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Chemical Structure| 29636-75-7 Chemical Structure| 29636-75-7

Structure of 29636-75-7

Chemical Structure| 29636-75-7

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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 [ 29636-75-7 ]

CAS No. :29636-75-7
Formula : C9H9BrO
M.W : 213.07
SMILES Code : O=C(C1=CC=CC=C1)CCBr
MDL No. :MFCD01428723

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