Design, synthesis, structural optimization, SAR, in silico prediction of physicochemical properties and pharmacological evaluation of novel & potent thiazolo[4,5-d]pyrimidine corticotropin releasing factor (CRF) receptor antagonists was written by Islam, Rabiul Md;Teleb, Mohamed;Karageorgos, Vlasios;Sakellaris, Stelios;Papadopoulos, Minas;Pirmettis, Ioannis;Fronczek, Frank R.;Liapakis, George;Fahmy, Hesham. And the article was included in European Journal of Pharmaceutical Sciences in 2022.Reference of 6590-96-1 This article mentions the following:
Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide secreted from the hypothalamus and is the main regulator of the hypothalamus-pituitary-adrenocortical (HPA) axis. CRF is the master hormone which modulates physiol. and behavioral responses to stress. Many disorders including anxiety, depression, addictive disorders and others are related to over activation of the CRF system. This suggests that new mols. which can interfere with CRF binding to its receptors may be potential candidates for neuropsychiatric drugs to treat stress-related disorders. Previously, three series of pyrimidine and fused pyrimidine CRF1 receptor antagonists were synthesized by our group and specific binding assays, competitive binding studies and determination of the ability to antagonize the agonist-stimulated accumulation of cAMP (the second messenger for CRF receptors) were reported. In continuation of our efforts in this direction, in the current manuscript, we report the synthesis & biol. evaluation of a new series of CRF1 receptor antagonists. Seven compounds showed promising binding affinity with the best two compounds (compounds 6 & 43) displaying a superior binding affinity to all of our previous compounds Compounds 6 & 43 have only 4 times and 2 times less binding affinity than the standard CRF antagonist antalarmin, resp. Thus, our two best lead compounds (compound 6 & 43) can be considered potent CRF receptor antagonists with binding affinity of 41.0 & 19.2 nM vs. 9.7 nM for antalarmin. In the experiment, the researchers used many compounds, for example, 2,4-Dichlorophenylisothiocyanate (cas: 6590-96-1Reference of 6590-96-1).
2,4-Dichlorophenylisothiocyanate (cas: 6590-96-1) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Reference of 6590-96-1
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics