- Design, synthesis and evaluation of 1-benzyl-1H-imidazole-5-carboxamide derivatives as potent TGR5 agonists
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TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The
- Zhao, Shizhen,Li, Xinping,Wang, Le,Peng, Wenjing,Ye, Wenling,Li, Weiguo,Wang, Yan-Dong,Chen, Wei-Dong
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- METALLOENZYME INHIBITOR COMPOUNDS
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Provided are compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Paragraph 1590; 1591; 1592; 1593
(2018/07/29)
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- Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.
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Paragraph 0476
(2017/01/23)
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- PYRIMIDINE OR PYRIDINE COMPOUNDS, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USES THEREOF
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The present invention disclosed a class of pyrimidine or pyridine compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof, preparation method therefor and pharmaceutical compositions and pharmaceutical uses thereof. The compounds can inhibit the variants of EGFR (Epidermis Growth Factor Receptor) proteinases, and therefore can inhibit the growth of a variety of tumor cells effectively. The compounds can be used to prepare antitumor drugs, used for the treatment, combined therapy or prevention of various different cancers. The compounds can overcome the drug resistance induced by the existing first-generation EGFR inhibitors such as gefitinib, erlotinib and so on. Particularly, the compounds can be used to prepare drugs for treating or preventing diseases, disturbances, disorders or conditions mediated by epidermis growth factor receptor variants (such as L858R activated mutants, Exon19 deletion activated mutants and T790M resistant mutants).
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Paragraph 0549-0550
(2017/09/19)
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- QUINAZOLINE BASED RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
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Compounds of Formula (I), wherein R1, R2, R3, R4 and n are defined herein, are useful as inhibitors of RSV.
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Page/Page column 49; 50
(2015/05/19)
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- RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
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Compounds of Formula (I): wherein R1, R2 and R3 are defined herein, are useful as inhibitors of RSV.
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Page/Page column 18
(2015/05/19)
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- 2-Phenoxy-nicotinamides are Potent Agonists at the Bile Acid Receptor GPBAR1 (TGR5)
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Potency with potential: 2-Phenoxy- nicotinamides were identified as potent agonists at the GPBAR1 receptor, a target in the treatment of obesity, type2 diabetes and metabolic syndrome. Extensive structure-activity relationship studies supported by homolog
- Martin, Rainer E.,Bissantz, Caterina,Gavelle, Olivier,Kuratli, Christoph,Dehmlow, Henrietta,Richter, Hans G. F.,ObstSander, Ulrike,Erickson, Shawn D.,Kim, Kyungjin,Pietranico-Cole, Sherrie Lynn,Alvarez-Sanchez, Ruben,Ullmer, Christoph
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supporting information
p. 569 - 576
(2013/08/22)
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- NON-SYSTEMIC TGR5 AGONISTS
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Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
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Page/Page column 89
(2013/07/05)
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- Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents
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A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models.
- Wang, Tong,Sepulveda, Mario,Gonzales, Paul,Gately, Stephen
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p. 4790 - 4793
(2013/09/02)
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- 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS
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This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.
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Page/Page column 25
(2011/08/04)
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- 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS
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This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula (I), wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.
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Page/Page column 54
(2011/08/08)
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- NOVEL PHENYL AMIDE OR PYRIDYL AMIDE DERIVATIVES
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This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.
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Page/Page column 48
(2010/05/13)
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- Bicyclic Benzimidazole Compounds and Their Use as Metabotropic Glutamate Receptor Potentiators
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Compounds of Formula I: wherein A, B, D, L, R1, R2, R3, R4, m, and n are as defined for Formula I in the description. The invention also relates to processes for the preparation of the compounds and to new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and to the use of the compounds in therapy.
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Page/Page column 55
(2009/08/14)
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- 4-(Benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: Potent and selective p70S6 kinase inhibitors
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We report herein the design and synthesis of 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-amine derivatives as inhibitors of p70S6 kinase. Screening hits containing the 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine scaffold were optimized for p70S6K potency and selectivity against related kinases. Structure-based design employing an active site homology model derived from PKA led to the preparation of benzimidazole 5-substituted compounds 26 and 27 as highly potent inhibitors (Ki 100-fold selectivity against PKA, ROCK and GSK3.
- Bandarage, Upul,Hare, Brian,Parsons, Jonathan,Pham, Ly,Marhefka, Craig,Bemis, Guy,Tang, Qing,Moody, Cameron Stuver,Rodems, Steve,Shah, Sundeep,Adams, Chris,Bravo, Jose,Charonnet, Emmanuelle,Savic, Vladimir,Come, Jon H.,Green, Jeremy
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scheme or table
p. 5191 - 5194
(2010/03/24)
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- COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE OF HYDROXAMIC ACID DERIVATIVES
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The invention encompasses a compound derived from hydroxamic acid that may be used to slow the expansion of cancer cells and thus is effective in the treatment of cancer. Generally, the disclosed compound includes a benzimidazole group coupled to a hydroxyamide of five or more unsubstituted carbon atoms and any pharmaceutically acceptable salts, solvates and chemically protected forms thereof. Also disclosed are pharmacological compositions including the compound and methods of using the compound to slow the expansion of cancer cells as well as methods of using the compound to treat cancer.
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Page/Page column 33
(2009/10/09)
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- INHIBITORS OF HISTONE DEACETYLASE
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Compounds which are histone deacetylase inhibitors and their use in treating various disorders, including Alzheimer's Disease.
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Page/Page column 86
(2010/01/29)
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- QUINOXALINONE DERIVATIVES AS INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
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The present invention relates to quinoxalinone derivatives of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated. Other preferred compounds are compounds of general formula (I), wherein R1, R2, R3, R4, R5 and R6 can be optionally substituted by one or more groups selected from Z.
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Page/Page column 25
(2009/10/22)
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- BENZIMIDAZOLYL COMPOUNDS AS POTENTIATORS OF MGLUR2 SUBTYPE OF GLUTAMATE RECEPTOR
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
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Page/Page column 58
(2010/11/30)
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- Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors
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A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).
- Zhang, Puwen,Terefenko, Eugene A.,McComas, Casey C.,Mahaney, Paige E.,Vu, An,Trybulski, Eugene,Koury, Elizabeth,Johnston, Grace,Bray, Jenifer,Deecher, Darlene
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scheme or table
p. 6067 - 6070
(2009/08/07)
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- INHIBITORS OF HISTONE DEACETYLASE
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This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the inven- tion provides for compounds of formula (I) wherein (B), Q, J, L and Z are as defined in the specification
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Page/Page column 126
(2008/12/07)
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- 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxamides with selective affinity for the 5-HT4 receptor: Synthesis and structure-affinity and structure-activity relationships of a new series of partial agonist and antagonist derivatives
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A series of 2,3-dihydro-2-oxo-1H-benzimidazole-l-carboxamide derivatives bearing a piperazine moiety was synthesized. Their in vitro 5-HT4, 5-HT3, and D2 receptors affinities were evaluated by radioligand binding assay. For selected compounds functional studies at the 5-HT4 receptor were made by using precontracted (by carbachol) preparations of rat esophageal tunica muscularis mucosae (TMM). The influence of the 3-substituent of the benzimidazole ring, the 4-substituent of the piperazine moiety, and the alkylene spacer was studied. Compounds with an ethyl or a cyclopropyl substituent in the 3-position of the benzimidazole ring showed moderate to high affinity (K(i) = 6.7-75.4 nM) for the 5-HT4 receptor with selectivity over 5-HT3 and D2 receptors and moderate antagonist activity (pK(b) = 6.19- 7.73). Compounds with an isopropyl substituent in the 3-benzimidazole position exhibited moderate and selective 5-HT4 affinity (K(i) ≥ 38.9 nM) and a partial agonist activity (5a, i.a. = 0.94) higher than that of the reference compound BIMU 8 (i.a. = 0.70). This reversal of the pharmacological activity due only to a small structural difference might confirm the existence of two binding sites on the 5-HT4 receptor. In the alkylene spacer, a two-methylene chain is favorable to optimize the affinity and the antagonist or the partial agonist activity. In the ethyl and cyclopropyl series, 5-HT4 antagonist activity seems to be unrelated to the size of the 4-substituent of the piperazine moiety, whereas a methyl group is optimal for high partial agonist activity in the isopropyl series; however, the presence of a butyl substituent is a favorable pattern for 5-HT4 antagonism and even causes a reversal of the pharmacological profile in the isopropyl series (5h, pK(b) = 7.94). N-Butyl quaternization of 5a led to an improvement in affinity for the 5-HT4 receptor and maintained the high partial agonist activity (5r, K(i) = 66.3 nM, i.a. = 0.93).
- Tapia, Inés,Alonso-Cires, Luisa,López-Tudanca, Pedro Luis,Mosquera, Ramón,Labeaga, Luis,Innerárity, Ana,Orjales, Aurelio
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p. 2870 - 2880
(2007/10/03)
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- New 2-piperazinylbenzimidazole derivatives as 5-HT3 antagonists. Synthesis and pharmacological evaluation
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A series of 2-piperazinylbenzimidazole derivatives were prepared and evaluated as 5-HT3 receptor antagonists. Their 5-HT3 receptor affinities were evaluated by radioligand binding assays, and their abilities to inhibit the 5-HT-induced Bezold-Jarisch reflex in anesthetized rats were determined. Compound 7e (lerisetron, pK(i) = 9.2) exhibited higher affinity for the 5- HT3 receptor than did tropisetron and granisetron, while compound 7q (pK(i) = 7.5) had very low affinity for this receptor, showing that substitution on the N1 atom of the benzimidazole ring is essential for affinity and activity. The effect of substitution on the aromatic ring of benzimidazole by several substituents in different positions is also discussed. A strong correlation between the 5-HT3 antagonistic activity of the studied compounds and the position of substitution on the aromatic ring was established. Thus, while the 4-methoxy derivative 7m showed weak affinity for the 5-HT3 receptor (pK(i) = 6.7), the 7-methoxy derivative 7n exhibited the highest affinity (pK(i) = 9.4). Compounds 7e and 7n are now under further investigation as drugs for the treatment of nausea and emesis evoked by cancer chemotherapy and radiation.
- Orjales, Aurelio,Mosquera, Ramón,Labeaga, Luis,Rodes, Rosa
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p. 586 - 593
(2007/10/03)
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- 6-beta(substituted)-(S)-hydroxymethylpenicillanic acids and derivatives thereof
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Antibacterial penicillins of the formula STR1 or a pharmaceutically acceptable salt thereof wherein R1 is a heterocyclic group and R is hydrogen, the residue of certian carboxy protecting groups or the residue of an ester group readily hydrolyzable in vivo having activity against resistant organisms.
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