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Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities.

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Title: Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities.
Authors: Jurica EA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States. Electronic address: Elizabeth.Jurica@bms.com., Wu X; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Williams KN; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Haque LE; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Rampulla RA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Mathur A; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Zhou M; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Cao G; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Cai H; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Wang T; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Liu H; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Xu C; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Kunselman LK; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Antrilli TM; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Hicks MB; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Sun Q; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Dierks EA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Apedo A; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Moore DB; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Foster KA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Cvijic ME; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Panemangalore R; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Khandelwal P; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Wilkes JJ; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Zinker BA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Robertson DG; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Janovitz EB; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Galella M; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Li YX; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Li J; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Ramar T; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Jalagam PR; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Jayaram R; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Whaley JM; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Barrish JC; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Robl JA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Ewing WR; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States., Ellsworth BA; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States.
Source: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2023 May 01; Vol. 85, pp. 117273. Date of Electronic Publication: 2023 Apr 04.
Publication Type: Journal Article
Journal Info: Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE
Database: MEDLINE Ultimate
FullText Text:
  Availability: 0
Header DbId: mdl
DbLabel: MEDLINE Ultimate
An: 37030194
AccessLevel: 2
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities.
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  Data: <searchLink fieldCode="AU" term="%22Jurica+EA%22">Jurica EA</searchLink>; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States. Electronic address: Elizabeth.Jurica@bms.com.<br /><searchLink fieldCode="AU" term="%22Wu+X%22">Wu X</searchLink>; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States.<br /><searchLink fieldCode="AU" term="%22Williams+KN%22">Williams KN</searchLink>; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States.<br /><searchLink fieldCode="AU" term="%22Haque+LE%22">Haque LE</searchLink>; Research and Development, Bristol Myers Squibb, Co., P.O. Box 4000, Princeton, NJ 08543-4000, United States.<br /><searchLink fieldCode="AU" term="%22Rampulla+RA%22">Rampulla RA</searchLink>; Research and Development, Bristol Myers Squibb, Co., P.O. 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  Data: <searchLink fieldCode="JN" term="%229413298%22">Bioorganic & medicinal chemistry</searchLink> [Bioorg Med Chem] 2023 May 01; Vol. 85, pp. 117273. <i>Date of Electronic Publication: </i>2023 Apr 04.
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