66021-70-3

Upstream product

• 10487-96-4 1-phenylcyclopentanol 
• 100-58-3 phenylmagnesium bromide 
• 591-50-4 iodobenzene 
• 120-92-3 cyclopentanone 
• 825-54-7 cyclopent-1-en-1-ylbenzene 

Downstream Products

• 825-54-7 cyclopent-1-en-1-ylbenzene 
• 1333494-90-8 N-((S)-2-amino-3-((S)-1-((S)-3-cyclohexyl-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(1-phenylcyclopentylamino)butan-2-ylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-2,5-dihydroxybenzamide 
• 1333494-89-5 N-((S)-2-amino-3-((S)-1-((S)-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(1-phenylcyclopentylamino)butan-2-ylamino)-4-methyl-1-oxopentan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-2,5-dihydroxybenzamide 
• 1333494-88-4 N-((S)-2-amino-3-((S)-1-((S)-3-cyclohexyl-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(1-phenylcyclopentylamino)butan-2-ylamino)-1-oxopropan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide 

Relevant academic research and scientific papers

Synthesis of 1-Pyrroline by Denitrogenative Ring Expansion of Cyclobutyl Azides under Thermal Conditions

We herein report an efficient and systematic synthesis of 1-pyrrolines from cyclobutyl azides under thermal and neutral conditions. The reaction proceeded without any additional reagents, and nitrogen was generated as the sole by-product. Furthermore, the generated 1-pyrrolines could be continuously transformed into pyrroles, N-Boc-amines, and oxaziridines in an one-pot manner. (Figure presented.).

Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy

Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERBβ plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentyl]amino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV-ERBβ and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure-activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERBβ and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERBβ antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15-fold greater REV-ERBβ inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells.

DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS

The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof : It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.

Structure-guided design and synthesis of P1′ position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors

Previously, we reported potent pentapeptidic BACE1 inhibitors with the hydroxymethylcarbonyl isostere as a substrate transition-state mimic. To improve the in vitro potency, we further reported pentapeptidic inhibitors with carboxylic acid bioisosteres at the P4 and P1′ positions. In the current study, we screened new P1′ position 1-phenylcycloalkylamine analogs to find non-acidic inhibitors that possess double-digit nanomolar range IC50 values. An extensive structure-activity relationship study was performed with various amine derivatives at the P1′ position. The most potent inhibitor of this pentapeptide series, KMI-1830, possessing 1-phenylcyclopentylamine at the P 1′ position had an IC50 value of 11.6 nM against BACE1 in vitro enzymatic assay.

Synthesis and Anticonvulsant Activity of 1-Phenylcyclohexylamine Analogues

Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay.In addition, we determined the binding affinities of the compounds for PCP acceptor sites in rat brain membranes labeled with -1-piperidine.Many of the analogues were protective against MES seizures (ED50s of 4-41 mg/kg, ip) and all of these compounds caused motor toxicity.The potencies in the motor toxicity and MES seizure tests showed a moderate correlation with the affinities for PCP sites.Several analogues exhibited a greater separation of potencies in the motor toxicity and MES seizure tests than did the parent compound PCA.These were obtained by (i) 3-methylation of the cyclohexyl ring trans to the phenyl ring, (ii) methoxylation at the ortho position on the phenyl ring, and (iii) contraction of the cyclohexane ring to form the corresponding cyclopentane.

Lewis Acid Catalyzed Conversion of Alkenes and Alcohols to Azides

Hydrazoic acid, though unreactive to alkenes, adds readily to enol ethers.In the presence of Lewis acids, in particular TiCl4, addition takes place readily to phenylethylenes or 1,1-disubstituted ethylenes to produce alkyl azides.Regiochemical, electronic, and steric influences were explored.TiCl4 also served to catalyze conversion of benzyl or tertiary alcohols to azides.Monosubstituted alkenes or primary alcohols are not affected.