New substituted pyrazolo-pyridine derivatives useful for treating and/or prophylaxis of e.g. congestive heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemia, vascular diseases, renal failure, and fibrotic diseases

摘要

Substituted pyrazolo-pyridine derivatives (I) are new. Substituted pyrazolo-pyridine derivatives of formula (I) and their N-oxides, salts, solvates, salts of N-oxides, and solvates of N-oxides and salts are new. A : N or CR3; R3 : H, D, halo, difluoromethyl, trifluoromethyl, 1-4C alkyl, cyclopropyl, cyclobutyl, OH or NH 2; L : T-CR41R42-(CR51R52) p-T1; T : point of attachment to C=O; T1 : point of attachment to pyrimidine or triazine ring; p : 0-2; either R41 : 1-4C alkyl (optionally substituted by 1-3 T2), H, F, OH or NH 2; and R42 : 1-4C alkyl (optionally substituted by 1-3 T2), H, F, trifluoromethyl, 1-4C alkoxy-carbonylamino or phenyl; or R41+R42+C to which it is bonded : 3-6-membered carbocyclyl or 4-6-membered heterocyclyl (both optionally substituted by 1 or 2 F or 1-4C alkyl), oxo or 2-4C alkenyl; T2 : F, trifluoromethyl, OH, hydroxycarbonyl, 1-4C alkoxycarbonyl or NH 2; R51 : H, F, 1-4C alkyl or OH; R52 : H, F, 1-4C alkyl or trifluoromethyl; R1 : H or F; and R2 : 5-6-membered heteroaryl (optionally substituted by 1-2 F). Independent claims are also included for: (1) preparing (I); and (2) a medicament comprising (I) in combination with an inert and non-toxic auxiliary agent. [Image] ACTIVITY : Cardiovascular-Gen; Antianginal; Hypotensive; Respiratory-Gen; Vasotropic; Nephrotropic; Thrombolytic; Antiinflammatory; Antiarteriosclerotic. MECHANISM OF ACTION : Soluble guanylate cyclase stimulator. The soluble guanylate cyclase stimulating effect of (I) was tested in recombinant guanylate cyclase reporter cell lines using a method described in F. Wunder et al., Anal. Biochem. 339, 104-112 (2005). The results showed that (Ia) exhibited a minimum effective concentration of 10 mu m.