847417-37-2

Upstream product

• 223131-01-9 tert-butyl ((cis)-4-(hydroxymethyl)cyclohexyl)carbamate 
• 364385-64-8 cis-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid methyl ester 
• 62456-15-9 methyl (1s,4s)-4-aminocyclohexane-1-carboxylate 
• 118785-97-0 cis-4-amino-cyclohexanecarboxylic acid hydrochloride 
• 327156-95-6 ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)acetic acid 
• 1069120-19-9 tert-butyl ((1s,4s)-4-(2-hydroxyethyl)cyclohexyl)carbamate 

Downstream Products

• 1069120-39-3 (E)-ethyl 4-((1s,4s)-4-(tert-butoxycarbonylamino)cyclohexyl)-2-methylbut-2-enoate 
• 791778-53-5 cis-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexanamine 
• 506427-91-4 tert-butyl (cis-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)carbamate 

Relevant academic research and scientific papers

D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine

Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-bi

A structure-activity analysis of biased agonism at the dopamine D2 receptor

Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin- 2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.

Antitumor compounds based on a natural product consensus pharmacophore

We report the design and highly enantioselective synthesis of a potent analogue of the spliceosome inhibitor FR901464, based on a non-natural product scaffold. The design of this compound was facilitated by a pharmacophore hypothesis that assumed key interaction types that are common to FR901464 and an otherwise unrelated natural product (pladienolide). The synthesis allows for the preparation of numerous novel analogues. We present results on the in vitro activity for this compound against several tumor cell lines.