- QUINOLINE COMPOUNDS AS SELECTIVE AND/OR DUAL MODULATORS OF BILE ACID RECEPTORS AND LEUKOTRIENE CYSTEINYL RECEPTORS
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The present invention relates to compounds of formula (I), their pharmaceutical compositions and uses, in particular for the treatment and/or prevention of diseases mediated by bile acid receptors, FXR and GPBAR1, and cysteinyl leukotriene receptors (CysLTR).
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Page/Page column 37-39; 56-57
(2022/02/15)
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- Synthesis of Vitisins A and D Enabled by a Persistent Radical Equilibrium
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The first total synthesis of the resveratrol tetramers vitisin A and vitisin D is reported. Electrochemical generation and selective dimerization of persistent radicals is followed by thermal isomerization of the symmetric C8b-C8c dimer to the C3c-C8b isomer, providing rapid entry into the vitisin core. Computational results suggest that this synthetic approach mimics Nature's strategy for constructing these complex molecules. Sequential acid-mediated rearrangements consistent with the proposed biogenesis of these compounds afford vitisin A and vitisin D. The rapid synthesis of these complex molecules will enable further study of their pharmacological potential.
- Romero, Kevin J.,Keylor, Mitchell H.,Griesser, Markus,Zhu, Xu,Strobel, Ethan J.,Pratt, Derek A.,Stephenson, Corey R.J.
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supporting information
p. 6499 - 6504
(2020/04/30)
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- Small-molecule allosteric activation of human glucokinase in the absence of glucose
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Synthetic allosteric activators of human glucokinase are receiving considerable attention as potential diabetes therapeutic agents. Although their mechanism of action is not fully understood, structural studies suggest that activator association requires
- Bowler, Joseph M.,Hervert, Katherine L.,Kearley, Mark L.,Miller, Brian G.
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supporting information
p. 580 - 584
(2013/07/26)
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- BENZAMIDE COMPOUNDS AS GLUCOKINASE ACTIVATORS AND THEIR PHARMACEUTICAL APPLICATION
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Benzamide compounds of formula (I), their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof useful as Glucokinase activators or modulators are disclosed. The disclosure further relates to
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Page/Page column 41
(2011/09/14)
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- IMIDAZOPYRIDINE COMPOUNDS
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Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of formula (I) wherein the variables are as defined herein.
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Page/Page column 78
(2010/04/23)
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- NOVEL ACTIVATORS OF GLUCOKINASE
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The present invention provides for novel compounds of Formulas I and II and pharmaceutically acceptable salts and co-crystals thereof which have glucokinsae activator activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucokinase activator is indicated, including Type 1 and 2 diabetes, impaired glucose tolerance, insulin resistence and hyperglycemia. The present invention also provides for processes of making the compounds of Formulas I and II, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.
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Page/Page column 120-122
(2009/04/25)
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- Discovery of potent and orally active 3-alkoxy-5-phenoxy-N-thiazolyl benzamides as novel allosteric glucokinase activators
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Identification and synthesis of novel 3-alkoxy-5-phenoxy-N-thiazolyl benzamides as glucokinase activators are described. Removal of an aniline structure of the prototype lead (2a) and incorporation of an alkoxy or phenoxy substituent led to the identifica
- Iino, Tomoharu,Tsukahara, Daisuke,Kamata, Kenji,Sasaki, Kaori,Ohyama, Sumika,Hosaka, Hideka,Hasegawa, Takuro,Chiba, Masato,Nagata, Yasufumi,Eiki, Jun-ichi,Nishimura, Teruyuki
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experimental part
p. 2733 - 2743
(2009/09/08)
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- NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
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Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n-Z-(CH2)m—PO(OR7)(OR8), —(CH2)nZ-(CH2)m—PO(OR7)Rg, —(CH2)n-Z-(CH2)m—OPO(OR7)Rg, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10);R5 and R6 are independently selected from H, alkyl and halogen;Y is R7(CH2)s or is absent; andX, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
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Page/Page column 99-100
(2008/06/13)
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- THERAPEUTIC COMPOUNDS
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This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein Rm, Rn, Rp, Rq, V, W, X, Y and R8 are as defined in the claims.
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Page/Page column 69
(2010/11/27)
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- 2 -HETEROCYCLYLOXYBENZOYL AMINO HETEROCYCLYL COMPOUNDS AS MODULATORS OF GLUCOKINASE FOR THE TREATMENT OF TYPE 2 DIABETES
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Compounds of formula (I) wherein R1, HET-1 and HET-2 are as described in the specification, and their salts, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.
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Page/Page column 55
(2010/11/25)
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- NOVEL COMPOUNDS AS AGONIST FOR PPAR GAMMA AND PPAR ALPHA, METHOD FOR PREPARATION OF THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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The present invention relates to novel compounds accelerating the activity of Peroxisome proliferator-activated receptor gamma (PPARγ) and alpha (PPARα), processes of preparing the same, and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 66-67
(2010/11/27)
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- HETEROARYL BENZAMIDE DERIVATIVES FOR USE AS GLK ACTIVATORS IN THE TREATMENT OF DIABETES
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Compounds of formula (I), wherein R1, R4, HET-1 and HET-2 are as described in the specification, and their salts and pro-drugs, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.
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Page/Page column 94
(2008/06/13)
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- COMPOUNDS
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Compounds of Formula (I) wherein: R1 is methyl; R2 is selected from -C (O) NR4R5, SO2NR4R5, S (O) pR4 and HET-2; HET-1 is a 5- or 6-membered, optionally substituted C-linked heteroaryl ring; HET-2 is a 4-, 5- or 6-membered, C- or N-linked optionally substituted heterocyclyl ring; R3 is selected from halo, fluoromethyl, difluoromethyl, trifluoromethyl, methyl, methoxy and cyano; R4 is selected from for example hydrogen, optionally substituted (1-4C) alkyl and HET-2; R5 is hydrogen or (1-4C) alkyl; or R4 and R5 together with the nitrogen atom to which they are attached may form a heterocyclyl ring system as defined by HET-3; HET-3 is for example an optionally substituted N-linked, 4, 5 or 6 membered, saturated or partially unsaturated heterocyclyl ring; p is (independently at each occurrence) 0, 1 or 2; m is 0 or 1; n is 0, 1 or 2; provided that when m is 0, then n is 1 or 2; or a salt, pro drug or solvate thereof, are described. Their use as GLK activators, pharmaceutical compositions containing them and processes for their preparation are also described.
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Page/Page column 78
(2008/06/13)
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- BENZOYL AMINO PYRIDYL CARBOXYLIC ACID DERIVATIVES USEFUL AS GLUCOKINASE (GLK) ACTIVATORS
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Compounds of Formula: (I); wherein: R1 is selected from: fluoro, chloro, C1-3alkyl and C1-3alkoxy; R2-X- is selected from: methyl, methoxymethyl and Formula: (X); n is 0,1 or 2; or a salt, pro-drug or solvate thereof are described. Their use as GLK activators, pharmaceutical compositions containing them, and processes for their preparation are also described.
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Page/Page column 31-32
(2010/02/12)
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- HETEROARYLCARBAMOYLBENZENE DERIVATIVE
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Compounds having glucokinase activating effects and being useful as treatments for diabetes, which are represented by the following formula (I): [wherein X1 represents oxygen, etc., X2 represents oxygen, etc., R1 represents a group on Ring A such as alkylsulfonyl, etc., R2 represents C3-7 cyclic alkyl optionally substituted with a halogen, etc., R3 represents a substituent on Ring B such as lower alkyl, etc., formula (II): represents 6- to 10-membered aryl, etc., and formula (III): represents monocyclic or bicyclic heteroaryl optionally having on Ring B a substituent represented by R3 above, wherein the carbon atom of Ring B which is bonded to the nitrogen atom of the amide group of formula (I) forms a C=N bond with the nitrogen atom of the ring], as well as their pharmaceutically acceptable salts.
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Page/Page column 74
(2008/06/13)
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- Discovery, synthesis and biological evaluation of novel glucokinase activators
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The identification, synthesis and SAR of a novel series of glucokinase activators is described. The interplay between lipophilicity, potency and physical properties is discussed, and compound 22 highlighted as having a suitable balance. In vivo pharmacoki
- McKerrecher, Darren,Allen, Joanne V.,Bowker, Suzanne S.,Boyd, Scott,Caulkett, Peter W. R.,Currie, Gordon S.,Davies, Christopher D.,Fenwick, Mark L.,Gaskin, Harold,Grange, Emma,Hargreaves, Rod B.,Hayter, Barry R.,James, Roger,Johnson, Keith M.,Johnstone, Craig,Jones, Clifford D.,Lackie, Sarah,Rayner, John W.,Walker, Rolf P.
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p. 2103 - 2106
(2007/10/03)
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- ASPARTYL PROTEASE INHIBITORS
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The present invention provides compounds having formula (I): wherein R’, R0, R1, X1, R2, R3, R3’, X2, X3, and R4 are as defined herein, and pharmaceuticals compositions thereof. The present invention also provides methods of inhibiting proteases, more specially aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer’s Disease). The present invention also provides methods for preparing compounds of the invention.
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Page 194-196
(2010/02/05)
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