71501-44-5

Usage

Chemical Properties

CLEAR BROWN LIQUID

InChI:InChI=1/C12H12Cl2O/c13-10-5-3-9(4-6-10)12(11(14)15)7-1-2-8-12/h3-6H,1-2,7-8H2

Upstream product

• 80789-69-1 1-(4-chlorophenyl)cyclopentane-1-carboxylic acid 
• 140-53-4 p-chlorobenzyl cyanide 
• 914106-85-7 1-(4-chlorophenyl)-1-cyclopentanecarboxylic acid methyl ester 
• 52449-43-1 (4-chloro-phenyl)-acetic acid methyl ester 
• 64399-26-4 1-(4-chlorophenyl)cyclopentanecarboxylic acid 

Downstream Products

• 143407-73-2 Sodium; (6R,7R)-7-{[1-(4-chloro-phenyl)-cyclopentanecarbonyl]-amino}-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate 
• 143407-77-6 Sodium; (6R,7R)-3-acetoxymethyl-7-{[1-(4-chloro-phenyl)-cyclopentanecarbonyl]-amino}-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate 
• 911056-42-3 1-(4-chloro-phenyl)-cyclopentanecarboxylic acid (thiophen-2-ylmethyl)-amide 
• 911056-53-6 1-(4-chlorophenyl)-N-methyl-N-(thiophen-2-ylmethyl)cyclopentanecarboxamide 
• 1072809-93-8 C₁₃H₁₆ClNO₂ 
• 1072809-96-1 C₁₉H₂₀ClNO₂ 

Relevant academic research and scientific papers

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.

Synthesis and Biological Activity of Arylcyclopentane-1-carboxylic Acids Aminoesters

1-Arylcyclopentane-1-carboxylic acids were synthesized by alkaline hydrolysis of the corresponding nitriles. Reactions of the acid chlorides with N,N-dialkylaminoalkyl-and hetarylalkylalkanols provided new aminoester derivatives of 1-arylcyclopentane-1-carboxylic acids. Sympatholytic and adrenolytic activity of the obtained amino esters hydrochlorides was studied.

Synthesis of 4H-1,3-Benzoxazines via Metal- and Oxidizing Reagent-Free Aromatic C-H Oxygenation

An unprecedented electrochemical aromatic C-H oxygenation reaction for the synthesis of 4H-1,3-benzoxazines from easily available N-benzylamides is reported. These oxidative cyclization reactions proceed in a transition metal- and oxidizing reagent-free fashion and produce H2 as only theoretical byproduct. Adapting the C-H oxygenation reaction in an electrochemical microreactor has been demonstrated.

Synthesis of β-, γ-, and δ-lactams via Pd(II)-catalyzed C-H activation reactions

Pd(II)-catalyzed intramolecular amination of sp2 and sp3 C-H bonds are developed using a combination of CuCl2 and AgOAc as the oxidant. The reaction protocol tolerates the presence of a double bond in the substrates. This catalytic reaction provides practical access to a wide range of β-, γ-, and δ-lactams. Copyright

BIPHENYLOXY-ACIDS

The present invention relates generally to substituted biphenyloxy acids (such as 4'-aryl-amido-biphenyl--4(3)-yloxy-acids and 4’-aryl-amidomethyl-biphenyl-4(3)-yloxy-acids) and methods of using them.

Ion channel modulating agents

The present invention relates to ion channel modulating agents. More particularly, the present invention relates to a particular class of chemical compounds that has proven useful as modulators of SK Ca, IK Ca and BK Ca channels. In further aspects, the present invention relates to the use of these SK/IK/BK channel modulating agents for the manufacture of medicaments, for methods of therapy, and pharmaceutical compositions comprising the SK/IK/BK channel modulating agents. The SK/IK/BK channel modulating agents of the invention are useful for the treatment or alleviation of diseases and conditions associated with the SK/IK/BK channels.

Novel (4-Phenylpiperidinyl)- and (4-Phenylpiperazinyl)alkyl-Spaced Esters of 1-Phenylcyclopentanecarboxylic Acids as Potent ?-Selective Compounds

A series of novel 4-phenylpiperidinyl and (4-phenylpiperazinyl)alkyl 1-1-phenylcyclopentanecarboxylates was synthesized and evaluated for affinity at ?1 and ?2 sites by inhibition of -(+)-pentazocine (PENT) and -1,3-di(2-tolyl)guanidine (DTG) binding in guinea pig brain. The phenylpiperidines were more potent ? ligands than the corresponding piperazines. Structural modifications varying the optimal spatial distance between the piperidine nitrogen and ester functions led to the identification of the propyl compound 24 (PENT Ki = 0.50 nM; DTG Ki = 1.17 nM) and the butyl derivative 32 (PENT Ki = 0.51 nM; DTG Ki = 0.69 nM) as novel high-affinity ?-selective agents. An ethylene spacer was optimum with para-substituted analogs. A notable finding was the discovery of 2-(4-phenylpiperidinyl)ethyl 1-(4-nitrophenyl)cyclopentanecarboxylate hydrochloride (15) (RLH-033), which demonstrated potent affinity for the PENT-defined ? site with a Ki of 50 pM, selectivity for ?1 over muscarinic M1 (>17600-fold), M2 (>34200-fold), dopamine D1 (>58000-fold), and D2 (>7000-fold) receptors, and inactivity at phenylcyclidine, NMDA, and opioid receptors. RLH-033 is a valuable tool which will aid further in understanding the biology of the ? recognition site. Information from this research has further defined the topography of the ? recognition site, which may provide an explanation for the diverse structures which bind with relatively high affinity.

Novel 1-Phenylcycloalkanecarboxylic Acid Derivatives Are Potent and Selective ?1 Ligands

Carbetapentane (1, 2-ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to ? sites and is a potent antitussive, anticonvulsant, and spasmolytic agent.However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug.In an attempt to determine whether these psychoactivities can be attributed to interaction at ? sites, a series of carbetapentane analogs were prepared.Phenyl ring substitution; contraction expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated.All of these novel analogs were evaluated for binding to ?1 and ?2 sites, and comparison of binding at muscarinic m1 and m2 and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed.All of the compounds were selective for ?1 over ?2 sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold).None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in >220-fold selectivity over muscarinic receptor binding.Therefore, several of these novel compounds are potent, ?1-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents.These studies may reveal whether ?1 sites play a role in the pharmacological actions of these drugs.