کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370051 | 981807 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool](/preview/png/1370051.png)
چکیده انگلیسی
This Letter describes the further lead optimization of the VU0486321 series of mGlu1 positive allosteric modulators (PAMs), driven by recent genetic data linking loss of function GRM1 to schizophrenia. Steep and caveat-laden SAR plagues the series, but ultimately potent mGlu1 PAMs (EC50s ∼5 nM) have resulted with good DMPK properties (low intrinsic clearance, clean CYP profile, modest Fu) and CNS penetration (Kps 0.25–0.97), along with up to >450-fold selectivity versus mGlu4 and mGlu5.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 3, 1 February 2016, Pages 751–756
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 3, 1 February 2016, Pages 751–756
نویسندگان
Pedro M. Garcia-Barrantes, Hyekyung P. Cho, Adam M. Metts, Anna L. Blobaum, Colleen M. Niswender, P. Jeffrey Conn, Craig W. Lindsley,