75970-99-9

Basic information

• Product Name: norastemizole
• Synonyms: norastemizole;1-(4-FLUOROBENZYL)-1H-BENZIMIDAZOL-2-YL](4-PIPERIDYL)AMINE;1-[(4-Fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine;N-(4-Piperidinyl)-1-(4-fluorobenzyl)-1H-benzoimidazole-2-amine;R-41232
• CAS NO: 75970-99-9
• Molecular Formula: C₁₉H₂₁FN₄
• Molecular Weight: 324.401
• Mol File: 75970-99-9.mol
• Article Data: 14

Chemical Properties

• Boiling Point: 519.8°C at 760 mmHg
• Flash Point: 268.2°C
• Appearance: /
• Density: 1.28g/cm³
• Vapor Pressure: 6.62E-11mmHg at 25°C
• Refractive Index: 1.658
• CAS DataBase Reference: norastemizole(CAS DataBase Reference)
• NIST Chemistry Reference: norastemizole(75970-99-9)
• EPA Substance Registry System: norastemizole(75970-99-9)

Safety Data

• Hazardous Substances Data: 75970-99-9(Hazardous Substances Data)

Usage

Uses

Antihistamine used in the treatment of allergic rhinitis[Note—The trivial name, norastemizole, has appeared in literature].

InChI:InChI=1/C19H21FN4/c20-15-7-5-14(6-8-15)13-24-18-4-2-1-3-17(18)23-19(24)22-16-9-11-21-12-10-16/h1-8,16,21H,9-13H2,(H,22,23)

Upstream product

• 35621-01-3 4-aminopiperidine dihydrochloride 
• 84946-20-3 2-chloro-1-(4-fluorobenzyl)-1H-benzimidazole 
• 84501-68-8 ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinecarboxylate 
• 58859-46-4 ethyl 4-aminopiperidine-1-carboxylate 
• 68844-77-9 astemizole 
• 73733-81-0 ethyl 4-{[(2-aminophenyl)aminothioxomethyl]amino}-1-piperidinecarboxylate 
• 73734-07-3 (1H-benzimidazol-2-yl)-(1-ethoxycarbonyl-piperidin-4-yl)amine 
• 73733-70-7 ethyl 4-isothiocyanato-1-piperidinecarboxylate 
• 459-46-1 4-Fluorobenzyl bromide 
• 4857-06-1 2-chloro-1H-benzoimidazole 
• 13035-19-3 4-aminopiperidine 
• 111782-98-0 2-bromo-1-(4-fluorophenylmethyl)-1H-benzimidazole 

Downstream Products

• 73735-71-4 1-<(4-fluorophenyl)methyl>-N-<1-<2-(4-pyridinyl)ethyl>-4-piperidinyl>-1H-benzimidazol-2-amine 
• 98088-84-7 1-(4-fluorobenzyl)-N-(1-phenethylpiperidin-4-yl)-1H-benzo[d]imidazol-2-amine 
• 98088-85-8 [1-(4-Fluoro-benzyl)-1H-benzoimidazol-2-yl]-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-amine 
• 1123619-93-1 C₂₈H₂₅ClFN₅ 
• 1345012-52-3 tert-butyl 4-(2-(4-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-ylamino)piperidin-1-yl)ethyl)piperazine-1-carboxylate 
• 1345012-53-4 (4-(2-(4-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-ylamino)piperidin-1-yl)ethyl)piperazin-1-yl)(1H-indol-2-yl)methanone 
• 75971-19-6 1-(4-fluorobenzyl)-N-(1-(3-methoxyphenethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2-amine 
• 73735-41-8 1-(4-fluorobenzyl)-N-(1-(2-methoxyphenethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2-amine 
• 68844-77-9 astemizole 
• 111782-97-9 1-(4-((1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)amino)piperidin-1-yl)-2-(4-methoxyphenyl)ethan-1-one 

Relevant articles and documents

Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2-EED Interaction

Disruption of EZH2-embryonic ectoderm development (EED) protein-protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery of astemizole, a small-molecule inhibitor targeting the EZH2-EED PPI. Herein, we report the cocrystal structure of EED in complex with astemizole at 2.15 ?. The structure elucidates the detailed binding mode of astemizole to EED and provides a structure-guided design for the discovery of a novel EZH2-EED interaction inhibitor, DC-PRC2in-01, with an affinityKdof 4.56 μM. DC-PRC2in-01 destabilizes the PRC2 complex, thereby leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. The proliferation of PRC2-driven lymphomas cells is effectively inhibited, and the cell cycle is arrested in the G0/G1 phase. Together, these data demonstrate that DC-PRC2in-01 could be an effective chemical probe for investigating the PRC2-related physiology and pathology and providing a promising chemical scaffold for further development.

METHODS AND COMPOSITIONS FOR TREATMENT OF CANCER

In an aspect, the disclosure pertains to inhibitors of ANGPTL4; synthesis methods for making disclosed compounds; pharmaceutical compositions comprising disclosed compounds; methods of treating disorders of uncontrolled cellular proliferation, e.g., a cancer; and methods of treating a disease associated with an ANGPTL4 dysfunction using disclosed compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Characterization of the active site properties of CYP4F12

Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12 that may impart an increased catalytic selectivity (decreased promiscuity) were explored through in vitro metabolite elucidation, kinetic isotope effect experiments, and computational modeling of the CYP4F12 active site. By using astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that although CYP4F12 favored astemizole O-demethylation as the primary route of metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on the molecule. Deuteration of astemizole at the site of O-demethylation resulted in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of clearance for astemizole by CYP4F12. Conversely, although an isotope effect of 3.8 was observed for the formation of the O-desmethyl metabolite when deuterated astemizole was metabolized by CYP3A4, there was no decrease in the clearance of astemizole. Development of a homology model of CYP4F12 based on the crystal structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that was approximately 76% of the active site volume of CYP3A4. As predicted, multiple favorable binding orientations were available for astemizole docked into the active site of CYP3A4, but only a single binding orientation with the site of O-demethylation oriented toward the heme was identified for CYP4F12. Overall, it appears that although CYP4F12 may be capable of binding similar ligands to other cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically favorable orientations may be inherently more difficult because of the increased steric constraints of the CYP4F12 active site. Copyright