic nervous system and glaucoma or as analgesics for the treatment of pain. Typical central nervous system disorders for which the subject compounds can be used include cognitive disorders of all ages, including senile dementia, Alzheimer's disease and other related disorders. The compounds are particularly developed to improve mental performance when a mental deficiency is diagnosed.
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(2008/06/13)

1-substituted-2-(3-amino-1-propynyl)pyrrolidine derivatives
Compounds of the formula: STR1 pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of central cholinergic disfunction in a mammal are disclosed.
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(2008/06/13)

Pyrrolidine derivatives
Pyrrolidine derivatives which have the formula SPC1 Wherein R and R1 each is hydrogen, --(CH2)6 COOH, --(CH2)6 COO-- lower alkyl, or --(CH2)6 COO benzyl and R2 is hydrogen, --CO--O--(CH2)5 CH3, --CO--NH--(CH2)5 CH3 --(CH2)7 CH3 or --CH=CH--CH(OH)--(CH2)4 --CH3, at least one of R and R1 is hydrogen and R1 and R2 are not both hydrogen, are new compounds which are useful as inhibitors of prostaglandin dehydrogenase and as potentiators of prostaglandin activity.
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(2008/06/13)