Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313259815> ?p ?o ?g. }
- W4313259815 endingPage "432" @default.
- W4313259815 startingPage "432" @default.
- W4313259815 abstract "Previous studies have confirmed that the binding of D3 receptor antagonists is competitively inhibited by endogenous dopamine despite excellent binding affinity for D3 receptors. This result urges the development of an alternative scaffold that is capable of competing with dopamine for binding to the D3 receptor. Herein, an SAR study was conducted on metoclopramide that incorporated a flexible scaffold for interaction with the secondary binding site of the D3 receptor. The alteration of benzamide substituents and secondary binding fragments with aryl carboxamides resulted in excellent D3 receptor affinities (Ki = 0.8–13.2 nM) with subtype selectivity to the D2 receptor ranging from 22- to 180-fold. The β-arrestin recruitment assay revealed that 21c with 4-(pyridine-4-yl)benzamide can compete well against dopamine with the highest potency (IC50 = 1.3 nM). Computational studies demonstrated that the high potency of 21c and its analogs was the result of interactions with the secondary binding site of the D3 receptor. These compounds also displayed minimal effects for other GPCRs except moderate affinity for 5-HT3 receptors and TSPO. The results of this study revealed that a new class of selective D3 receptor antagonists should be useful in behavioral pharmacology studies and as lead compounds for PET radiotracer development." @default.
- W4313259815 created "2023-01-06" @default.
- W4313259815 creator A5013971949 @default.
- W4313259815 creator A5031580802 @default.
- W4313259815 creator A5059770390 @default.
- W4313259815 creator A5065755908 @default.
- W4313259815 creator A5081298897 @default.
- W4313259815 creator A5090256508 @default.
- W4313259815 date "2022-12-27" @default.
- W4313259815 modified "2023-09-30" @default.
- W4313259815 title "Design and Synthesis of Conformationally Flexible Scaffold as Bitopic Ligands for Potent D3-Selective Antagonists" @default.
- W4313259815 cites W1565905255 @default.
- W4313259815 cites W1943467734 @default.
- W4313259815 cites W1966092598 @default.
- W4313259815 cites W1972931244 @default.
- W4313259815 cites W1976752955 @default.
- W4313259815 cites W1979129023 @default.
- W4313259815 cites W1980277133 @default.
- W4313259815 cites W1992947643 @default.
- W4313259815 cites W1995650083 @default.
- W4313259815 cites W2003327647 @default.
- W4313259815 cites W2007781367 @default.
- W4313259815 cites W2009521275 @default.
- W4313259815 cites W2017578012 @default.
- W4313259815 cites W2021520922 @default.
- W4313259815 cites W2026446059 @default.
- W4313259815 cites W2027192373 @default.
- W4313259815 cites W2034475831 @default.
- W4313259815 cites W2034996573 @default.
- W4313259815 cites W2036001291 @default.
- W4313259815 cites W2036218676 @default.
- W4313259815 cites W2064671909 @default.
- W4313259815 cites W2066414494 @default.
- W4313259815 cites W2068326346 @default.
- W4313259815 cites W2068825785 @default.
- W4313259815 cites W2075285753 @default.
- W4313259815 cites W2075837642 @default.
- W4313259815 cites W2076356878 @default.
- W4313259815 cites W2077331067 @default.
- W4313259815 cites W2084511377 @default.
- W4313259815 cites W2086627093 @default.
- W4313259815 cites W2090096265 @default.
- W4313259815 cites W2090518397 @default.
- W4313259815 cites W2090891087 @default.
- W4313259815 cites W2096037950 @default.
- W4313259815 cites W2104961861 @default.
- W4313259815 cites W2105668062 @default.
- W4313259815 cites W2105891411 @default.
- W4313259815 cites W2119097756 @default.
- W4313259815 cites W2140831051 @default.
- W4313259815 cites W2148455827 @default.
- W4313259815 cites W2155207556 @default.
- W4313259815 cites W2155208284 @default.
- W4313259815 cites W2160536323 @default.
- W4313259815 cites W2162337394 @default.
- W4313259815 cites W2169678694 @default.
- W4313259815 cites W2195476037 @default.
- W4313259815 cites W2206954826 @default.
- W4313259815 cites W2334233199 @default.
- W4313259815 cites W2337340160 @default.
- W4313259815 cites W2339958462 @default.
- W4313259815 cites W2509180953 @default.
- W4313259815 cites W2510893874 @default.
- W4313259815 cites W2528026532 @default.
- W4313259815 cites W2561598420 @default.
- W4313259815 cites W2612598385 @default.
- W4313259815 cites W2752805271 @default.
- W4313259815 cites W2767956701 @default.
- W4313259815 cites W2883956246 @default.
- W4313259815 cites W2901989624 @default.
- W4313259815 cites W2941591985 @default.
- W4313259815 cites W2949640461 @default.
- W4313259815 cites W2950671078 @default.
- W4313259815 cites W2957081927 @default.
- W4313259815 cites W2974132559 @default.
- W4313259815 cites W3016132807 @default.
- W4313259815 cites W3134477031 @default.
- W4313259815 cites W3142157181 @default.
- W4313259815 cites W3165231150 @default.
- W4313259815 cites W3199531963 @default.
- W4313259815 cites W3206085463 @default.
- W4313259815 cites W4241694975 @default.
- W4313259815 cites W4280566711 @default.
- W4313259815 cites W944154379 @default.
- W4313259815 doi "https://doi.org/10.3390/ijms24010432" @default.
- W4313259815 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36613875" @default.
- W4313259815 hasPublicationYear "2022" @default.
- W4313259815 type Work @default.
- W4313259815 citedByCount "1" @default.
- W4313259815 countsByYear W43132598152023 @default.
- W4313259815 crossrefType "journal-article" @default.
- W4313259815 hasAuthorship W4313259815A5013971949 @default.
- W4313259815 hasAuthorship W4313259815A5031580802 @default.
- W4313259815 hasAuthorship W4313259815A5059770390 @default.
- W4313259815 hasAuthorship W4313259815A5065755908 @default.
- W4313259815 hasAuthorship W4313259815A5081298897 @default.
- W4313259815 hasAuthorship W4313259815A5090256508 @default.
- W4313259815 hasBestOaLocation W43132598151 @default.