- Enantioselectivity Induced by Stereoselective Interlocking: A Novel Core Motif for Tropos Ligands
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Well-defined supramolecular interactions are a powerful tool to control the stereochemistry of a catalytic reaction. In this paper, we report a novel core motif for fluxional 2,2′-biphenyl ligands carrying (S)-amino acid-derived interaction sites in 5,5′-
- Scholtes, Jan Felix,Trapp, Oliver
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- Design and synthesis of acetylenyl benzamide derivatives as novel glucokinase activators for the treatment of t2dm
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Novel acetylenyl-containing benzamide derivatives were synthesized and screened using an in vitro assay measuring increases in glucokinase activity stimulated by 10 mM glucose concentration and glucose uptake in rat hepatocytes. Lead optimization of an acetylenyl benzamide series led to the discovery of several active compounds via in vitro enzyme assays (EC50 40% at 50 mg/kg). Of the active compounds tested, 3-(3-amino-phenylethynyl)-5-(2-methoxy-1-methyl-ethoxy)-N-(1-methyl-1H-pyrazol-3-yl)-benzamide (19) was identified as a potent glucokinase activator exhibiting an EC50 of 27 nM and eliciting a 2.16-fold increase in glucose uptake. Compound 19 caused a glucose AUC reduction of 47.4% (30 mg/kg) in an OGTT study in C57BL/6J mice compared to 22.6% for sitagliptin (30 mg/kg). Single treatment of the compound 19 in C57BL/6J mice elicited basal glucose lowering activity without any significant evidence for hypoglycemia risk. Compound 19 was therefore selected as a candidate for further preclinical development for the treatment of type 2 diabetes.
- Park, Kaapjoo,Lee, Byoung Moon,Hyun, Kwan Hoon,Han, Taedong,Lee, Dong Hoon,Choi, Hyun Ho
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- NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES
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The present invention relates to novel heteroaryl-triazole and heteroaryl-tetrazole compounds of the general formula (I), in which the structural elements R1, R2, R3, R4 and R5 have the meaning given in the description, to formulations and compositions comprising such compounds and for their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.
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Page/Page column 120-121; 132-133
(2021/01/29)
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- NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES
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The present invention relates to novel heteroaryl-triazole compounds of the general formula (I), in which the structural elements X, R1, R2, R3, R4 and R5 have the meaning given in the description, to
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Page/Page column 105
(2021/06/04)
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- NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES
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The present invention relates to novel heteroaryl-triazole compounds of the general formula (I), in which the structural elements X, R1, R2, R3 and R4 have the meaning given in the description, to formulations and compositions comprising such compounds and for their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.
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Page/Page column 90-91
(2021/11/13)
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- 1,3-THIAZOL-2-YL SUBSTITUTED BENZAMIDES
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The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.
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Page/Page column 140
(2016/07/05)
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- Design, Synthesis, and Evaluation of Novel Auxin Mimic Herbicides
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Due to the key roles of auxins as master regulators of plant growth, there is considerable interest in the development of compounds with auxin-like properties for growth management and weed control applications. Herein, we describe the design and multiste
- Do-Thanh, Chi-Linh,Vargas, Jose J.,Thomas, Joseph W.,Armel, Gregory R.,Best, Michael D.
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p. 3533 - 3537
(2016/06/01)
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- AMIDOMETHYL-BIARYL DERIVATIVES COMPLEMENT FACTOR D INHIBITORS AND USES THEREOF
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The present invention provides a compound of formula (I): (I) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 57
(2016/06/28)
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- SELECTIVE SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND COMBINATION THERAPY THEREWITH
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Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided, including compounds which modulate subtype 1 of the S1P receptor, and methods of their therapeutic and/or prophylactic use in combination with at least one other medicament adapted for treatement of a malcondition for which activation of S1P1 is medically indicated, such as multiple sclerosis.
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Page/Page column 105
(2015/05/19)
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- DERIVATIVES OF 1 H-PYRAZOLO[3,4-B]PYRIDINE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
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The present invention discloses compounds according to Formula (I): wherein R1, R2, R3, R4, L, and X are as defined herein. The present invention relates to compounds,methods for their production, pharmaceutical
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Paragraph 00282
(2015/03/13)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
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The present invention discloses compounds according to Formula I: wherein R1, R2, R3, R4, L, and X are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical
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Paragraph 0551; 0552
(2015/03/28)
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- NOVEL CHARTREUSIN ANALOGUES
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The present invention relates to novel Chartreusin analogues of formula (I), pharmaceutical compositions comprising the same and to their use for the treatment of cancer and other diseases.
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Page/Page column 13; 40; 41
(2014/02/16)
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- Synthetic remodeling of the chartreusin pathway to tune antiproliferative and antibacterial activities
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Natural products of the benzonaphthopyranone class, such as chartreusin, elsamicin A, gilvocarcin, and polycarcin, represent potent leads for urgently needed anticancer therapeutics and antibiotics. Since synthetic protocols for altering their architectur
- Ueberschaar, Nico,Xu, Zhongli,Scherlach, Kirstin,Metsae-Ketelae, Mikko,Bretschneider, Tom,Dahse, Hans-Martin,Goerls, Helmar,Hertweck, Christian
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supporting information
p. 17408 - 17416
(2014/01/06)
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- Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands
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The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodom
- Hewings, David S.,Fedorov, Oleg,Filippakopoulos, Panagis,Martin, Sarah,Picaud, Sarah,Tumber, Anthony,Wells, Christopher,Olcina, Monica M.,Freeman, Katherine,Gill, Andrew,Ritchie, Alison J.,Sheppard, David W.,Russell, Angela J.,Hammond, Ester M.,Knapp, Stefan,Brennan, Paul E.,Conway, Stuart J.
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supporting information
p. 3217 - 3227
(2013/06/04)
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- 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors
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New pyridazin-3(2H)-one derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).
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Page/Page column 23
(2012/01/03)
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- An efficient synthesis of substituted meta-halophenols and their methyl ethers: insight into the reaction mechanism
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An expeditious synthetic methodology leading to substituted meta-halophenols and their corresponding methyl ether derivatives through acid-mediated fragmentation of suitably substituted dihalonorbornyl ketones has been devised. The reaction sequence consi
- Khan, Faiz Ahmed,Choudhury, Sumit
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experimental part
p. 2954 - 2970
(2010/08/20)
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- (3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors
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New (3-oxo)pyridazin-4-ylurea derivatives having the chemcial structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).
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Page/Page column 43
(2010/07/03)
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- AMIDE COMPOUNDS, COMPOSITIONS AND USES THEREOF
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Compounds are provided according to formula (1 ) : where A, B, W, X', L, R1, R3, R4b, and m' are as defined herein. Provided compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.
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Page/Page column 112
(2009/10/22)
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- Anti-cancer agents and uses thereof
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The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
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Page/Page column 61
(2008/12/08)
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- ANTI-CANCER AGENTS ANS USES THEREOF
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The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula (I): and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3 R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6- 10 carbons in the ring portion, an optionally-substituted 6- membered heteroaryl group having 1- 3 nitrogen atoms in the ring portion, an optionally-substituted 5- membered heteroaryl group having 0- 4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6- membered ring is fused either to a 5- membered ring or to a 6- membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
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- Solid-phase synthesis of phenols and pyridinones via arylboronation/oxidation protocol using aryl bromides
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A sequence of two known reactions, palladium catalyzed arylboronation of arybromide and subsequent oxidation of arylboronate with oxone, has been carried out to prepare functionalized phenols and pyridin-2(1H)-one which were later loaded on to resin for solid-phase synthesis. Using these resin-bound templates, a number of solid-phase methods were developed to generate libraries of substituted phenols and pyridin-2(1H)-one.
- Lee, Younghee,Kelly, Martha J.
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p. 4897 - 4901
(2007/10/03)
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