- Detailed structure-activity relationship of indolecarboxamides as H 4 receptor ligands
-
A series of 76 derivatives of the indolecarboxamide 1 were synthesized, which allows a detailed SAR investigation of this well known scaffold. The data enable the definition of a predictive QSAR model which identifies several compounds with an activity comparable to 1. A selection of these new H 4R antagonists was synthesized and a comparison of predicted and measured values demonstrates the robustness of the model (47-55). In addition to the H4-receptor activity general CMC and DMPK properties were investigated. Some of the new analogs are not only excellently soluble, but display a significantly increased half-life in mouse liver microsomes as well. These properties qualify these compounds as a possible new standard for future in vivo studies (e.g 51, 52 and 55). Moreover, the current studies also provide valuable information on the potential receptor ligand interactions between the indolcarboxamides and the H4R protein.
- Engelhardt, Harald,De Esch, Iwan J.P.,Kuhn, Daniel,Smits, Rogier A.,Zuiderveld, Obbe P.,Dobler, Julia,Mayer, Moriz,Lips, Sebastian,Arnhof, Heribert,Scharn, Dirk,Haaksma, Eric E.J.,Leurs, Rob
-
p. 660 - 668
(2012/09/07)
-
- Chemical development of the casein kinase i - Epsilon inhibitor: 3-(3-fluorophenyl)sulfanyl-1 H -pyrrolo[3,2- b pyridine-2-carboxylic acid amide
-
The development of a scalable process for 3-arylsulfanyl-1H-pyrrolo[3,2- bpyridine-2-carboxylic acid amides (1), potent casein kinase I inhibitors, is described. The rapid identification of suitable reaction conditions expedited the lab scale synthesis of drug substances for early toxicological evaluations. Further improvements were made to achieve a safe and cost-effective process to meet increasing demands for drug substances to support clinical studies. This paper describes the synthesis at multikilogram scale.
- Huang, Bao-Guo,Kubiak, Gregory,Shay, John J.,Pemberton, Clive,Peers, James,Hanna, Reda G.,Powers, Matthew R.,Gamboa, Juan A.,Gelormini, Ann M.,Yarabe, Hyacinthe,Rudisill, Duane E.
-
body text
p. 1040 - 1045
(2011/12/21)
-
- PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE
-
Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are inhibitors of glycogen phosphorylase and are useful in the prophylactic or therapeutic treatment of diabetes, hyperglycemia, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis or tissue ischemia e.g. myocardial ischemia, and as cardioprotectants.
- -
-
-
- Azaindole derivatives as Factor Xa inhibitors
-
The present invention relates to compounds of the formula I wherein R0 ; R1 ; R2 ;Q; V, G and M have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
- -
-
-
