TH82384A - Aryl derivatives 1,4-displaced pyracin - Google Patents

Abstract

DC60 (05/06/49) This invention is directed at the compound of structural formula I, described herein, as well as its pharmaceutically acceptable salt, represented as CRF1 antagonist, and its potential use in the treatment of diseases and disorders associated with CRF receptors, including diseases and disorders associated with the CNS. This invention is directed at the compound of structural formula I, described herein, as well as its pharmaceutically acceptable salt, represented as CRF1 antagonist, and its potential use in the treatment of diseases and disorders associated with CRF receptors, including diseases and disorders associated with the CNS.

Claims (15)

1. Pharmaceutically acceptable compounds of structural formula I (chemical formula) or their salts, where R1 is C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkinyl, C(O) C1-C6 alkyl, C(O) C1-C6 alkenyl, or C(O) C1-C6 alkinyl; R2 is C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkinyl; R22 is C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkinyl; R3 is C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkinyl, halogen, OC1-C6 alkyl, OC1-C6 alkinyl, or OC1-C6 alkinyl; R4 is C1-C6 alkyl, C1-C6 alkenil, C1-C6 alkinil, halogen, OC1-C6 alkyl, OC1-C6 alkinil, or NR5R6; R5 is halogen, C1-C6 alkyl, C1-C6 alkinil, or C1-C6 alkinil; and R6 is halogen, C1-C6 alkyl, C1-C6 alkinil, or C1-C6 alkinil. 2. Compound of claim 1 where R1 is ethyl or C(O)CH3. 3. Compounds of claim 1 where R2 is ethyl and R22 is ethyl. 4. Compounds of claim 1 where R3 is a C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkinyl. 5. The compound of claim 1 where R4 is NR5R6. 6. Compounds of claim 5 where R3 is a C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkinyl. 7. The compound of claim 6 where R3 is methyl and R4 is N(CH3)2. 8. Selected compounds from the group containing (1R,2S) acetic acid 1-[5-(6-dimethylamino-2-methyl-pyridin-3-yl)-3,6-diethyl-pyrazin-2-ylamino]-indan-2-yl ester; (1R,2S) acetic acid 1-[5-(6-dimethylamino-2-methyl-pyridin-3-yl)-3,6-diethyl-pyrazin-2-ylamino]-indan-2-yl ester toluene 4-sulfonic acid; and (1R,2S) [5-(6-dimethylamino-2-methyl-pyridin-3-il)-3,6-diethyl-pyrazine-2-il]-(2-ethoxy-indan-1-il)-amine 9. A pharmaceutical mixture containing a pharmaceutically acceptable carrier and the compounds as per Claim 1. 10. Use of the compounds under Claim 1 for the preparation of medicines for the treatment of selected disorders from the following groups: generalized anxiety disorder, social anxiety disorder, panic disorder, hallucinogenic disorder, anxiety with depression and related disorders, affective disorders, anxiety, eating disorders, bipolar disorder, and mammalian depression. 11. Use of the compounds under claim 1 for the preparation of pharmaceuticals to treat apparent CRF secretion disorders in mammals. 12. The use of the compounds under claim 1 for the selection of ligands for the CRF1 receptor is described by a method comprising: a) performing analytical assays on competitive binding to the CRF1 receptor, the compounds under claim 1 labeled with the detectable label, and the competing ligands; and b) determining the ability of the aforementioned competing ligands to replace the labeled compounds. 13. The use of the compounds under claim 1 for the measurement of CRF receptors in tissues containing: a) exposure to the compounds under claim 1 labeled with tissue-measurable labels, under conditions allowing tissue binding of the compounds; and b) measurement of the compounds labeled with tissue. 14. The use of the compound described in claim 1 for the preparation of drugs to inhibit the binding of CRF to CRF1 receptors involves exposure of the compound described in claim 1 to a solution containing cells expressing CRF1 receptors, where the compound is present in the solution at a concentration sufficient to inhibit the binding of CRF to CRF1 receptors. 15. Method for reducing the level of CRF-bound cells in vitro in test tubes expressing CRF1 receptors, where a compound is present in solution at a concentration sufficient to reduce the level of CRF-bound cells in vitro.