- 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
-
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.
- Watanabe, Hitoshi,Ishida, Kyoji,Yamamoto, Masanori,Horiguchi, Masakuni,Isobe, Yoshiaki
-
supporting information
(2020/10/02)
-
- NOVEL and IMPROVED SYNTHESIS OF ANTIPSYCHOTIC DRUG
-
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.
- -
-
Page/Page column 15-17
(2020/01/08)
-
- Design, synthesis and anticancer activity evaluation of diazepinomicin derivatives
-
A series of diazepinomicin derivatives were synthesized and evaluated in vitro for their growth inhibitory activity against the human carcinoma cell lines. The results indicated the anticancer selectivity of this kind of compounds. Based on the results, preliminary structure-activity relationships were discussed.
- Yu, Yongguo,Wu, Jianbo,Lei, Fan,Chen, Lei,Wan, Weili,Hai, Li,Guan, Mei,Wu, Yong
-
p. 369 - 373
(2013/07/26)
-
- COMPOUNDS WITH 7-MEMBER CYCLE AND THE PHARMACEUTICAL USE THEREOF FOR PREVENTING AND TREATING DIABETES AND METABOLISM SYNDROME
-
The invention discloses a new use of a class of heptacyclic compounds in the preparation of formulations for the prevention and treatment of diabetes and metabolic syndromes; the present invention also discloses a new class of heptacyclic compounds; the present invention also discloses a process for preparing the heptacyclic compounds and a composition containing the same. The heptacyclic compounds of the present invention can be used to effectively preventing or treating diseases such as diabetes and metabolic syndromes.
- -
-
Page/Page column 35
(2010/07/06)
-
- DIBENZO[b,e][1,4]DIAZEPINE MODULATORS OF DOPAMINE RECEPTORS, SEROTONIN RECEPTORS, ADRENERGIC RECEPTORS, ACETYLCHOLINE RECEPTORS, AND/OR HISTAMINE RECEPTORS
-
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.
- -
-
-
- NON-STEROIDAL PROGESTERONE RECEPTOR MODULATORS
-
The present invention provides compounds according to general Formula (I), a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a prodrug thereof. More particularly, the present invention provides high affinity non-steroidal compounds which are agonists, partial agonists or antagonists of the progesterone receptor.
- -
-
Page/Page column 18; 64-65
(2010/02/07)
-
- Synthesis and preliminary pharmacological evaluation of 4′-arylmethyl analogues of clozapine. I - The effect of aromatic substituents
-
As part of a research program to develop compounds with mixed dopamine D4 and serotonin 5-HT2A antagonist activity with potential for the treatment of schizophrenia, we report a family of compounds based on structural modification of the atypical antipsychotic, clozapine (2). The chemical synthesis, structural characterization and pharmacological evaluation of a series 4′-arylmethyl analogues of clozapine are described. Preliminary receptor binding data are presented, examining primarily the electronic and positional effects of substituents on the introduced arylmethyl group, and secondarily the nature of the aryl ring.
- Capuano, Ben,Crosby, Ian T.,Lloyd, Edward J.,Taylor, David A.
-
p. 565 - 576
(2007/10/03)
-
- Dibenzodiazepines
-
This invention provides dibenzodiazepines represented by the formula STR1 wherein R is STR2 The compounds of this invention are useful as antischizophrenics.
- -
-
-
