Preparation of tetrahydroisoquinoline and tetrahydrobenzoazepine derivatives for use as GPR120 modulators.

Jane Brown (Opfinder), Stephen Connolly (Opfinder), Steffen V. F. Hansen (Opfinder), Gavin Milne (Opfinder), Bharat Shimpukade (Opfinder), Don Smyth (Opfinder), Gerard Thomas (Opfinder), Trond Ulven (Opfinder), Matjaz Brvar (Opfinder), Aaron. Rigby (Opfinder)

Publikation: Patent

Abstract

Title compds. I [A = CO2H, CH2OH, tetrazolyl, etc.; E and L independently = (un)substituted alkyl, alkoxy, cycloalkyl, etc.; G = (un)substituted aryl, heteroaryl, or fused aryl or heteroaryl ring; J = C(R1)2, O, NR1, or S; M = aryl, heteroaryl, or cycloalkyl; X = absent, O, S, or C(R1)2; Y = absent, O, or C(R1)2; Z = absent or C(R1)2; X and Y, Y and Z, or X and Z may be combined to form an (un)substituted cycloalkyl ring; each R1 independently = H, D, halo, or (un)substituted alkyl; n = 1 or 2; with provisions], and their pharmaceutically acceptable salts, are prepd. and disclosed as GPR120 modulators. Thus, e.g., II was prepd. by a multistep procedure (prepn. given). I were evaluated in human GPR120-B arrestin 2 bio-luminescence resonance energy transfer (BRET) agonist assays, e.g., II demonstrated a pEC50 value of 7.4. [on SciFinder(R)]
OriginalsprogEngelsk
PatentnummerWO2018172727A1
Land/OmrådeDanmark
StatusUdgivet - 27 sep. 2018

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