863317-29-7Relevant academic research and scientific papers
Synthesis and structure-activity relationships of 3,4,5-trisubstituted-1,2,4-triazoles: High affinity and selective somatostatin receptor-4 agonists for Alzheimer's disease treatment
Crider, A. Michael,Farr, Susan A.,Frare, Rafael,Hospital, Audrey,Kontoyianni, Maria,Kukielski, Stephen G.,Minaeian, Mahsa,Mobayen, Shirin,Neumann, William L.,Niehoff, Michael L.,Sandoval, Karin E.,Slater, Olivia,Srabony, Khush N.,Witt, Ken A.
, p. 1352 - 1365 (2021/11/09)
Somatostatin receptor-4 (SST4) is highly expressed in brain regions affiliated with learning and memory. SST4 agonist treatment may act to mitigate Alzheimer's disease (AD) pathology. An integrated approach to SST4 agonist lead optimization is presented herein. High affinity and selective agonists with biological efficacy were identified through iterative cycles of a structure-based design strategy encompassing computational methods, chemistry, and preclinical pharmacology. 1,2,4-Triazole derivatives of our previously reported hit (4) showed enhanced SST4 binding affinity, activity, and selectivity. Thirty-five compounds showed low nanomolar range SST4 binding affinity, 12 having a Ki 500-fold affinity for SST4 as compared to SST2A. SST4 activities were consistent with the respective SST4 binding affinities (EC50 600-fold selectivity over SST2A) display a favorable physiochemical profile, and was advanced to learning and memory behavior evaluations in the senescence accelerated mouse-prone 8 model of AD-related cognitive decline. Chronic administration enhanced learning with i.p. dosing (1 mg kg-1) compared to vehicle. Chronic administration enhanced memory with both i.p. (0.01, 0.1, 1 mg kg-1) and oral (0.01, 10 mg kg-1) dosing compared to vehicle. This study identified a novel series of SST4 agonists with high affinity, selectivity, and biological activity that may be useful in the treatment of AD. This journal is
3,4,5-TRISUBSTITUTED-1,2,4-TRIAZOLES AND 3,4,5-TRISUBSTITUTED-3-THIO-1,2,4-TRIAZOLES AND USES THEREOF
-
Paragraph 0158; 0193; 0201, (2018/12/02)
The present disclosure describes novel compounds that are somatostatin receptor type 4 agonists.
Acetylcholinesterase inhibition activity of some quinolinyl substituted triazolothiadiazole derivatives
Rafiq, Muhammad,Saleem, Muhammad,Hanif, Muhammad,Abbas, Qamar,Lee, Ki Hwan,Seo, Sung-Yum
, p. 170 - 177 (2015/04/14)
A series of aralkanoic acids was converted into aralkanoic acid hydrazides through their esters formation. The aralkanoic acid hydrazides upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazinate salts, which on refluxing with aqueous hydrazine hydrate yielded 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles. The target compounds, 3-aralkyl-6-(substitutedquinolinyl) [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, were synthesized by condensing various quinolinyl substituted carboxylic acids with 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles in phosphorus oxychloride. The structures of the newly synthesized triazolothiadiazoles were characterized by IR, 1H NMR, 13C NMR, and elemental analysis studies. The structure of one of the 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles was unambiguously deduced by single crystal X-ray diffraction analysis. All the synthesized compounds were screened for their acetylcholinesterase inhibition activities. Four of the triazolothiadiazoles exhibited excellent acetylcholinesterase inhibition activities as compared to the reference inhibitor.
HETEROCYCLIC INHIBITORS OF GLUTAMINASE
-
Page/Page column 136; 137, (2013/06/06)
The invention relates to the heterocyclic compounds of Formula (I) as defined further herein, and pharmaceutical preparations thereof. The invention further relates to methods of treating cancer, immunological or neurological diseases using the heterocyclic compounds of the invention.
3-(3-PYRIMIDIN-2-YLBENZYL)-1,2,4-TRIAZOLO[4,3-B]PYRIDAZINE DERIVATIVES AS MET KINASE INHIBITORS
-
Page/Page column 19, (2011/05/03)
Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular of Met kinase, and can be employed, inter alia, for the treatment of tumours.
3 (3-Pyrimidin-2-ylbenzyl)-1,2,4-triazolo[4,3-b]pyridazine derivatives
-
Page/Page column 18, (2011/10/31)
Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for th
Identification of novel urease inhibitors by high-throughput virtual and in vitro screening
Abid, Obaid-Ur-Rahman,Babar, Tariq Mahmood,Ali, Farukh Iftakhar,Ahmed, Shahzad,Wadood, Abdul,Rama, Nasim Hasan,Uddin, Reaz,Zaheer-Ul-Haq,Khan, Ajmal,Choudhary, M. Iqbal
scheme or table, p. 145 - 149 (2010/10/19)
Ureases are important in both agriculture and human health. Bacterial ureases are directly involved in many farm-field problems and pathological conditions. Here, we report a structure-based virtual screening of an in-house compound bank of about 6000 molecular entities by computational docking and binding free energy calculations followed by in vitro screening. Applied protocol leads to the identification of novel urease inhibitors, which can serve as starting points for structural optimization.
Synthesis and SAR evaluation of 1,2,4-triazoles as A2A receptor antagonists
Alanine, Alexander,Anselm, Lilli,Steward, Lucinda,Thomi, Stefan,Vifian, Walter,Groaning, Michael D.
, p. 817 - 821 (2007/10/03)
The synthesis and in vitro structure-activity relationships (SAR) of a series of triazoles as A2A receptor antagonists is reported. This resulted in the identification of potent, selective and permeable 1,2,4-triazoles such as 42 for further op
