515133-99-0

Basic information

• Product Name: Benzoic acid, 4-chloro-2-(phenoxymethyl)-
• CAS NO: 515133-99-0
• Molecular Formula: C14H11ClO3
• Molecular Weight: 262.693
• Mol File: 515133-99-0.mol

Chemical Properties

• CAS DataBase Reference: Benzoic acid, 4-chloro-2-(phenoxymethyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzoic acid, 4-chloro-2-(phenoxymethyl)-(515133-99-0)
• EPA Substance Registry System: Benzoic acid, 4-chloro-2-(phenoxymethyl)-(515133-99-0)

Safety Data

• Hazardous Substances Data: 515133-99-0(Hazardous Substances Data)

Upstream product

• 15365-28-3 ethyl α-Bromo-4-chloro-o-toluate 
• 15393-58-5 4-chloro-2-methyl-benzoic acid ethyl ester 
• 7499-07-2 4-chloro-2-methylbenzoic acid 
• 515133-98-9 C₁₅H₁₃ClO₃ 

Relevant articles and documents

MONO HALOGEN OR METHYL-SUBSTITUTED 5-HT2B ANTAGONISTS WITH INCREASED ACTIVITY

Disclose herein are mono halogen or methyl-substituted 5-HT 2B antagonist compounds, which have been found with increased binding activity to 5-HT 2B receptor due to the substitution of halogen or methyl, and the method of using the compounds of treating or preventing a disorder mediated by 5-HT 2B.

Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor-Ligand Interactions

Here, we predicted the potential halogen bonding interaction between compound 2 and the 5-hydroxytryptamine 2B (5-HT2B) receptor and systematically assessed this interaction via structure-activity relationship analysis and molecular dynamics simulations. A physics-based computational protocol was then developed to further explore the opportunity of "designing in" halogen bonding interactions in structure-based ligand design for the 5-HT2B receptor, which not only facilitated the identification of previously uncharacterized halogen bonds in known 5-HT2B ligands but also enabled the rational design of halogen bonding interactions for the optimization of 5-HT2B ligands. As a proof-of-concept, a series of halogen-substituted analogues of doxepin was synthesized and evaluated, which showed improved in vitro and in vivo potency.

Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs

Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H1/H4 receptor ligand (pKi: 8.11 (human H1R (hH1R)), 7.55 (human H4R (hH4R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH1R (pKi: 6.8–8.7), but no or moderate affinity to the hH4R (pKi: ≤ 5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH1R (pKi: 8.83 (R), 7.63 (S)) and the guinea-pig H1R (gpH1R) (pKi: 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH1R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH1R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH1R or hH4R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH1/h5-HT2A receptor ligand (pKi: 9.23 (hH1R), 8.74 (h5-HT2AR), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH1R antagonist (pKi: 8.44 (hH1R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles receptor selectivity and specificity.

Doxepin analogs and methods of use thereof

The invention relates to novel antihistamines and methods of modulating sleep by administering a doxepin analog or a pharmaceutically effective salt thereof.

METHODS OF TREATING SLEEP DISORDERS

The invention relates to novel antihistamines and methods of modulating sleep by administering a doxepin analog or a pharmaceutically effective salt thereof.