- Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols
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Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectivel
- Macmillan, David W. C.,Oswood, Christian J.
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supporting information
p. 93 - 98
(2022/01/03)
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- Compound JK-03M having higher protein kinase G inhibitory activity or pharmaceutically acceptable salt thereof and preparation method thereof
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The invention discloses a compound which has higher protein kinase G inhibitory activity and is shown in a formula I or pharmaceutically acceptable salt thereof and a preparation method thereof. The compound JK-03M having the higher protein kinase G inhibitory activity comprises a pharmaceutical composition of a new compound and application of the new compound in treatment of pain, in particular to chronic pain. The formula (1) is shown in the description.
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Paragraph 0093; 0118; 0135-0137
(2018/11/03)
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- Compounds with higher PKG (protein kinase G) inhibitory activity and preparation method of compounds
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The invention discloses compounds which have higher PKG (protein kinase G) inhibitory activity and are represented as a formula I, pharmaceutically acceptable salts, pharmaceutical composition containing the novel compounds, as well as an application of the novel compounds in treatment of pain, especially chronic pain. The invention further discloses a preparation method of the compounds and new intermediates. R1 and R2 are the same or different and are selected from a group comprising halogen (such as F or Cl), C1-C6 alkoxy, C1-C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R3 is a terminal group and is selected from a group comprising H, halogen, alkyl, naphthenic base, alkenyl, alkynyl, aryl and heteroaryl; n is the number of repetitive units and is an integer in a range from 1 to 15.
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Paragraph 0160; 0161; 0162; 0163; 0164; 0165
(2016/10/08)
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- COMPOUND HAVING HIGHER INHIBITION OF PROTEIN KINASE G ACTIVITY AND PREPARATION METHOD THEREFOR
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Disclosed are a compound of Formula I having higher inhibition of protein kinase G (PKG) activity and pharmaceutically acceptable salts thereof. In Formula I, R1 and R2 are the same or different, each being independently chosen from the halogens, the C1-C6 alkoxyl group, the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group; R3 is chosen from H, the halogens, the substituted or unsubstituted C1-C6 alkyl group, C3-C6 cycloalkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group, aryl group, and heteroaryl group; and n is an integer between 0 and 15. Also disclosed is a pharmaceutical composition comprising said compound, the use of the compound in treating pains, in particular chronic pain, a preparation method for the compound, and a new intermediate.
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Paragraph 0075; 0076
(2016/12/12)
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- PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.
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Page/Page column 87; 88
(2015/09/28)
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- HETEROCYCLE DERIVATIVE HAVING PGD2 RECEPTOR ANTAGONIST ACTIVITY
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The present invention is related to a compound represented by formula (I), wherein X1, X2, X3, X4, X5, R5, R6, R7, R8, n, p, q, ring A and ring B are as described in the specification, or a
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Paragraph 0431-0432
(2014/07/22)
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- A broadly applicable and practical oligomeric (salen)Co catalyst for enantioselective epoxide ring-opening reactions
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The (salen)Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen)Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen)Co monomer 1 for each reaction class.
- White, David E.,Tadross, Pamela M.,Lu, Zhe,Jacobsen, Eric N.
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p. 4165 - 4180
(2014/06/09)
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- Five-membered iminocyclitol α-glucosidase inhibitors: Synthetic, biological screening and in silico studies
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The design and synthesis of a small library of pyrrolidine iminocyclitol inhibitors with a structural similarity to 1,4-dideoxy-1,4-imino-d-arabitol (DAB-1) is reported. This library was specifically designed to gain a better insight into the mechanism of inhibition of glycosidases by polyhydroxylated pyrrolidines or iminocyclitols. Pyrrolidine-3,4-diol 15a and pyrrolidine-3,4-diol diacetate 15b had emerged as the most potent α-glucosidase inhibitors in the series. Docking studies performed with an homology model of α-glucosidase disclosed binding poses for compounds 15a, 15b, 16a, and 16a′ occupying the same region as the NH group of the terminal ring of acarbose and suggest a closer and stronger binding of compound 15a and 15b with the enzyme active site residues. Our studies indicate that 2 or 5-hydroxyl substituents appear to be vital for high inhibitory activity.
- Guerreiro, Luis R.,Carreiro, Elisabete P.,Fernandes, Luis,Cardote, Teresa A.F.,Moreira, Rui,Caldeira, Ana T.,Guedes, Rita C.,Burke
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p. 1911 - 1917
(2013/04/23)
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- TRIAZOLOPYRIDINE COMPOUNDS AS PIM KINASE INHIBITORS
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Compounds of Formula I: in which R1, R2, R3, R4 and R10 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by PIM-1 and/or PIM-2 and/or PIM-3 kinases.
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Page/Page column 148
(2012/12/13)
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- Low-generation dendrimers with a calixarene core and based on a chiral C2-symmetric pyrrolidine as iminosugar mimics
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The preparation of low-generation dendrimers based on a simple calix[4]arene scaffold by insertion of the iminosugar-analogue C 2-symmetric 3, 4-dihydroxypyrrolidine is described. This methodology allows a rapid incorporation of a considerable number of iminosugar-like moieties in a reduced volume and in a well-defined geometry. The inclusion of alkali-metal ions (sodium and potassium) in the polar cavity defined by the acetamide moieties at the lower rim of the calixarene was demonstrated, which allows also the rigidification of the dendrimer structure and the iminosugar presentation in the clusters. The combination of the supra-molecular properties of calixarenes with the advantage of a dendrimeric presentation of repetitive units opens up the possibility of generating well-defined multivalent and multifaceted systems with more complex and/or biologically relevant iminosugars.
- Marradi, Marco,Cicchi, Stefano,Sansone, Francesco,Casnati, Alessandro,Goti, Andrea
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supporting information; experimental part
p. 951 - 957
(2012/08/29)
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- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
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Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
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Page/Page column 109
(2011/07/09)
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- Synthesis of iminodiacetaldehyde derivatives as building blocks for pharmacologically active agents
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The preparation of iminodiacetaldehyde derivatives is reported via oxidative cleavage of 3,4-dihydroxypyrrolidines with sodium periodate. High yields of iminodiacetaldehydes are obtained starting from N-acyl-protected pyrrolidines, whereas the basic N-benzyl-protected derivative does not yield the expected dialdehyde. A cis-configured dihydroxypyrrolidine, prepared from 2,5-dihydropyrrole, reacts considerably faster with sodium periodate than the corresponding trans-configured derivatives which are obtained in three steps from (R,R)-tartaric acid. Georg Thieme Verlag Stuttgart.
- Fricke, Yvonne,Kopp, Nicole,Wuensch, Bernhard
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experimental part
p. 791 - 796
(2010/09/11)
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- Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold
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Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic
- Blum, Andreas,B?ttcher, Jark,Heine, Andreas,Klebe, Gerhard,Diederich, Wibke E.
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p. 2078 - 2087
(2008/12/22)
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- VLA-4 INHIBITORY DRUG
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There is provided a VLA-4 inhibitory drug having good oral absorbability and exhibiting sufficient anti-inflammatory effects when administered orally. A compound represented by the following formula (I): wherein R1 represents a hydrogen atom or a C1-8 alkyl group; R2 represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group, orabenzyloxygroupwhichmaybe substituted; Q represents a monocyclic or bicyclic nitrogen-containing heterocyclic group which may be substituted, and has a nitrogen atom as the bonding site; Y represents an oxygen atom or CH2; W represents a bicyclic aromatic hydrocarbon ring group which may be substituted, or a bicyclic aromatic heterocyclic group whichmaybe substituted; R3a, R3b and R3c each independently represent a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group; and A1 represents a nitrogen atom or C-R3d (wherein R3d represents a hydrogen atom, a halogen atom, a C1-8 alkoxy group or a C1-8 alkyl group), or a salt thereof, or a VLA-4 inhibitory drug comprising the compound or the salt as an active ingredient.
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Page/Page column 122
(2008/12/08)
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- Asymmetric addition of diethylzinc to ketones promoted by tartaric acid derivatives
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The preparation of new sulfonamide ligands derived from L-tartaric acid and camphor sulfonyl chloride are described. The employment in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to ketones has been studied. The best enantiomeric excess is up to 99% with 7 mol% catalyst loading at room temperature. Copyright Taylor & Francis Group, LLC.
- Hui, Ailing,Zhang, Jintang,Wang, Zhiyong
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p. 2374 - 2384
(2008/09/21)
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- Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases
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The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure l- or d-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found.
- Rejman, Dominik,Ko?alka, Petr,Budě?ínsky, Milo?,Pohl, Radek,Rosenberg, Ivan
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p. 1243 - 1253
(2007/10/03)
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- Chiral pyrrolidine thioethers: Effective nitrogen-sulfur donating ligands in palladium-catalyzed asymmetric allylic alkylations
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Enantiomeric cyclic, five-membered alcohols and vic-diols were converted into the corresponding mono- and bis(arylsulfanyl) derivatives with complete inversion of configuration at one or both stereogenic centers. The thus obtained chiral thioethers were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. The purely S,S-donating C2-symmetric chiral ligands showed poor to moderate enantioselectivity (up to 42%), while 1-alkyl-3,4-bis(arylthio)pyrrolidines afforded much higher results, 81-89% ee. When chiral pyrrolidine mono-thioethers were applied the observed enantioselectivity improved further to 86-90% ee. These results suggest that the pyrrolidine thioethers served as the N(sp 3),S-donating chiral ligands. Examination of molecular models showed that the sense of stereoinduction, namely (R)-product from with (3R)-1-benzyl-3-(arylthio)pyrrolidine is in agreement with the nucleophilic attack being directed at the allylic carbon located trans to the sulfur atom in the intermediate η3-allylpalladium complex.
- Siedlecka, Renata,Wojaczynska, Elzbieta,Skarzewski, Jacek
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p. 1437 - 1444
(2007/10/03)
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