- Synthesis of illudalic acid and analogous phosphatase inhibitors
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Developing an efficient, concise synthesis of the fungal natural product illudalic acid has been a long-standing challenge, made more pressing by the recent discovery that illudalic acid and analogs are selective phosphatase inhibitors. Syntheses of illudalic acid have become progressively more efficient over the decades yet remain strategically grounded in a 17-step synthesis reported in 1977. Here we validate a two-step process—convergent [4 + 2] benzannulation and one-pot coordinated functional group manipulations—for preparing the key trifunctional pharmacophore of illudalic acid. The modular building blocks are readily available in 2-3 steps, for a longest linear sequence (LLS) of 5 steps to illudalic acid from 3,3-dimethylcyclopentanone. A small collection of analogous indanes and tetralins featuring the same pharmacophore were prepared by a similar route. These compounds potently and selectively inhibit the human leukocyte common antigen-related (LAR) subfamily of protein tyrosine phosphatases (PTPs). Evidence supporting a postulated covalent ligation mechanism is provided herein.
- Ahmed, Kh Tanvir,Barrios, Amy M.,Batsomboon, Paratchata,Dudley, Gregory B.,Fulo, Harvey F.,Gaston, Robert,Rueb, Nicole J.
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supporting information
p. 10596 - 10600
(2021/12/27)
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- Br?nsted Acid Catalyzed Tandem Defunctionalization of Biorenewable Ferulic acid and Derivates into Bio-Catechol
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An efficient conversion of biorenewable ferulic acid into bio-catechol has been developed. The transformation comprises two consecutive defunctionalizations of the substrate, that is, C?O (demethylation) and C?C (de-2-carboxyvinylation) bond cleavage, occurring in one step. The process only requires heating of ferulic acid with HCl (or H2SO4) as catalyst in pressurized hot water (250 °C, 50 bar N2). The versatility is shown on a variety of other (biorenewable) substrates yielding up to 84 % di- (catechol, resorcinol, hydroquinone) and trihydroxybenzenes (pyrogallol, hydroxyquinol), in most cases just requiring simple extraction as work-up.
- Bal, Mathias,Bomon, Jeroen,Liao, Yuhe,Maes, Bert U. W.,Sels, Bert F.,Sergeyev, Sergey,Van Den Broeck, Elias,Van Speybroeck, Veronique
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supporting information
p. 3063 - 3068
(2020/02/05)
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- C-Bridged Bispyrrolidines and Bispiperidines as New Ligands
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The preparation of methylene-bridged C2-symmetric nitrogen-heterocycles as a new class of ligands is described, including methylene-bridged pyridines, quinolones, piperidines and pyrrolidines. These methylene-bridged aromatic systems are obtained via a microwave assisted Ziegler-type reaction. The separation of diastereomers and the application of the copper complexes of these ligands for cyclopropanation reactions proves the applicability of these new types of ligands.
- Stumpf, Tim-Daniel J.,Steinbach, Manfred,H?ltke, Magdalene,Heuger, Gerold,Grasemann, Franka,Fr?hlich, Roland,Schindler, Siegfried,G?ttlich, Richard
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p. 5538 - 5547
(2018/10/25)
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- BICYCLIC HETEROCYCLE DERIVATIVES AS BROMODOMAIN INHIBITORS
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The invention relates to novel bicyclic heterocycle derivatives of formula (I) wherein Cy1,Cy2, R1,R2 and L have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are usefulas bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.
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Page/Page column 43; 44
(2017/01/23)
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- BICYCLIC HETEROCYCLIC DERIVATIVES AS BROMODOMAIN INHIBITORS
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The present disclosure provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R1, R2, R3, R4, L1, L2, Cy1, Cy2, X, n, and dotted line have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorders, in particular their use in diseases or disorders associated as bromodomain inhibitors. The present disclosure also provides preparation of compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent, or excipient.
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Paragraph 0151
(2017/04/04)
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- TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.
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Paragraph 0889; 0890
(2017/01/23)
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- BICYCLIC HETEROCYCLIC DERIVATIVES AS BROMODOMAIN INHIBITORS
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The present invention provides bicyclic heterocyclic derivatives of formula (I), which may be therapeutically useful, more particularly as bromodomain inhibitors; (I), in which R1, R2, R3, R4, L1, L2, Cy1, Cy2, X, n and dotted line are have the same meaning given in the specification, and pharmaceutically acceptable salts or pharmaceutically acceptable stereoisomers thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder associated as bromodomain inhibitors. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of bicyclic heterocyclic derivatives of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
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Page/Page column 31
(2015/07/23)
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- PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein A1, A2, Ra, Rb, Rc, Rd, R3, R4, R5 and T are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.
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Paragraph 0131; 0132
(2015/02/19)
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- ANTHELMINTIC COMPOUNDS AND COMPOSITIONS AND METHOD OF USING THEREOF
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The present invention relates to novel anthelmintic compounds of formula (I) below: wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X1, X2, X3, X4, X5, X6, X7 and X8 are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.
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Paragraph 0462; 0463
(2014/05/25)
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- Developing Pd(II) catalyzed double sp3 C-H alkoxylation for synthesis of symmetric and unsymmetric acetals
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An effective Pd(II) catalyzed double unactivated C(sp3)-H alkoxylation has been developed to prepare both symmetric and unsymmetric acetals. This new reaction demonstrates good functional group tolerance, excellent reactivity, and high yields. A variety of novel acetals can be readily accessed via this new method. (Chemical Equation Presented).
- Zong, Yu,Rao, Yu
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supporting information
p. 5278 - 5281
(2015/01/09)
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- PROCESS FOR THE PREPARATION OF 1-ARYL-PYRAZOL-3-ONE INTERMEDIATES USEFUL IN THE SYNTHESIS OF SIGMA RECEPTORS INHIBITORS
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The invention relates to a process for preparing 1-aryl-pyrazol-3-one intermediates, tautomers, and salts thereof, to novel intermediates, and to the use of the intermediates in the preparation of sigma receptor inhibitors.
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Page/Page column 31
(2012/02/13)
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- Intermediates for the preparation of 1-aryl-pyrazol-3-one compounds useful as sigma receptors inhibitors
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The invention relates to a process for preparing 1-aryl-pyrazol-3-one intermediates, tautomers, and salts thereof, to novel intermediates, and to the use of the intermediates in the preparation of sigma receptor inhibitors.
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Page/Page column 26
(2012/03/08)
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- Theramutein modulators
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This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
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Page/Page column 170-171
(2010/02/17)
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- GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE
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The present invention relates to compounds of general formula (I), wherein ring A, ring B, R1, R2, R3, Z, and L1 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.
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Page/Page column 118
(2009/12/23)
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- THERAMUTEIN MODULATORS
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This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
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Page/Page column 202
(2008/12/07)
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- SUBSTITUTED FUSED[1,2]IMIDAZO[4,5-C] RING COMPOUNDS AND METHODS
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[1,2]Imidazo[4,5-c] ring compounds (e.g., imidazo[4,5-c]quinolines, imidazo[4,5-c]naphthyridines, and imidazo[4,5-c]pyridines) substituted with a fused ring containing an oxygen and/or nitrogen atom attached at the 1- and/or 2-position, pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.
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Page/Page column 107
(2008/06/13)
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- 2-(4-Alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists
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With the aim of identifying structurally novel, centrally acting histamine H3 antagonists, a series of 2-(4-alkylpiperazin-1-yl)quinolines was prepared. Systematic variation of the substituents led to highly potent histamine H3 antagonists with low polar surface area and appropriate log P for blood-brain barrier penetration.
- Zaragoza, Florencio,Stephensen, Henrik,Peschke, Bernd,Rimvall, Karin
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p. 306 - 311
(2007/10/03)
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- Action de l'hydroxyuree sur les esters α-acetyleniques
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Hydroxyurea, in its oxanion form NH2-CO-NHO(1-), reacts in basic medium by a 1,4-addition to α-acetylenic esters leading to the E and Z ethylenic β-ureidoxy esters isomers.The E isomer can be isolated and identified from reaction with ethyl tetrolate and ethyl propiolate.The Z isomer undergoes cyclisation in situ to give the 2-carboxamido-5-methyl-3-isoxazolone.With phenyl propiolate, the 3-hydroxy-5-phenyl isoxazole is directly obtained without isolation of the intermediate N-carboxamido derivative.In the case of ethyl propiolate two cyclic compounds are obtained: 3-hydroxyisoxazole and 2-N-carboxamido-5-ethoxy-3-isoxazolidinone.The formation of the former is due to the in situ cyclisation of the Z isomer.The isolation of the latter compound can be explained by solvent addition to the E β-ureidoxyacrylate intermadiate in a Michael addition followed by cyclisation.
- Lassalvy, Christiane,Petrus, Clement,Petrus, Francoise
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p. 175 - 180
(2007/10/02)
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