- PYRROLIDINE-PYRAZOLES AS PYRUVATE KINASE ACTIVATORS
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The subject matter described herein is directed to pyruvate kinase activating compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for the treatment of diseases associated with PKR and/or PKM2, such as pyruvate kinase deficiency, sickle cell disease, and beta-thalassemia.
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Paragraph 186-189
(2021/10/11)
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- PYRROLOPYRROLE COMPOSITIONS AS PYRUVATE KINASE (PKR) ACTIVATORS
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The disclosure relates to modulating pyruvate kinase and provides novel chemical compounds of formula (I) useful as activators of PKR, as well as various uses of these compounds. PKR activating compounds are useful in the treatment of diseases and disorders associated with PKR and/or PKM2, such as pyruvate kinase deficiency (PKD), sickle cell disease (SCD), and thalassemia.
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Paragraph 00148-00149
(2018/10/19)
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- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.
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Paragraph 00742
(2017/02/09)
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- Enantioseparation of typical pesticides using cellulose carbamate stationary phases by capillary liquid chromatography
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Cellulose-tris(3,5-dimethylphenylcarbamate) was initially synthesized as the chiral selector, then stable coated and bonded chiral stationary phases were prepared, respectively, using aminopropyl-functionalized silica gel as the support media. The prepared stationary phases were used for micro-column chiral separation by self-installed capillary high performance liquid chromatography system. Eighteen kind of chiral compounds including some typical pesticides were tested on both prepared chiral stationary phases and different chromatographic parameters such as resolution and retention time were comparatively investigated.
- Bai, Lian-Yang,Zhang, Yu-Ping,Deng, Pu-Hong,Zhang, Yi-Jun,Chen, Jun
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experimental part
p. 4917 - 4922
(2012/10/08)
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- High-performance liquid chromatography separation of enantiomers of mandelic acid and its analogs on a chiral stationary phase
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The enantiomers of mandelic acid and its analogs have been chromatographically separated on a chiral stationary phase (CSP) derived from 4-(3,5-dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these compounds is discussed with respect to the method development for determining enantiomeric purity and possibility of obtaining enantiomerically pure materials by high-pressure liquid chromatography. The relationship of analyte structure to the extent of enantiomeric separation has been examined and separation factors (a) are presented for various groups of structurally related compounds. Chiral recognition models have been suggested to account for the observed separations. These models provide mechanistic insights into the chiral recognition process.
- Aneja, Ritu,Luthra, Pratibha Mehta,Ahuja, Satinder
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experimental part
p. 479 - 485
(2010/08/20)
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- Enantiopure tert-butyl(phenyl)phosphine oxide. Chirality-recognition ability and mechanism
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When enantiopure tert-butyl(phenyl)phosphine oxide 1 was used as a resolving agent, it showed an acceptable to good chirality-recognition ability for several kinds of racemic carboxylic acids 2. A study on a chirality-recognition mechanism based on X-ray crystallographic analyses of the diastereomeric complexes of 2 with 1 revealed that the complex crystals consisted of helical columns and that 1 was not responsible for the formation of the helical column and occupied a void between the columns; although 1 interacted with 2 via a hydrogen bond to primarily form a pair with 2, the complex crystals were mainly stabilized by the accumulation of weak interactions, such as CH/π, π/π and CH...O interactions, between 1/1, 1/2 and 2/2.
- Ribeiro, Nigel,Saigo, Kazuhiko
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experimental part
p. 2704 - 2708
(2010/04/29)
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- MUSCARINIC RECEPTOR ANTAGONISTS
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This present invention generally relates to muscarinic receptor antagonists of Formula (I), which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the prepration of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors.
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Page/Page column 31
(2008/06/13)
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- Enzymatic kinetic resolution of tropic acid
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A new strategy has been developed for the CAL-B catalysed kinetic resolution of tropic acid by which both enantiomers of tropic acid can be obtained in good enantiomeric excess. (R)-Tropic acid was synthesised with 90% ee and (S)-tropic acid butyl ester in 99% ee by the hydrolysis of tropic acid butyl ester. The other enantiomers were available through the enzymatically catalysed reaction of tropic acid lactone with butanol to give (S)-tropic acid lactone and (R)-tropic acid ester in >98% ee.
- Klomp, Dirk,Peters, Joop A.,Hanefeld, Ulf
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p. 3892 - 3896
(2007/10/03)
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- Markedly enhancing enzymatic enantioselectivity in organic solvents by forming substrate salts
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A new approach is proposed to enhance enzymatic enantioselectivity in organic solvents. It is based on the presumption that the less reactive substrate enantiomer experiences greater steric hindrances in the enzyme- bound transition state than the more re
- Ke, Tao,Klibanov, Alexander M.
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p. 3334 - 3340
(2007/10/03)
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- Differential analgesic activity of the enantiomers of atropine derivatives does not correlate with their muscarinic subtype selectivity
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The enantiomers of several tropic and p-substituted tropic acid esters related to atropine obtained by esterification under non-racemizing conditions after resolution of the corresponding racemic acids [(+)- and (-)-18, (+)- and (-)-19] are reported. They were tested in vitro on muscarinic subtype receptors and in vivo for their analgesic activity on mice. As in the case of the lead compound, R-(+)-hyoscyamine, these substances show enantioselectivity in analgesic tests, the eutomers being the R-(+) or R-(+)-p-substituted tropic acid derivatives. However, this property, which is a consequence of increased central release of ACh, seems unrelated to muscarinic subtype selectivity insofar as the compounds are unable to discriminate muscarinic subtype receptors. A possible explanation of these results which does not involve subtype selectivity is proposed, based on the recently developed concept of inverse agonism.
- Dei,Bartolini,Bellucci,Ghelardini,Gualtieri,Manetti,Romanelli,Scapecchi,Teodori
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p. 595 - 605
(2007/10/03)
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- Enzyme catalyzed monohydrolysis of 2-aryl-1 3-propanediol diacetates. A study of structural effects of the aryl moiety on the enantioselectivity
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PPL catalyzed monohydrolysis of 2-aryl substituted 13-propanediol diacetates afforded the corresponding monoacetates in acceptable to fair chemical and optical yields. Electronic effects in the aromatic ring were examined. Elaboration of some 2-arylpropanediol monoacetates to optically active 2-arylpropanols and propanoic acids was performed.
- Guanti, Giuseppe,Narisano, Enrica,Podgorski, Tadeusz,Thea, Sergio,Williams, Andrew
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p. 7081 - 7092
(2007/10/02)
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- Molecular Modification of Anticholinergics as Probes for Muscarinic Receptors. Amino Esters of α-Substituted Phenylacetic Acid and Related Analogues
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Two series of compounds having the general structure of C6H5CRR'COOCH2CH2NEt2 were synthesized and examined for their antispasmodic activities.These compounds were selected as structural probes for exploring the nature of muscarinic cholinergic receptor binding sites that interact with atropine-like anticholinergics.These studies indicate a rather strict size limitation for the hydrophobic region of the receptor and suggest intramolecular hydrogen bonding as a possible means to explain the observed stereoselectivity.
- Lu, Mattias C.,Wung, Walley E.,Shih, Lisa B.,Callejas, Soledad,Gearien, James E.,Thompson, Emmanuel B.
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p. 273 - 278
(2007/10/02)
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