- SMALL MOLECULE AUTOPHAGY INDUCERS FOR THE TREATMENT OF CANCER AND NEURODEGENERATIVE DISEASES
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Disclosed herein are compounds and methods for treating cancer and neurodegenerative diseases. In some examples, the compounds increase autophagy.
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Page/Page column 45
(2020/11/03)
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- NOVEL MACROCYCLIC DERIVATIVES, PROCESS FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
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Compound of formula (I): wherein A1, A2, Ra, Rb, Rc, Rd, R3, R4, X, Y and G are as defined in the description, and their use in the manufacture of medicaments.
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Paragraph 0135-0137; 0476-0478
(2020/08/25)
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- Development of inhibitors against mycobacterium abscessus tRNA (m1G37) Methyltransferase (TrmD) Using Fragment-Based Approaches
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Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in accelerated lung function decline and premature death. There is therefore an urgent need to develop novel antibiotics with improved efficacy. tRNA (m1G37) methyltransferase (TrmD) is a promising target for novel antibiotics. It is essential in Mab and other mycobacteria, improving reading frame maintenance on the ribosome to prevent frameshift errors. In this work, a fragment-based approach was employed with the merging of two fragments bound to the active site, followed by structure-guided elaboration to design potent nanomolar inhibitors against Mab TrmD. Several of these compounds exhibit promising activity against mycobacterial species, including Mycobacterium tuberculosis and Mycobacterium leprae in addition to Mab, supporting the use of TrmD as a target for the development of antimycobacterial compounds.
- Whitehouse, Andrew J.,Thomas, Sherine E.,Brown, Karen P.,Fanourakis, Alexander,Chan, Daniel S.-H.,Libardo, M. Daben J.,Mendes, Vitor,Boshoff, Helena I. M.,Floto, R. Andres,Abell, Chris,Blundell, Tom L.,Coyne, Anthony G.
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p. 7210 - 7232
(2019/08/20)
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- IMIDAZOTHIADIAZOLE AND IMIDAZOPYRIDAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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The present invention provides imidazothiadiazole compounds of Formula (I); Wherein W,Y, R0, R2, R4, Ra, Rb, X1, X2, X3 and X4 are as defined herein,, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
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Paragraph 00152
(2013/11/18)
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- 8-Substituted isoquinoline derivative and the use thereof
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The present invention relates to a compound represented by the following formula (1): wherein D1, A1, D2, R1, D3, and R2 each have the same meaning as defined in the present specification or a salt thereof. The compound represented by the formula (1) or a salt thereof has an IKKβ inhibiting activity and the like and is useful for the prevention and/or treatment of IKKβ-associated diseases or symptoms and the like.
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Page/Page column 119
(2010/11/03)
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- Substituted Diphenylethers, -Amines, -Sulfides and -Methanes for the Treatment of Respiratory Disease
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The invention relates to substituted diphenylethers, -amines, -sulfides, and -methanes as useful pharmaceutical compounds for treating respiratory-disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 41
(2009/01/20)
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- NOVEL COMPOUNDS
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The invention relates to substituted phenylacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 65
(2008/06/13)
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- Quinolinone derivaties and uses thereof
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The invention provides compounds of the formula: and pharmaceutically acceptable salts or prodrugs thereof, wherein m, p, q, r, A, E, X, Y, R1, R4, R5, R6, R7, R8, R9 and are as defined herein. The invention also provides methods for preparing, compositions comprising, and methods for using compounds of formula I.
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Page/Page column 20-21
(2008/06/13)
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- Binding and preliminary evaluation of 5-hydroxy- and 10-hydroxy- 2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines as dopamine receptor ligands
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The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10- hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D1-like and D2-like subtypes. All compounds showed very low D1 affinities. This could be ascribed to the absence of a catechol nucleus or of the β-phenyldopamine pharmacophore. Only the N-methyl-5- hydroxy- (5a), N-methyl-10-hydroxy-(6a), and N-methyl-4-bromo-10-methoxy- 2,3,12,12a-tetrahydro-1H-[1]-benzoxepino[2,3,4-ij]isoquinolines (26a) bound the D2 receptors with low affinity, in the same range as dopamine. In compounds 5a and 6a, the 2-(3-hydroxyphenyl)-ethylamine moiety does not meet the requirements of the D2 agonist pharmacophore: namely, the 2-(3- hydroxyphenyl)ethylamine does not reach the trans, fully extended conformation. The three compounds did not interact with recombinant human D4 receptors, and only 5a showed low affinity for rat recombinant D3 receptors. Analysis of the influence of Na+ on [3H]spiperone binding showed that 5a displays a potential dopamine D2 agonist profile, whereas 6a probably has a dopamine D2 antagonist activity. The D2 agonist activity of 5a was proved by the effects on prolactin release from primary cultures of rat anterior pituitary cells.
- Claudi, Francesco,Di Stefano, Antonio,Napolitani, Fabrizio,Cingolani, Gian Mario,Giorgioni, Gianfabio,Fontenla, Josè A.,Montenegro, Gisela Y.,Rivas, Maria E.,Rosa, Elizabeth,Michelotto, Barbara,Orlando, Giustino,Brunetti, Luigi
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p. 599 - 608
(2007/10/03)
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