Literature DB >> 27933953

Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABAA) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic Efficacy.

Michael M Poe1, Kashi Reddy Methuku1, Guanguan Li1, Ashwini R Verma1, Kelly A Teske1, Douglas C Stafford1, Leggy A Arnold1, Jeffrey W Cramer2, Timothy M Jones2, Rok Cerne2, Michael J Krambis2, Jeffrey M Witkin2, Enrique Jambrina3, Sabah Rehman4, Margot Ernst4, James M Cook1, Jeffrey M Schkeryantz2.   

Abstract

1,4-Benzodiazepines are used in the treatment of anxiety disorders but have limited long-term use due to adverse effects. HZ-166 (2) has been shown to have anxiolytic-like effects with reduced sedative/ataxic liabilities. A 1,3-oxazole KRM-II-81 (9) was discovered from a series of six bioisosteres with significantly improved pharmacokinetic and pharmacodynamic properties as compared to 2. Oxazole 9 was further characterized and exhibited improved anxiolytic-like effects in a mouse marble burying assay and a rat Vogel conflict test.

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Year:  2016        PMID： 27933953      PMCID： PMC5215686          DOI： 10.1021/acs.jmedchem.6b01332

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  30 in total

1.  Molecular and neuronal substrate for the selective attenuation of anxiety.

Authors:  K Löw; F Crestani; R Keist; D Benke; I Brünig; J A Benson; J M Fritschy; T Rülicke; H Bluethmann; H Möhler; U Rudolph
Journal:  Science       Date:  2000-10-06       Impact factor: 47.728

2.  Anxiolytic-like effects of 8-acetylene imidazobenzodiazepines in a rhesus monkey conflict procedure.

Authors:  Bradford D Fischer; Stephanie C Licata; Rahul V Edwankar; Zhi-Jian Wang; Shengming Huang; Xiaohui He; Jianming Yu; Hao Zhou; Edward M Johnson; James M Cook; Roman Furtmüller; Joachim Ramerstorfer; Werner Sieghart; Bryan L Roth; Samarpan Majumder; James K Rowlett
Journal:  Neuropharmacology       Date:  2010-08-18       Impact factor: 5.250

3.  NS11821, a partial subtype-selective GABAA agonist, elicits selective effects on the central nervous system in randomized controlled trial with healthy subjects.

Authors:  Rob G J A Zuiker; Xia Chen; Ole Østerberg; Naheed R Mirza; Pierandrea Muglia; Marieke de Kam; Erica S Klaassen; Joop M A van Gerven
Journal:  J Psychopharmacol       Date:  2015-12-10       Impact factor: 4.153

4.  Evidence for a significant role of alpha 3-containing GABAA receptors in mediating the anxiolytic effects of benzodiazepines.

Authors:  Rebecca Dias; Wayne F A Sheppard; Rosa L Fradley; Elizabeth M Garrett; Joanna L Stanley; Spencer J Tye; Simon Goodacre; Rachael J Lincoln; Susan M Cook; Rachel Conley; David Hallett; Alexander C Humphries; Sally A Thompson; Keith A Wafford; Leslie J Street; J Luis Castro; Paul J Whiting; Thomas W Rosahl; John R Atack; Ruth M McKernan; Gerard R Dawson; David S Reynolds
Journal:  J Neurosci       Date:  2005-11-16       Impact factor: 6.167

5.  Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist.

Authors:  J R Atack; D J Hallett; S Tye; K A Wafford; C Ryan; S M Sanabria-Bohórquez; Wai-Si Eng; R E Gibson; H D Burns; G R Dawson; R W Carling; L J Street; A Pike; I De Lepeleire; K Van Laere; G Bormans; J N de Hoon; A Van Hecken; R M McKernan; M G Murphy; R J Hargreaves
Journal:  J Psychopharmacol       Date:  2010-02-15       Impact factor: 4.153

6.  Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes.

Authors:  U Rudolph; F Crestani; D Benke; I Brünig; J A Benson; J M Fritschy; J R Martin; H Bluethmann; H Möhler
Journal:  Nature       Date:  1999-10-21       Impact factor: 49.962

7.  The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes.

Authors:  Joachim Ramerstorfer; Roman Furtmüller; Elisabeth Vogel; Sigismund Huck; Werner Sieghart
Journal:  Eur J Pharmacol       Date:  2010-03-19       Impact factor: 4.432

8.  Rodent pharmacokinetics and receptor occupancy of the GABAA receptor subtype selective benzodiazepine site ligand L-838417.

Authors:  P Scott-Stevens; J R Atack; B Sohal; P Worboys
Journal:  Biopharm Drug Dispos       Date:  2005-01       Impact factor: 1.627

9.  Contribution of alpha1 subunit-containing gamma-aminobutyric acidA (GABAA) receptors to motor-impairing effects of benzodiazepines in squirrel monkeys.

Authors:  Stephanie C Licata; Donna M Platt; James M Cook; Michael L Van Linn; James K Rowlett
Journal:  Psychopharmacology (Berl)       Date:  2008-11-25       Impact factor: 4.530

Review 10.  A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model.

Authors:  Terry Clayton; Michael M Poe; Sundari Rallapalli; Poonam Biawat; Miroslav M Savić; James K Rowlett; George Gallos; Charles W Emala; Catherine C Kaczorowski; Douglas C Stafford; Leggy A Arnold; James M Cook
Journal:  Int J Med Chem       Date:  2015-11-10
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  9 in total

1.  Antinociceptive Effects of a Novel α2/α3-Subtype Selective GABAA Receptor Positive Allosteric Modulator.

Authors:  Lakeisha A Lewter; Janet L Fisher; Justin N Siemian; Kashi Reddy Methuku; Michael M Poe; James M Cook; Jun-Xu Li
Journal:  ACS Chem Neurosci       Date:  2017-02-13       Impact factor: 4.418

2.  Design, synthesis and characterization of novel gamma‑aminobutyric acid type A receptor ligands.

Authors:  Kamal P Pandey; Zubair Ahmed Khan; Lalit K Golani; Prithu Mondal; Yeunus Mian; Farjana Rashid; V V N Phani Babu Tiruveedhula; Daniel E Knutson; Dishary Sharmin; Taukir Ahmed; Sepideh Rezvanian; Nicolas M Zahn; Leggy A Arnold; Jeffrey M Witkin; James M Cook
Journal:  ARKIVOC       Date:  2020-12-02       Impact factor: 1.140

3.  The Positive Allosteric Modulator of α2/3-Containing GABAA Receptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury.

Authors:  Jeffrey M Witkin; Guanguan Li; Lalit K Golani; Wenhui Xiong; Jodi L Smith; Xingjie Ping; Farjana Rashid; Rajwana Jahan; Rok Cerne; James M Cook; Xiaoming Jin
Journal:  J Pharmacol Exp Ther       Date:  2019-11-06       Impact factor: 4.030

4.  The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats.

Authors:  J M Witkin; R Cerne; P G Davis; K B Freeman; J M do Carmo; J K Rowlett; K R Methuku; A Okun; S D Gleason; X Li; M J Krambis; M Poe; G Li; J M Schkeryantz; R Jahan; L Yang; W Guo; L K Golani; W H Anderson; J T Catlow; T M Jones; F Porreca; J L Smith; K L Knopp; J M Cook
Journal:  Pharmacol Biochem Behav       Date:  2019-02-27       Impact factor: 3.533

Review 5.  GABAA receptors: structure, function, pharmacology, and related disorders.

Authors:  Amr Ghit; Dina Assal; Ahmed S Al-Shami; Diaa Eldin E Hussein
Journal:  J Genet Eng Biotechnol       Date:  2021-08-21

6.  Improved Synthesis of Anxiolytic, Anticonvulsant and Antinociceptive α2/α3-GABA(A)ergic Receptor Subtype Selective Ligands as Promising Agents to Treat Anxiety, Epilepsy, as well as Neuropathic Pain.

Authors:  Guanguan Li; Lalit K Golani; Rajwana Jahan; Farjana Rashid; James M Cook
Journal:  Synthesis (Stuttg)       Date:  2018-10       Impact factor: 3.157

7.  8-Substituted Triazolobenzodiazepines: In Vitro and In Vivo Pharmacology in Relation to Structural Docking at the α1 Subunit-Containing GABAA Receptor.

Authors:  Lalit K Golani; Donna M Platt; Daniela Rüedi-Bettschen; Chitra Edwanker; Shenming Huang; Michael M Poe; Roman Furtmüller; Werner Sieghart; James M Cook; James K Rowlett
Journal:  Front Pharmacol       Date:  2021-04-20       Impact factor: 5.810

8.  Metal-free synthesis of 1,4-benzodiazepines and quinazolinones from hexafluoroisopropyl 2-aminobenzoates at room temperature.

Authors:  Jiewen Chen; En Liang; Jie Shi; Yinrong Wu; Kangmei Wen; Xingang Yao; Xiaodong Tang
Journal:  RSC Adv       Date:  2021-01-28       Impact factor: 3.361

9.  Hydrochloride Salt of the GABAkine KRM-II-81.

Authors:  Md Yeunus Mian; Branka Divović; Dishary Sharmin; Kamal P Pandey; Lalit K Golani; V V N Phani Babu Tiruveedhula; Rok Cerne; Jodi L Smith; Xingjie Ping; Xiaoming Jin; Gregory H Imler; Jeffrey R Deschamps; Arnold Lippa; James M Cook; Miroslav M Savić; James Rowlett; Jeffrey M Witkin
Journal:  ACS Omega       Date:  2022-07-27
  9 in total

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