دورية أكاديمية
Development of a Novel Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist (CH5447240), a Potent and Orally Available Small Molecule for Treatment of Hypoparathyroidism.
| العنوان: | Development of a Novel Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist (CH5447240), a Potent and Orally Available Small Molecule for Treatment of Hypoparathyroidism. |
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| المؤلفون: | Nishimura Y; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Esaki T; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Isshiki Y; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Okamoto N; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Furuta Y; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Kotake T; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Watanabe Y; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Ohta M; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Nakagawa T; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Noda H; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Shimizu M; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Saito H; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Tamura T; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan., Sato H; Research Division , Chugai Pharmaceutical Co., Ltd. , Komakado 1-135 , Gotemba , Shizuoka 412-8513 , Japan. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2018 Jul 26; Vol. 61 (14), pp. 5949-5962. Date of Electronic Publication: 2018 Jul 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Drug Discovery*, Hypoparathyroidism/*drug therapy , Methylurea Compounds/*therapeutic use , Receptor, Parathyroid Hormone, Type 1/*agonists , Small Molecule Libraries/*pharmacokinetics , Small Molecule Libraries/*pharmacology , Sulfones/*therapeutic use , Urea/*pharmacokinetics , Urea/*pharmacology, Administration, Oral ; Biological Availability ; Cell Line ; Humans ; Methylurea Compounds/administration & dosage ; Methylurea Compounds/pharmacology ; Small Molecule Libraries/administration & dosage ; Small Molecule Libraries/therapeutic use ; Sulfones/administration & dosage ; Sulfones/pharmacology ; Urea/administration & dosage ; Urea/therapeutic use |
| مستخلص: | During the course of derivatization of HTS hit 4a, we have identified a novel small-molecule hPTHR1 agonist, 1-(3,5-dimethyl-4-(2-((2-((1 R,4 R)-4-methylcyclohexyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-8-yl)sulfonyl)ethyl)phenyl)-1-methylurea (CH5447240, 14l). Compound 14l exhibited a potent in vitro hPTHR1 agonist effect with EC |
| المشرفين على المادة: | 0 (CH5447240) 0 (Methylurea Compounds) 0 (PTH1R protein, human) 0 (Receptor, Parathyroid Hormone, Type 1) 0 (Small Molecule Libraries) 0 (Sulfones) 8W8T17847W (Urea) |
| تواريخ الأحداث: | Date Created: 20180623 Date Completed: 20190624 Latest Revision: 20210709 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1021/acs.jmedchem.8b00182 |
| PMID: | 29932656 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.8b00182 |