50373-22-3Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of 11-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepines with clozapine-like receptor occupancy at dopamine D1/D2 receptor
Watanabe, Hitoshi,Ishida, Kyoji,Yamamoto, Masanori,Horiguchi, Masakuni,Isobe, Yoshiaki
, (2020/10/02)
Clozapine-like compound without agranulocytosis risk is need to cure the treatment resistant schizophrenia (TRS). We discovered (S)-3 as Clozapine-like dopamine D2/D1 receptor selectivity and improved reactive metabolites formation profile by the modification of piperazine moiety in Clozapine. The optimization of (S)-3 gave compound 5 to be best compound (approximately 10-fold stronger affinity for D2/D1 receptor and similar D2/D1 selectivity ratio with Clozapine). Clozapine-like D2/D1 receptor occupancy profile was proved by in vivo evaluation. In addition, the reactive metabolites derived agranulocytosis risk of compound 5 was considered to be lower than Clozapine. The pharmacology detail of compound 5 is being investigated to develop it for TRS treatment.
NOVEL and IMPROVED SYNTHESIS OF ANTIPSYCHOTIC DRUG
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, (2020/01/08)
The present invention relates to novel as well as improved process for the preparation of Clozapine of Formula I which involves anti-narcotic and highly cost effective raw materials.
Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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, (2017/01/23)
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.
The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs
Chen, Xin,Choo, Hyunah,Huang, Xi-Ping,Yang, Xiaobao,Stone, Orrin,Roth, Bryan L.,Jin, Jian
, p. 476 - 484 (2015/03/30)
Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand-receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure-activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10000-fold selectivity for hM3Dq over hM3.
DIBENZO[b,e][1,4]DIAZEPINE MODULATORS OF DOPAMINE RECEPTORS, SEROTONIN RECEPTORS, ADRENERGIC RECEPTORS, ACETYLCHOLINE RECEPTORS, AND/OR HISTAMINE RECEPTORS
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, (2010/07/08)
The present invention relates to new dibenzo[b,e][1,4]diazepine modulators of dopamine receptors, serotonin receptors, adrenergic receptors, acetylcholine receptors, and/or histamine receptors, pharmaceutical compositions thereof, and methods of use thereof.
INHIBITORS OF HISTONE DEACETYLASE
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, (2010/01/29)
Compounds which are histone deacetylase inhibitors and their use in treating various disorders, including Alzheimer's Disease.
Synthesis and evaluation of dibenzothiazepines: A novel class of selective cannabinoid-1 receptor inverse agonists
Pettersson, Hanna,Bülow, Anne,Ek, Fredrik,Jensen, Jacob,Ottesen, Lars K.,Fejzic, Alma,Ma, Jian-Nong,Tredici, Andria L. Del,Currier, Erika A.,Gardell, Luis R.,Tabatabaei, Ali,Craig, Darren,McFarland, Krista,Ott, Thomas R.,Piu, Fabrice,Burstein, Ethan S.,Olsson, Roger
supporting information; experimental part, p. 1975 - 1982 (2009/12/31)
A novel class of CB1 inverse agonists was discovered. To efficiently establish structure-activity relationships (SARs), new synthetic methodologies amenable for parallel synthesis were developed. The compounds were evaluated in a mammalian cell-based func
INHIBITORS OF HISTONE DEACETYLASE
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Page/Page column 105-106, (2008/12/07)
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
Synthesis and preliminary pharmacological evaluation of 4′-arylalkyl analogues of clozapine. IV. the effects of aromaticity and isosteric replacement
Capuano, Ben,Crosby, Ian T.,Lloyd, Edward J.,Podloucka, Anna,Taylor, David A.
experimental part, p. 930 - 940 (2009/04/06)
We report the synthesis and preliminary pharmacological activity of a new series of tricyclic analogues of clozapine as potential antipsychotic agents for the treatment of schizophrenia. These compounds were designed based on a revised structural model, a
