72456-64-5

Upstream product

• 5406-18-8 3-(p-methoxyphenyl)-1-propanol 
• 124-63-0 methanesulfonyl chloride 
• 7143-01-3 Methanesulfonic anhydride 
• 1929-29-9 3-(4-methoxyphenyl)propanoic acid 

Downstream Products

• 36397-23-6 3-(4-methoxyphenyl)propylamine 
• 200400-73-3 N-<3-(4-methoxyphenyl)propyl>-2-<4-(3-pyridylcarbonyl)phenyl>-4-oxazolecarboxamide 
• 281678-00-0 5,11-dihydro-5-[2-[N-[3-(4-methoxyphenyl)propyl]-N-methylamino]ethyl]dibenzo[b,e][1,4]oxazepine 
• 113379-13-8 3-(4-methoxyphenyl)-1-iodopropane 
• 72457-25-1 4-(4-methoxyphenyl)butanenitrile 

Relevant academic research and scientific papers

Copper-Catalyzed Cross-Coupling between Alkyl (Pseudo)halides and Bicyclopentyl Grignard Reagents

The development of a copper-catalyzed cross-coupling between primary and secondary (pseudo)halides and bicyclopentyl Grignard reagents is reported. Highly strained bicyclopentanes can be cross-coupled with a large panel of primary alkyl mesylates and secondary alkyl iodides. The catalytic system is simple and cheap, and the reaction is general and chemoselective.

Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin

To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.

The synthesis of three isotopomers of 2-methyl-2-(4-[3-[1-(4-methylbenzyl)- 5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]propyl]phenoxy)propionic acid, a potent and selective peroxisome proliferator-activated receptor alpha agonist

Although fenofibrate (1a) is commercially available and clinically effective in lowering serum triglycerides, its activity and sub-type selectivity at the PPARα receptors are only moderate; therefore, there exists a need for more potent and sub-type selec

Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: Drugs for cystic fibrosis and chronic bronchitis

Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent short-circuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloríde and displayed the lowest IC50 value ever reported for an ENaC blocker.

Novel benzopyridothiadiazepines as potential active antitumor agents

The synthesis of novel thiadiazepine derivatives, that could be considered as constraint analogues of E-7010, are reported. These molecules were evaluated for their antiproliferative activity toward the murine L1210 leukemia cell line. Flow cytometric studies performed on L1210 cells with the most cytotoxic compounds showed an accumulation of the cells in the G2/M phases of the cell cycle with a significant percentage of tetraploid cells (8N DNA content). Submicromolar cytotoxicities were observed with compounds 2b, 4b, 4e, 4g, and 4i. Two of them, compounds 2b and 4b, were found to be potent inhibitors of tubulin polymerization with IC50 of respectively 3.8 and 2.4 μM compared to 2.4 μM for desoxypodophyllotoxin. A 4-methoxyphenylethyl substitution on the pyridinyl nitrogen of the benzopyridothiadiazepine was found to be essential for the antiproliferative activity. The in vitro activities of compounds 2b and 4b make benzopyridothiadiazepine dioxides a promising new class of tubulin binders which warrant further in vivo evaluation.

Matrix metalloproteinase inhibitors

A compound, which is an amine derivative of formula (I) wherein W is —CNHOH or —COOH: R1and R2are each hydrogen or an organic residue, R3is an organic group, Q is a secondary or tertiary acyclic or cyclic amido group, and

Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted ω-phenyl-ω-(3-pyridyl)alkenoic acid derivatives and related compounds

A novel series of oxazolecarboxamide-substituted ω-phenyl-ω-(3- pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4- [4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept- 6-enoic acid (14) with K(d) = 9.9 ± 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 ± 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, 'shunt' effect to elevate PGI2 level, and absence of agonist activity.

Reactions of γ-arylalkanols via aryl radical cation and alkoxyl radical intermediates. Part 3. Reactions of 3-arylprop-1-yl hydroperoxides with iron(II) in the presence of copper(II)

A strategy for comparing the 1,5- and 1,6-cyclisation reactions of 3-phenylpropan-1-oxyl radicals is described.Iron(II)-catalysed reduction of 3-(p-methylphenyl)prop-1-yl hydroperoxide and its para-chloro and para-methoxy-substituted analogues, carried out in the presence of copper(II), has been found to give in each case the appropriate para-substituted 3-phenylpropan-1-ol, 3-phenylpropanal and a low yield of a mixture of isomeric 6- and 7-substituted chromans.The alcohols are proposed to form via reduction of either the hydroperoxide or the resulting alkoxyl radical or its cyclised intermediates, and the aldehydes as a result of rearrangement of the alkoxyl radical to an α-hydroxy alkyl radical which subsequently undergoes oxidation.The 7-substituted chromans, which arise directly from 1,6-cyclisation of the alkoxyl radical, were found to dominate the 6-substituted isomers which result from rearrangement of 1,5-cyclised intermediates.This effect is attributed to inefficient interception of the 1,5-cyclised radical intermediate which permits equilibration to the thermodynamically more stable 1,6-cyclised radical isomer to occur.The effect of pH on the reactions has been investigated and although no products typical of the intermediacy of aryl radical cations were detected (even under highly acidic conditions), the formation of such intermediates cannot be excluded.Semiempirical MO calculations have been carried out (at the PM3 level of approximation) on a series of model compounds, yielding results which have clarified our understanding of the effect of substituents on the stabilities of the various intermediates arising from the cyclisation reactions of 3-phenylpropan-1-oxyl radicals.Furthermore, these calculations have supported our assumptions regarding the probability and specificity of rearrangements of the spirodienyl intermediates.

7-oxabicycloheptyl substituted heterocyclic amide or ester prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease

7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasopastic disease have the structural formula STR1 wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is --(CH2)2 --, --CH=CH-- or STR2 wherein Y is O, a single bond or vinyl, with the proviso that when n is 0, if Z is STR3 then Y cannot be O, and Z is --CH=CH--, n is 1, 2, 3 or 4; and when Y=vinyl, n=0; R is CO2 H, CO2 lower alkyl, CH2 OH, CO2 alkali metal, CONHSOR3, CONHR3a or --CH2 --5-tetrazolyl, X is O, S or NH; and where R1, R2, R3 and R3a are as defined herein.