- Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs
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In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, serotonin 5-HT1A and 5-HT2A receptors, but also exhibited low potency for α1A, H1 and 5-HT2C receptors, indicating a low propensity of side effects like orthostatic hypotension and weight gain. Furthermore, 7h exhibited more potent antipsychotic-like effect than aripiprazole in behavioral studies. The preliminary results were promising enough for further research around this scaffold.
- Xu, Mingshuo,Wang, Yu,Yang, Feipu,Wu, Chunhui,Wang, Zhen,Ye, Bin,Jiang, Xiangrui,Zhao, Qingjie,Li, Jianfeng,Liu, Yongjian,Zhang, Junchi,Tian, Guanghui,He, Yang,Shen, Jingshan,Jiang, Hualiang
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supporting information
p. 606 - 611
(2018/02/06)
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- MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
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Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
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Paragraph 00909
(2018/09/12)
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- cGAS ANTAGONIST COMPOUNDS
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Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
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Paragraph 0241
(2017/11/06)
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- 3- HETEROARYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS
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The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.
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Page/Page column 37; 38
(2018/04/11)
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- TETRAHYDRONAPHTHYRIDINE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
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Provided are quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1, R 2, L, X 1, X 2, and X 3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.
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Page/Page column 61
(2016/03/22)
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- Discovery, design, and synthesis of indole-based EZH2 inhibitors
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The discovery and optimization of a series of small molecule EZH2 inhibitors is described. Starting from dimethylpyridone HTS hit (2), a series of indole-based EZH2 inhibitors were identified. Biochemical potency and microsomal stability were optimized during these studies and afforded compound 22. This compound demonstrates nanomolar levels of biochemical potency (IC50 = 0.002 μM), cellular potency (EC50 = 0.080 μM), and afforded tumor regression when dosed (200 mpk SC BID) in an EZH2 dependent tumor xenograft model.
- Gehling, Victor S.,Vaswani, Rishi G.,Nasveschuk, Christopher G.,Duplessis, Martin,Iyer, Priyadarshini,Balasubramanian, Srividya,Zhao, Feng,Good, Andrew C.,Campbell, Robert,Lee, Christina,Dakin, Les A.,Cook, Andrew S.,Gagnon, Alexandre,Harmange, Jean-Christophe,Audia, James E.,Cummings, Richard T.,Normant, Emmanuel,Trojer, Patrick,Albrecht, Brian K.
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supporting information
p. 3644 - 3649
(2015/08/11)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Paragraph 0315; 0316
(2015/11/25)
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- Modulators of methyl modifying enzymes, compositions and uses thereof
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Paragraph 100; 101
(2015/12/26)
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- BENZIMIDAZOLE DERIVATIVES AS MCH RECEPTOR ANTAGONISTS
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The present invention provides an aromatic ring compound having a melanin-concentrating hormone receptor antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula (I) wherein each symbol as defined in the specification, or a salt thereof.
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Page/Page column 220; 221
(2013/07/25)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Paragraph 00212; 00213
(2013/06/05)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
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Paragraph 00166; 00167
(2013/06/05)
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- PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
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MCHR1 antagonists are provided having the following Formula I: wherein A1 and A2 are independently C or N; E is C or N; D1 is a bond, -CR8R9X-, -XCR8R9-, -CHR8CHR
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Page/Page column 70-71
(2010/10/03)
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- Inhibition of chorismate-utilising enzymes by 2-amino-4-carboxypyridine and 4-carboxypyridone and 5-carboxypyridone analogues
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Several 2-amino-4-carboxypyridine, 4- and 5-carboxypyridone-based compounds were prepared and tested against three members of the chorismate-utilising enzyme family, anthranilate synthase, isochorismate synthase and salicylate synthase. Most compounds exhibited low micromolar inhibition of these three enzymes. The most potent inhibitor was a 4-carboxypyridone analogue bearing a lactate side chain on the pyridyl nitrogen which exhibited inhibition constants of 5, 91 and 54 μM against anthranilate synthase, isochorismate synthase and salicylate synthase respectively. The Royal Society of Chemistry 2010.
- Payne, Richard J.,Bulloch, Esther M. M.,Kerbarh, Olivier,Abell, Chris
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experimental part
p. 3534 - 3542
(2010/08/21)
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- COMPOUNDS
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The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
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Page/Page column 41-42
(2009/12/05)
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- BIS-PYRIDYLPYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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The invention provides novel bis-pyridylpyridones which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), pharmaceutical compositions containing them, processes for their preparation, and their use in therapy and for the treatment of obesity and/or diabetes.
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Page/Page column 30
(2009/07/17)
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- HETEROCYCLIC PHENYL CARBAMATES AS NOVEL FAAH-INHIBITORS
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Fatty acid amide hydrolase inhibitors of the Formula (I) are provided, wherein R is a heterocyclic or heterocyclic carbonyl moiety and R' is a group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted
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Page/Page column 74
(2008/12/08)
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- SUBSTITUTED PYRAZOLE COMPOUNDS USEFUL AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
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Disclosed are compounds active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same.
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Page/Page column 102
(2008/06/13)
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- Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate
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(Chemical Equation Presented) Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5′-triphosphate (UTP), and adenosine-5′-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2- hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phospho-nodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.
- Taylor, Scott D.,Mirzaei, Farzad,Sharifi, Ali,Bearne, Stephen L.
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p. 9420 - 9430
(2007/10/03)
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- Discovery of an N-(2-aminopyridin-4-ylmethyl)nicotinamide derivative: A potent and orally bioavailable NCX inhibitor
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Ca2+ overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium-hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca 2+ overload, because NCX inhibitors can directly inhibit the influx of Ca2+ into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reperfusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23h) with an IC 50 value of 0.12 μM against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23h are discussed.
- Kuramochi, Takahiro,Kakefuda, Akio,Yamada, Hiroyoshi,Tsukamoto, Issei,Taguchi, Taku,Sakamoto, Shuichi
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p. 4022 - 4036
(2007/10/03)
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- Process for the preparation of 2-hydroxypyridine or quinoline compounds
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The present invention relates to a process for the preparation of hydroxypyridine based compounds. The process comprises the step of: in water, reacting a pyridine based compound with the proviso that the second position on the nitrogen ring is unsubstituted and the fourth position in the nitrogen ring is not substituted with halogen, with elemental fluorine at a temperature of about -25° to about +30° C. for a time sufficient to form a 2-hydroxypyridine based compound. The resulting 2-hydroxypyridine or quinoline carboxylic acids and esters are useful as herbicide and pharmaceutical intermediates.
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