Enhanced erythropoiesis and iron metabolism

1. A method for overcoming or ameliorating cytokine-induced impairment of erythropoiesis in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes hypoxia inducible factor α (HIFα), thereby overcoming or ameliorating the cytokine-induced impairment of erythropoiesis in the subject.

2. The method of claim 1 , wherein the cytokine-induced impairment of erythropoiesis is suppression of EPO production.

3. The method of claim 1 , wherein the cytokine-induced impairment of erythropoiesis is impairment of iron metabolism.

4. The method of claim 1 , wherein the cytokine is an inflammatory cytokine.

5. The method of claim 1 , wherein the cytokine is selected from the group consisting of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ).

6. The method of claim 1 , wherein the heterocyclic carboxamide compound that stabilizes of HIFα is a compound of Formula I:

wherein

A is 1,2-arylidene, 1,3-arylidene, 1,4-arylidene: or (C 1 -C 4 )-alkylene, optionally substituted by one or two halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) Hal g , (C 1 -C 6 )-fluoroalkoxy, (C 1 -C 8 )-fluoroalkenyloxy, (C 1 -C 8 )-fluoroalkynyloxy, —OCF 2 Cl, —O—CF 2 —CHFCl; (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino, N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl; or by a substituted (C 6 -C 12 )-aryloxy, (C 7 -C 11 )-aralkyloxy, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl radical, which carries in the aryl moiety one to five identical or different substituents selected from halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) Hal g , —OCF 2 Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkysulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl; or wherein A is —CR 5 R 6 and R 5 and R 6 are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or a substituent of the α-carbon atom of an α-amino acid, wherein the amino acid is a natural L-amino acid or its D-isomer;

B is —CO 2 H, —NH 2 , —NHSO 2 CF 3 , tetrazolyl, 3-hydroxyisoxazolyl, —CONHCOR′″, —CONHSOR′″, CONHSO 2 R′″, where R′″ is aryl, heteroaryl, (C 3 -C 7 )-cycloalkyl, or (C 1 -C 4 )-alkyl, optionally monosubstituted by heteroaryl, (C 6 -C 12 )-aryl, heteroaryl, OH, SH, (C 1 -C 4 )-alkyl (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-thioalkyl, (C 1 -C 4 )-sulfinyl, (C 1 -C 4 )-sulfonyl, CF 3 , Cl, Br, F, I, NO 2 , —COOH, (C 2 -C 5 )-alkoxycarbonyl, NH 2 , mono-(C 1 -C 4 -alkyl)-amino, di-(C 1 -C 4 -alkyl)-amino, or (C 1 -C 4 )-perfluoroalkyl; or wherein B is a CO 2 -G carboxyl radical, where G is a radical of an alcohol G-OH in which G is selected from (C 1 -C 20 )-alkyl radical, (C 3 -C 8 ) cycloalkyl radical, (C 2 -C 20 )-alkenyl radical, (C 3 -C 8 )-cycloalkenyl radical, retinyl radical, (C 2 -C 20 )-alkynyl radical, (C 4 -C 20 )-alkenynyl radical, where the alkenyl, cycloalkenyl, alkynyl, and alkenynyl radicals contain one or more multiple bonds; (C 6 -C 16 )-carbocyclic aryl radical, (C 7 -C 16 )-carbocyclic aralkyl radical, heteroaryl radical, or heteroaralkyl radical, wherein a heteroaryl radical or heteroaryl moiety of a heteroaralkyl radical contains 5 or 6 ring atoms; and wherein radicals defined for G are substituted by one or more hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 5 -C 8 )-cycloalkenyl, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 12 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, —O—[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 12 )-alkenylcarbonyl, (C 2 -C 12 )-alkynylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, acyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-carbamoyl, N—(C 6 -C 16 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 1 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-arloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 2 -C 12 )-alkenylamino, (C 2 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C—C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 ) arylcarbonylamino, (C 7 -C 16 )-aralkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N-(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 1 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkylcarbonylamino(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-alkylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, or N—((C 1 -C 10 )-alkyl-(C 7 -C 16 -aralkylsulfonamido; wherein radicals which are aryl or contain an aryl moiety, may be substituted on the aryl by one to five identical or different hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkyl-carbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 ) aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 2 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aryloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 1 -C 8 )-cycloalkylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 2 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkylaralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 )-arylcarbonylamino, (C 7 -C 16 )-alkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkylcarbonylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 15 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;

X is O or S;

Q is O, S, NR′, or a bond;

where, if Q is a bond, R 4 is halogen, nitrite, or trifluoromethyl;

or where, if Q is O, S, or NR′, R 4 is hydrogen, (C 1 -C 10 )-alkyl radical, (C 2 -C 10 )-alkenyl radical, (C 1 -C 10 )-alkynyl radical, wherein alkenyl or alkynyl radical contains one or two C—C multiple bonds; unsubstituted fluoroalkyl radical of the formula —[CH 2 ] x —C f H (2f+1−g) —F g , (C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl radical, (C 1 -C 6 )-alkoxy-(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl radical, aryl radical, heteroaryl radical, (C 7 -C 11 )-aralkyl radical, or a radical of the formula Z

—[CH 2 ] v —[O] w —[CH 2 ] t -E  (Z)

where

E is a heteroaryl radical, a (C 3 -C 8 )-cycloalkyl radical, or a phenyl radical of the formula F

v is 0-6,

w is 0 or 1,

t is 0-3, and

R 7 , R 8 , R 9 , R 10 , and R 11 are identical or different and are hydrogen, halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 —Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 8 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 8 )-alkylcarbamoyl, N,N-di-(C 1 -C 8 )-alkylcarbamoyl, or (C 7 -C 11 )-aralkylcarbamoyl, optionally substituted by fluorine, chlorine, bromine, trifluoromethyl, (C 1 -C 6 )-alkoxy, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, phenyl, benzyl, phenoxy, benzyloxy, NR Y R Z wherein R y and R z are independently selected from hydrogen, (C 1 -C 12 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 3 -C 12 )-alkenyl, (C 3 -C 12 )-alkynyl, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 7 -C 12 )aralkoxy, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 ) arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl; or further wherein R y and R z together are —[CH2] h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 4 )-alkylcarbonylamino, or N—(C 1 -C 4 )-alkoxycarbonylamino; phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 8 )-alkylsulfamoyl, or N, N-di-(C 1 -C 8 )-alkylsulfamoyl; or alternatively R 7 and R 8 , R 8 and R 9 , R 9 and R 10 , or R 10 and R 11 , together are a chain selected from —[CH 2 ] n — or —CH═CH—CH═CH—, where a CH 2 group of the chain is optionally replaced by O, S, SO, SO 2 , or NR Y ; and n is 3, 4, or 5; and if E is a heteroaryl radical, said radical can carry 1-3 substituents selected from those defined for R 7 -R 11 , or if E is a cycloalkyl radical, the radical can carry one substituent selected from those defined for R 7 -R 11 ;

or where, if Q is NR′, R 4 is alternatively R″, where R′ and R″ are identical or different and are hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkylcarbonyl, optionally substituted (C 7 -C 16 )-aralkylcarbonyl, or optionally substituted C 6 -C 12 )-arylcarbonyl; or R′ and R″ together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, N-acylamino, or N—(C 1 -C 10 )-alkoxycarbonylamino, and h is 3 to 7;

Y is N or CR 3 ;

R 1 , R 2 and R 3 are identical or different and are hydrogen, hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 20 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 7 -C 16 )-aralkenyl, (C 7 -C 16 )-aralkynyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, (C 1 -C 20 )-alkoxy, (C 2 -C 20 )-alkenyloxy, (C 2 -C 20 )-alkynyloxy, retinyloxy, (C 1 -C 20 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 16 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkenyloxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkynyloxy-(C 1 -C 6 )-alkyl, retinyloxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x CfH (2f+1−g) F g , —OCF 2 Cl, —OCF 2 CHFCl, (C 1 -C 20 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 20 )-alkenylcarbonyl, (C 2 -C 20 )-alkynylcarbonyl, (C 1 -C 20 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 20 )-alkenyloxycarbonyl, retinyloxycarbonyl, (C 2 -C 20 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N(C 1 -C 10 )-alkyl-N-aralkylcarbamoyl, N—((C 1 -C 18 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N-(C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl; CON(CH 2 ) h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 16 )-alkylimino, and h is from 3 to 7; a carbamoyl radical of the formula R

in which

R x and R v are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 1 -C 7 )-cycloalkyl, aryl, or the substituent of an α-carbon of an α-amino acid, to which the L- and D-amino acids belong,

s is 1-5,

T is OH, or NR*R**, and R*, R** and R*** are identical or different and are selected from hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, (+)-dehydroabietyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, optionally substituted (C 6 -C 12 )-aroyl; or R* and R** together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, SO, SO 2 , N-acylamino, N—(C 1 -C 10 )-alkoxycarbonylimino, N—(C 1 -C 8 )-alkylimino, (C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 -alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxyamino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino(C 1 -C 10 )-alkyl, (C 1 -C 20 )-alkylmercapto, (C 1 -C 20 )-alkylsulfinyl, (C 1 -C 20 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, (C 1 -C 12 )-alkylmercapto-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfinyl-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfonyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylmercapto-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfinyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfonyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylmercapto-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfinyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfonyl-(C 1 -C 6 )-alkyl, sulfamoyl, N—(C 1 -C 10 )-sulfamoyl, N,N-di-(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-arylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, and N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido, where an aryl radical may be substituted by 1 to 5 substituents selected from hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 2 -C 16 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 16 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 16 )-alkoxy, (C 1 -C 16 )-alkenyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 8 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 16 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, CON(CH 2 ) h , in which a CH 2 group can be replaced by, O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylamino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 16 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 6 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 10 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;

or wherein R 1 and R 2 , or R 2 and R 3 form a chain [CH 2 ] o , which is saturated or unsaturated by a C═C double bond, in which 1 or 2 CH 2 groups are optionally replaced by O, S, SO, SO 2 , or NR′, and R′ is hydrogen, (C 6 -C 12 )-aryl, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, or optionally substituted (C6-C12)-aroyl; and o is 3, 4 or 5;

or wherein the radicals R 1 and R 2 , or R 2 and R 3 , together with the pyridine or pyridazine carrying them, form a 5,6,7,8-tetrahydroisoquinoline ring, a 5,6,7,8-tetrahydroquinoline ring, or a 5,6,7,8-tetrahydrocinnoline ring;

or wherein R 1 and R 2 , or R 2 and R 3 form a carbocyclic or heterocyclic 5- or 6-membered aromatic ring;

or where R 1 and R 2 , or R 2 and R 3 , together with the pyridine or pyridazine carrying them, form an optionally substituted heterocyclic ring systems selected from thienopyridine, furanopyridines, pyridopyridines, pyrimidinopyridines, imidazopyridines, thiazolopyridines, oxazolopyridines, quinoline, isoquinoline, and cinnoline; where quinoline, isoquinoline or cinnoline preferably satisfy the formulae Ia, Ib and Ic:

and the substituents R 12 to R 23 in each case independently of each other have the meaning of R 1 , R 2 and R 3 ;

or wherein the radicals R 1 and R 2 , together with the pyridine carrying them, form a compound of Formula Id;

where V is S, O, or NR k , and R k is selected from hydrogen, (C 1 -C 6 )-alkyl, aryl, or benzyl; where an aryl radical may be optionally substituted by 1 to 5 substituents as defined above; and

R 24 , R 25 , R 26 , and R 27 in each case independently of each other have the meaning of R 1 , R 2 and R 3 ;

f is 1 to 8;

g is 0 or 1 to (2f+1);

x is 0 to 3; and

h is 3 to 7;

including the physiologically active salts derived therefrom.