202058-46-6

Upstream product

• 104618-32-8 2-(4-oxocyclohexyl)-1H-isoindole-1,3(2H)-dione 
• 22509-74-6 N-ethoxycarbonylphthalimide 
• 27489-62-9 trans-4-hydroxycyclohexylamine 
• 99337-98-1 2-((1R,4R)-4-hydroxycyclohexyl) isoindoline-1,3-dione 

Downstream Products

• 104618-33-9 2-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)isoindoline-1,3-dione 
• 106006-83-1 2,6-diamino-4,5,6,7-tetrahydro-benzthiazole 

Relevant academic research and scientific papers

Pharmacological characterization of a new series of carbamoylguanidines reveals potent agonism at the H2R and D3R

Even today, the role of the histamine H2 receptor (H2R) in the central nervous system (CNS) is widely unknown. In previous research, many dimeric, high-affinity and subtype-selective carbamoylguanidine-type ligands such as UR-NK22 (5, pKi = 8.07) were reported as H2R agonists. However, their applicability to the study of the H2R in the CNS is compromised by their molecular and pharmacokinetic properties, such as high molecular weight and, consequently, a limited bioavailability. To address the need for more drug-like H2R agonists with high affinity, we synthesized a series of monomeric (thio)carbamoylguanidine-type ligands containing various spacers and side-chain moieties. This structural simplification resulted in potent (partial) agonists (guinea pig right atrium, [35S]GTPγS and β-arrestin2 recruitment assays) with human (h) H2R affinities in the one-digit nanomolar range (pKi (139, UR-KAT523): 8.35; pKi (157, UR-MB-69): 8.69). Most of the compounds presented here exhibited an excellent selectivity profile towards the hH2R, e.g. 157 being at least 3800-fold selective within the histamine receptor family. The structural similarities of our monomeric ligands to pramipexole (6), a dopamine receptor agonist, suggested an investigation of the binding behavior at those receptors. The target compounds were (partial) agonists with moderate affinity at the hD2longR and agonists with high affinity at the hD3R (e.g. pKi (139, UR-KAT523): 7.80; pKi (157, UR-MB-69): 8.06). In summary, we developed a series of novel, more drug-like H2R and D3R agonists for the application in recombinant systems in which either the H2R or the D3R is solely expressed. Furthermore, our ligands are promising lead compounds in the development of selective H2R agonists for future in vivo studies or experiments utilizing primary tissue to unravel the role and function of the H2R in the CNS.

METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

IMPROVED PROCESS FOR THE PREPARATION OF BIOLOGICALLY ACTIVE TETRAHYDROBENZTHIAZOLE DERIVATIVE

Improved process for the preparation of the intermediate compound of formula II for formation pramipezole of formula (I) as well as the biological active tetrahydrobenzothiazole compound of formula (I) and/or its pharmaceutically acceptable salts or solvates.