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Chemical Structure| 26346-85-0 Chemical Structure| 26346-85-0

Structure of 26346-85-0

Chemical Structure| 26346-85-0

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Product Citations

Product Citations

Dinh, Le Vi ; Dangerfield, Jesse ; DeBono, Aaron ; Keller, Andrew N ; Josephs, Tracy M ; Gregory, Karen J , et al.

Abstract: The calcium-sensing receptor (CaSR) is a validated therapeutic target in the treatment of hyperparathyroidism and related diseases. The CaSR ago-positive allosteric modulator (PAM), AC265347 (1), exhibits a chemically and pharmacologically unique profile compared to current approved CaSR PAM therapeutics. Herein, we report a series of ‘next-generation’ analogues of AC265347, investigating the impact of structural modifications at the stereogenic centre on CaSR PAM activity. Compounds 5 and 7b featuring the alcohol functional group showed ago-PAM profiles comparable to 1, whilst compounds 6, 7 and 9 devoid of this functionality were ‘pure’ PAMs with no intrinsic agonism. These novel chemical tools provide an opportunity to explore the therapeutic potential of AC265347-like PAMs as a function of affinity, cooperativity and intrinsic agonism.

Keywords: positive allosteric modulator ; PAM ; calcium-sensing receptor ; AC265347 ; stereogenic centre

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Product Details of [ 26346-85-0 ]

CAS No. :26346-85-0
Formula : C10H11BrO
M.W : 227.09
SMILES Code : CC1=CC=C(C(CBr)=O)C(C)=C1
MDL No. :MFCD00017872
InChI Key :GSCCVWPVPFIRJP-UHFFFAOYSA-N
Pubchem ID :2063450

Safety of [ 26346-85-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Application In Synthesis of [ 26346-85-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 26346-85-0 ]

[ 26346-85-0 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 110-86-1 ]
  • [ 26346-85-0 ]
  • [ 59224-30-5 ]
  • 2
  • [ 625-57-0 ]
  • [ 26346-85-0 ]
  • [ 99842-63-4 ]
  • 3
  • [ 817-73-2 ]
  • [ 26346-85-0 ]
  • [ 100192-05-0 ]
  • 4
  • [ 89-74-7 ]
  • [ 26346-85-0 ]
YieldReaction ConditionsOperation in experiment
52% With copper(I) bromide; In ethyl acetate; for 3h;Heating / reflux; Reference Example 1 (2',4'-dimethyl)phenyl-2-bromoacetophenone (1) (2',4'-Dimethyl)-2-acetophenone (14.8 g, 100 mmol) was dissolved in ethyl acetate (200 ml) and copper bromide (45.0 g, 200 mmol) was added. The mixture was heated under reflux for 3 hrs. After cooling, solid was filtered off. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, which was then converted to a powder from isopropyl ether to give the title compound (11.9 g, 52%). 1H-NMR (200Hz, CDCl3) δ: 2.37(3H, s), 2.52 (3H, s), 4.42 (2H, s), 7.09 (1H, d, J = 7.0 Hz), 7.11(1H, s), 7.62 (1H, d, J = 7.0 Hz).
With hydrogen bromide; bromine; acetic acid; at 0 - 5℃; General procedure: General procedure to obtainα-bromoacetophenonederivatives Acetophenone derivative (10 mmol) was solved in acetic acid(50 mL) and hydrobromic acid (0.5 mL) mixture. Bromine(10 mmol, 0.52 mL) was added dropwise to this mixture at 0-5Ctemperatureandthemixturewasstirredfor6-7h.Afterthisperiod, the mixture was poured into ice-water, collapsed portionwas filtrated and after dryness it was crystallized from ethanol.
With N-Bromosuccinimide; toluene-4-sulfonic acid; In ethyl acetate; at 20℃; for 12h; 0.22g (1.5mmol) 2,4- dimethyl acetophenone, 0.27g (1.5mmol) N- bromosuccinimide and 0.03g (0.15mmol) of p-toluenesulfonic acid dissolved in 15mL ethyl acetate. The reaction was stirred for 12 hours at room temperature, TLC tracking, completion of the reaction, deionized water (3 × 10mL) and washed, the organic solvent was removed under reduced pressure to give the crude product α- bromo - (2,4-dimethyl) phenylacetyl ketone, 95% yield, was used directly without purification in the next reaction.
With copper(ll) bromide; In ethyl acetate; at 80℃;Inert atmosphere; General procedure: To a solution of 2-ethoxyacetophenone (4.71 g, 28.7 mmol) inAcOEt was added copper bromide (7.37 g, 31.6 mmol). The solutionwas heated at 80 C under nitrogen protection. When the solid in theflask turned from black to white, the solution was cooled to roomtemperature. The solid was removed by filtration. The filter cake waswashed with AcOEt. The combined filtrates were concentrated in vacuoto afford G (6.14 g, 88.08%) which was used directly in the next stepwithout purification.

  • 5
  • [ 1779-81-3 ]
  • [ 26346-85-0 ]
  • [ 802270-16-2 ]
  • 7
  • [ 26346-85-0 ]
  • [ 19398-12-0 ]
  • 3-(2,4-dimethyl-phenyl)-5,10-dihydro-benzo[<i>e</i>]thiazolo[3,2-<i>a</i>][1,3]diazepine [ No CAS ]
  • 8
  • [ 616-47-7 ]
  • [ 26346-85-0 ]
  • [ 103793-29-9 ]
  • 10
  • [ 26346-85-0 ]
  • [ 18197-26-7 ]
  • [ 129972-98-1 ]
  • 11
  • [ 26346-85-0 ]
  • [ 18197-26-7 ]
  • [ 129972-94-7 ]
  • 14
  • [ 26346-85-0 ]
  • ethyl 3-amino-3-(4-phenylpiperazino)propenoate [ No CAS ]
  • 5-(2,4-Dimethyl-phenyl)-2-(4-phenyl-piperazin-1-yl)-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]
  • 15
  • [ 26346-85-0 ]
  • ethyl 3-amino-3-<4-(4-chlorophenyl)piperazino>propenoate [ No CAS ]
  • 2-[4-(4-Chloro-phenyl)-piperazin-1-yl]-5-(2,4-dimethyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester [ No CAS ]
  • 16
  • [ 54503-96-7 ]
  • [ 26346-85-0 ]
  • 5'-(2,4-Dimethyl-phenyl)-2,3,4,5-tetrahydro-1'H-[1,2']bipyrrolyl-3'-carbonitrile [ No CAS ]
  • 18
  • [ 26346-85-0 ]
  • [ 202405-59-2 ]
  • 3,6-Diamino-4-(2-chloro-phenyl)-2-(2,4-dimethyl-benzoyl)-thieno[2,3-b]pyridine-5-carbonitrile [ No CAS ]
  • 19
  • [ 26346-85-0 ]
  • N-methylmorpholinium 6-amino-3,5-dicyano-4-ethylpyridine-2-thiolate [ No CAS ]
  • 2-amino-6-[2-(2,4-dimethyl-phenyl)-2-oxo-ethylsulfanyl]-4-ethyl-pyridine-3,5-dicarbonitrile [ No CAS ]
  • 20
  • [ 26346-85-0 ]
  • N-methylmorpholinium 3-cyano-5-[(phenylamino)carbonyl]-4-(2-furyl)-6-methyl-1,4-dihydropyridine-2-thiolate [ No CAS ]
  • 5-cyano-6-[2-(2,4-dimethyl-phenyl)-2-oxo-ethylsulfanyl]-4-furan-2-yl-2-methyl-1,4-dihydro-pyridine-3-carboxylic acid phenylamide [ No CAS ]
  • 21
  • [ 26346-85-0 ]
  • [ 332175-09-4 ]
  • 2-amino-6-[2-(2,4-dimethyl-phenyl)-2-oxo-ethylsulfanyl]-4-ethyl-pyridine-3,5-dicarbonitrile [ No CAS ]
  • 22
  • [ 26346-85-0 ]
  • N-methylmorpholinium 3-cyano-6-methyl-5-(2-methylphenyl)carbamoyl-4-(2-thienyl)-1,4-dihydropyridine-2-thiolate [ No CAS ]
  • 5-cyano-6-[2-(2,4-dimethyl-phenyl)-2-oxo-ethylsulfanyl]-2-methyl-4-thiophen-2-yl-1,4-dihydro-pyridine-3-carboxylic acid <i>o</i>-tolylamide [ No CAS ]
  • 23
  • [ 131-56-6 ]
  • [ 26346-85-0 ]
  • (2,4-dimethyl-phenyl)-(6-hydroxy-3-phenyl-benzofuran-2-yl)-methanone [ No CAS ]
  • 24
  • [ 26346-85-0 ]
  • [ 92549-46-7 ]
  • (2,4-dimethyl-phenyl)-[6-hydroxy-3-(2-methoxy-benzyl)-benzofuran-2-yl]-methanone [ No CAS ]
  • 25
  • [ 26346-85-0 ]
  • (2,4-dihydroxy-phenyl)-naphthalen-1-yl-methanone [ No CAS ]
  • (2,4-dimethyl-phenyl)-(6-hydroxy-3-naphthalen-1-yl-benzofuran-2-yl)-methanone [ No CAS ]
  • 26
  • [ 26346-85-0 ]
  • [ 89-74-7 ]
  • [ 497957-92-3 ]
  • 27
  • [ 1193-62-0 ]
  • [ 26346-85-0 ]
  • methyl 1-[2-(2,4-dimethylphenyl)-2-oxoethyl]pyrrole-2-carboxylate [ No CAS ]
  • 28
  • [ 26346-85-0 ]
  • [ 640724-27-2 ]
  • 2-[2-(2,4-dimethyl-phenyl)-2-oxo-ethylsulfanyl]-5-isopropyl-6-naphthalen-1-ylmethyl-3<i>H</i>-pyrimidin-4-one [ No CAS ]
  • 29
  • [ 26346-85-0 ]
  • [ 762-42-5 ]
  • dimethyl 2-(2,4-dimethylphenyl)furan-3,4-dicarboxylate [ No CAS ]
  • 30
  • [ 26346-85-0 ]
  • (S)-2-bromo-1-(2,4-dimethylphenyl)-ethanol [ No CAS ]
  • (R)-2-bromo-1-(2,4-dimethylphenyl)-ethanol [ No CAS ]
  • 33
  • [ 26346-85-0 ]
  • 3-(2,4-dimethylphenyl)-2-methyl-1-pyrrolo[1,2-a]pyrazinone [ No CAS ]
  • 34
  • [ 26346-85-0 ]
  • [ 409365-53-3 ]
 

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Technical Information

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