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• W2314644705 endingPage "9755" @default.
• W2314644705 startingPage "9737" @default.
• W2314644705 abstract "From a high-throughput screening campaign aiming at the identification of novel S1P1 receptor agonists, the pyrazole derivative 2 emerged as a hit structure. Medicinal chemistry efforts focused not only on improving the potency of the compound but in particular also on resolving its inherent instability issue. This led to the discovery of novel bicyclo[3.1.0]hexane fused thiophene derivatives. Compounds with high affinity and selectivity for S1P1 efficiently reducing the blood lymphocyte count in the rat were identified. For instance, compound 85 showed EC50 values of 7 and 2880 nM on S1P1 and S1P3, respectively, had favorable pharmacokinetic properties in rat and dog, distributed well into brain tissue, and efficiently and dose dependently reduced the blood lymphocyte count in the rat. After oral administration to spontaneously hypertensive rats, the S1P1 selective compound 85 showed no effect on mean arterial blood pressure and affected the heart rate during the wake phase of the animals only." @default.
• W2314644705 created "2016-06-24" @default.
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• W2314644705 date "2013-11-22" @default.
• W2314644705 modified "2023-10-07" @default.
• W2314644705 title "Novel S1P₁ Receptor Agonists – Part 1: From Pyrazoles to Thiophenes" @default.
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• W2314644705 doi "https://doi.org/10.1021/jm4014373" @default.
• W2314644705 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24266709" @default.
• W2314644705 hasPublicationYear "2013" @default.
• W2314644705 type Work @default.

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