Synthesis and Structure−Activity Relationships of Novel Histamine H1 Antagonists: Indolylpiperidinyl Benzoic Acid Derivatives

التفاصيل البيبلوغرافية
العنوان:	Synthesis and Structure−Activity Relationships of Novel Histamine H1 Antagonists: Indolylpiperidinyl Benzoic Acid Derivatives
المؤلفون:	Fonquerna, S., Miralpeix, M., Pages, L., Puig, C., Cardus, A., Anton, F., Cardenas, A., Vilella, D., Aparici, M., Calaf, E., Prieto, J., Gras, J., Huerta, J. M., Warrellow, G., Beleta, J., Ryder, H.
المصدر:	Journal of Medicinal Chemistry; December 2004, Vol. 47 Issue: 25 p6326-6337, 12p
مستخلص:	A series of indolylpiperidinyl derivatives were prepared and evaluated for their activity as histamine H1 antagonists. Structure−activity relationship studies were directed toward improving in vivo activity and pharmacokinetic profile of our first lead (1). Substitution of fluorine in position 6 on the indolyl ring led to higher in vivo activity in the inhibition of histamine-induced cutaneous vascular permeability assay but lower selectivity toward 5HT2 receptor. Extensive optimization was carried out within this series and a number of histamine H1 antagonists showing potency and long duration of action in vivo and low brain penetration or cardiotoxic potential were identified. Within this novel series, indolylpiperidines 15, 20, 48, 51 and 52 exhibited a long half-life in rat and have been selected for further preclinical evaluation.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804