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N‑Alkyl and N‑Aryl Aminopyrazole Spirocarbamates: A Two-Pronged Lead Optimization Strategy to Identify Orally Bioavailable Plasma Kallikrein Inhibitors.

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Title: N‑Alkyl and N‑Aryl Aminopyrazole Spirocarbamates: A Two-Pronged Lead Optimization Strategy to Identify Orally Bioavailable Plasma Kallikrein Inhibitors.
Authors: Merchant RR; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Chernyak N; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Lopez JA; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Sharp PP; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Mandal M; Department of Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United States., He J; Department of Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Hruza A; Department of Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Rearden P; Pharmacokinetics, Dynamics, Metabolism and Bioanalytics, Merck & Co., Inc., South San Francisco, California 94080, United States., Tatosian DA; Pharmacokinetics, Dynamics, Metabolism and Bioanalytics, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Esmay J; Pharmacokinetics, Dynamics, Metabolism and Bioanalytics, Merck & Co., Inc., South San Francisco, California 94080, United States., Yang S; Computational and Structural Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Cheng AC; Computational and Structural Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Ellsworth K; Quantitative Biosciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Ogawa A; Quantitative Biosciences, Merck & Co., Inc., South San Francisco, California 94080, United States., Piou T; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Fier P; Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Hicks J; Department of Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey 07065, United States., Sinz C; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States., Ogawa AK; Department of Discovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States.
Source: ACS medicinal chemistry letters [ACS Med Chem Lett] 2026 Feb 24; Vol. 17 (3), pp. 744-749. Date of Electronic Publication: 2026 Feb 24 (Print Publication: 2026).
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101521073 Publication Model: eCollection Cited Medium: Print ISSN: 1948-5875 (Print) Linking ISSN: 19485875 NLM ISO Abbreviation: ACS Med Chem Lett Subsets: PubMed not MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1948-5875
DOI:10.1021/acsmedchemlett.6c00066