AU2013200138A1 - Carboxamide compounds and their use as calpain inhibitors - Google Patents

Abstract

CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN The present invention relates to.novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R' R2, Ra , R3b, W, Y and X have the meanings mentioned in the claims and 15 the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula I A.a' and I-A.a" in which m, E, R', R , R, R2 , RY, Rw and Rw6 * have the meanings mentioned in the claims, n is 0, 1 or 2, the tautomers thereof and the pharmaceutically suitable salts thereof. (R )n R I2H XN R 3 (I-A.a) R-W-Y N ( N N 1 3b 3a R2 HR R (RW,)m (R')n O R x N N \ (-A a") N:: E (R" )m

Description

1 Carboxamide compounds and their use as calpain inhibitors Description 5 The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. 10 Calpains are intracellular, proteolytic enzymes from the cysteine protease group and are found in many cells. The enzyme calpain is activated by elevated calcium concentration, with a distinction being made between calpain I or p-calpain, which is activated by p-molar concentrations of calcium ions, and calpain II or m-calpain, which 15 is activated by m-molar concentrations of calcium ions. Currently, further calpain isoenzymes are also postulated (M.E. Saez et al.; Drug Discovery Today 2006, 11 (19/20), pp. 917-923; K. Suzuki et al., Biol. Chem. Hoppe-Seyler, 1995, 376 (9), pp.523-9). 20 Calpains play an important role in various physiological processes. These processes include the cleavage of different regulatory proteins such as protein kinase C, cytoskeletal proteins such as MAP 2 and spectrin, and muscle proteins, protein degradation in rheumatoid arthritis, proteins in the activation of platelets, neuropeptide metabolism, proteins in mitosis, and others which are listed in: M.J.Barrett et al., Life 25 Sci. 1991, 48, pp.1659-69; K. Wang et al., Trends in Pharmacol.Sci. 1994, 15, pp. 412 419. Elevated calpain levels have been measured in various pathophysiological processes, for example: ischemias of the heart (e.g. myocardial infarction), the kidney or the 30 central nervous system (e.g. stroke), inflammations, muscular dystrophies, cataracts of the eyes, diabetes, HIV disorders, injuries to the central nervous system (e.g. brain trauma), Alzheimer's, Huntington's, Parkinson's diseases, multiple sclerosis etc. (see K.K. Wang, above). It is assumed that there is a connection between these diseases and generally or persistently elevated intracellular calcium levels. This results in 35 calcium-dependent processes becoming hyperactivated and no longer being subject to normal physiological control. A corresponding hyperactivation of calpains can also trigger pathophysiological processes. For this reason, it was postulated that inhibitors of calpain could be of use for treating 40 these diseases. This postulate was confirmed by a variety of investigations. Thus, Seung-Chyul Hong et al., Stroke 1994, 25 (3), pp. 663-669, and R. T. Bartus et al., Neurological Res. 1995, 17, pp. 249-258, have demonstrated that calpain inhibitors 2 have a neuroprotective effect in acute neurodegenerative impairments or ischemias such as occur after cerebral stroke. K. E. Saatman et al., Proc. Nati. Acad. Sci. USA, 1996, 93, pp. 3428-3433 describe that following experimental brain traumas, calpain inhibitors also improved recovery from the memory performance deficits and 5 neuromotor impairments. C. L. Edelstein et al., Proc. NatI. Acad. Sci. USA, 1995, 92, pp. 7662-6, found that calpain inhibitors have a protective effect on hypoxia-damaged kidneys. Yoshida, Ken Ischi et al., Jap. Circ. J. 1995, 59 (1), pp. 40-48, pointed out that calpain inhibitors had favorable effects following cardiac damage which was produced by ischemia or reperfusion. 10 It has been shown in recent years that both the function and the metabolism of a number of important proteins involved in the development of Alzheimer's disease are modulated by calpain. Various external influences such as, for example, excitotoxins, oxidative stress or else the action of amyloid protein lead to hyperactivation of calpain 15 in the nerve cell, causing, as cascade, a dysregulation of the CNS-specific kinase cdk5 and subsequently a hyperphosphorylation of the so-called tau protein. Whereas the actual task of the tau protein consists of stabilizing the microtubules and thus the cytoskeleton, phosphorylated tau is no longer able to fulfil this function; the cytoskeleton collapses, axonal transport of matter is impaired and thus eventually the 20 nerve cell degenerates (G. Patrick et al., Nature 1999, 402, pp. 615-622; E. A. Monaco et al.; Curr. Alzheimer Res. 2004, 1 (1), pp. 33-38). Accumulation of phosphorylated tau additionally leads to the formation of so-called neurofibrillary tangles (NFTs) which, together with the well-known amyloid plaques, represent an important feature of Alzheimer's disease. Similar changes in the tau protein, generally referred to as 25 tauopathies are also observed in other (neuro)degenerative disorders such as, for example, following stroke, inflammations of the brain, Parkinsonism, in normal pressure hydrocephalus and Creutzfeldt-Jakob disease. It has been possible to demonstrate the involvement of calpain in neurodegenerative 30 processes in transgenic mice with the aid of appropriate inhibitors (Higuchi et al.; J. Biol. Chem. 2005, 280 (15), pp. 15229-15237). It was possible with the aid of a calpain inhibitor to reduce markedly the clinical signs of acute autoimmune encephalomyelitis in a mouse model of multiple sclerosis (F. Mokhtarian et al.; J. Neuroimmunology 2006, Vol. 180, pp. 135-146). It has further been shown that 35 calpain inhibitors on the one hand block the AG-induced degeneration of neurons (Park et al.; J. Neurosci. 2005, 25, pp. 5365-5375), and in addition reduce the release of the p-amyloid precursor protein (P APP) (J. Higaki et al., Neuron, 1995, 14, pp. 651-659). With this background, calpain inhibitors having sufficient CNS availability represent a novel therapeutic principle for the treatment of neurodegenerative disorders in general 40 and in particular also of Alzheimer's disease. The release of interleukin-la is likewise inhibited by calpain inhibitors (N. Watanabe et 3 al., Cytokine 1994, 6(6), pp. 597-601). It has additionally been found that calpain inhibitors show cytotoxic effects on tumor cells (E. Shiba et al. 20th Meeting Int. Ass. Breast Cancer Res., Sendai Jp, 1994, 25.-28.Sept., Int. J. Oncol. S(Suppl.), 1994, 381). 5 The involvement of calpain in HIV disorders has only recently been shown. Thus, it has been demonstrated that the HIV-induced neurotoxicity is mediated by calpain (O'Donnell et al.; J. Neurosci. 2006, 26 (3), pp. 981-990). Calpain involvement in the replication of the HIV virus has also been shown (Teranishi et al.; Biochem. Biophys. 10 Res. Comm. 2003, 303 (3), pp. 940-946). Recent investigations indicate that calpain plays a part in so-called nociception, the perception of pain. Calpain inhibitors showed a distinctly beneficial effect in various preclinically relevant models of pain, e.g. in the thermally induced hyperalgesia in rats 15 (Kunz et al.; Pain 2004, 110, pp.409-418), in Taxol-induced neuropathy (Wang et al.; Brain 2004, 127, pp.671-679) and in acute and chronic inflammatory processes (Cuzzocrea et al.; American Journal of Pathololgy 2000, 157 (6), pp. 2065-2079). Further possible applications of calpain inhibitors are detailed in: M.E. Saez et al.; Drug 20 Discovery Today 2006, 11 (19/20), pp. 917-923; N. 0. Carragher, Curr. Pharm. Design 2006, 12, pp. 615-638; K. K. Wang et al.; Drugs of the Future 1998, 23 (7), pp. 741 749; and Trends in Pharmacol.Sci., 1994, 15, pp. 412-419. With the calpain inhibitors described to date a general distinction is made between 25 irreversible and reversible inhibitors, and peptide and non-peptide inhibitors. Irreversible inhibitors are usually alkylating substances. They have the disadvantage that they firstly react unselectively and/or are unstable in the body. Thus, corresponding inhibitors often show unwanted side effects such as toxicity, and 30 application thereof is therefore markedly restricted. The irreversible inhibitors include for example epoxides such as E64, a-halo ketones, and disulfides. A large number of known reversible calpain inhibitors are peptide aldehydes which are derived in particular from di- or tripeptides such as, for example, Z-Val-Phe-H 35 (MDL 28170). Derivatives and prodrugs structurally derived from aldehydes are also described, especially corresponding acetals and hemiacetals (e.g. hydroxytetrahydro furans, hydroxyoxazolindines, hydroxymorpholines and the like), but also imines or hydrazones. However, under physiological conditions, peptide aldehydes and related compounds usually have the disadvantage that, owing to their reactivity, they are 40 frequently unstable, are rapidly metabolized and are prone to unspecific reactions which may likewise cause toxic effects (J. A. Fehrentz and B.Castro, Synthesis 1983, pp. 676-78).

4 In recent years, a number of non-peptide carboxamides having a p-keto function in the amine moiety and inhibiting calpain have been described. Thus, WO-98/16512 describes 3-amino-2-oxo carboxylic acid derivatives whose amino group is amidated 5 with a 4-piperidinecarboxylic acid compound. WO-99/17775 describes similar compounds which are amidated with a quinolinecarboxylic acid. WO-98/25883, WO-98/25899 and WO-99/54294 describe 3-amino-2-oxo carboxylic acid derivatives whose amino group is amidated with a substituted benzoic acid. WO-99/61423 describes 3-amino-2-oxo carboxylic acid derivatives whose amino group is amidated 10 with an aromatic carboxylic acid carrying a tetrahydroquinoline/isoquinoline and 2,3 dihydroindole/isoindole residue. Similar compounds in which the aromatic carboxylic acid residue carries a heterocyloalkyl radical or (hetero)aryl radical which is optionally connected via a linker are described in WO-99/54320, WO-99/54310, WO-99/54304 and WO-99/54305. WO-99/54293 describes benzamides of 4-amino-3-oxo carboxylic 15 acid derivatives. WO-03/080182 describes the use of the aforementioned amides for the treatment of pulmonary diseases. The nonpeptide calpain inhibitors mentioned therein also have a number of disadvantages, in particular a low or absent selectivity in respect of related cysteine proteases, such as various cathepsins, likewise possibly leading to unwanted side effects. 20 The present invention is thus based on the object of providing compounds which inhibit, in particular selectively, calpain even at low serum concentrations. The compounds were intended in particular to display a high selectivity in relation to the inhibition of calpain, i.e. inhibit other cystein proteases, e.g. cathepsin, not at all or only 25 at higher concentrations. This object and further objects are achieved by the carboxamide compounds of the general formula I described below, the pharmaceutically suitable salts, the prodrugs and the tautomers thereof: 30 0 R R2-W-Y N I R3b 3a HR R in which

R

1 is hydrogen, C1-C1o-alkyl, C 2

-C

10 -alkenyl, C 2

-C

10 -alkynyl, where the last 3 radicals 35 mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Ria, C3-C7-cycloalkyl, C3-C 7 -cycloalkyl-C-C4-alkyl, where a CH 2 group in the cycloalkyl moiety of the last two radicals mentioned may be replaced by 0, NH, 5 or S, or two adjacent C atoms may form a double bond, where the cycloalkyl moiety may further have 1, 2, 3 or 4 radicals Rib, aryl, hetaryl, aryl-Ci-C6-alkyl, aryl-C2-Cs-alkenyl, hetaryl-Cl-C4-alkyl or hetaryl C2-C6-alkenyl, where aryl and hetaryl in the last 6 radicals mentioned may be 5 unsubstituted or carry 1, 2, 3 or 4 identical or different radicals Ric; where Ria is selected independently of one another from OH, SH, COOH, CN,

OCH

2 COOH, Ci-C6-alkoxy, Ci-Cs-halolkoxy, C 3 -C7-cycloalkyloxy, CrC-6 alkylthio, C-C 6 -haloalkylthio, COORal, CONRa 2 Ra 3 , SO 2 NRa 2 Ra 3 , -NRa 2 . 10 SO 2 -Ra 4 , NRa 2 -CO-Ra 5 , SO 2 -Ra 4 , NRaSRa 7 , Rib is selected independently of one another from OH, SH, COOH, CN,

OCH

2 COOH, halogen, phenyl which optionally has 1, 2 or 3 substituents Rid, or Cl-C6-alkyl, Cl-C 6 -alkoxy, Cr-C 6 -alkylthio, where the alkyl moieties -in the last 3 substituents mentioned may be partly or completely 15 halogenated and/or have 1, 2 or 3 substituents Ria, COORbi, CONR2Rb3, SO 2 NRb2Rb3, NRb2-SO 2 rRb4, NRb2-CO-Rb5, SO 2 -Rb4, N RbsRb7, in addition two Rib radicals may together form a Ce-C 4 -alkylene group, or 2 Rib radicals bonded to adjacent C atoms of cycloalkyl may form together 20 with the carbon atoms to which they are bonded also a benzene ring, Ric is selected independently of one another from OH, SH, halogen, NO 2 , NH 2 , CN, CF3, CHF 2 , CH 2 F, O-CF 3 , O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, Cl-C 6 -alkyl, CI-C 6 -alkoxy, C1-C6-alkoxy-Cr-C 4 -alkyl, C-C 6 -alkylthio, where the alkyl moieties in the last 4 substituents mentioned may be partly or 25 completely halogenated and/or have 1, 2 or 3 substituents Ria, C3-C 7 -cycloalkyl, C 3

-C

7 -cycloalkyl-C-C4-alkyl, C 3

-C

7 -cycloalkyloxy, where the cycloalkyl moiety of the last three radicals mentioned may have 1, 2, 3 or 4 Rib radicals, aryl, hetaryl, O-aryl, O-CH2-aryl, where the last three radicals mentioned 30 are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 Rid radicals, COORci, CONRc 2 Rc 3 , SO 2 NRc 2 Rc 3 , NRc 2

-SO

2 rRc 4 , NRc 2 -CO-Rc 5 , SO 2 Rc 4 ,

-(CH

2 )p-NRc 6 Rc7 with p = 0, 1, 2, 3, 4, 5 or 6 and

O-(CH

2 )q-NR 6

R

7 with q = 2, 3, 4, 5 or 6; where 35 Ral, Rbi and Ri are independently of one another H, C-C 6 -alkyl, C1C-6 haloalkyl, Cr1C6-alkyl which has 1, 2 or 3 substituents Ria, or C2-C6 alkenyl, C2-C6-alkynyl, C 3

-C

7 -cycloalkyl, C 3 -C-cycloalkyl-Ci-C4-alkyl,

C

3

-C

7 -heterocycloalkyl-Ci-C4-alkyl, C1C6-alkoxy-Cr-C4-alkyl, aryl, 40 aryl-Cl-C4-alkyl, hetaryl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, 6 Ra 2 , Rb2 and Rc 2 are independently of one another H, C-C 6 -alkyl, C 1

-C

6 haloalkyl, Cl-C6-alkyl which has 1, 2 or 3 substituents Ria, or C 2

-C

6 alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C3-C 7 -cycloalkyl-C-C4-alkyl, C3-C 7 -heterocycloalkyl-C-C4-alkyl, C-C6-alkoxy-C-C4-alkyl, aryl, 5 aryl-C-C4-alkyl, hetaryl or hetaryl-C-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, and Ra3, Rb3 and Rc3 are independently of one another H, C-C 6 -alkyl, C 1

-C

6 10 haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Ria, or C 2

-C

6 alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 -cycloalkyl-C-C 4 -alkyl,

C

3

-C

7 -heterocycloalkyl-Cr-C4-alkyl, C-C 6 -alkoxy-Cl-C4-alkyl, aryl, aryl-C-C 4 -alkyl, hetaryl or hetaryl-C-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 15 substituents R'd, or the two radicals Ra2 and Ra 3 , or Rb2 and Rb3 or Rc 2 and Rc3 form together with the N atom a 3 to 7-membered, optionally substituted nitrogen heterocycle which may optionally have 1, 2 or 3 further different or identical heteroatoms from the group of 0, N, S as ring 20 members, Ra4, Rb4 and Rc4 are independently of one another Cl-C 6 -alkyl, C-C 6 haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Ria, or C 2

-C

6 alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 -cycloalkyl-C-C4-alkyl,

C

3

-C

7 -heterocycloalkyl-Cr-C 4 -alkyl, C-C 6 -alkoxy-C-C4-alkyl, aryl, 25 aryl-C-C4-alkyl, hetaryl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, and Ra 5 , Rb5 and Rc5 have independently of one another one of the meanings mentioned for Rai, Rbl and Rci; 30 Ra6, Rb6 and Rce are independently of one another H, C-C 6 -alkyl, C1-C 6 alkoxy, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents

R

1 a, or C 2

-C

6 -alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 cycloalkyl-Cr-C 4 -alkyl, C3-C 7 -heterocycloalkyl-C-C 4 -alkyl, CrC6 alkoxy-C-C 4 -alkyl, CO-C-C 6 -alkyl, CO-0-C-Ce-alkyl, S0rCrC6 35 alkyl, aryl, hetaryl, O-aryl, OCH2-aryl, aryl-C-C4-alkyl, hetaryl-Cl-C4-alkyl, CO-aryl, CO hetaryl, CO-(aryl-C-C4-alkyl), CO-(hetaryl-C-C4-alkyl), CO-0-aryl, CO-0-hetaryl, CO-O-(aryl-C-C4-alkyl), CO-O-(hetaryl-C-C4-alkyl), 40 S02-aryl, S02-hetaryl, S02-(aryl-C-C4-alkyl) or S0 2 -(hetaryl-C-C4 alkyl), where aryl and hetaryl in the last 18 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, and 7

RW

7 , R7 and Rc7 are independently of one another H, Cl-Ce-alkyl, C1-C6 haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Ria, or C 2

-C

6 alkenyl, C 2 -Cs-alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 -cycloalkyl-Cl-C4-alkyl,

C

3

-C

7 -heterocycloalkyl-Ci-C4-alkyl, Cl-C 6 -alkoxy-C-C4-alkyl, aryl, 5 aryl-C-C4-alkyl, hetaryl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, or the two radicals Rae and Ra7, or Rb6 and Rb7 or Rc6 and Re7 form together with the N atom a 3 to 7-membered, optionally substituted 10 nitrogen heterocycle which may optionally have 1, 2 or 3 further different or identical heteroatoms from the group of 0, N and S as ring members, or two radicals Rib and Ric bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, 15 optionally substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from the group of 0, N and S as ring members; Rid is selected from halogen, OH, SH, N02, COOH, C(O)NH 2 , CHO, CN, NH 2 ,

OCH

2 COOH, Cr-C6-alkyl, Cr-C 6 -haloalkyl, C-C 6 -alkoxy, Cl-C 6 -haloalkoxy, 20 Ci-C 6 -alkylthio, C-C 6 -haloalkylthio, CO-Cl-C 6 -alkyl, CO-O-CI-C 6 -alkyl,

NH-C-C

6 -alkyl, NHCHO, NH-C(O)C-C6-alkyl, and S0 2 -Cl-C6-alkyl;

R

2 is hydrogen, Cl-Cio-alkyl, Cr-C 10 -alkoxy, C 2

-C

10 -alkenyl, C 2

-C

10 -alkynyl, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 25 2 or 3 substituents R 2 a,

C

3

-C

7 -cycloalkyl, C 3 -Cr-cycloalkyl-C-C4-alkyl, where a CH 2 group in the cycloalkyl moiety of the last two radicals mentioned may be replaced by 0, NH, or S, or two adjacent C atoms may form a double bond, where the cycloalkyl 30 moiety may additionally have 1, 2, 3 or 4 R2b radicals; aryl, 0-aryl, O-CH 2 -aryl, hetaryl, aryl-Ci-C-alkyl, aryl-C2-Ce-alkenyl, hetaryl

C-C

4 -alkyl or hetaryl-C 2 -C6-alkenyl, where aryl and hetaryl in the last 8 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different R2c radicals; where 35 R2a has one of the meanings indicated for Ria, R2b has one of the meanings indicated for Rib, and

R

2 c has one of the meanings indicated for Ric; 40 R3a and R3b are independently of one another hydroxy or Cr 1

C

4 -alkoxy, or together with the carbon atom to which they are bonded are C=0; 8 X is hydrogen or a radical of the formulae C(=O)-0-Rxl, C(=O)-NRx 2 Rx 3 , C(=0)-N(Rx4)-(Cr C-alkylene)-NRx 2 Rx 3 or C(=O)-N(Rx 4 )NRx 2 Rx 3 , in which 5 Rxi is hydrogen, Cl-C 6 -alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or C 2

-C

6 -alkenyl, C 2 -C6-alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 cycloalkyl-C-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C4-alkyl, Cl-C 6 -alkoxy C1C4-alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, heterocycloalkyl in the last 6 radicals mentioned are unsubstituted or have 10 1, 2 or 3 substituents Rxa, or aryl, aryl-Cl-C4-alkyl, hetaryl or hetaryl-Cl-C4 alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, Rx 2 is H, OH, CN, C-C 6 -alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or C 2

-C

6 -alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 15 cycloalkyl-C-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C4-alkyl, Cl-C6-alkoxy

C-C

4 -alkyl, CO-C-C 6 -alkyl, CO-0-C-C 6 -alkyl, SO 2 -Cl-C 6 -alkyl, O-C-C 6 alkyl, where alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl in the last 10 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxa, 20 aryl, O-aryl, O-CH2-aryl, hetaryl, O-CH 2 -hetaryl, aryl-C-C 4 -alkyl, hetaryl

C-C

4 -alkyl, CO-aryl, CO-hetaryl, CO-(aryl-C-C 4 -alkyl), CO-(hetaryl-C-C4 alkyl), CO-O-aryl, CO-0-hetaryl, CO-O-(aryl-Cr-C4-alkyl), CO-O-(hetaryl

C

1

-C

4 -alkyl), S02-aryl, S0 2 -hetaryl, SO 2 -(aryl-C-C4-alkyl) or SO 2 -(hetaryl Cr-C 4 -alkyl), where aryl and hetaryl in the last 19 radicals mentioned are 25 unsubstituted or have 1, 2 or 3 substituents Rxd, and Rx 3 is H, C-C 6 -alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or C 2 -C-alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 cycloalkyl-C-C4-alkyl, C 3

-C

7 -heterocycloalkyl-Cr-C4-alkyl, C-C 6 -alkoxy Cl-C4-alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, 30 heterocycloalkyl in the last 6 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxa, aryl, aryl-C-C4-alkyl, hetaryl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, or 35 the two radicals Rx 2 and Rx3 form together with the N atom a 3 to 7 membered nitrogen heterocycle which may optionally have 1, 2 or 3 further different or identical heteroatoms from the group of 0, N, S as ring members, and which may have 1, 2 or 3 substituents Rxb, Rx 4 is H, OH, CN, Cr-Ce-alkyl, C-C 6 -haloalkyl, C-CO-alkyl which has 1, 2 or 3 40 substituents Rxa, or C 2

-C

6 -alkenyl, C 2 -C6-alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 cycloalkyl-Cl-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C4-alkyl, C-C 6 -alkoxy

C-C

4 -alkyl, CO-C-C 6 -alkyl, CO-0-Cl-C6-alkyl, SO 2

-C-C

6 -alkyl, where 9 alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, heterocycloalkyl in the last 9 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxa, aryl, O-aryl, O-CH2-aryl, hetaryl, aryl-C1-C4-alkyl, hetaryl-Cl-C4-alkyl, CO aryl, CO-hetaryl, CO-(aryl-C1-C4-alkyl), CO-(hetaryl-C1-C4-alkyl), CO-0-aryl, 5 CO-0-hetaryl, CO-O-(aryl-C-C4-alkyl), CO-0-(hetaryl-C-C4-alkyl), SO 2 aryl, SO 2 -hetaryl, SO 2 -(aryl-Cl-C4-alkyl) or SO 2 -(hetaryl-C1-C4-alkyl), where aryl and hetaryl in the last 18 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, and 10 where Rxa has one of the meanings indicated for Ria, Rxb has one of the meanings indicated for Rib, and Rxd has one of the meanings indicated for Rid; Y is a divalent, aromatic or 6-membered heteroaromatic radical which has 1 or 2 15 nitrogen atoms as ring members and which optionally has 1 or 2 identical or different substituents RY: RY is selected independently of one another from OH, SH, halogen, NO2, NH 2 , CN, CF 3 , CHF 2 , CH 2 F, 0-CF 3 , O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, 20 C-C 6 -alkyl, C-C 6 -alkoxy, C-C 6 -alkoxy-Ci-C4-alkyl, C-C 6 -alkylthio, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Rya,

C

3

-C

7 -cycloalkyl, C 3 -C7-cycloalkyl-C-C4-alkyl,

C

3

-C

7 -cycloalkyl-O, where the cycloalkyl moiety in the last three radicals mentioned may have 1, 2, 3 25 or 4 RYb radicals, aryl, O-aryl, CH2-aryl, O-CH 2 -aryl, where the last 4 radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals Ryd, COORi, CONRy 2 Ry 3 , SO 2 NRy 2 Ry 3 , -NH-SO 2

-R

4 ,

NH-CO-RY

5 , SO 2 -Ry 4 , 30 -(CH 2 )p-NR 6 Ry 7 with p = 0, 1, 2, 3, 4, 5 or 6 and 0-(CH 2

)-NR

6

R

7 with q = 2, 3, 4, 5 or 6; or two RY radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally 35 substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from the group of 0, N, S as ring members, where Rya has one of the meanings indicated for Rla, 40 Ryb has one of the meanings indicated for Rib, Ryd has one of the meanings indicated for Rid, Ry' has one of the meanings indicated for Rci, 10 Ry 2 has one of the meanings indicated for Rc2, Ry 3 has one of the meanings indicated for Rc3,

RY

4 has one of the meanings indicated for Re4, Ry 5 has one of the meanings indicated for Rc5, 5 RY 6 has one of the meanings indicated for Rc , and

RY

7 has one of the meanings indicated for Rc7; W is a radical of the formulae W1 or W2 which is linked via nitrogen: * * N N N(Rw)m (Rw)m (Wi) (W2) 10 in which * means the linkage to Y, and # means the linkage to R 2 , m is 0, 1 or 2, and Rw is selected from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, 0-CF 3 , 15 O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, C-C 6 -alkyl, C-C 6 -alkoxy, C 1 -C6 alkoxy-Ci-C4-alkyl, CI-C 6 -alkylthio, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Rwa, C3-C 7 -cycloalkyl, C 3 -C7-cycloalkyl-Cl-C4-alkyl,

C

3

-C

7 -cycloalkyloxy, where the cycloalkyl moiety of the last three radicals mentioned may have 1, 2, 3 20 or 4 radicals Rwb, aryl, O-aryl, O-CH2-aryl, hetaryl, where the last four radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals Rwd, COORwI, CONRw2Rw 3 , SO 2 NRw 2 Rw 3 , NRw 2

-SO

2 -Rw 4 , NRw 2 -CO-Rw 5 , SO 2 -Rw 4 , 25 -(CH 2 )p-NRw 6 Rw 7 with p = 0, 1, 2, 3, 4, 5 or 6 and 0-(CH 2 )q-NRw 6 Rw7 with q = 2, 3, 4, 5 or 6; or two Rw radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally 30 substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from the group of 0, N, S as ring members, where Rwa has one of the meanings indicated for Rla, Rwb has one of the meanings indicated for Rib, 35 Rwd has one of the meanings indicated for Rid, Rwi has one of the meanings indicated for Ri, Rw 2 has one of the meanings indicated for Rc2, Rw 3 has one of the meanings indicated for RcS, 11 Rw4 has one of the meanings indicated for Re4, Rw5 has one of the meanings indicated for Rc5, RwS has one of the meanings indicated for Rc6, Rw7 has one of the meanings indicated for RC7, 5 or W forms together with R 2 a bi- or tricyclic radical of the formulae W3, W4, W5, W6, W7 or W8 which is linked via nitrogen: 10 * N NN N N (R/ ) (R" )m (w3* (R*)m (R )m (W3) (W4) (W5) * * N E N ( R ) m (R" )m (R E (W6) (W7) (W8) 15 in which * means the linkage to Y, m is 0, 1 or 2, and Rw 3 -, Rw4*, RwY, RWe, Rw7* and Rw8* have independently of one another one of the meanings indicated for Rw, 20 E has one of the following meanings: -CRE 2

RE

3 -, -CH RE 2

-CHRE

3 , CH 2

-CH

2 CH 2 -, -CO-, -CO-NRE 1 -, -NRE 1 -CO-, -0-, -CH 2 -O-, -O-C

H

r, -S-, -S-CH 2 -, -CH 2 - S-, -SO-, CH 2 -SO-, -SO-CH 2 -, -SO 2 -, -CH 2- S0 2 -, -SO 2 CH 2 -, -NRE 1 -, -NRE 1 -CH2-, -CH 2

-NRE

1 , -S02-NRE 1 -,

-NRE

1 -SO2-, -CO-0-, -O-CO-, -C(=CRE 2

RE

3 )-, -CRE 2

=CRE

3 -, 25 RE 1 is H, C-C6-alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents REla, or C 2

-C

6 -alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -Cycloalkyl, C 3 -0 7 cycloalkyl-C-C 4 -alkyl, C 3 -C-heterocycloalkyl-C-C 4 -alkyl, Cl-C 6 -alkoxy Cl-C 4 -alkyl, CO-CrlC6-alkyl, CO-0-Cl-C6-alkyl, S0 2 -0-C-alkyl, aryl, hetaryl, aryl-CrC4-alkyl, hetaryl-CrC4-alkyl, CO-aryl, CO-hetaryl, CO-(aryl- 12

C

1

-C

4 -alkyl), CO-(hetaryl-C-C4-alkyl), CO-O-aryl, CO-0-hetaryl, CO-0 (aryl-C-C4-alkyl), CO-O-(hetaryl-C-C 4 -alkyl), S02-aryl, S0 2 -hetaryl, SO 2 (aryl-Cl-C4-alkyl) or S0 2 -(hetaryl-C-C 4 -alkyl), where aryl and hetaryl in the last 16 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents 5 RE1d, and

RE

2 , RE 3 are independently of one another selected from hydrogen, C-C 6 -alkyl, CI-C6-alkoxy, C-C6-alkenyl, C 2

-C

6 -alkynyl, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents REla, 10 C3-C 7 -cycloalkyl, C 3

-C

7 -cycloalkyl-Cr-C4-alkyl, C 3

-C

7 -cycloalkyl-O, where a

CH

2 group in the cycloalkyl moiety of the last three radicals mentioned may be replaced by 0, NH, or S, or two adjacent C atoms may form a double bond, where the cycloalkyl moiety may further have 1, 2, 3 or 4 RElb radicals, 15 aryl, hetaryl, aryl-Cl-C6-alkyl, or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals RE1d; and where REla has one of the meanings indicated for Ria, REib has one of the meanings indicated for Rib, and REId has one of the meanings indicated for 20 Rid. The present invention therefore relates to the carboxamide compounds of the general formula 1, their tautomers, the pharmaceutically suitable salts of the carboxamide compounds I, the prodrugs of I and the pharmaceutically suitable salts of the prodrugs 25 or tautomers of I. The carboxamide compounds of the invention of the formula I, their salts, their prodrugs and their tautomers effectively inhibit calpain even at low concentrations. They are additionally distinguished by a high selectivity in relation to the inhibition of 30 the calpain compared with other cysteine proteases such as cathepsin B, cathepsin K, cathepsin L and cathepsin S. The carboxamide compounds of the invention of the formula 1, their salts, their prodrugs and their tautomers are therefore particularly suitable for treating disorders 35 and conditions in creatures, especially human creatures, which are associated with an elevated calpain activity. The invention therefore also relates to the use of carboxamide compounds of the formula l, their tautomers and their pharmaceutically suitable salts for the manufacture 40 of a medicament, in particular of a medicament which is suitable for the treatment of a disorder or a condition which is associated with an elevated calpain activity.

13 The invention further relates to a medicament, in particular a medicament which is suitable for the treatment of a disorder or a condition which is associated with an elevated calpain activity. The medicament comprises at least one carboxamide compound of the formula I, as described herein, a tautomer or a pharmaceutically 5 suitable salt of the compound I or of the tautomer or a prodrug of 1, or a salt or tautomer of said prodrug. The carboxamide compounds of the formula I may be in the form of B-keto compounds, i.e. the radicals R 3 a and R3b in the compounds of the formula I form together with the 10 carbon atom to which they are bonded a carbonyl group as shown in the formula on the left in Scheme A. The compounds of the invention may also be in the form of a hydrate, i.e. the radicals R 3 a and R3b are each OH, as shown in the formula on the right in Scheme A. R 1 , R 2 , W, X and Y in Scheme A have the aforementioned meanings. 15 Scheme A: R2-W-Y N X R2-W-Y N H HO OH I (R3a/R3b = 0) 1 (R 3 a= R3b = OH) In the presence of water, especially under physiological conditions, usually both the B keto form and the hydrate form are present in a mixture. 20 Where only the &-keto form is indicated in the following formulae and descriptions, this is intended to include also the hydrate and mixtures thereof with the B-keto form unless indicated otherwise. Hydrates and &-keto forms are equally suitable as calpain inhibitors. 25 The carboxamide compounds of the invention of the formula I are also able to form tautomers when R3a and R3b form a carbonyl group together with the carbon atom to which they are bonded. The tautomers are equally suitable as calpain inhibitors. Particular examples of tautomers to be mentioned are the compounds of the formula 30 1-T: 0 R 2 ~ X R2-W-Y N l-T H O,H h

R

1 , R 2 , W, X and Y in formula l-T have the aforementioned meanings.

14 The carboxamide compounds of the invention of the formula I can also form hemiacetals, hemiketals, acetals or ketals with alkanols. These compounds are equally suitable as calpain inhibitors as they are prodrugs of the compounds I, where CR3aR3b 5 is a carbonyl group (i.e. C=O) or C(OH) 2 . Accordingly, compounds where one or both radicals R3a and R3b are a radical derived from an alkanol, and especially C-C 6 -alkoxy, can also be used according to the invention. The term prodrug, as used herein and in the claims refers to a compound which is 10 transformed under metabolic conditions into a compound of the formula 1. Apart from the aforementioned hemiacetals, hemiketals, acetals and ketals prodrugs of the compounds I include the compounds of the formula 1, wherein R3a and R3b together form a group O-Alk-O, S-Alk-O or S-Alk-S, where Alk is linear C 2 -C-alkandiyl, which may be unsubstituted or substituted with 1, 2, 3 or 4 radicals selected from Cr-C 4 -alkyl 15 or halogen, examples for such groups including O(CH 2

)

2 0, O(CH 2

)

5 0, O(CH 2

)

4 0,

S(CH

2

)

2 0, S(CH 2

)

5 0, S(CH2) 4 0, etc. Further prodrugs or the compounds I include the compounds of the formula 1, wherein R 3 a and R3b together whith the carbon atom form a group C=NR 3 , where R 3 is selected from H, C-C 6 -alkyl, C-C 6 -alkoxy, C 2

-C

6 -alkenyl, C3-C6-cycloalkyl, C 3

-C

6 -cycloalkyl-C1-C4-alkyl, C32-C6-alkenyloxy, C 3 -C6-cycloalkyloxy, 20 C3-C6-cycloalkyl-C-C4-alkyloxy. Under metabolic conditions, the aforementioned prodrugs are transformed into the corresponding B -keto compounds of the formula I (CR3aR3b is C=O) or into the hydrates thereof (CR3aR3b is C(OH) 2 ). Therefore, said prodrugs and their pharmaceutically acceptable salts are also part of the invention. 25 It is equally possible to use pharmaceutically suitable salts of the carboxamide compounds of the formula I of their tautomers or of their prodrugs, especially acid addition salts with physiologically tolerated organic or inorganic acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, organic sulfonic acids 30 having 1 to 12 carbon atoms, e.g. C-C 4 -alkylsulfonic acids such as methanesulfonic acid, cycloaliphatic sulfonic acids such as S-(+)-10-camphorsulfonic acids, and aromatic sulfonic acids such as benzenesulfonic acid and toluenesulfonic acid, di- and tricarboxylic acids and hydroxy carboxylic acids having 2 to 10 carbon atoms, such as oxalic acid, malonic acid, maleic acid, fumaric acid, mucic acid, lactic acid, tartaric acid, 35 citric acid, glycolic acid and adipic acid, as well as cis- and trans-cinnamic acid, furan 2-carboxylic acid and benzoic acid. Further suitable acids are described in Fortschritte der Arzneimittelforschung, Volume 10, pages 224 et seq., Birkh5user Verlag, Basel and Stuttgart, 1966. The physiologically tolerated salts of the compounds of the formula I may be in the form of mono-, di-, tri- or tetrasalts, meaning that they may comprise 1, 40 2, 3 or 4 of the aforementioned acid molecules per molecule of the formula 1. The acid molecules may be present in their acidic form or as anion.

15 The compounds of the invention may be in the form of a mixture of diastereomers, or of a mixture of diastereomers in which one of the two diastereomers is enriched, or of essentially diastereomerically pure compounds (diastereomeric excess de > 90%). The compounds are preferably in the form of essentially diastereomerically pure 5 compounds (diastereomeric excess de > 90%). The compounds I of the invention may furthermore be in the form of a mixture of enantiomers (for example as racemate), of a mixture of enantiomers in which one of the two enantiomers is enriched, or essentially in enantiomerically pure compounds (enantiomeric excess ee > 90%). However, the compounds of the invention are frequently prone to racemization in relation to the 10 stereochemistry of the carbon atom which carries the radical R 1 , so that mixtures are frequently obtained in relation to this carbon atom, or compounds which exhibit a uniform stereochemistry in relation to this C atom form mixtures under physiological conditions. However, in relation to other stereocenters and the occurrence, associatied therewith, of enantiomers and diastereomers, it is preferred to employ the compounds 15 enantiomerically pure or diastereomerically pure. In the context of the present description, unless stated otherwise, the terms "alkyl", "alkoxy", "alkylthio", "haloalkyl", "haloalkoxy", "haloalkylthio", "alkenyl", "alkynyl", "alkylene" and radicals derived therefrom always include both unbranched and 20 branched "alkyl", "alkoxy", "alkylthio", "haloalkyl", "haloalkoxy", "haloalkylthio", "alkenyl", "alkynyl" and "alkylene", respectively. The prefix CO-Cm- indicates the respective number of carbons in the hydrocarbon unit. Unless indicated otherwise, halogenated substituents preferably have one to five 25 identical or different halogen atoms, especially fluorine atoms or chlorine atoms. Co Alkylene or (CH 2 )o or similar expressions in the context of the description designate, unless indicated otherwise, a single bond. The term "halogen" designates in each case, fluorine, bromine, chlorine or iodine, 30 specifically fluorine, chlorine or bromine. Examples of other meanings are: Alkyl, and the alkyl moieties for example in alkoxy, alkylthio, arylalkyl, hetarylalkyl, 35 cycloalkylalkyl or alkoxyalkyl: saturated, straight-chain or branched hydrocarbon radicals having one or more C atoms, e.g. 1 to 4, 1 to 6 or 1 to 10 carbon atoms, e.g. Cl-C6-alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 40 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 16 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1 -ethyl-i -methylpropyl, 1 -ethyl-2-methylpropyl. In one embodiment of the invention, alkyl stands for small alkyl groups such as C1-C4-alkyl. In another embodiment of the invention, alkyl stands for larger alkyl groups such as C5-C 10 -alkyl. 5 Haloalkyl: an alkyl radical having ordinarily 1 to 6 or 1 to 4 C atoms as mentioned above, whose hydrogen atoms are partly or completely replaced by halogen atoms such as fluorine, chlorine, bromine and/or iodine, e.g. chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, 10 d ichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2 difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 15 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2 fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl and nonafluorobutyl. Cycloalkyl, and the cycloalkyl moieties for example in cycloalkoxy or cycloalkyl-C1-Ce 20 alkyl: monocyclic, saturated hydrocarbon groups having three or more C atoms, e.g. 3 to 7 carbon ring members, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. Alkenyl, and alkenyl moieties for example in aryl-(C 2 -C6)-alkenyl: monounsaturated, straight-chain or branched hydrocarbon radicals having two or more C atoms, e.g. 2 to 25 4, 2 to 6 or 2 to 10 carbon atoms and one double bond in any position, e.g. C 2

-C

6 alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2 propenyl, I -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl 1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2 30 butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2 propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl 2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1 pentenyl, 2-methyl-1 -pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2 pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3 35 pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4 pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl 2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2 dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3 butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3 40 dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3 butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1 -methyl-2-propenyl, 1-ethyl-2-methyl-1- 17 propenyl, 1-ethyl-2-methyl-2-propeny. Alkynyl: straight-chain or branched hydrocarbon groups having two or more C atoms, e.g. 2 to 4, 2 to 6 or 2 to 10 carbon atoms and one or two triple bonds in any position 5 but nonadjacent, e.g. C 2

-C

6 -alkynyl such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1 butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 10 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3 butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl 2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1 -methyl-2-propynyl. 15 Alkoxy or alkoxy moieties for example in alkoxyalkyl: Alkyl as defined above having preferably 1 to 6 or 1 to 4 C atoms, which is linked via an o atom: e.g. methoxy, ethoxy, n-propoxy, 1 -methylethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 20 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1 -methylpropoxy or 1 -ethyl-2-methylpropoxy. 25 Haloalkoxy: alkoxy as described above, in which the hydrogen atoms of these groups are partly or completely replaced by halogen atoms, i.e. for example C-C 6 -haloalkoxy, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, 30 chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2 difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromo 35 propoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy, 1-(fluoromethyl)-2-fluoroethoxy, 1-(chloromethyl)-2-chloroethoxy, 1-(bromomethyl)-2-bromoethoxy, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, nonafluorobutoxy, 5-fluoro-1-pentoxy, 5-chloro-1-pentoxy, 5-bromo-1-pentoxy, 5-iodo 1-pentoxy, 5,5,5-trichloro-1-pentoxy, undecafluoropentoxy, 6-fluoro-1-hexoxy, 6-chloro 40 1-hexoxy, 6-bromo-1-hexoxy, 6-iodo-1-hexoxy, 6,6,6-trichloro-1-hexoxy or dodeca fluorohexoxy, specifically chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoro methoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trifluoroethoxy.

18 Alkoxyalkyl: an alkyl radical ordinarily having 1 to 4 C atoms, in which one hydrogen atom is replaced by an alkoxy radical ordinarily having 1 to 6 or 1 to 4 C atoms. Examples thereof are CH 2

-OCH

3 , CH 2

-OC

2

H

5 , n-propoxymethyl, CH 2

-OCH(CH

3

)

2 , 5 n-butoxymethyl, (1-methylpropoxy)methyl, (2-methylpropoxy)methyl, CH 2

-OC(CH

3

)

3 , 2-(methoxy)ethyl, 2-(ethoxy)ethyl, 2-(n-propoxy)ethyl, 2-(1-methylethoxy)ethyl, 2-(n-butoxy)ethyl, 2-(1-methylpropoxy)ethyl, 2-(2-methylpropoxy)ethyl, 2-(1,1-dimethyl ethoxy)ethyl, 2-(methoxy)propyl, 2-(ethoxy)propyl, 2-(n-propoxy)propyl, 2-(1-methyl ethoxy)propyl, 2-(n-butoxy)propyl, 2-(1-methylpropoxy)propyl, 2-(2-methylpropoxy) 10 propyl, 2-(1,1-dimethylethoxy)propyl, 3-(methoxy)propyl, 3-(ethoxy)propyl, 3-(n-propoxy)propyl, 3-(1-methylethoxy)propyl, 3-(n-butoxy)propyl, 3-(1-methyl propoxy)propyl, 3-(2-methylpropoxy)propyl, 3-(1, 1 -d imethylethoxy)propyl, 2-(methoxy) butyl, 2-(ethoxy)butyl, 2-(n-propoxy)butyl, 2-(l-methylethoxy)butyl, 2-(n-butoxy)butyl, 2-(1-methylpropoxy)butyl, 2-(2-methylpropoxy)butyl, 2-(1,1-dimethylethoxy)butyl, 15 3-(methoxy)butyl, 3-(ethoxy)butyl, 3-(n-propoxy)butyl, 3-(1 -methylethoxy)butyl, 3-(n-butoxy)butyl, 3-(1-methylpropoxy)butyl, 3-(2-methylpropoxy)butyl, 3-(1,1-dimethyl ethoxy)butyl, 4-(methoxy)butyl, 4-(ethoxy)butyl, 4-(n-propoxy)butyl, 4-(1-methyl ethoxy)butyl, 4-(n-butoxy)butyl, 4-(1-methylpropoxy)butyl, 4-(2-methylpropoxy)butyl, 4-(1,1-dimethylethoxy)butyl, etc. 20 Alkylthio: alkyl as defined above preferably having 1 to 6 or 1 to 4 C atoms, which is linked via an S atom, e.g. methylthio, ethylthio, n-propylthio and the like. Haloalkylthio: haloalkyl as defined above preferably having 1 to 6 or 1 to 4 C atoms, 25 which is linked via an S atom, e.g. fluoromethylthio, difluoromethylthio, trifluoromethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, pentafluoroethylthio, 2-fluoropropylthio, 3-fluoropropylthio, 2,2-difluoropropylthio, 2,3 difluoropropylthio, and heptafluoropropylthio. 30 Aryl: a mono-, bi- or tricyclic aromatic hydrocarbon radical such as phenyl or naphthyl, especially phenyl. Heterocyclyl: a heterocyclic radical which may be saturated, partly unsaturated or aromatic and which ordinarily has 3, 4, 5, 6, 7 or 8 ring atoms, where ordinarily 1, 2, 3 35 or 4, in particular 1, 2 or 3, of the ring atoms are heteroatoms such as N, S or 0, besides carbon atoms as ring members. Examples of saturated heterocycles are in particular: 40 Heterocycloalkyl: i.e. a saturated heterocyclic radical which ordinarily has 3, 4, 5, 6 or 7 ring atoms, where ordinarily 1, 2 or 3 of the ring atoms are heteroatoms such as N, S or 0, besides carbon atoms as ring members. These include for example: 19 C-bonded, 3-4-membered saturated rings such as 2-oxiranyl, 2-oxetanyl, 3-oxetanyl, 2-aziridinyl, 3-thiethanyl, 1-azetidinyl, 2-azetidinyl. 5 C-bonded, 5-membered saturated rings such as tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3 yl, tetrahyd ropyrrol-2-yi, tetra hyd ropyrrol-3-yl, tetrahydropyrazol-3-yl, tetrahydro pyrazol-4-yl, tetrahydroisoxazol-3-yl, tetrahydroisoxazol-4-yl, tetra hyd roisoxazol 10 5-yl, 1,2-oxathiolan-3-yl, 1,2-oxathiolan-4-yl, 1,2-oxathiolan-5-yi, tetrahydroiso thiazol-3-yl, tetrahydroisothiazol-4-yi, tetrahydroisothiazol-5-yl, 1,2-dithiolan-3-yl, 1,2-dithiolan-4-yl, tetrahydroimidazol-2-yl, tetrahydroimidazol-4-yl, tetra hydrooxazol-2-yl, tetrahydrooxazol-4-yl, tetrahyd rooxazol-5-yl, tetrahyd rothiazol-2-yl, tetrahydrothiazol-4-y, tetrahydrothiazol-5-yl, 1,3-dioxolan 15 2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-y, 1,3-oxathiolan-4-yl, 1,3-oxathiolan-5 yl, 1,3-dithiolan-2-y, 1,3-dithiolan-4-yl, 1,3,2-dioxathiolan-4-yl. C-bonded, 6-membered saturated rings such as: tetrahydropyran-2-yl, tetrahyd ropyran-3-yl, tetrahydropyran-4-yl, piperidin-2-yl, 20 piperidin-3-yl, piperidin-4-yl, tetrahydrothiopyran-2-yl, tetrahyd rothiopyran-3-yl, tetrahyd rothiopyran-4-yl, 1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl, 1,4-dioxan-2-yl, 1,3-dithian-2-yi, 1,3-dithian-4-yl, 1,3-dithian-5-yl, 1,4-dithian-2-yi, 1,3-oxathian-2-yl, 1,3-oxathian-4-yl, 1,3-oxathian-5-yi, 1,3-oxathian-6-yl, 1,4-oxathian-2-yi, 1,4-oxathian-3-yl, 1,2-dithian-3-yi, 1,2-dithian-4-yl, 25 hexahydropyrimidin-2-yl, hexahydropyrimidin-4-yl, hexahydropyrimidin-5-yl, hexahydropyrazin-2-yl, hexahydropyridazin-3-yl, hexahydropyridazin-4-yl, tetrahydro-1,3-oxazin-2-yl, tetrahyd ro- 1,3-oxazin-4-yl, tetrahyd ro-1,3-oxazin-5-yl, tetrahydro-1 ,3-oxazin-6-yl, tetrahyd ro- 1, 3-thiazin-2-yl, tetra hyd ro-1,3-thiazin-4-yl, tetrahydro-1 ,3-thiazin-5-yl, tetrahydro-1 ,3-thiazin-6-yl, tetrahyd ro-1,4-thiazin-2-yl, 30 tetrahydro-1,4-thiazin-3-yl, tetrahydro-1,4-oxazin-2-yl, tetrahyd ro-1,4-oxazin-3-yl, tetrahydro-1 ,2-oxazin-3-yl, tetrahyd ro-1,2-oxazin-4-yl, tetrahyd ro-1,2-oxazin-5-yl, tetrahydro-1,2-oxazin-6-yl. N-bonded, 5-membered saturated rings such as: 35 tetrahydropyrrol-1 -yl, tetrahydropyrazol-1 -yl, tetrahydroisoxazol-2-yl, tetrahydroisothiazol-2-yl, tetrahydroimidazol-1-yl, tetrahyd rooxazol-3-yl, tetrahydrothiazol-3-yl. N-bonded, 6-membered saturated rings such as: 20 piperidin-1-yl, hexahydropyrimidin-1-yl, hexahydropyrazin-1-yl, hexahydro pyridazin-1-yl, tetrahydro-1,3-oxazin-3-yl, tetrahydro-1,3-thiazin-3-yl, tetrahydro 1,4-thiazin-4-yl, tetrahydro-1,4-oxazin-4-yl, tetrahydro-1,2-oxazin-2-yl. 5 Unsaturated heterocyclic radicals which ordinarily have 4, 5, 6 or 7 ring atoms, where ordinarily 1, 2 or 3 of the ring atoms are heteroatoms such as N, S or 0, besides carbon atoms as ring members. These include for example: C-bonded, 5-membered, partially unsaturated rings such as: 10 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydro furan-3-yl, 4,5-dihydrofuran-2-yl, 4,5-dihydrofuran-3-y, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,5-dihydrothien-2-yl, 2,5-dihydrothien-3-yl, 4,5-dihydro thien-2-yl, 4,5-dihydrothien-3-yl, 2,3-dihydro-1 H-pyrrol-2-yl, 2,3-dihydro-1 H-pyrrol 3-yl, 2,5-dihydro-1 H-pyrrol-2-yl, 2,5-dihydro-1 H-pyrrol-3-yl, 4,5-dihydro-1 H-pyrrol 15 2-yl, 4,5-dihydro-1 H-pyrrol-3-yl, 3,4-dihydro-2H-pyrrol-2-yl, 3,4-dihydro-2H-pyrrol 3-yl, 3,4-dihydro-5H-pyrrol-2-yi, 3,4-dihydro-5H-pyrrol-3-yl, 4,5-dihydro-1 H pyrazol-3-yl, 4,5-dihydro-1 H-pyrazol-4-yl, 4,5-dihydro-1 H-pyrazol-5-yl, 2,5 dihydro-1 H-pyrazol-3-yl, 2,5-dihydro-1 H-pyrazol-4-yl, 2,5-dihydro-1 H-pyrazol-5-y, 4,5-dihydroisoxazol-3-yl, 4,5-dihydroisoxazol-4-yi, 4,5-dihydroisoxazol-5-yl, 2,5 20 dihydroisoxazol-3-yl, 2,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-5-yl, 2,3 dihydroisoxazol-3-yl, 2,3-dihydroisoxazol-4-yl, 2,3-dihydroisoxazol-5-yl, 4,5 dihydroisothiazol-3-yl, 4,5-dihydroisothiazol-4-yl, 4,5-dihydroisothiazol-5-yl, 2,5 dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-4-yl, 2,5-dihydroisothiazol-5-yl, 2,3 dihydroisothiazol-3-yl, 2,3-dihydroisothiazol-4-yl, 2,3-dihydroisothiazol-5-yl, 4,5 25 dihydro-1 H-imidazol-2-yl, 4,5-dihydro-1 H-imidazol-4-yl, 4,5-dihydro-1 H-imidazol 5-yl, 2,5-dihydro-1 H-imidazol-2-yl, 2,5-dihydro-1 H-imidazol-4-yl, 2,5-dihydro-1 H imidazol-5-yl, 2,3-dihydro-1 H-imidazol-2-yl, 2,3-dihydro-1 H-imidazol-4-yl, 4,5 dihydrooxazol-2-yl, 4,5-dihydrooxazol-4-yl, 4,5-dihydrooxazol-5-yl, 2,5 dihydrooxazol-2-yl, 2,5-dihydrooxazol-4-yl, 2,5-dihydrooxazol-5-yl, 2,3 30 dihydrooxazol-2-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 4,5 dihydrothiazol-2-yl, 4,5-dihydrothiazol-4-yl, 4,5-dihydrothiazol-5-yl, 2,5 dihydrothiazol-2-yl, 2,5-dihydrothiazol-4-yl, 2,5-dihydrothiazol-5-yl, 2,3 dihydrothiazol-2-yl, 2,3-dihydrothiazol-4-yl, 2,3-dihydrothiazol-5-yl, 1,3-dioxol-2-yl, 1,3-dioxol-4-yl, 1,3-dithiol-2-yi, 1,3-dithiol-4-yi, 1,3-oxathiol-2-yi, 1,3-oxathiol-4-yl, 35 1,3-oxathiol-5-yl. C-bonded, 6-membered, partially unsaturated rings such as: 2H-3,4-dihydropyran-6-yl, 21H-3,4-dihydropyran-5-yl, 2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl, 2H-3,4-dihydropyran-2-yl, 2H-3,4-dihydrothiopyran-6- 21 yI, 2H-3,4-dihydrothiopyran-5-yI, 2H-3,4-dihydrothiopyran-4-yi, 2H-3,4 dihydrothiopyran-3-yI, 2H-3,4-dihydrothiopyran-2-yI, I ,2,3,4-tetrahydropyridin-6 yI, 1 ,2,3,4-tetrahydropyridin-5-yI, I ,2,3,4-tetrahydropyridin-4-yi, 1 ,2,3,4-tetra hydropyridin-3-yl, 1 ,2,3,4-tetrahydropyridin-2-y, 2H-5,6-dihydropyran-2-yl, 2H 5 5,6-d ihyd ropyran-3-yI, 2H-5,6-di hydropyran-4-yi, 2H-5,6-di hydropyran-5-y, 2 H 5,6-d ihyd ropyran-6-yI, 2H-5,6-di hydrothiopyran-2-yI, 2H-5,6-di hydrothiopyra n-3 yI, 2H-5,6-dihydrothiopyran-4-yI, 2H-5,6-dihydrothiopyran-5-yi, 2H-5,6 d ihyd rothiopyran-6-yI, 1 ,2,5,6-tetrahyd ropyridin-2-yi, 1 ,2,5,6-tetrahydropyridin-3 yI, 1 ,2,5,6-tetrahydropyridin-4-yi, I ,2,5,6-tetrahydropyridin-5-yl, I ,2,5,6-tetra 10 hydropyridin-6-yI, 2,3,4,5-tetrahydropyridin-2-y, 2,3,4,5-tetrahydropyridin-3-y, 2,3 ,4,5-tetrahydropyridin-4-yi, 2,3,4,5-tetrahydropyridin-5-yt, 2,3,4,5-tetrahydro pyrid in-6-yI, 4 H-pyran-2-yI, 4 H-pyran-3-yI, 4 H-pyran-4-yI, 4 H-thiopyran-2-yI, 4 H thiopyran-3-yi, 4 H-thiopyran-4-yI, 1 ,4-d ihydropyrid in-2-yI, I ,4-d ihyd ropyrid in-3-yl, 1 ,4-d ihyd ropyrid in-4-yI, 2 H-pyran-2-yI, 2H-pyran-3-yI, 2 H-pyran-4-yI, 2 H-pyran-5 15 yI, 2H-pyran-6-yi, 2H-thiopyran-2-yI, 2H-thiopyran-3-yi, 2H-thiopyran-4-yI, 2H thiopyran-5-yI, 2H-thiopyran-6-yI, 1 ,2-dihydropyridin-2-y, 1 ,2-dihydropyridin-3-yl, 1 ,2-d ihydropyrid in-4-yI, 1 ,2-d ihyd ropyridin-5-yi, 1 ,2-dihyd ropyrid in-6-yI, 3 ,4-d ihyd ropyrid in-2-yI, 3,4-d ihyd ropyridin-3-yI, 3,4-d ihyd ropyridin-4-yi, 3 ,4-d ihyd ropyridin-5-yI, 3,4-dihyd ropyrid in-6-yI, 2, 5-d ihydropyridin-2-yI, 20 2, 5-d ihyd ropyrid in-3-yi, 2, 5-d ihyd ropyridin-4-yI, 2,5-dihyd ropyridin-5-yI, 2 ,5-d ihyd ropyrid in-6-yI, 2 ,3-d ihyd ropyridin-2-yI, 2,3-d ihydropyridin-3-yI, 2,3-dihydropyridin-4-y, 2,3-dihydropyridin-5-y, 2,3-dihydropyridin-6-y, 2H-5,6 dihydro-1 ,2-oxazin-3-yI, 2H-5,6-dihydro-1 ,2-oxazin-4-yI, 2H-5,6-dihydro-1 ,2 oxazin-5-yi, 2H-5,6-d ihyd ro-1 ,2-oxazin-6-yI, 2H-5,6-dihyd ro-1 ,2-thiazin-3-yI, 25 2H-5,6-dihydro-1 ,2-thiazin-4-yI, 2H-5,6-dihydro-1 ,2-thiazin-5-yI, 2H-5,6-dihydro 1 ,2-thiazin-6-yI, 4H-5,6-dihydro-1 ,2-oxazin-3-yI, 4H-5,6-dihydro-1 ,2-oxazin-4-yI, 4H-5,6-dihydro-1 ,2-oxazin-5-yi, 4H-5,6-dihydro-1 ,2-oxazin-6-yI, 4H-5,6-dihydro 1 ,2-thiazin-3-yI, 4H-5,6-dihydro-1 ,2-thiazin-4-yi, 4H-5,6-dihydro-1 ,2-thiazin-5-yI, 4H-5,6-dihydro-1 ,2-thiazin-6-yI, 2H-3,6-dihydro-1 ,2-oxazin-3-yI, 2H-3,6-dihydro 30 1 ,2-oxazin-4-yI, 2H-3,6-dihydro-1 ,2-oxazin-5-yI, 2H-3,6-dihydro-1 ,2-oxazin-6-yI, 2H-3 ,6-dihydro-1 ,2-thiazin-3-yI, 2H-3,6-dihydro-1 ,2-thiazin-4-yt, 2H-3,6-dihydro 1 ,2-thiazin-5-yI, 2H-3,6-dihydro-1 ,2-thiazin-6-yl, 2H-3,4-dihydro-1 ,2-oxazin-3-yI, 2H-3,4-dihydro-1 ,2-oxazin-4-yI, 2H-3,4-dihydro-1 ,2-oxazin-5-yI, 2H-3,4-dihydro 1 ,2-oxazin-6-yI, 2H-3,4-dihydro-1 ,2-thiazin-3-yI, 2H-3,4-dihydro-1 ,2-thiazin-4-yI, 35 2 H-3,4-dihydro-1 ,2-thiazin-5-yI, 2H-3,4-dihydro-1 ,2-thiazin-6-yI, 2,3,4,5-tetra hydropyridazin-3-yi, 2 ,3,4,5-tetrahydropyridazin-4-y, 2 ,3,4,5-tetra hydropyridazin 5-yI, 2,3,4,5-tetrahydropyridazin-6-y, 3,4 ,5,6-tetrahyd ropyridazin-3-yI, 3,4,5,6 tetra hyd ropyridazi n-4-yI, 1 ,2,5,6-tetrahydropyridazin-3-y, I ,2,5,6-tetrahydro pyridazin-4-yi, 1,2 ,5,6-tetrahydropyridazin-5-y, I ,2,5,6-tetra hydropyridazin-6-yI, 22 1,2,3,6-tetrahydropyridazin-3-yl, 1,2,3,6-tetrahydropyridazin-4-yl, 4H-5,6-dihydro 1,3-oxazin-2-yl, 4H-5,6-dihydro-1,3-oxazin-4-yl, 4H-5,6-dihydro-1,3-oxazin-5-yl, 4H-5,6-dihydro-1,3-oxazin-6-yi, 4H-5,6-dihydro-1,3-thiazin-2-yl, 4H-5,6-dihydro 1,3-thiazin-4-yl, 4H-5,6-dihydro-1,3-thiazin-5-yl, 4H-5,6-dihydro-1,3-thiazin-6-yl, 5 3,4,5-6-tetrahydropyrimidin-2-yl, 3,4,5,6-tetrahydropyrimidin-4-yl, 3,4,5,6-tetra hydropyrimidin-5-yl, 3,4,5,6-tetrahydropyrimidin-6-yl, 1,2,3,4-tetrahydropyrazin-2 yl, 1,2,3,4-tetrahydropyrazin-5-yl, 1,2,3,4-tetrahydropyrimidin-2-yl, 1,2,3,4-tetra hydropyrimidin-4-yl, 1,2,3,4-tetrahydropyrimidin-5-yl, 1,2,3,4-tetrahydropyrimidin 6-yl, 2,3-dihydro-1,4-thiazin-2-yl, 2,3-dihydro-1,4-thiazin-3-yl, 2,3-dihydro-1,4 10 thiazin-5-yl, 2,3-dihydro-1,4-thiazin-6-yl, 2H-1,3-oxazin-2-yl, 2H-1,3-oxazin-4-yl, 2H-1,3-oxazin-5-yl, 2H-1,3-oxazin-6-yl, 2H-1,3-thiazin-2-yl, 2H-1,3-thiazin-4-yl, 2H-1,3-thiazin-5-yl, 2H-1,3-thiazin-6-yl, 4H-1,3-oxazin-2-yl, 4H-1,3-oxazin-4-yl, 4H-1,3-oxazin-5-yl, 4H-1,3-oxazin-6-yl, 4H-1,3-thiazin-2-yl, 4H-1,3-thiazin-4-yl, 4H-1,3-thiazin-5-yl, 4H-1,3-thiazin-6-yl, 6H-1,3-oxazin-2-yl, 6H-1,3-oxazin-4-yl, 15 6H-1,3-oxazin-5-yl, 6H-1,3-oxazin-6-yl, 6H-1,3-thiazin-2-yl, 6H-1,3-oxazin-4-y, 6H-1,3-oxazin-5-yl, 6H-1,3-thiazin-6-yl, 2H-1,4-oxazin-2-yl, 2H-1,4-oxazin-3-yl, 2H-1,4-oxazin-5-yl, 2H-1,4-oxazin-6-yl, 2H-1,4-thiazin-2-yl, 2H-1,4-thiazin-3-yl, 2H-1,4-thiazin-5-yl, 2H-1,4-thiazin-6-yl, 4H-1,4-oxazin-2-yl, 4H-1,4-oxazin-3-yi, 4H-1,4-thiazin-2-yl, 4H-1,4-thiazin-3-yl, 1,4-dihydropyridazin-3-yl, 1,4-dihydro 20 pyridazin-4-yl, 1,4-dihydropyridazin-5-yl, 1,4-dihydropyridazin-6-yl, 1,4-dihydro pyrazin-2-yl, 1,2-dihydropyrazin-2-yl, 1,2-dihydropyrazin-3-yl, 1,2-dihydropyrazin 5-yl, 1,2-dihydropyrazin-6-yl, 1,4-dihydropyrimidin-2-yl, 1,4-dihydropyrimidin-4-yl, 1,4-dihydropyrimidin-5-yl, 1,4-dihydropyrimidin-6-yl, 3,4-dihydropyrimidin-2-yl, 3,4-dihydropyrimidin-4-yl, 3,4-dihydropyrimidin-5-yl or 3,4-dihydropyrimidin-6-yl. 25 N-bonded, 5-membered, partially unsaturated rings such as: 2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, 4,5-dihydro-1H-pyrazol-1 yl, 2,5-dihydro-1 H-pyrazol-1 -yl, 2,3-dihydro-1 H-pyrazol-1 -yl, 2,5-dihydroisoxazol 2-yl, 2,3-dihydroisoxazol-2-yl, 2,5-dihydroisothiazol-2-yl, 2,3-dihydroisoxazol-2-yl, 30 4,5-dihydro-1 H-imidazol-1-yl, 2,5-dihydro-1 H-imidazol-1 -yl, 2,3-dihydro-1 H imidazol-1-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrothiazol-3-yl. N-bonded, 6-membered, partially unsaturated rings such as: 1,2,3,4-tetrahydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl, 1,4-dihydropyridin-1 35 yl, 1,2-dihydropyridin-1-yl, 2H-5,6-dihydro-1,2-oxazin-2-yl, 2H-5,6-dihydro-1,2 thiazin-2-yl, 2H-3,6-dihydro-1,2-oxazin-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl, 2H 3,4-dihydro-1,2-oxazin-2-yl, 2H-3,4-dihydro-1,2-thiazin-2-yl, 2,3,4,5-tetrahydro pyridazin-2-yl, 1,2,5,6-tetrahydropyridazin-1-yl, 1,2,5,6-tetrahydropyridazin-2-yl, 1,2,3,6-tetrahydropyridazin-1-yl, 3,4,5,6-tetrahydropyrimidin-3-yl, 1,2,3,4- 23 tetrahydropyrazin-1 -yl, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydro pyrimidin-3-yl, 2,3-dihydro-1,4-thiazin-4-yl, 2H-1,2-oxazin-2-yl, 2H-1,2-thiazin-2 yl, 4H-1,4-oxazin-4-yl, 4H-1,4-thiazin-4-yl, 1,4-dihydropyridazin-1-yl, 1,4 dihydropyrazin-1-yl, 1,2-dihydropyrazin-1-yl, 1,4-dihydropyrimidin-1-yl or 3,4 5 dihydropyrimidin-3-yl. Hetaryl: a 5- or 6-membered aromatic heterocyclic radical which ordinarily has 1, 2, 3 or 4 nitrogen atoms or a heteroatom selected from oxygen and sulfur and, if appropriate, 1, 2 or 3 nitrogen atoms as ring members besides carbon atoms as ring 10 members: for example C-bonded, 5-membered heteroaromatic radicals having 1, 2, 3 or 4 nitrogen atoms or a heteroatom selected from oxygen and sulfur and, if appropriate, having 1, 2 or 3 nitrogen atoms as ring members, such as: 15 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-3-yl, pyrazol-4 yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-y, isothiazol-4-yl, isothiazol-5-yl, imidazol-2-yl, imidazol-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yi, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4,-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,3-thiadiazol 20 4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4 thiadiazolyl-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl, tetrazol-5-yl. C-bonded, 6-membered heteroaromatic radicals having 1, 2, 3 or 4 nitrogen atoms as ring members, such as: 25 pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,4,5-tetrazin-3-yl. N-bonded, 5-membered heteroaromatic radicals having 1, 2, 3 or 4 nitrogen 30 atoms as ring members, such as: pyrrol-1 -yl, pyrazol-1 -yl, imidazol-1 -yl, 1,2,3-triazol-1 -yl, 1,2,4-triazol-1 -yl, tetrazol 1 -yl. Heterocyclyl also includes bicyclic heterocycles which have one of the aforementioned 35 5- or 6-membered heterocyclic rings and a further saturated, unsaturated or aromatic carbocycle fused thereto, for example a benzene, cyclohexane, cyclohexene or cyclohexadiene ring, or a further 5- or 6-membered heterocyclic ring fused thereto, where the latter may likewise be saturated, unsaturated or aromatic. These include for example quinolinyl, isoquinolinyl, indolyl, indolizynyl, isoindolyl, indazolyl, benzofuryl, 40 benzothienyl, benzo[b]thiazolyl, benzoxazolyl, benzthiazolyl and benzimidazolyl.

24 Examples of 5- to 6-membered heteroaromatic compounds comprising a fused benzene ring include dihydroindolyl, dihydroindolizynyl, dihydroisoindolyl, dihydroquinolinyl, dihydroisoquinolinyl, chromenyl and chromanyl. 5 Arylalkyl: an aryl radical as defined above which is linked via an alkylene group, in particular via a methylene, 1,1-ethylene or 1,2-ethylene group, e.g. benzyl, 1-phenyl ethyl and 2-phenylethyl. Arylalkenyl: an aryl radical as defined above, which is linked via an alkenylene group, 10 in particular via a 1,1-ethenyl, 1,2-ethenyl or 1,3-propenyl group, e.g. 2-phenylethen-1 yl and 1-phenylethen-1-yl. Cycloalkoxy: a cycloalkyl radical as defined above which is linked via an oxygen atom, e.g. cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy. 15 Cycloalkylalkyl: a cycloalkyl radical as defined above which is linked via an alkylene group, in particular via a methylene, 1,1-ethylene or 1,2-ethylene group, e.g. cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl. 20 Heterocyclylalkyl and hetarylalkyl: a heterocyclyl or hetaryl radical as defined above which is linked via an alkylene group, in particular via a methylene, 1,1-ethylene or 1,2 ethylene group. The expression "optionally substituted" means in the context of the present invention 25 that the respective moiety is substituted or has 1, 2 or 3, in particular 1, substituents which are selected from halogen, C 1

-C

4 -alkyl, OH, SH, CN, CF 3 , O-CF 3 , COOH,

O-CH

2 -COOH, C1-C6-alkoxy, C 1

-C

6 -alkylthio, C3-C 7 -cycloalkyl, COO-Cl-C6-alkyl,

CONH

2 , CONH-Cl-C6-alkyl, SO 2

NH-C-C

6 -alkyl, CON-(Ci-C6-alkyl)2, SO 2

N-(C-C

6 alkyl)2, NH-S0 2 -Cl-Cs-alkyl, NH-CO-C-Cs-alkyl, S0 2

-C-C

6 -alkyl, 0-phenyl, O-CH 2 30 phenyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2 NH-hetaryl, S0 2 -phenyl, NH-S02-phenyl, NH-CO-phenyl, NH-S0 2 -hetaryl and NH-CO-hetaryl, where phenyl and hetaryl in the last 11 radicals mentioned are unsubstituted or may have 1, 2 or 3 substituents which are selected from halogen, C-C 4 -alkyl, Cl-C 4 -haloalkyl, C-C 4 alkoxy and Cl-C 4 -haloalkoxy. 35 In relation to their use as calpain inhibitors, the variables R 1 , R 2 , W, X and Y preferably have the following meanings, where these represent, both considered on their own and in combination with one other, special configurations of the compounds of the formula 1: 40 R 1 C-Cio-alkyl, preferably C 3

-C

8 -alkyl, which may be partly or completely halogenated and/or have 1, 2 or 3 substituents Rla, in particular unsubstituted 25 Ci-Cio-alkyl, specifically unsubstituted C 3

-C

8 -alkyl, C3-C7-cycloalkyl-C-C4-alkyl, specifically C3-C 7 -cycloalkylmethyl, 1 -(C 3

-C

7 cycloalkyl)ethyl or 2-(C3-C7-cycloalkyl)ethyl, where the cycloalkyl moiety may 5 have 1, 2, 3 or 4 radicals Rib, very specifically cyclohexylmethyl, phenyl-C-C 4 -alkyl and hetaryl-C-C4-alkyl, in particular benzyl, 1-phenylethyl, 2-phenylethyl, hetarylmethyl, 1-hetarylethyl, 2-hetarylethyl such as thienylmethyl, pyridinylmethyl, where phenyl and hetaryl in the last radicals mentioned may be 10 unsubstituted or carry 1, 2, 3 or 4 identical or different radicals RiC. In this connection, Ria, Rib and Ric where present have the aforementioned meanings. In particular: Ria is C-C 4 -alkoxy or C-C 4 -haloalkoxy; 15 Rib is halogen, C-C 4 -alkyl, Cl-C4-haloalkyl, C-C 4 -alkoxy or C-C 4 -haloalkoxy; and Ric is halogen, Cl-C4-alkyl, OH, SH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, Cl-Ce-alkoxy, C-C 6 -alkylthio, C 3

-C

7 -cycloalkyl, COO-C-C 6 -alkyl, CONH 2 ,

CONH-C-C

6 -alkyl, SO 2 NH-C-C6-alkyl, CON-(CI-C6-alkyl)2, SO 2 N-(Cl-C 6 20 alkyl)2, NH-S0 2 -Cl-C 6 -alkyl, NH-CO-Cl-C 6 -alkyl, S0 2 -Cl-C6-alkyl, O-phenyl, O-CH2-phenyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO2NH-hetaryl, S02-phenyl, NH-SO 2 -phenyl, NH-CO-phenyl, NH-SO 2 hetaryl, NH-CO-hetaryl where phenyl and hetaryl in the last 11 radicals mentioned are unsubstituted or may have 1, 2 or 3 substituents which are 25 selected from halogen, CI-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy and CrC 4 -haloalkoxy, -(CH2)p-NRc 6 Rc 7 with p = 0, 1, 2, 3, 4, 5 or 6, in particular 0, and -0-(CH2)q-NR 6 Rc 7 with q = 2, 3, 4, 5 or 6, in particular 2, where Rc6, Rc7 are independently of one another hydrogen or Cl-C 6 -alkyl, or 30 together with the nitrogen atom to which they are bonded, are a morpholine, piperidine, pyrrolidine, azetidine or piperazine residue, where the last 5 radicals mentioned are unsubstituted or may carry 1, 2, 3 or 4 radicals selected from C-C 4 -alkyl, C-C 4 -haloalkyl, Cl-C 4 -alkoxy or C-C 4 haloalkoxy. Ric is in particular halogen, C-C 4 -alkyl, Cr-C 4 -haloalkyl, C1-C4 35 alkoxy or C-C 4 -haloalkoxy.

R

2 one of the aforementioned radicals different from hydrogen, in particular: Ci-Cio-alkyl which may be partly or completely halogenated and/or carry 1, 2 or 3 40 substituents R 2 a, aryl or hetaryl, where aryl and hetaryl in the last 2 radicals mentioned may be 26 unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R2c, aryl-C-C6-alkyl, aryl-C2-C6-alkenyl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 3 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 5 identical or different radicals R 2 c. Preferred among these are those compounds of the general formula I in which R 2 is selected from aryl and hetaryl, specifically from phenyl, thienyl and pyridyl, where aryl and hetaryl (or phenyl, thienyl and pyridyl) may be unsubstituted or 10 carry 1, 2, 3 or 4, in particular 1 or 2, identical or different radicals R 2 c. In this connection, R2a, R2b and R2c where present have the aforementioned meanings. In particular:

R

2 a is OH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, Cl-C 6 -alkoxy, C1-C6 15 alkylthio, COO-C-C 6 -alkyl, CONIH 2 , CONH-Cl-C 6 -alkyl, SO 2 NH-Cl-C 6 -alkyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2 NH-hetaryl, CON (Cl-C6-alkyl)2, SO 2 N-(Cl-C 6 -alkyl)2, NH-S0 2 -Cl-C 6 -alkyl, NH-CO-C-C 6 alkyl, S0 2

-C-C

6 -alkyl, S02-phenyl, NH-S0 2 -phenyl, NH-CO-phenyl, NH S02-hetaryl, NH-CO-hetaryl, NRa 6 Ra 7 , where 20 Ra6, Ra7 are independently of one another hydrogen or CI-C6-alkyl, or together with the nitrogen atom to which they are bonded are a morpholine, piperidine, pyrrolidine, azetidine or piperazine residue, where the last 5 radicals mentioned are unsubstituted or may carry 1, 2, 3 or 4 radicals selected from C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy or C1-C4 25 haloalkoxy; R2b is halogen, Cl-C4-alkyl, OH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, C1-C6 alkoxy, Cr 1

C

6 -alkylthio, COO-CrC 6 -alkyl, CONIH 2 , CONH-Cr-C 6 -alkyl,

SO

2 NH-Cr-C 6 -alkyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2

NH

hetaryl, CON-(Cl-C6-alkyl)2, SO 2 N-(Cl-C 6 -alkyl)2, NH-S0 2 -Cl-C6-alkyl, NH 30 CO-Cr-C--alkyl, S0 2 -OC-Ce-alkyl, S0 2 -phenyl, NH-SO 2 -phenyl, NH-CO phenyl, NH-S02-hetaryl, NH-CO-hetaryl or NRb6Rb 7 , where Rb6, Rb7 are independently of one another hydrogen or C 1 Ce-alkyl, or together with the nitrogen atom to which they are bonded are a morpholine, piperidine, pyrrolidine, azetidine or piperazine residue, where the last 5 radicals 35 mentioned are unsubstituted or may carry 1, 2, 3 or 4 radicals selected from Cr 1

C

4 -alkyl, Cr 1

C

4 -haloalkyl, C 1

C

4 -alkoxy or Cr 1

C

4 -haloalkoxy; and

R

2 c is halogen, Cl-C4-alkyl, OH, SH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, C-Co-alkoxy, Cr 1 Ce-alkylthio, C3-Cr-cycloalkyl, COO-CC 6 -alkyl, CONH 2 , CONH-Cr 1 Ce-alkyl, SO 2 NH-CiC--alkyl, CON-(Cl-C-alkyl)2, SO 2 N-(CrC 6 40 alkyl)2, NH-S0 2 -OCl-C6-alkyl, NH-CO-Cr 1

C

6 -alkyl, S0 2 -OCl-C6-alkyl, 0-phenyl, O-CH 2 -phenyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl,

SO

2 NH-hetaryl, S02-phenyl, NH-SO 2 -phenyl, NH-CO-phenyl, NH-SO 2

-

27 hetaryl, NH-CO-hetaryl, where phenyl and hetaryl in the last 11 radicals mentioned are unsubstituted or may have 1, 2 or 3 substituents which are selected from halogen, Cr-C 4 -alkyl, C-C4-haloalkyl, C-C 4 -alkoxy and Cr-C 4 -haloalkoxy, 5 -(CH 2 )p-NRc 6 Rc7 with p = 0, 1, 2, 3, 4, 5 or 6, in particular 0, and -0-(CH2)q-NR6R 7 with q = 2, 3, 4, 5 or 6, in particular 2, where Rc6, Rc7 are independently of one another hydrogen or C-C 6 -alkyl, or together with the nitrogen atom to which they are bonded are a morpholine, piperidine, pyrrolidine, azetidine or piperazine residue, where the last 5 10 radicals mentioned are unsubstituted or may carry 1, 2, 3 or 4 radicals selected from C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy or C-C 4 haloalkoxy.

R

3 a, R3b in particular OH or the group CR3aR3b is a carbonyl group. 15 W a radical of the formulae W1 or W2 or the group W-R 2 is a radical of the formula W6. In the formulae W1 and W2, R 2 is preferably bonded to the carbon in position 3 or 20 4, as shown in the following formulae W1a, W1b and W2a: * * * N N N N (Rw)m (R)m)m Wia W1b W2a In the formulae W1a, W1b and W2a, the meanings of *, #, m and Rw are those 25 mentioned above. In particular, m is 0 or 1 and specifically 0. Where m is 1, Rw is preferably selected from halogen, C-C 6 -alkyl, C-C 6 -alkyl which is substituted by 1, 2 or 3 substituents Rwa, or OH, SH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, Cl-C 6 -alkoxy, Cl-C 6 -alkylthio, C3-C 7 -cycloalkyl, COO-C-C 6 -alkyl, CONH 2 , CONH Cl-C 6 -alkyl, SO 2 NH-Cl-C6-alkyl, CON-(Cl-C6-alkyl)2, SO 2 N-(Cl-C6-alkyl)2, NH 30 S0 2 -Cl-C6-alkyl, NH-CO-Cl-C6-alkyl, S0 2

-C-C

6 -alkyl, O-phenyl, O-CH 2 -phenyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2 NH-hetaryl, S02-phenyl, NH S0 2 -phenyl, NH-CO-phenyl, NH-SO-hetaryl, NH-CO-hetaryl, where phenyl and hetaryl in the last 11 radicals mentioned are unsubstituted or may have 1, 2 or 3 substituents which are selected from halogen, Cr-C 4 -alkyl, Cr-C 4 -haloalkyl, C 1

-C

4 35 alkoxy and C-C 4 -haloalkoxy. Rw is in particular selected from OH, F, Cl, CN, CF 3 , Cl-C6-alkyl which is unsubstituted or may have 1, 2 or 3 substituents Rwa, or 28 Cl-C 6 -haloalkyl, C-C 6 -alkoxy, Cl-C6-haloalkoxy and C3-C7-cycloalkyl. In this connection, Rwa has the aforementioned meanings and is in particular C 1

-C

4 alkoxy or C-C 4 -haloalkoxy. Rw is particularly preferably selected from F, Cl, CN,

CF

3 , CH 3 , C 2

H

5 and OCH 3 . 5 Where the group W-R 2 is a radical of the formula W6,;m is preferably 0 or 1 and specificially 0. Where m is 1, Rw6* is preferably selected from halogen, CI-C6 alkyl, C-C6-alkyl which is substituted by 1, 2 or 3 substituents Rwa, or OH, SH, CN, CF 3 , 0-CF 3 , COOH, O-CH 2 -COOH, C-C 6 -alkoxy, C-C 6 -alkylthio, C 3

-C

7 10 cycloalkyl, COO-C-C 6 -alkyl, CONIH 2 , CONH-C-C 6 -alkyl, SO 2 NH-Cl-C 6 -alkyl,

CON-(C-C

6 -alkyl) 2 , SO 2

N-(C-C

6 -alkyl) 2 , NH-SO 2

-C-C

6 -alkyl, NH-CO-C-C 6 alkyl, S0 2

-C-C

6 -alkyl, 0-phenyl, O-CH 2 -phenyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2 NH-hetaryl, S0 2 -phenyl, NH-SO 2 -phenyl, NH-CO-phenyl, NH S0 2 -hetaryl, NH-CO-hetaryl where phenyl and hetaryl in the last 11 radicals 15 mentioned are unsubstituted or may have 1, 2 or 3 substituents which are selected from halogen, Cl-C4-alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy and C-C 4 haloalkoxy. Rw 6 * is in particular selected from OH, F, Cl, CN, CF 3 , C-C 6 -alkyl which is unsubstituted or may have 1, 2 or 3 substituents Rwa, or C-C 6 -haloalkyl, Cl-C 6 -alkoxy, C-C 6 -haloalkoxy and C 3

-C

7 -cycloalkyl. In this connection, Rwa has 20 the aforementioned meanings and is in particular C-C 4 -alkoxy or C 1

-C

4 haloalkoxy. E in W6 preferably has one of the following meanings: CH 2 , CH 2

CH

2 , CO, CO-NH, 0, CH=CH, CH 2 0, OCH 2 , SO 2 , SO2NRE 1 or NRE 1 SO2, and is in particular CH 2 , CH 2

CH

2 , 0, CH=CH, CH 2 0, OCH 2 , S02, SO2NRE 1 or NRE 1 SO2. In this connection, RE 1 has one of the aforementioned meanings and is in particular 25 hydrogen or C-C 4 -alkyl. Compounds of the formula I which are particularly preferred among the compounds of the invention of the general formula I are those in which W is a radical W1a, and particularly preferred among these are those in which m is 0 or 30 1 and specifically 0. Compounds of the formula I which are particularly preferred among the compounds of the invention of the general formula I are those in which W-R 2 is a radical W6, and particularly preferred among these are those in which m is 0 or 1 35 and specifically 0. X is a radical C(=O)-NRx2Rx 3 in which Rx2 and Rx3 have one of the aforementioned meanings. Compounds preferred among these are those in which: Rx 2 is H, OH, CN, C-Ce-alkyl, C-C-haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 40 substituents Rxa, or C 2

-C

6 -alkenyl, C 2

-C

6 -alkynyl, C 3

-C

7 -cycloalkyl, C 3

-C

7 cycloalkyl-Cl-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C 4 -alkyl, C-C 6 -alkoxy

C-C

4 -alkyl, aryl, hetaryl, aryl-Cl-C 4 -alkyl or hetaryl-C-C 4 -alkyl, where aryl 29 and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd. In particular, Rx 2 is hydrogen, C-C 6 -alkyl, C 1

-C

6 haloalkyl, C-C 6 -alkyl which has 1 or 2 substituents Rxa, C 3 -C7-cycloalkyl

C-C

4 -alkyl, C 3 -C7-heterocycloalkyl-C 1

-C

4 -alkyl, aryl, hetaryl, aryl-C-C4 5 alkyl or hetaryl-Cr-C 4 -alkyl. Rx 2 is very particularly preferably hydrogen. Rx 3 is H, C 1

-C

6 -alkyl, Cl-C6-haloalkyl or C-Ce-alkyl which has 1, 2 or 3 substituents Rxa. In particular, Rx 3 is hydrogen, C-C6-alkyl, Cl-C6-haloalkyl,

C

1

-C

6 -alkyl which has 1 or 2 substituents Rxa. Rx 3 is very particularly preferably hydrogen. 10 Compounds of the formula I which are likewise preferred are those in which the group NRx2Rx3 is a nitrogen heterocycle of the following formulae: RX5 Rx5 Rx R R R X5 -N 0 -N N-R -N -N -N 15 in which Rx 5 is hydrogen or has the meaning indicated for Rxb. In particular, Rx 5 is Cl-C 6 -alkyl, C-C 6 -haloalkyl, C 1

-C

6 -alkyl which has 1, 2 or 3 substituents Rxa, or

C

3 -Cr-cycloalkyl-C-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C4-alkyl, C-C6-alkoxy 20 Cr-C 4 -alkyl, aryl-C-C4-alkyl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, or

COO-C-C

6 -alkyl, CONIH 2 , CONH-C-C 6 -alkyl, SO 2

NH-C-C

6 -alkyl, CON-(CrC 6 alkyl)2, SO 2 N-(Cl-C 6 -alkyl)2, NH-S0 2

-C-C

6 -alkyl, CONH-phenyl, SO 2 NH-phenyl, CONH-hetaryl, SO 2 NH-hetaryl, where phenyl and hetaryl in the last 4 radicals 25 mentioned are unsubstituted or may have 1, 2 or 3 substituents which are selected from the halogen, C-C 4 -alkyl, Ce-C 4 -haloalkyl, Cl-C 4 -alkoxy and C 1

-C

4 haloalkoxy. In particular, Rx 5 is hydrogen or C-C 4 -alkyl. In a particularly preferred embodiment of the invention, X is C(O)-NH 2 . 30 In another embodiment of the invention, X is hydrogen. In another embodiment of the invention, X is C(O)ORxi in which Rxi has the aforementioned meanings. In particular, R 1 is C-C 6 -Alkyl, C-C 6 -haloalkyl, C-C 6 35 alkyl which has 1, 2 or 3 substituents Rxa, or C 3

-C

7 -cycloalkyl, C 3

-C

7 -cycloalkyl C-C4-alkyl, C 3

-C

7 -heterocycloalkyl-C-C 4 -alkyl, C-C 6 -alkoxy-C-C4-alkyl, aryl, hetaryl, aryl-C-C4-alkyl or hetaryl-Cr-C4-alkyl stands, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd.

30 In this connection, Rxa has the aforementioned meanings and is in particular

C

1

-C

4 -alkoxy or C 1

-C

4 -haloalkoxy. In this connection, Rxd has the aforementioned meanings and is preferably F, CI, OH, COOH, C(O)NH 2 , CN, NH 2 , OCH 2 COOH, Cl-C 4 -alkyl, Cl-C 4 -haloalkyl, Cr-C 4 -alkoxy, C-C 4 -haloalkoxy, C-C 4 -alkylthio, 5 C-C 4 -haloalkylthio, CO-C-C 4 -alkyl, CO-O-C-C 4 -alkyl, NH-C-C 4 -alkyl, NH

C(O)C

1

-C

4 -alkyl or S0 2

-C-C

4 -alkyl. Y a divalent, 6-membered heteroaromatic radical which has 1 or 2 nitrogen atoms as ring members and which is preferably selected from pyridinediyl and 10 pyrimidinediyl and which optionally has 1 or 2 identical or different substituents RY. Y is in particular pyridinedlyl which is unsubstituted or has 1 or 2 identical or different substituents Ry. Y is in particular unsubstituted or has one substituent Ry. 15 W is preferably bonded to a C atom of Y which is located in the position ortho to the C atom of Y which is connected to the carbonyl group. Accordingly, Y is preferably selected from pyridine-2,3-diyl, pyridine-3,4-diyl and pyrimidine-5,6 diyl. A nitrogen atom is preferably present at the other position ortho to the C atom of Y to which W is bonded. 20 Where RY is present, RY is preferably selected from OH, F, Cl, NH 2 , CN, CE 3 ,

CHF

2 , 0-CF 3 , O-CHF 2 , O-CH 2 F, Cl-C6-alkyl, C 3

-C

7 -cycloalkyl, C-C 6 -alkylamino, Cl-C 6 -dialkylamino, pyrrolidinyl, piperidinyl, morpholinyl, imidazolyl, CI-C 4 -alkoxy, Cl-C 4 -alkoxy-C-C4-alkyl, CONRy 2 Ry 3 , SO 2 NRy 2 Ry 3 , NH-S0 2

-R

4 , -(CH 2 )p-NRy 6 Ry 7 , 25 NH-CO-Ry 5 , in which p is 0, 1, 2, 3, 4, or 5, and in which Ry 2 , RY 3 , Ry 4 , RY 5 , Ry 6 , Ry 7 have the aforementioned meanings, preferably the meanings mentioned as preferred below, and are in particular H and C-C 6 -alkyl, phenyl, benzyl and O-benzyl, where the phenyl ring in the last 3 groups mentioned may have 1, 2 or 3 substituents selected from halogen, OH, SH, NO 2 , 30 COOH, C(O)NH 2 , CHO, CN, NH 2 , OCH 2 COOH, C-C 6 -alkyl, C-C 6 -haloalkyl, Cl-C6-alkoxy, Cl-C6-haloalkoxy, C-C 6 -alkylthio, C-C 6 -haloalkylthio, CO-C 1

-C

6 alkyl, CO-O-C-C6-alkyl, NH-C-C 6 -alkyl, NHCHO, NH-C(O)C-C 6 -alkyl, and S02-CrC 6 -alkyl. 35 In particular, RV is OH, F, Cl, NH 2 , CN, CF 3 , CHF 2 , 0-CF 3 , O-CHF 2 , O-CH 2 F, Cl-C 6 -alkyl, C 3

-C

7 -cycloalkyl, C-C 6 -alkylamino, C-C 6 -dialkylamino, pyrrolidinyl, piperidinyl, morpholinyl, imidazolyl, C-C 4 -alkoxy, Cl-C 4 -alkoxy-C-C 4 -alkyl,

CONH-C-C

6 -alkyl, SO 2 N(Cl-C6-alkyl)2, NH-S0 2

-C-C

6 -alkyl, NH-CO-CI-C6-alkyl,

(CH

2 )p-N(Cl-Ce-alkyl)2, in which p is 2, 3 or 4. 40 RY is particularly preferably F, Cl, CN, CF 3 , CHF 2 , O-CF 3 , O-CHF 2 , O-CH 2 F or

C-C

3 -alkyl.

31 Otherwise, the radicals Rx4, Rya, Rwa, REla, Ryb, Rwb, RE1b, Ryd, Rwd, RE1d, Ra1, Rbi, Rei, Ry 1 , Rwl, Ra2, Rb2, Rc 2 , Ry 2 , Rw2, Ra3, Rb3, Rc3, Rv 3 , Rw 3 , Ra4, R4, Re4, Ry 4 , Rw4, Ra 5 , Rb5, Rc5, Ry 5 , Rw5, Ra6, Rb6, Rc6, Ry 6 , Rw6, Ra7, Rb7, Rc7, Ry 7 and Rw7 have, unless otherwise 5 indicated, independently of one another preferably one of the following meanings: Rx 4 : hydrogen or C-C 6 -alkyl. Rya, Rwa, REa independently of one another: C-C 4 -alkoxy or C-C 4 -haloalkoxy. 10 Ryb, Rwb, REib independently of one another: halogen, C-C 4 -alkyl, C-C 4 -haloalkyl, Cr

C

4 -alkoxy or C-C 4 -haloalkoxy. Ryd, Rwd, REId independently of one another: F, Cl, OH, COOH, C(O)NH 2 , CN, NH 2 , 15 OCH 2 COOH, C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy, C-C 4 -haloalkoxy, C-C 4 alkylthio, C 1

-C

4 -haloalkylthio, CO-C-C 4 -alkyl, CO-0-Cl-C4-alkyl, NH-C-C 4 -alkyl, NH

C(O)C-C

4 -alkyl or S0 2 -Cl-C 4 -alkyl. Ra1, Rbi, Rd1, Ryi, Rwi independently of one another: hydrogen, CI-C 6 -alkyl, C-C 6 20 haloalkyl, phenyl, benzyl, hetaryl and hetarylmethyl, where phenyl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents which are selected from halogen, C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy and C-C4 haloalkoxy. 25 Ra2, Rb2, Rc2, Ry 2 , Rw2 independently of one another: hydrogen, Ci-Ce-alkyl, phenyl, benzyl, hetaryl and hetarylmethyl, where phenyl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents which are selected from halogen, C-C 4 -alkyl, Cl-C 4 -haloalkyl, C-C 4 -alkoxy and C-C 4 -haloalkoxy. 30 Ra 3 , Rb3, Rc 3 , Ry, Rw3 independently of one another: hydrogen or Cl-C 6 -alkyl, or Ra 2 with Ra 3 (and likewise Rb2 with Rb3, Re 2 with Rc 3 , Ry 2 with Ry 3 and Rw 2 with Rw 3 ) together with the nitrogen atom to which they are bonded are a morpholine, piperidine, pyrrolidine, azetidine or piperazine residue, where the last 5 radicals mentioned are 35 unsubstituted or may carry 1, 2, 3 or 4 radicals selected from C-C 4 -alkyl, C 1

-C

4 haloalkyl, C-C4-alkoxy or C-C 4 -haloalkoxy. Ra 4 , R4, Re4, Rv 4 , Rw4 independently of one another: hydrogen, CI-C 6 -alkyl, phenyl, benzyl, hetaryl and hetarylmethyl, where phenyl and hetaryl in the last 4 radicals 40 mentioned are unsubstituted or have 1, 2 or 3 substituents which are selected from halogen, C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy and C-C 4 -haloalkoxy.

32 Ra5, Rb5, Rc5, RY 5 , Rw5 independently of one another: hydrogen, C-C 6 -alkyl, phenyl, benzyl, hetaryl and hetarylmethyl, where phenyl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents which are selected from halogen, Cl-C4-alkyl, Cl-C4-haloalkyl, C-C 4 -alkoxy and C-C 4 -haloalkoxy. 5 Ra6, Rb6, Rc6, Ry 6 , Rw6 independently of one another: hydrogen, Cl-C6-alkyl, phenyl, benzyl, hetaryl and hetarylmethyl, where phenyl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents which are selected from halogen, C-C 4 -alkyl, C-C 4 -haloalkyl, C-C 4 -alkoxy and C-C 4 -haloalkoxy. 10 Ra7, Rb7, Rc7, Rv 7 , Rw7 independently of one another: hydrogen or C-C 6 -alkyl, or Ra 6 with Ra 7 (and likewise Rb6 with Rb7, Rc 6 with Rc 7 , Ry 6 with Ry 7 and Rw 6 with Rw7) together with the nitrogen atom to which they are bonded are a morpholine, piperidine, 15 pyrrolidine, azetidine or piperazine residue, where the last 5 radicals mentioned are unsubstituted or may carry 1, 2, 3 or 4 radicals selected from Cl-C4-alkyl, C1-C 4 haloalkyl, C-C 4 -alkoxy or C-C 4 -haloalkoxy. Compounds preferred among the carboxamide compounds of the invention of the 20 formula I are those which correspond to the general formula I-A, (R')n O R1 2 N (I-A) 3 HR R 'Y4 W-R 2 in which X, W, R 1 , R 2 , R3a, R3b, RY have the aforementioned meanings, in particular the 25 meanings mentioned as preferred, n is 0, 1 or 2, in particular 0 or 1, one of the variables Yi, Y2, y 3 and Y 4 is a nitrogen atom and the remaining variables Yi, Y2, Y 3 or

Y

4 are CH (or C-RY if n is different from 0). Also preferred are the tautomers of I-A, the pharmaceutically suitable salts thereof and the tautomers thereof. 30 Compounds in turn preferred among the carboxamide compounds of the invention of the formula I-A are those which correspond to the general formulae I-A' or I-A", 33 0 R '\y x YN (-A') 3 H Re Ra "' N-N (Rw)m (R ) 0 R 1 Y N Y| H R3b 3a 1-A" N H R Ns E 5 in which m, X, E, R 1 , R 2 , R3a, R3b, RY, Rw and Rw6 have the aforementioned meanings, in particular the meanings mentioned as preferred, n is 0, 1 or 2, in particular 0 or 1, one of the variables Y1, Y2, Y3 and Y 4 is a nitrogen atom and the remaining variables

Y

1 , Y 2 , Y 3 or Y 4 are CH (or C-RY if n is different from 0). Also preferred are the tautomers of I-A' and I-A", the pharmaceutically suitable salts thereof and the 10 tautomers thereof. Compounds preferred in turn among the carboxamide compounds of the invention of the formula I-A are those which correspond to the general formula l-A.a, (RY )n O R41 x N (1-A.a) I 3b 3a H R 2 15 N W-R in which X, W, R 1 , R 2 , R3a, R3b, RY have the aforementioned meanings, especially those mentioned as preferred, and n is 0, 1 or 2, in particular 0 or 1. Also preferred are the tautomers of I-A.a, the pharmaceutically acceptable salts thereof and the tautomers 20 thereof. Compounds in turn preferred among the carboxamide compounds of the invention of 34 the formula l-A.a are those which correspond to the general formulae I-A.a' or l-A.a", (R')n O R1 x N (1-A.a') 3bX 3a HR R N N-N (RW)m R (R) O R MX (R' n0 R 1 N x N H 3b a l-A.a" HR R N N N- E (R )m 5 in which m, E, R 1 , R3a, R3b, R 2 , RY, Rw and Rw6 have the aforementioned meanings, especially those mentioned as preferred, and n is 0, 1 or 2, in particular 0 or 1. Also preferred are the tautomers of I-A.a' and I-A.a", the pharmaceutically suitable salts 10 thereof and the tautomers thereof. The compounds of the general formula 1-A.a which are indicated in Tables 1 to 20 below and in which CR3aR3b is a carbonyl function or a C(OH) 2 group, and their tautomers, prodrugs and pharmaceutically acceptable salts, represent per se preferred 15 embodiments of the present invention. The meanings for R 1 , R 2 and W indicated in Table A below represent embodiments of the invention which are likewise preferred independently of one another and especially in combination.

35 0 R 1 0 R' 4 4 3 X 3 X J 2 I 2 N /2 H 6 N HHO OH N W N W 2 2 RR CR3aR3b = C=O (I-A.a) CR3aR3b = C(OH) 2 Table 1 Compounds of the formula l-A.a in which the group C(R3aR 3 b) is C=0, X is carbamoyl, 5 n = 0, i.e. (RY)n is absent, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 2 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=0, X is carbamoyl, 10 (Ry)n is 5-F, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 3 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=0, X is carbamoyl, 15 (Ry)n is 5-Cl, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 4 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=0, X is carbamoyl, 20 (Ry)r is 5-CN, and the combination of R', R 2 and W for a compound in each case corresponds to one line of Table A. Table 5 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=0, X is carbamoyl, 25 (Ry)n is 5-CH 3 , and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 6 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=0, X is 30 -C(O)NHCH 3 , n = 0, i.e. (Ry)n is absent, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A.

36 Table 7 Compounds of the formula I-A.a in which the group C(RaaR3b) is C=0, X is

-C(O)NHCH

3 , (Ry), is 5-F, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 5 Table 8 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=O, X is

-C(O)NHCH

3 , (Ry), is 5-Cl, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 10 Table 9 Compounds of the formula l-A.a in which the group C(R3aR3b) is C=O, X is

-C(O)NHCH

3 , (RY), is 5-CN, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 15 Table 10 Compounds of the formula l-A.a in which the group C(R3aR 3 b) is C=O, X is -C(O)NHCH3, (Ry)n is 5-CH 3 , and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 20 Table 11 Compounds of the formula I-A.a in which the group C(RaaR3b) is C(OH) 2 , X is carbamoyl, n = 0, i.e. (Ry)n is absent, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 25 Table 12 Compounds of the formula l-A.a in which the group C(R3aR 3 b) is C(OH) 2 , X is carbamoyl, (Ry), is 5-F, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 30 Table 13 Compounds of the formula l-A.a in which the group C(R3aRab) is C(OH) 2 , X is carbamoyl, (Ry)n is 5-Cl, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 35 Table 14 Compounds of the formula I-A.a in which the group C(R3aR3b) is C(OH) 2 , X is carbamoyl, (Ry)n is 5-CN, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. 40 Table 15 Compounds of the formula l-A.a in which the group C(R3aR3b) is C(OH) 2 , X is 37 carbamoyl, (Ry)n is 5-CH 3 , and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 16 5 Compounds of the formula l-A.a in which the group C(R3aR3b) is C(OH) 2 , X is

-C(O)NHCH

3 , n = 0, i.e. (Ry)n is absent, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 17 10 Compounds of the formula l-A.a in which the group C(R3aR3b) is C(OH) 2 , X is

-C(O)NHCH

3 , (Ry), is 5-F, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 18 15 Compounds of the formula l-A.a in which the group C(R3aR 3 b) is C(OH) 2 , X is -C(O)NHCH3, (Ry)n is 5-Cl, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 19 20 Compounds of the formula l-A.a in which the group C(R3aR3b) is C(OH) 2 , X is

-C(O)NHCH

3 , (Ry), is 5-CN, and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table 20 25 Compounds of the formula 1-A.a in which the group C(R3aR3b) is C(OH) 2 , X is

-C(O)NHCH

3 , (Ry)n is 5-CH 3 , and the combination of R 1 , R 2 and W for a compound in each case corresponds to one line of Table A. Table A 30 No. R1 R2 W A-1 n-Butyl Phenyl W1 a (m= 0) A-2 n-Butyl 2-Methylphenyl W1 a (m= 0) A-3 n-Butyl 2-Methoxyphenyl W1 a (m= 0) A-4 n-Butyl 2-Chlorophenyl W1a (m= 0) A-5 n-Butyl 2-Fluorophenyl W1a (m= 0) A-6 n-Butyl 2-Trifluoromethylphenyl W1a (m= 0) A-7 n-Butyl 3-Methylphenyl W1a (m= 0) A-8 n-Butyl 3-Methoxyphenyl W1a (m= 0) A-9 n-Butyl 3-Chlorophenyl W1 a (m= 0) A-10 n-Butyl 3-Fluorophenyl W1 a (m= 0) 38 No. R1 R2 W A-1 1 n-Butyl 3-Trifluoromethyl Wi a (m= 0) A-12 n-Butyl 3-[(Phenylmethyl)oxy]phenyl Wia (m= 0) A-1 3 n-Butyl 3-Morpholin-4-ylphenyl WI a (m= 0) A-14 n-Butyl 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-1 5 n-Butyl 3-Pyrrolidin-1 -ylphenyl Wi a (m= 0) A-16 n-Butyl 4-Methylphenyl Wia (m= 0) A-17 n-Butyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-18 n-Butyl 4-Methoxyphenyl Wia (m= 0) A-19 n-Butyl 4-Chlorophenyl Wia (m= 0) A-20 n-Butyl 4-Fluorophenyl Wia (m= 0) A-21 n-Butyl 4-Trifluoromethylphenyl Wia (m= 0) A-22 n-Butyl 4-Diethylaminophenyl Wia (m= 0) A-23 n-Butyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-24 n-Butyl 4-Cyanophenyl Wia (m= 0) A-25 n-Butyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-26 n-Butyl 4-(4-Methylpiperazin-1-yl)phenyl Wia (m= 0) A-27 n-Butyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-28 n-Butyl 4-(1 H-Imidazol-1-yl)phenyl Wia (m= 0) A-29 n-Butyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-30 n-Butyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-31 n-Butyl 2,4-Difluorophenyl Wia (m= 0) A-32 n-Butyl 2,6-Difluorophenyl Wia (m= 0) A-33 n-Butyl 3,5-Difluorophenyl Wia (m= 0) A-34 n-Butyl 2,4-Dichlorophenyl Wia (m= 0) A-35 n-Butyl 2,6-Dichlorophenyl Wia (m= 0) A-36 n-Butyl 3,5-Dichlorophenyl Wia (m= 0) A-37 n-Butyl 2-Chloro-4-fluorophenyl Wia (m= 0) A-38 n-Butyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-39 n-Butyl 2-Fluoro-4-morpholin-4-ylphenyl WI a (m= 0) A-40 n-Butyl Pyridin-2-yl Wi a (m= 0) A-41 n-Butyl Pyridin-4-yl Wia (m= 0) A-42 n-Butyl Thien-2-yl WI a (m= 0) A-43 n-Butyl 2,3-Dihydrobenzo[b]furan-5-y Wia (m= 0) A-44 Isobutyl Phenyl Wia (m= 0) A-45 Isobutyl 2-Methylphenyl Wia (m= 0) A-46 Isobutyl 2-Methoxyphenyl Wia (m= 0) A-47 Isobutyl 2-Chlorophenyl Wia (m= 0) A-48 Isobutyl 2-Fluorophenyl Wia (m= 0) A-49 Isobutyl 2-Trifluoromethylphenyl WI a (m= 0) 39 No. RW R2 W A-50 Isobutyl 3-Methylphenyl Wia (m= 0) A-51 Isobutyl 3-Methoxyphenyl Wia (m= 0) A-52 Isobutyl 3-Chlorophenyl Wia (m= 0) A-53 Isobutyl 3-Fluorophenyl Wia (m= 0) A-54 Isobutyl 3-Trifluoromethyl Wia (m= 0) A-55 Isobutyl 3-[(Phenylmethyl)oxy]phenyl Wia (m= 0) A-56 Isobutyl 3-Morpholin-4-ylphenyl Wia (m= 0) A-57 Isobuty 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-58 Isobutyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-59 Isobutyl 4-Methylphenyl Wia (m= 0) A-60 Isobutyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-61 Isobutyl 4-Methoxyphenyl Wia (m= 0) A-62 Isobutyl 4-Chlorophenyl Wia (m= 0) A-63 Isobutyl 4-Fluorophenyl Wia (m= 0) A-64 Isobutyl 4-Trifluoromethylphenyl Wia (m= 0) A-65 Isobutyl 4-Diethylaminophenyl Wia (m= 0) A-66 Isobutyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-67 Isobutyl 4-Cyanophenyl Wia (m= 0) A-68 Isobutyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-69 Isobutyl 4-(4-Methylpiperazin-1 -yl)phenyl WI a (m= 0) A-70 Isobutyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-71 Isobutyl 4-(1H-Imidazol-1-yl)phenyl Wia (m= 0) A-72 Isobutyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-73 Isobutyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-74 Isobutyl 2,4-Difluorophenyl Wia (m= 0) A-75 Isobutyl 2,6-Difluorophenyl Wia (m= 0) A-76 Isobutyl 3,5-Difluorophenyl Wia (m= 0) A-77 Isobutyl 2,4-Dichlorophenyl Wia (m= 0) A-78 Isobutyl 2,6-Dichlorophenyl Wia (m= 0) A-79 Isobutyl 3,5-Dichlorophenyl Wia (m= 0) A-80 Isobutyl 2-Chloro-4-fluorophenyl Wia (m= 0) A-81 Isobutyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-82 Isobutyl 2-Fluoro-4-morpholin-4-ylphenyl Wia (m= 0) A-83 Isobutyl Pyridin-2-yl Wia (m= 0) A-84 Isobutyl Pyridin-4-yl Wia (m= 0) A-85 Isobutyl Thien-2-yl Wia (m= 0) A-86 Isobutyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-87 Benzyl Phenyl Wia (m= 0) A-88 Benzyl 2-Methylphenyl Wia (m= 0) 40 No. R1 R2 W A-89 Benzyl 2-Methoxyphenyl W1 a (m= 0) A-90 Benzyl 2-Chlorophenyl WI a (m= 0) A-91 Benzyl 2-Fluorophenyl W1a (m= 0) A-92 Benzyl 2-Trifluoromethylphenyl W1 a (m= 0) A-93 Benzyl 3-Methylphenyl W1a (m= 0) A-94 Benzyl 3-Methoxyphenyl W1a (m= 0) A-95 Benzyl 3-Chlorophenyl W1a (m= 0) A-96 Benzyl 3-Fluorophenyl W1a (m= 0) A-97 Benzyl 3-Trifluoromethyl W1a (m= 0) A-98 Benzyl 3-[(Phenylmethyl)oxy]phenyl W1a (m= 0) A-99 Benzyl 3-Morpholin-4-ylphenyl W1a (m= 0) A-100 Benzyl 3-(Morpholin-4-ylmethyl)phenyl W1a (m= 0) A-101 Benzyl 3-Pyrrolidin-1-ylphenyl WIa (m= 0) A-102 Benzyl 4-Methylphenyl W1a (m= 0) A-103 Benzyl 4-(1-Methylethyl)phenyl W1a (m= 0) A-104 Benzyl 4-Methoxyphenyl W1a (m= 0) A-105 Benzyl 4-Chlorophenyl W1a (m= 0) A-106 Benzyl 4-Fluorophenyl W1a (m= 0) A-107 Benzyl 4-Trifluoromethylphenyl W1a (m= 0) A-108 Benzyl 4-Diethylaminophenyl W1a (m= 0) A-109 Benzyl 4-[(Diethylamino)methyl]phenyl WIa (m= 0) A-110 Benzyl 4-Cyanophenyl W1a (m= 0) A-1 11 Benzyl 4-(Piperidin-1 -yl)phenyl W1 a (m= 0) A-112 Benzyl 4-(4-Methylpiperazin-1-yl)phenyl W1a (m= 0) A-113 Benzyl 4-Pyrrolidin-1-ylphenyl W1a (m= 0) A-1 14 Benzyl 4-(1 H-Imidazol-1 -yl)phenyl W1 a (m= 0) A-1 15 Benzyl 4-Morpholin-4-ylphenyl W1 a (m= 0) A-1 16 Benzyl 4-(Morpholin-4-ylmethyl)phenyl W1 a (m= 0) A-1 17 Benzyl 2,4-Difluorophenyl WI a (m= 0) A-1 18 Benzyl 2,6-Difluorophenyl WI a (m= 0) A-1 19 Benzyl 3,5-Difluorophenyl W1 a (m= 0) A-120 Benzyl 2,4-Dichlorophenyl W1a (m= 0) A-121 Benzyl 2,6-Dichlorophenyl W1a (m= 0) A-122 Benzyl 3,5-Dichlorophenyl W1a (m= 0) A-123 Benzyl 2-Chloro-4-fluorophenyl W1a (m= 0) A-124 Benzyl 2-Chloro-4-morpholin-4-ylphenyl W1a (m= 0) A-125 Benzyl 2-Fluoro-4-morpholin-4-ylphenyl W1a (m= 0) A-126 Benzyl Pyridin-2-yl W1a (m= 0) A-127 Benzyl Pyridin-4-yl W1a (m= 0) 41 No. R1 R2 W A-128 Benzyl Thien-2-yl Wia (m= 0) A-129 Benzyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-130 4-Chlorobenzyl Phenyl Wia (m= 0) A-131 4-Chlorobenzyl 2-Methylphenyl Wia (m= 0) A-132 4-Chlorobenzyl 2-Methoxyphenyl Wia (m= 0) A-133 4-Chlorobenzyl 2-Chlorophenyl Wia (m= 0) A-1 34 4-Chlorobenzyl 2-Fluorophenyl Wi a (m= 0) A-135 4-Chlorobenzyl 2-Trifluoromethylphenyl Wia (m= 0) A-136 4-Chlorobenzyl 3-Methylphenyl Wia (m= 0) A-137 4-Chlorobenzyl 3-Methoxyphenyl Wia (m= 0) A-138 4-Chlorobenzyl 3-Chlorophenyl Wia (m= 0) A-139 4-Chlorobenzyl 3-Fluorophenyl Wia (m= 0) A-140 4-Chlorobenzyl 3-Trifluoromethyl Wia (m= 0) A-141 4-Chlorobenzyl 3-[(Phenylmethyl)oxy]phenyl Wia (m= 0) A-142 4-Chlorobenzyl 3-Morpholin-4-ylphenyl Wia (m= 0) A-143 4-Chlorobenzyl 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-144 4-Chlorobenzyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-145 4-Chlorobenzyl 4-Methylphenyl Wia (m= 0) A-146 4-Chlorobenzyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-147 4-Chlorobenzyl 4-Methoxyphenyl Wia (m= 0) A-148 4-Chlorobenzyl 4-Chlorophenyl Wia (m= 0) A-149 4-Chlorobenzyl 4-Fluorophenyl Wia (m= 0) A-150 4-Chlorobenzyl 4-Trifluoromethylphenyl Wia (m= 0) A-151 4-Chlorobenzyl 4-Diethylaminophenyl Wia (m= 0) A-152 4-Chlorobenzy 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-153 4-Chlorobenzyl 4-Cyanophenyl Wia (m= 0) A-154 4-Chlorobenzyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-155 4-Chlorobenzyl 4-(4-Methylpiperazin-1-yl)phenyl Wia (m= 0) A-156 4-Chlorobenzyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-157 4-Chlorobenzyl 4-(l H-Imidazol-1-yl)phenyl Wia (m= 0) A-158 4-Chlorobenzyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-159 4-Chlorobenzyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-160 4-Chlorobenzyl 2,4-Difluorophenyl Wia (m= 0) A-161 4-Chlorobenzyl 2,6-Difluorophenyl Wia (m= 0) A-162 4-Chlorobenzyl 3,5-Difluorophenyl Wia (m= 0) A-163 4-Chlorobenzyl 2,4-Dichlorophenyl Wia (m= 0) A-164 4-Chlorobenzyl 2,6-Dichlorophenyl Wia (m= 0) A-165 4-Chlorobenzyl 3,5-Dichlorophenyl Wia (m= 0) A-166 4-Chlorobenzyl 2-Chloro-4-fluorophenyl Wia (m= 0) 42 No. RW R2 W A-167 4-Chlorobenzyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-168 4-Chlorobenzyl 2-Fluoro-4-morpholin-4-ylphenyl Wia (m= 0) A-169 4-Chlorobenzyl Pyridin-2-yl Wia (m= 0) A-170 4-Chlorobenzyl Pyridin-4-yl Wia (m= 0) A-171 4-Chlorobenzyl Thien-2-yl Wia (m= 0) A-172 4-Chlorobenzyl 2,3-Dihydrobenzo[b]furan-5-y Wia (m= 0) A-173 4-Methoxybenzyl Phenyl Wia (m= 0) A-174 4-Methoxybenzyl 2-Methylphenyl Wia (m= 0) A-175 4-Methoxybenzyl 2-Methoxyphenyl Wia (m= 0) A-176 4-Methoxybenzyl 2-Chlorophenyl Wia (m= 0) A-177 4-Methoxybenzyl 2-Fluorophenyl Wia (m= 0) A-178 4-Methoxybenzyl 2-Trifluoromethylphenyl Wia (m= 0) A-179 4-Methoxybenzyl 3-Methylphenyl Wia (m= 0) A-1 80 4-Methoxybenzyl 3-Methoxyphenyl Wi a (m= 0) A-181 4-Methoxybenzyl 3-Chlorophenyl Wia (m= 0) A-182 4-Methoxybenzyl 3-Fluorophenyl Wia (m= 0) A-183 4-Methoxybenzyl 3-Trifluoromethyl Wia (m= 0) A-184 4-Methoxybenzyl 3-[(Phenylmethyl)oxy]phenyl Wia (m= 0) A-185 4-Methoxybenzyl 3-Morpholin-4-ylphenyl Wia (m= 0) A-186 4-Methoxybenzyl 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-187 4-Methoxybenzyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-188 4-Methoxybenzyl 4-Methylphenyl Wia (m= 0) A-189 4-Methoxybenzyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-190 4-Methoxybenzyl 4-Methoxyphenyl Wia (m= 0) A-191 4-Methoxybenzyl 4-Chlorophenyl Wia (m= 0) A-192 4-Methoxybenzyl 4-Fluorophenyl Wia (m= 0) A-193 4-Methoxybenzyl 4-Trifluoromethylphenyl Wia (m= 0) A-194 4-Methoxybenzyl 4-Diethylaminophenyl Wia (m= 0) A-195 4-Methoxybenzyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-196 4-Methoxybenzyl 4-Cyanophenyl Wia (m= 0) A-197 4-Methoxybenzyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-198 4-Methoxybenzyl 4-(4-Methylpiperazin-1-yl)phenyl Wia (m= 0) A-199 4-Methoxybenzyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-200 4-Methoxybenzyl 4-(1H-Imidazol-1-yl)phenyl Wia (m= 0) A-201 4-Methoxybenzyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-202 4-Methoxybenzyl 4-(Morpholin-4-ylmethyl)phenyl Wi a (m= 0) A-203 4-Methoxybenzyl 2,4-Difluorophenyl Wia (m= 0) A-204 4-Methoxybenzyl 2,6-Difluorophenyl Wia (m= 0) A-205 4-Methoxybenzyl 3,5-Difluorophenyl Wia (m= 0) 43 No. RW R2 W A-206 4-Methoxybenzyl 2,4-Dichlorophenyl Wia (m= 0) A-207 4-Methoxybenzyl 2,6-Dichlorophenyl Wia (m= 0) A-208 4-Methoxybenzyl 3,5-Dichlorophenyl Wia (m= 0) A-209 4-Methoxybenzyl 2-Chloro-4-fluorophenyl Wi a (m= 0) A-210 4-Methoxybenzyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-211 4-Methoxybenzyl 2-Fluoro-4-morpholin-4-ylphenyl WI a (m= 0) A-212 4-Methoxybenzyl Pyridin-2-yl Wia (m= 0) A-213 4-Methoxybenzyl Pyridin-4-yl Wia (m= 0) A-214 4-Methoxybenzyl Thien-2-yl Wia (m= 0) A-215 4-Methoxybenzyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-216 Cyclohexylmethyl Phenyl Wia (m= 0) A-217 Cyclohexylmethyl 2-Methylphenyl Wia (m= 0) A-218 Cyclohexylmethyl 2-Methoxyphenyl Wia (m= 0) A-219 Cyclohexylmethyl 2-Chlorophenyl Wia (m= 0) A-220 Cyclohexylmethyl 2-Fluorophenyl Wia (m= 0) A-221 Cyclohexylmethyl 2-Trifluoromethylphenyl Wia (m= 0) A-222 Cyclohexylmethyl 3-Methylphenyl Wia (m= 0) A-223 Cyclohexylmethyl 3-Methoxyphenyl WI a (m= 0) A-224 Cyclohexylmethyl 3-Chlorophenyl Wi a (m= 0) A-225 Cyclohexylmethyl 3-Fluorophenyl WI a (m= 0) A-226 Cyclohexylmethyl 3-Trifluoromethyl Wia (m= 0) A-227 Cyclohexylmethyl 3-[(Phenylmethyl)oxy]phenyl Wi a (m= 0) A-228 Cyclohexylmethyl 3-Morpholin-4-ylphenyl Wi a (m= 0) A-229 Cyclohexylmethyl 3-(Morpholin-4-ylmethyl)phenyl Wi a (m= 0) A-230 Cyclohexylmethyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-231 Cyclohexylmethyl 4-Methylphenyl Wia (m= 0) A-232 Cyclohexylmethyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-233 Cyclohexylmethyl 4-Methoxyphenyl Wi a (m= 0) A-234 Cyclohexylmethyl 4-Chlorophenyl Wia (m= 0) A-235 Cyclohexylmethyl 4-Fluorophenyl Wia (m= 0) A-236 Cyclohexylmethyl 4-Trifluoromethylphenyl Wia (m= 0) A-237 Cyclohexylmethyl 4-Diethylaminophenyl Wia (m= 0) A-238 Cyclohexylmethyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-239 Cyclohexylmethyl 4-Cyanophenyl Wia (m= 0) A-240 Cyclohexylmethyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-241 Cyclohexylmethyl 4-(4-Methylpiperazin-1-yl)phenyl Wia (m= 0) A-242 Cyclohexylmethyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-243 Cyclohexylmethyl 4-(1H-Imidazol-1-yl)phenyl Wia (m= 0) A-244 Cyclohexylmethyl 4-Morpholin-4-ylphenyl Wi a (m= 0) 44 No. R 1 R2 W A-245 Cyclohexylmethyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-246 Cyclohexylmethyl 2,4-Difluorophenyl Wia (m= 0) A-247 Cyclohexylmethyl 2,6-Difluorophenyl Wia (m= 0) A-248 Cyclohexylmethyl 3,5-Difluorophenyl Wia (m= 0) A-249 Cyclohexylmethyl 2,4-Dichlorophenyl Wia (m= 0) A-250 Cyclohexylmethyl 2,6-Dichlorophenyl Wia (m= 0) A-251 Cyclohexylmethyl 3,5-Dichlorophenyl Wia (m= 0) A-252 Cyclohexylmethyl 2-Chloro-4-fluorophenyl Wia (m= 0) A-253 Cyclohexylmethyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-254 Cyclohexylmethyl 2-Fluoro-4-morpholin-4-ylphenyl WI a (m= 0) A-255 Cyclohexylmethyl Pyridin-2-yl WI a (m= 0) A-256 Cyclohexylmethyl Pyridin-4-yl Wia (m= 0) A-257 Cyclohexylmethyl Thien-2-yl Wia (m= 0) A-258 Cyclohexylmethyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-259 2-Thienylmethyl Phenyl Wia (m= 0) A-260 2-Thienylmethyl 2-Methylphenyl Wi a (m= 0) A-261 2-Thienylmethyl 2-Methoxyphenyl WI a (m= 0) A-262 2-Thienylmethyl 2-Chlorophenyl Wia (m= 0) A-263 2-Thienylmethyl 2-Fluorophenyl Wia (m= 0) A-264 2-Thienylmethyl 2-Trifluoromethylphenyl Wia (m= 0) A-265 2-Thienylmethyl 3-Methylphenyl Wia (m= 0) A-266 2-Thienylmethyl 3-Methoxyphenyl Wi a (m= 0) A-267 2-Thienylmethyl 3-Chlorophenyl Wia (m= 0) A-268 2-Thienylmethyl 3-Fluorophenyl Wia (m= 0) A-269 2-Thienylmethyl 3-Trifluoromethyl Wia (m= 0) A-270 2-Thienylmethyl 3-[(Phenylmethyl)oxy]phenyl Wi a (m= 0) A-271 2-Thienylmethyl 3-Morpholin-4-ylphenyl Wia (m= 0) A-272 2-Thienylmethyl 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-273 2-Thienylmethyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-274 2-Thienylmethyl 4-Methylphenyl Wia (m= 0) A-275 2-Thienylmethyl 4-(1-Methylethyl)phenyl WI a (m= 0) A-276 2-Thienylmethyl 4-Methoxyphenyl Wia (m= 0) A-277 2-Thienylmethyl 4-Chlorophenyl Wia (m= 0) A-278 2-Thienylmethyl 4-Fluorophenyl Wia (m= 0) A-279 2-Thienylmethyl 4-Trifluoromethylphenyl Wia (m= 0) A-280 2-Thienylmethyl 4-Diethylaminophenyl Wia (m= 0) A-281 2-Thienylmethyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-282 2-Thienylmethyl 4-Cyanophenyl Wia (m= 0) A-283 2-Thienylmethyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) 45 No. R1 R2 W A-284 2-Thienylmethyl 4-(4-Methylpiperazin-1 -yl)phenyl Wi a (m= 0) A-285 2-Thienylmethyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-286 2-Thienylmethyl 4-(1H-Imidazol-1-yl)phenyl Wia (m= 0) A-287 2-Thienylmethyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-288 2-Thienylmethyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-289 2-Thienylmethyl 2,4-Difluorophenyl Wia (m= 0) A-290 2-Thienylmethyl 2,6-Difluorophenyl Wia (m= 0) A-291 2-Thienylmethyl 3,5-Difluorophenyl Wia (m= 0) A-292 2-Thienylmethyl 2,4-Dichlorophenyl Wia (m= 0) A-293 2-Thienylmethyl 2,6-Dichlorophenyl Wia (m= 0) A-294 2-Thienylmethyl 3,5-Dichlorophenyl Wia (m= 0) A-295 2-Thienylmethyl 2-Chloro-4-fluorophenyl Wia (m= 0) A-296 2-Thienylmethyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-297 2-Thienylmethyl 2-Fluoro-4-morpholin-4-ylphenyl Wia (m= 0) A-298 2-Thienylmethyl Pyridin-2-yl WI a (m= 0) A-299 2-Thienylmethyl Pyridin-4-yl Wi a (m= 0) A-300 2-Thienylmethyl Thien-2-yl Wia (m= 0) A-301 2-Thienylmethyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-302 Pyridin-3-ylmethyl Phenyl Wia (m= 0) A-303 Pyridin-3-ylmethyl 2-Methylphenyl Wia (m= 0) A-304 Pyridin-3-ylmethyl 2-Methoxyphenyl Wia (m= 0) A-305 Pyridin-3-ylmethyl 2-Chlorophenyl Wia (m= 0) A-306 Pyridin-3-ylmethyl 2-Fluorophenyl Wia (m= 0) A-307 Pyridin-3-ylmethyl 2-Trifluoromethylphenyl Wi a (m= 0) A-308 Pyridin-3-ylmethyl 3-Methylphenyl Wia (m= 0) A-309 Pyridin-3-ylmethyl 3-Methoxyphenyl Wia (m= 0) A-310 Pyridin-3-ylmethyl 3-Chlorophenyl Wia (m= 0) A-31 1 Pyridin-3-ylmethyl 3-Fluorophenyl Wia (m= 0) A-312 Pyridin-3-ylmethyl 3-Trifluoromethyl Wia (m= 0) A-313 Pyridin-3-ylmethyl 3-[(Phenylmethyl)oxy]phenyl Wia (m= 0) A-314 Pyridin-3-ylmethyl 3-Morpholin-4-ylphenyl Wia (m= 0) A-315 Pyridin-3-ylmethyl 3-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-316 Pyridin-3-ylmethyl 3-Pyrrolidin-1-ylphenyl Wia (m= 0) A-317 Pyridin-3-ylmethyl 4-Methylphenyl Wia (m= 0) A-318 Pyridin-3-ylmethyl 4-(1-Methylethyl)phenyl Wia (m= 0) A-319 Pyridin-3-ylmethyl 4-Methoxyphenyl Wia (m= 0) A-320 Pyridin-3-ylmethyl 4-Chlorophenyl Wia (m= 0) A-321 Pyridin-3-ylmethyl 4-Fluorophenyl Wia (m= 0) A-322 Pyridin-3-ylmethyl 4-Trifluoromethylphenyl WIa (m= 0) 46 No. R1 R2 W A-323 Pyridin-3-ylmethyl 4-Diethylaminophenyl Wia (m= 0) A-324 Pyridin-3-ylmethyl 4-[(Diethylamino)methyl]phenyl Wia (m= 0) A-325 Pyridin-3-ylmethyl 4-Cyanophenyl Wia (m= 0) A-326 Pyridin-3-ylmethyl 4-(Piperidin-1-yl)phenyl Wia (m= 0) A-327 Pyridin-3-ylmethyl 4-(4-Methylpiperazin-1 -yl)phenyl WI a (m= 0) A-328 Pyridin-3-ylmethyl 4-Pyrrolidin-1-ylphenyl Wia (m= 0) A-329 Pyridin-3-ylmethyl 4-(1H-Imidazol-1-yl)phenyl Wia (m= 0) A-330 Pyridin-3-ylmethyl 4-Morpholin-4-ylphenyl Wia (m= 0) A-331 Pyridin-3-ylmethyl 4-(Morpholin-4-ylmethyl)phenyl Wia (m= 0) A-332 Pyridin-3-ylmethyl 2,4-Difluorophenyl Wia (m= 0) A-333 Pyridin-3-ylmethyl 2,6-Difluorophenyl Wia (m= 0) A-334 Pyridin-3-ylmethyl 3,5-Difluorophenyl Wia (m= 0) A-335 Pyridin-3-ylmethyl 2,4-Dichlorophenyl Wia (m= 0) A-336 Pyridin-3-ylmethyl 2,6-Dichlorophenyl Wia (m= 0) A-337 Pyridin-3-ylmethyl 3,5-Dichlorophenyl Wia (m= 0) A-338 Pyridin-3-ylmethyl 2-Chloro-4-fluorophenyl Wia (m= 0) A-339 Pyridin-3-ylmethyl 2-Chloro-4-morpholin-4-ylphenyl Wia (m= 0) A-340 Pyridin-3-ylmethyl 2-Fluoro-4-morpholin-4-ylphenyl Wia (m= 0) A-341 Pyridin-3-ylmethyl Pyridin-2-yl Wia (m= 0) A-342 Pyridin-3-ylmethyl Pyridin-4-yl Wia (m= 0) A-343 Pyridin-3-ylmethyl Thien-2-yl Wia (m= 0) A-344 Pyridin-3-ylmethyl 2,3-Dihydrobenzo[b]furan-5-yl Wia (m= 0) A-345 n-Butyl Phenyl Wib (m = 0) A-346 n-Butyl 2-Methylphenyl Wib (m = 0) A-347 n-Butyl 2-Methoxyphenyl WIb (m = 0) A-348 n-Butyl 2-Chlorophenyl Wib (m = 0) A-349 n-Butyl 2-Fluorophenyl WI b (m = 0) A-350 n-Butyl 2-Trifluoromethylphenyl Wib (m = 0) A-351 n-Butyl 3-Methylphenyl Wlb (m = 0) A-352 n-Butyl 3-Methoxyphenyl WIb (m = 0) A-353 n-Butyl 3-Chlorophenyl Wib (m = 0) A-354 n-Butyl 3-Fluorophenyl WIb (m = 0) A-355 n-Butyl 3-Trifluoromethyl Wib (m = 0) A-356 n-Butyl 3-[(Phenylmethyl)oxy]phenyl WIb (m = 0) A-357 n-Butyl 3-Morpholin-4-ylphenyl WIb (m = 0) A-358 n-Butyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-359 n-Butyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-360 n-Butyl 4-Methylphenyl WIb (m = 0) A-361 n-Butyl 4-(1-Methylethyl)phenyl Wib (m = 0) 47 No. RW R2 W A-362 n-Butyl 4-Methoxyphenyl Wib (m = 0) A-363 n-Butyl 4-Chlorophenyl Wib (m = 0) A-364 n-Butyl 4-Fluorophenyl WIb (m = 0) A-365 n-Butyl 4-Trifluoromethylphenyl WIb (m = 0) A-366 n-Butyl 4-Diethylaminophenyl Wib (m = 0) A-367 n-Butyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-368 n-Butyl 4-Cyanophenyl Wib (m = 0) A-369 n-Butyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-370 n-Butyl 4-(4-Methylpiperazin-1-yl)pheny Wib (m = 0) A-371 n-Butyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-372 n-Butyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-373 n-Butyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-374 n-Butyl 4-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-375 n-Butyl 2,4-Difluorophenyl Wib (m = 0) A-376 n-Butyl 2,6-Difluorophenyl Wib (m = 0) A-377 n-Butyl 3,5-Difluorophenyl Wib (m = 0) A-378 n-Butyl 2,4-Dichlorophenyl Wib (m = 0) A-379 n-Butyl 2,6-Dichlorophenyl Wib (m = 0) A-380 n-Butyl 3,5-Dichlorophenyl Wib (m = 0) A-381 n-Butyl 2-Chloro-4-fluorophenyl Wib (m = 0) A-382 n-Butyl 2-Chloro-4-morpholin-4-ylphenyl WIb (m = 0) A-383 n-Butyl 2-Fluoro-4-morpholin-4-ylphenyl WIb (m = 0) A-384 n-Butyl Pyridin-2-yl Wib (m = 0) A-385 n-Butyl Pyridin-4-yl Wib (m = 0) A-386 n-Butyl Thien-2-yl WIb (m = 0) A-387 n-Butyl 2,3-Dihydrobenzo[b]furan-5-yl Wib (m = 0) A-388 Isobutyl Phenyl Wib (m = 0) A-389 Isobutyl 2-Methylphenyl Wib (m = 0) A-390 Isobutyl 2-Methoxyphenyl Wib (m = 0) A-391 Isobutyl 2-Chlorophenyl Wib (m = 0) A-392 Isobutyl 2-Fluorophenyl Wib (m = 0) A-393 Isobutyl 2-Trifluoromethylphenyl Wib (m = 0) A-394 Isobutyl 3-Methylphenyl Wib (m = 0) A-395 Isobutyl 3-Methoxyphenyl Wib (m = 0) A-396 Isobutyl 3-Chlorophenyl Wib (m = 0) A-397 Isobutyl 3-Fluorophenyl Wib (m = 0) A-398 Isobutyl 3-Trifluoromethyl Wib (m = 0) A-399 Isobutyl 3-[(Phenylmethyl)oxy]phenyl Wib (m = 0) A-400 Isobutyl 3-Morpholin-4-ylphenyl Wib (m = 0) 48 No. R1 R2 W A-401 Isobutyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-402 Isobutyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-403 Isobutyl 4-Methylphenyl Wib (m = 0) A-404 Isobutyl 4-(1-Methylethyl)phenyl Wib (m = 0) A-405 Isobutyl 4-Methoxyphenyl Wib (m = 0) A-406 Isobutyl 4-Chlorophenyl Wib (m = 0) A-407 Isobutyl 4-Fluorophenyl Wib (m = 0) A-408 Isobutyl 4-Trifluoromethylphenyl WIb (m = 0) A-409 Isobutyl 4-Diethylaminophenyl Wib (m = 0) A-410 Isobutyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-41 1 Isobutyl 4-Cyanophenyl WIb (m = 0) A-412 Isobutyl 4-(Piperidin-1-yi)phenyl Wib (m = 0) A-413 Isobutyl 4-(4-Methylpiperazin-1-yl)phenyl Wib (m = 0) A-414 Isobutyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-415 Isobutyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-416 Isobutyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-417 Isobutyl 4-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-418 Isobutyl 2,4-Difluorophenyl Wib (m = 0) A-419 Isobutyl 2,6-Difluorophenyl Wib (m = 0) A-420 Isobutyl 3,5-Difluorophenyl Wib (m = 0) A-421 Isobutyl 2,4-Dichlorophenyl Wib (m = 0) A-422 Isobutyl 2,6-Dichlorophenyl Wib (m = 0) A-423 Isobutyl 3,5-Dichlorophenyl Wib (m = 0) A-424 Isobutyl 2-Chloro-4-fluorophenyl Wib (m = 0) A-425 Isobutyl 2-Chloro-4-morpholin-4-ylphenyl Wib (m = 0) A-426 Isobutyl 2-Fluoro-4-morpholin-4-ylphenyl Wib (m = 0) A-427 Isobutyl Pyridin-2-yl Wib (m = 0) A-428 Isobutyl Pyridin-4-yl Wib (m = 0) A-429 Isobutyl Thien-2-yl Wlb (m = 0) A-430 Isobutyl 2,3-Dihydrobenzo[b]furan-5-yl Wib (m = 0) A-431 Benzyl Phenyl Wib (m = 0) A-432 Benzyl 2-Methylphenyl WIb (m = 0) A-433 Benzyl 2-Methoxyphenyl Wib (m = 0) A-434 Benzyl 2-Chlorophenyl Wib (m = 0) A-435 Benzyl 2-Fluorophenyl WIb (m = 0) A-436 Benzyl 2-Trifluoromethylphenyl Wib (m = 0) A-437 Benzyl 3-Methylphenyl Wib (m = 0) A-438 Benzyl 3-Methoxyphenyl WIb (m = 0) A-439 Benzyl 3-Chlorophenyl WI b (m = 0) 49 No. R1 R2 W A-440 Benzyl 3-Fluorophenyl WIb (m = 0) A-441 Benzyl 3-Trifluoromethyl Wib (m = 0) A-442 Benzyl 3-[(Phenylmethyl)oxy]phenyl WI b (m = 0) A-443 Benzyl 3-Morpholin-4-ylphenyl WI b (m = 0) A-444 Benzyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-445 Benzyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-446 Benzyl 4-Methylphenyl WIb (m = 0) A-447 Benzyl 4-(1-Methylethyl)phenyl Wib (m = 0) A-448 Benzyl 4-Methoxyphenyl Wib (m = 0) A-449 Benzyl 4-Chlorophenyl Wib (m = 0) A-450 Benzyl 4-Fluorophenyl Wib (m = 0) A-451 Benzyl 4-Trifluoromethylphenyl Wib (m = 0) A-452 Benzyl 4-Diethylaminophenyl Wi b (m = 0) A-453 Benzyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-454 Benzyl 4-Cyanophenyl Wib (m = 0) A-455 Benzyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-456 Benzyl 4-(4-Methylpiperazin-1-yl)pheny Wib (m = 0) A-457 Benzyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-458 Benzyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-459 Benzyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-460 Benzyl 4-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-461 Benzyl 2,4-Difluorophenyl Wib (m = 0) A-462 Benzyl 2,6-Difluorophenyl Wib (m = 0) A-463 Benzyl 3,5-Difluorophenyl Wib (m = 0) A-464 Benzyl 2,4-Dichlorophenyl Wib (m = 0) A-465 Benzyl 2,6-Dichlorophenyl Wib (m = 0) A-466 Benzyl 3,5-Dichlorophenyl WIb (m = 0) A-467 Benzyl 2-Chloro-4-fluorophenyl Wib (m = 0) A-468 Benzyl 2-Chloro-4-morpholin-4-ylphenyl Wib (m = 0) A-469 Benzyl 2-Fluoro-4-morpholin-4-ylphenyl WIb (m = 0) A-470 Benzyl Pyridin-2-yl Wib (m = 0) A-471 Benzyl Pyridin-4-yl Wib (m = 0) A-472 Benzyl Thien-2-yl Wib (m = 0) A-473 Benzyl 2,3-Dihydrobenzo[b]furan-5-y Wib (m = 0) A-474 4-Chlorobenzyl Phenyl Wib (m = 0) A-475 4-Chlorobenzyl 2-Methylphenyl Wib (m = 0) A-476 4-Chlorobenzyl 2-Methoxyphenyl Wib (m = 0) A-477 4-Chlorobenzyl 2-Chlorophenyl WIb (m = 0) A-478 4-Chlorobenzyl 2-Fluorophenyl WIb (m = 0) 50 No. R1 R2 W A-479 4-Chlorobenzyl 2-Trifluoromethylphenyl Wi b (m = 0) A-480 4-Chlorobenzyl 3-Methylphenyl Wib (m = 0) A-481 4-Chlorobenzyl 3-Methoxyphenyl WIb (m = 0) A-482 4-Chlorobenzyl 3-Chlorophenyl WIb (m = 0) A-483 4-Chlorobenzyl 3-Fluorophenyl WIb (m = 0) A-484 4-Chlorobenzyl 3-Trifluoromethyl WIb (m = 0) A-485 4-Chlorobenzyl 3-[(Phenylmethyl)oxy]phenyl WIb (m = 0) A-486 4-Chlorobenzyl 3-Morpholin-4-ylphenyl Wib (m = 0) A-487 4-Chlorobenzyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-488 4-Chlorobenzyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-489 4-Chlorobenzyl 4-Methylphenyl Wib (m = 0) A-490 4-Chlorobenzyl 4-(1-Methylethyl)phenyl Wib (m = 0) A-491 4-Chlorobenzyl 4-Methoxyphenyl Wib (m = 0) A-492 4-Chlorobenzyl 4-Chlorophenyl Wib (m = 0) A-493 4-Chlorobenzyl 4-Fluorophenyl WIb (m = 0) A-494 4-Chlorobenzyl 4-Trifluoromethylphenyl WIb (m = 0) A-495 4-Chlorobenzyl 4-Diethylaminophenyl Wib (m = 0) A-496 4-Chlorobenzyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-497 4-Chlorobenzyl 4-Cyanophenyl Wi b (m = 0) A-498 4-Chlorobenzyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-499 4-Chlorobenzyl 4-(4-Methylpiperazin-1-yl)phenyl Wib (m = 0) A-500 4-Chlorobenzyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-501 4-Chlorobenzyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-502 4-Chlorobenzyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-503 4-Chlorobenzyl 4-(Morpholin-4-ylmethyl)phenyl WIb (m = 0) A-504 4-Chlorobenzyl 2,4-Difluorophenyl Wib (m = 0) A-505 4-Chlorobenzyl 2,6-Difluorophenyl Wib (m = 0) A-506 4-Chlorobenzyl 3,5-Difluorophenyl Wib (m = 0) A-507 4-Chlorobenzyl 2,4-Dichlorophenyl WIb (m = 0) A-508 4-Chlorobenzyl 2,6-Dichlorophenyl Wib (m = 0) A-509 4-Chlorobenzyl 3,5-Dichlorophenyl Wib (m = 0) A-510 4-Chlorobenzyl 2-Chloro-4-fluorophenyl Wib (m = 0) A-51 1 4-Chlorobenzyl 2-Chloro-4-morpholin-4-ylphenyl Wi b (m = 0) A-512 4-Chlorobenzyl 2-Fluoro-4-morpholin-4-yiphenyl Wi b (m = 0) A-513 4-Chlorobenzyl Pyridin-2-yl Wib (m = 0) A-514 4-Chlorobenzyl Pyridin-4-yl Wib (m = 0) A-515 4-Chlorobenzyl Thien-2-yl Wib (m = 0) A-516 4-Chlorobenzyl 2,3-Dihydrobenzo[b]furan-5-yl Wib (m = 0) A-517 4-Methoxybenzyl Phenyl Wib (m = 0) 51 No. R1 R2 W A-518 4-Methoxybenzyl 2-Methylphenyl WI b (m = 0) A-519 4-Methoxybenzyl 2-Methoxyphenyl WIb (m = 0) A-520 4-Methoxybenzyl 2-Chlorophenyl WIb (m = 0) A-521 4-Methoxybenzyl 2-Fluorophenyl Wib (m = 0) A-522 4-Methoxybenzyl 2-Trifluoromethylphenyl Wib (m = 0) A-523 4-Methoxybenzyl 3-Methylphenyl Wib (m = 0) A-524 4-Methoxybenzyl 3-Methoxyphenyl Wi b (m = 0) A-525 4-Methoxybenzyl 3-Chlorophenyl Wib (m = 0) A-526 4-Methoxybenzyl 3-Fluorophenyl Wib (m = 0) A-527 4-Methoxybenzyl 3-Trifluoromethyl WIb (m = 0) A-528 4-Methoxybenzyl 3-[(Phenylmethyl)oxy]phenyl WIb (m = 0) A-529 4-Methoxybenzyl 3-Morpholin-4-ylphenyl Wib (m = 0) A-530 4-Methoxybenzyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-531 4-Methoxybenzyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-532 4-Methoxybenzyl 4-Methylphenyl Wib (m = 0) A-533 4-Methoxybenzyl 4-(l-Methylethyl)phenyl Wib (m = 0) A-534 4-Methoxybenzyl 4-Methoxyphenyl WI b (m = 0) A-535 4-Methoxybenzyl 4-Chlorophenyl Wi b (m = 0) A-536 4-Methoxybenzyl 4-Fluorophenyl Wib (m = 0) A-537 4-Methoxybenzyl 4-Trifluoromethylphenyl WIb (m = 0) A-538 4-Methoxybenzyl 4-Diethylaminophenyl WI b (m = 0) A-539 4-Methoxybenzyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-540 4-Methoxybenzyl 4-Cyanophenyl Wib (m = 0) A-541 4-Methoxybenzyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-542 4-Methoxybenzyl 4-(4-Methylpiperazin-1 -yl)phenyl WI b (m = 0) A-543 4-Methoxybenzyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-544 4-Methoxybenzyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-545 4-Methoxybenzyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-546 4-Methoxybenzyl 4-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-547 4-Methoxybenzyl 2,4-Difluorophenyl Wib (m = 0) A-548 4-Methoxybenzyl 2,6-Difluorophenyl Wib (m = 0) A-549 4-Methoxybenzyl 3,5-Difluorophenyl Wib (m = 0) A-550 4-Methoxybenzyl 2,4-Dichlorophenyl Wib (m = 0) A-551 4-Methoxybenzyl 2,6-Dichlorophenyl WIb (m = 0) A-552 4-Methoxybenzyl 3,5-Dichlorophenyl Wib (m = 0) A-553 4-Methoxybenzyl 2-Chloro-4-fluorophenyl Wib (m = 0) A-554 4-Methoxybenzyl 2-Chloro-4-morpholin-4-ylphenyl Wib (m = 0) A-555 4-Methoxybenzyl 2-Fluoro-4-morpholin-4-ylphenyl Wib (m = 0) A-556 4-Methoxybenzyl Pyridin-2-yl WI b (m = 0) 52 No. R1 R2 W A-557 4-Methoxybenzyl Pyridin-4-yi W1b (m = 0) A-558 4-Methoxybenzyl Thien-2-yl W1b (m = 0) A-559 4-Methoxybenzyl 2,3-Dihydrobenzo[b]furan-5-yl W1b (m = 0) A-560 Cyclohexylmethyl Phenyl W1b (m = 0) A-561 Cyclohexylmethyl 2-Methylphenyl Wib (m = 0) A-562 Cyclohexylmethyl 2-Methoxyphenyl W1b (m = 0) A-563 Cyclohexylmethyl 2-Chlorophenyl W1b (m = 0) A-564 Cyclohexylmethyl 2-Fluorophenyl W1b (m = 0) A-565 Cyclohexylmethyl 2-Trifluoromethylphenyl W1b (m = 0) A-566 Cyclohexylmethyl 3-Methylphenyl W1b (m = 0) A-567 Cyclohexylmethyl 3-Methoxyphenyl W1b (m = 0) A-568 Cyclohexylmethyl 3-Chlorophenyl W1b (m = 0) A-569 Cyclohexylmethyl 3-Fluorophenyl W1b (m = 0) A-570 Cyclohexylmethyl 3-Trifluoromethyl WIb (m = 0) A-571 Cyclohexylmethyl 3-[(Phenylmethyl)oxy]phenyl W1b (m = 0) A-572 Cyclohexylmethyl 3-Morpholin-4-ylphenyl W1b (m = 0) A-573 Cyclohexylmethyl 3-(Morpholin-4-ylmethyl)phenyl W1b (m = 0) A-574 Cyclohexylmethyl 3-Pyrrolidin-1-ylphenyl W1b (m = 0) A-575 Cyclohexylmethyl 4-Methylphenyl W1b (m = 0) A-576 Cyclohexylmethyl 4-(1-Methylethyl)phenyl W1b (m = 0) A-577 Cyclohexylmethyl 4-Methoxyphenyl W1b (m = 0) A-578 Cyclohexylmethyl 4-Chlorophenyl W1b (m = 0) A-579 Cyclohexylmethyl 4-Fluorophenyl W1b (m = 0) A-580 Cyclohexylmethyl 4-Trifluoromethylphenyl W1b (m = 0) A-581 Cyclohexylmethyl 4-Diethylaminophenyl W1b (m = 0) A-582 Cyclohexylmethyl 4-[(Diethylamino)methyl]phenyl W1b (m = 0) A-583 Cyclohexylmethyl 4-Cyanophenyl W1b (m = 0) A-584 Cyclohexylmethyl 4-(Piperidin-1-yl)phenyl W1b (m = 0) A-585 Cyclohexylmethyl 4-(4-Methylpiperazin-1-yl)pheny W1b (m = 0) A-586 Cyclohexylmethyl 4-Pyrrolidin-1-ylphenyl W1b (m = 0) A-587 Cyclohexylmethyl 4-(1H-imidazol-1-yl)phenyl W1b (m = 0) A-588 Cyclohexylmethyl 4-Morpholin-4-ylphenyl W1b (m = 0) A-589 Cyclohexylmethyl 4-(Morpholin-4-ylmethyl)phenyl W1b (m = 0) A-590 Cyclohexylmethyl 2,4-Difluorophenyl W1 b (m = 0) A-591 Cyclohexylmethyl 2,6-Difluorophenyl W1b (m = 0) A-592 Cyclohexylmethyl 3,5-Difluorophenyl W1b (m = 0) A-593 Cyclohexylmethyl 2,4-Dichlorophenyl W1b (m = 0) A-594 Cyclohexylmethyl 2,6-Dichlorophenyl W1b (m = 0) A-595 Cyclohexylmethyl 3,5-Dichlorophenyl W1b (m = 0) 53 No. R1 R2 W A-596 Cyclohexylmethyl 2-Chloro-4-fluorophenyl Wi b (m = 0) A-597 Cyclohexylmethyl 2-Chloro-4-morpholin-4-ylphenyl Wib (m = 0) A-598 Cyclohexylmethyl 2-Fluoro-4-morpholin-4-ylphenyl Wib (m = 0) A-599 Cyclohexylmethyl Pyridin-2-yl Wib (m = 0) A-600 Cyclohexylmethyl Pyridin-4-yl Wib (m = 0) A-601 Cyclohexylmethyl Thien-2-yl Wib (m = 0) A-602 Cyclohexylmethyl 2,3-Dihydrobenzo[b]furan-5-yl Wib (m = 0) A-603 2-Thienylmethyl Phenyl WIb (m = 0) A-604 2-Thienylmethyl 2-Methylphenyl WIb (m = 0) A-605 2-Thienylmethyl 2-Methoxyphenyl Wib (m = 0) A-606 2-Thienylmethyl 2-Chlorophenyl Wib (m = 0) A-607 2-Thienylmethyl 2-Fluorophenyl WIb (m = 0) A-608 2-Thienylmethyl 2-Trifluoromethylphenyl Wib (m = 0) A-609 2-Thienylmethyl 3-Methylphenyl Wib (m = 0) A-610 2-Thienylmethyl 3-Methoxyphenyl Wib (m = 0) A-61 1 2-Thienylmethyl 3-Chlorophenyl Wi b (m = 0) A-612 2-Thienylmethyl 3-Fluorophenyl Wib (m = 0) A-613 2-Thienylmethyl 3-Trifluoromethyl WIb (m = 0) A-614 2-Thienylmethyl 3-[(Phenylmethyl)oxy]phenyl Wib (m = 0) A-615 2-Thienylmethyl 3-Morpholin-4-ylphenyl WIb (m = 0) A-616 2-Thienylmethyl 3-(Morpholin-4-ylmethyl)phenyl WIb (m = 0) A-617 2-Thienylmethyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-618 2-Thienylmethyl 4-Methylphenyl Wib (m = 0) A-619 2-Thienylmethyl 4-(1-Methylethyl)phenyl Wib (m = 0) A-620 2-Thienylmethyl 4-Methoxyphenyl Wib (m = 0) A-621 2-Thienylmethyl 4-Chlorophenyl Wib (m = 0) A-622 2-Thienylmethyl 4-Fluorophenyl Wib (m = 0) A-623 2-Thienylmethyl 4-Trifluoromethylphenyl Wib (m = 0) A-624 2-Thienylmethyl 4-Diethylaminophenyl Wib (m = 0) A-625 2-Thienylmethyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-626 2-Thienylmethyl 4-Cyanophenyl WIb (m = 0) A-627 2-Thienylmethyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-628 2-Thienylmethyl 4-(4-Methylpiperazin-1-yl)phenyl Wib (m = 0) A-629 2-Thienylmethyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-630 2-Thienylmethyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) A-631 2-Thienylmethyl 4-Morpholin-4-ylphenyl Wib (m = 0) A-632 2-Thienylmethyl 4-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-633 2-Thienylmethyl 2,4-Difluorophenyl WI b (m = 0) A-634 2-Thienylmethyl 2,6-Difluorophenyl Wib (m = 0) 54 No. RW R2 W A-635 2-Thienylmethyl 3,5-Difluorophenyl Wib (m = 0) A-636 2-Thienylmethyl 2,4-Dichlorophenyl Wib (m = 0) A-637 2-Thienylmethyl 2,6-Dichlorophenyl Wib (m = 0) A-638 2-Thienylmethyl 3,5-Dichlorophenyl Wib (m = 0) A-639 2-Thienylmethyl 2-Chloro-4-fluorophenyl WIb (m = 0) A-640 2-Thienylmethyl 2-Chloro-4-morpholin-4-ylphenyl WIb (m = 0) A-641 2-Thienylmethyl 2-Fluoro-4-morpholin-4-ylphenyl Wib (m = 0) A-642 2-Thienylmethyl Pyridin-2-yl Wib (m = 0) A-643 2-Thienylmethyl Pyridin-4-yl Wib (m = 0) A-644 2-Thienylmethyl Thien-2-yl Wib (m = 0) A-645 2-Thienylmethyl 2,3-Dihydrobenzo[b]furan-5-yl Wib (m = 0) A-646 Pyridin-3-ylmethyl Phenyl Wib (m = 0) A-647 Pyridin-3-ylmethyl 2-Methylphenyl Wib (m = 0) A-648 Pyridin-3-ylmethyl 2-Methoxyphenyl Wib (m = 0) A-649 Pyridin-3-ylmethyl 2-Chlorophenyl Wib (m = 0) A-650 Pyridin-3-ylmethyl 2-Fluorophenyl Wib (m = 0) A-651 Pyridin-3-ylmethyl 2-Trifluoromethylphenyl Wib (m = 0) A-652 Pyridin-3-ylmethyl 3-Methylphenyl Wib (m = 0) A-653 Pyridin-3-ylmethyl 3-Methoxyphenyl Wib (m = 0) A-654 Pyridin-3-ylmethyl 3-Chlorophenyl Wib (m = 0) A-655 Pyridin-3-ylmethyl 3-Fluorophenyl WIb (m = 0) A-656 Pyridin-3-ylmethyl 3-Trifluoromethyl Wib (m = 0) A-657 Pyridin-3-ylmethyl 3-[(Phenylmethyl)oxy]phenyl WIb (m = 0) A-658 Pyridin-3-ylmethyl 3-Morpholin-4-ylphenyl Wlb (m = 0) A-659 Pyridin-3-ylmethyl 3-(Morpholin-4-ylmethyl)phenyl Wib (m = 0) A-660 Pyridin-3-ylmethyl 3-Pyrrolidin-1-ylphenyl Wib (m = 0) A-661 Pyridin-3-ylmethyl 4-Methylphenyl Wib (m = 0) A-662 Pyridin-3-ylmethyl 4-(1-Methylethyl)phenyl Wib (m = 0) A-663 Pyridin-3-ylmethyl 4-Methoxyphenyl WIb (m = 0) A-664 Pyridin-3-ylmethyl 4-Chlorophenyl Wib (m = 0) A-665 Pyridin-3-ylmethyl 4-Fluorophenyl Wib (m = 0) A-666 Pyridin-3-ylmethyl 4-Trifluoromethylphenyl WIb (m = 0) A-667 Pyridin-3-ylmethyl 4-Diethylaminophenyl Wib (m = 0) A-668 Pyridin-3-ylmethyl 4-[(Diethylamino)methyl]phenyl Wib (m = 0) A-669 Pyridin-3-ylmethyl 4-Cyanophenyl WIb (m = 0) A-670 Pyridin-3-ylmethyl 4-(Piperidin-1-yl)phenyl Wib (m = 0) A-671 Pyridin-3-ylmethyl 4-(4-Methylpiperazin-1-yl)phenyl WIb (m = 0) A-672 Pyridin-3-ylmethyl 4-Pyrrolidin-1-ylphenyl Wib (m = 0) A-673 Pyridin-3-ylmethyl 4-(1H-Imidazol-1-yl)phenyl Wib (m = 0) 55 No. R1 R2 W A-674 Pyridin-3-ylmethyl 4-Morpholin-4-ylphenyl W1b (m = 0) A-675 Pyridin-3-ylmethyl 4-(Morpholin-4-ylmethyl)phenyl W1b (m = 0) A-676 Pyridin-3-ylmethyl 2,4-Difluorophenyl W1b (m = 0) A-677 Pyridin-3-ylmethyl 2,6-Difluorophenyl W1b (m = 0) A-678 Pyridin-3-ylmethyl 3,5-Difluorophenyl W1b (m = 0) A-679 Pyridin-3-ylmethyl 2,4-Dichlorophenyl W1b (m = 0) A-680 Pyridin-3-ylmethyl 2,6-Dichlorophenyl W1b (m = 0) A-681 Pyridin-3-ylmethyl 3,5-Dichlorophenyl W1 b (m = 0) A-682 Pyridin-3-ylmethyl 2-Chloro-4-fluorophenyl W1 b (m = 0) A-683 Pyridin-3-ylmethyl 2-Chloro-4-morpholin-4-ylphenyl W1b (m = 0) A-684 Pyridin-3-ylmethyl 2-Fluoro-4-morpholin-4-ylphenyl W1b (m = 0) A-685 Pyridin-3-ylmethyl Pyridin-2-yl W1b (m = 0) A-686 Pyridin-3-ylmethyl Pyridin-4-yl W1b (m = 0) A-687 Pyridin-3-ylmethyl Thien-2-yl W1b (m = 0) A-688 Pyridin-3-ylmethyl 2,3-Dihydrobenzo[b]furan-5-yl W1b (m = 0) A-689 n-Butyl Phenyl W2a (m = 0) A-690 n-Butyl 2-Methylphenyl W2a (m = 0) A-691 n-Butyl 2-Methoxyphenyl W2a (m = 0) A-692 n-Butyl 2-Chlorophenyl W2a (m = 0) A-693 n-Butyl 2-Fluorophenyl W2a (m = 0) A-694 n-Butyl 2-Trifluoromethylphenyl W2a (m = 0) A-695 n-Butyl 3-Methylphenyl W2a (m = 0) A-696 n-Butyl 3-Methoxyphenyl W2a (m = 0) A-697 n-Butyl 3-Chlorophenyl W2a (m = 0) A-698 n-Butyl 3-Fluorophenyl W2a (m = 0) A-699 n-Butyl 3-Trifluoromethyl W2a (m = 0) A-700 n-Butyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-701 n-Butyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-702 n-Butyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-703 n-Butyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-704 n-Butyl 4-Methylphenyl W2a (m = 0) A-705 n-Butyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-706 n-Butyl 4-Methoxyphenyl W2a (m = 0) A-707 n-Butyl 4-Chlorophenyl W2a (m = 0) A-708 n-Butyl 4-Fluorophenyl W2a (m = 0) A-709 n-Butyl 4-Trifluoromethylphenyl W2a (m = 0) A-710 n-Butyl 4-Diethylaminophenyl W2a (m = 0) A-71 1 n-Butyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-712 n-Butyl 4-Cyanophenyl W2a (m = 0) 56 No. RW R2 W A-713 n-Butyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-714 n-Butyl 4-(4-Methylpiperazin-1-yl)phenyl W2a (m = 0) A-715 n-Butyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-716 n-Butyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-717 n-Butyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-718 n-Butyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-719 n-Butyl 2,4-Difluorophenyl W2a (m = 0) A-720 n-Butyl 2,6-Difluorophenyl W2a (m = 0) A-721 n-Butyl 3,5-Difluorophenyl W2a (m = 0) A-722 n-Butyl 2,4-Dichlorophenyl W2a (m = 0) A-723 n-Butyl 2,6-Dichlorophenyl W2a (m = 0) A-724 n-Butyl 3,5-Dichlorophenyl W2a (m = 0) A-725 n-Butyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-726 n-Butyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-727 n-Butyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-728 n-Butyl Pyridin-2-yl W2a (m = 0) A-729 n-Butyl Pyridin-4-yl W2a (m = 0) A-730 n-Butyl Thien-2-yl W2a (m = 0) A-731 n-Butyl 2,3-Dihydrobenzo[b]furan-5-y W2a (m = 0) A-732 Isobutyl Phenyl W2a (m = 0) A-733 Isobutyl 2-Methylphenyl W2a (m = 0) A-734 Isobutyl 2-Methoxyphenyl W2a (m = 0) A-735 Isobutyl 2-Chlorophenyl W2a (m = 0) A-736 Isobutyl 2-Fluorophenyl W2a (m = 0) A-737 Isobutyl 2-Trifluoromethylphenyl W2a (m = 0) A-738 Isobutyl 3-Methylphenyl W2a (m = 0) A-739 Isobutyl 3-Methoxyphenyl W2a (m = 0) A-740 Isobutyl 3-Chlorophenyl W2a (m = 0) A-741 Isobutyl 3-Fluorophenyl W2a (m = 0) A-742 Isobutyl 3-Trifluoromethyl W2a (m = 0) A-743 Isobutyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-744 Isobutyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-745 Isobutyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-746 Isobutyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-747 Isobutyl 4-Methylphenyl W2a (m = 0) A-748 Isobutyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-749 Isobutyl 4-Methoxyphenyl W2a (m = 0) A-750 Isobutyl 4-Chlorophenyl W2a (m = 0) A-751 Isobutyl 4-Fluorophenyl W2a (m = 0) 57 No. R1 R2 W A-752 Isobutyl 4-Trifluoromethylphenyl W2a (m = 0) A-753 Isobutyl 4-Diethylaminophenyl W2a (m = 0) A-754 Isobutyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-755 Isobutyl 4-Cyanophenyl W2a (m = 0) A-756 Isobutyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-757 Isobutyl 4-(4-Methylpiperazin-1-yl)pheny W2a (m = 0) A-758 Isobutyl 4-Pyrrolidin-1-yiphenyl W2a (m = 0) A-759 Isobutyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-760 isobutyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-761 Isobutyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-762 Isobutyl 2,4-Difluorophenyl W2a (m = 0) A-763 Isobutyl 2,6-Difluorophenyl W2a (m = 0) A-764 Isobutyl 3,5-Difluorophenyl W2a (m = 0) A-765 Isobutyl 2,4-Dichlorophenyl W2a (m = 0) A-766 Isobutyl 2,6-Dichlorophenyl W2a (m = 0) A-767 Isobutyl 3,5-Dichlorophenyl W2a (m = 0) A-768 Isobutyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-769 Isobutyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-770 Isobutyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-771 Isobutyl Pyridin-2-yl W2a (m = 0) A-772 Isobutyl Pyridin-4-yl W2a (m = 0) A-773 Isobutyl Thien-2-yl W2a (m = 0) A-774 Isobutyl 2,3-Dihydrobenzo[b]furan-5-yi W2a (m = 0) A-775 Benzyl Phenyl W2a (m = 0) A-776 Benzyl 2-Methylphenyl W2a (m = 0) A-777 Benzyl 2-Methoxyphenyl W2a (m = 0) A-778 Benzyl 2-Chlorophenyl W2a (m = 0) A-779 Benzyl 2-Fluorophenyl W2a (m = 0) A-780 Benzyl 2-Trifluoromethylphenyl W2a (m = 0) A-781 Benzyl 3-Methylphenyl W2a (m = 0) A-782 Benzyl 3-Methoxyphenyl W2a (m = 0) A-783 Benzyl 3-Chlorophenyl W2a (m = 0) A-784 Benzyl 3-Fluorophenyl W2a (m = 0) A-785 Benzyl 3-Trifluoromethyl W2a (m = 0) A-786 Benzyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-787 Benzyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-788 Benzyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-789 Benzyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-790 Benzyl 4-Methylphenyl W2a (m = 0) 58 No. R 1 R2 W A-791 Benzyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-792 Benzyl 4-Methoxyphenyl W2a (m = 0) A-793 Benzyl 4-Chlorophenyl W2a (m = 0) A-794 Benzyl 4-Fluorophenyl W2a (m = 0) A-795 Benzyl 4-Trifluoromethylphenyl W2a (m = 0) A-796 Benzyl 4-Diethylaminophenyl W2a (m = 0) A-797 Benzyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-798 Benzyl 4-Cyanophenyl W2a (m = 0) A-799 Benzyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-800 Benzyl 4-(4-Methylpiperazin-1-yl)phenyl W2a (m = 0) A-801 Benzyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-802 Benzyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-803 Benzyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-804 Benzyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-805 Benzyl 2,4-Difluorophenyl W2a (m = 0) A-806 Benzyl 2,6-Difluorophenyl W2a (m = 0) A-807 Benzyl 3,5-Difluorophenyl W2a (m = 0) A-808 Benzyl 2,4-Dichlorophenyl W2a (m = 0) A-809 Benzyl 2,6-Dichlorophenyl W2a (m = 0) A-810 Benzyl 3,5-Dichlorophenyl W2a (m = 0) A-811 Benzyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-812 Benzyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-813 Benzyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-814 Benzyl Pyridin-2-yl W2a (m = 0) A-815 Benzyl Pyridin-4-yl W2a (m = 0) A-816 Benzyl Thien-2-yl W2a (m = 0) A-817 Benzyl 2,3-Dihydrobenzo[b]furan-5-yl W2a (m = 0) A-818 4-Chlorobenzyl Phenyl W2a (m = 0) A-819 4-Chlorobenzyl 2-Methylphenyl W2a (m = 0) A-820 4-Chlorobenzyl 2-Methoxyphenyl W2a (m = 0) A-821 4-Chlorobenzyl 2-Chlorophenyl W2a (m = 0) A-822 4-Chlorobenzyl 2-Fluorophenyl W2a (m = 0) A-823 4-Chlorobenzyl 2-Trifluoromethylphenyl W2a (m = 0) A-824 4-Chlorobenzyl 3-Methylphenyl W2a (m = 0) A-825 4-Chlorobenzyl 3-Methoxyphenyl W2a (m = 0) A-826 4-Chlorobenzyl 3-Chlorophenyl W2a (m = 0) A-827 4-Chlorobenzyl 3-Fluorophenyl W2a (m = 0) A-828 4-Chlorobenzyl 3-Trifluoromethyl W2a (m = 0) A-829 4-Chlorobenzyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) 59 No. R1 R2 W A-830 4-Chlorobenzyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-831 4-Chlorobenzyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-832 4-Chlorobenzyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-833 4-Chlorobenzyl 4-Methylphenyl W2a (m = 0) A-834 4-Chlorobenzyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-835 4-Chlorobenzyl 4-Methoxyphenyl W2a (m = 0) A-836 4-Chlorobenzyl 4-Chlorophenyl W2a (m = 0) A-837 4-Chlorobenzyl 4-Fluorophenyl W2a (m = 0) A-838 4-Chlorobenzyl 4-Trifluoromethylphenyl W2a (m = 0) A-839 4-Chlorobenzyl 4-Diethylaminophenyl W2a (m = 0) A-840 4-Chlorobenzyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-841 4-Chlorobenzyl 4-Cyanophenyl W2a (m = 0) A-842 4-Chlorobenzyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-843 4-Chlorobenzyl 4-(4-Methylpiperazin-1-yl)phenyl W2a (m = 0) A-844 4-Chlorobenzyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-845 4-Chlorobenzyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-846 4-Chlorobenzyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-847 4-Chlorobenzyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-848 4-Chlorobenzyl 2,4-Difluorophenyl W2a (m = 0) A-849 4-Chlorobenzyl 2,6-Difluorophenyl W2a (m = 0) A-850 4-Chlorobenzyl 3,5-Difluorophenyl W2a (m = 0) A-851 4-Chlorobenzyl 2,4-Dichlorophenyl W2a (m = 0) A-852 4-Chlorobenzyl 2,6-Dichlorophenyl W2a (m = 0) A-853 4-Chlorobenzyl 3,5-Dichlorophenyl W2a (m = 0) A-854 4-Chlorobenzyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-855 4-Chlorobenzyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-856 4-Chlorobenzyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-857 4-Chlorobenzyl Pyridin-2-yl W2a (m = 0) A-858 4-Chlorobenzyl Pyridin-4-yl W2a (m = 0) A-859 4-Chlorobenzyl Thien-2-yl W2a (m = 0) A-860 4-Chlorobenzyl 2,3-Dihydrobenzo[b]furan-5-yl W2a (m = 0) A-861 4-Methoxybenzyl Phenyl W2a (m = 0) A-862 4-Methoxybenzyl 2-Methylphenyl W2a (m = 0) A-863 4-Methoxybenzyl 2-Methoxyphenyl W2a (m = 0) A-864 4-Methoxybenzyl 2-Chlorophenyl W2a (m = 0) A-865 4-Methoxybenzyl 2-Fluorophenyl W2a (m = 0) A-866 4-Methoxybenzyl 2-Trifluoromethylphenyl W2a (m = 0) A-867 4-Methoxybenzyl 3-Methylphenyl W2a (m = 0) A-868 4-Methoxybenzyl 3-Methoxyphenyl W2a (m = 0) 60 No. R1 R2 W A-869 4-Methoxybenzyl 3-Chlorophenyl W2a (m = 0) A-870 4-Methoxybenzyl 3-Fluorophenyl W2a (m = 0) A-871 4-Methoxybenzyl 3-Trifluoromethyl W2a (m = 0) A-872 4-Methoxybenzyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-873 4-Methoxybenzyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-874 4-Methoxybenzyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-875 4-Methoxybenzyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-876 4-Methoxybenzyl 4-Methylphenyl W2a (m = 0) A-877 4-Methoxybenzyl 4-(1 -Methylethyl)phenyl W2a (m = 0) A-878 4-Methoxybenzyl 4-Methoxyphenyl W2a (m = 0) A-879 4-Methoxybenzyl 4-Chlorophenyl W2a (m = 0) A-880 4-Methoxybenzyl 4-Fluorophenyl W2a (m = 0) A-881 4-Methoxybenzyl 4-Trifluoromethylphenyl W2a (m = 0) A-882 4-Methoxybenzyl 4-Diethylaminophenyl W2a (m = 0) A-883 4-Methoxybenzyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-884 4-Methoxybenzyl 4-Cyanophenyl W2a (m = 0) A-885 4-Methoxybenzyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-886 4-Methoxybenzyl 4-(4-Methylpiperazin-1 -yl)phenyl W2a (m = 0) A-887 4-Methoxybenzyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-888 4-Methoxybenzyl 4-(1 H-Imidazol-1-yl)phenyl W2a (m = 0) A-889 4-Methoxybenzyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-890 4-Methoxybenzyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-891 4-Methoxybenzyl 2,4-Difluorophenyl W2a (m = 0) A-892 4-Methoxybenzyl 2,6-Difluorophenyl W2a (m = 0) A-893 4-Methoxybenzyl 3,5-Difluorophenyl W2a (m = 0) A-894 4-Methoxybenzyl 2,4-Dichlorophenyl W2a (m = 0) A-895 4-Methoxybenzyl 2,6-Dichlorophenyl W2a (m = 0) A-896 4-Methoxybenzyl 3,5-Dichlorophenyl W2a (m = 0) A-897 4-Methoxybenzy 2-Chloro-4-fluorophenyl W2a (m = 0) A-898 4-Methoxybenzyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-899 4-Methoxybenzyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-900 4-Methoxybenzyl Pyridin-2-yl W2a (m = 0) A-901 4-Methoxybenzyl Pyridin-4-yl W2a (m = 0) A-902 4-Methoxybenzyl Thien-2-yl W2a (m = 0) A-903 4-Methoxybenzyl 2,3-Dihydrobenzo[b]furan-5-y W2a (m = 0) A-904 Cyclohexylmethyl Phenyl W2a (m = 0) A-905 Cyclohexylmethyl 2-Methylphenyl W2a (m = 0) A-906 Cyclohexylmethyl 2-Methoxyphenyl W2a (m = 0) A-907 Cyclohexylmethyl 2-Chlorophenyl W2a (m = 0) 61 No. R1 R2 W A-908 Cyclohexylmethyl 2-Fluorophenyl W2a (m = 0) A-909 Cyclohexylmethyl 2-Trifluoromethylphenyl W2a (m = 0) A-910 Cyclohexylmethyl 3-Methylphenyl W2a (m = 0) A-91 1 Cyclohexylmethyl 3-Methoxyphenyl W2a (m = 0) A-912 Cyclohexylmethyl 3-Chlorophenyl W2a (m = 0) A-913 Cyclohexylmethyl 3-Fluorophenyl W2a (m = 0) A-914 Cyclohexylmethyl 3-Trifluoromethyl W2a (m = 0) A-915 Cyclohexylmethyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-916 Cyclohexylmethyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-917 Cyclohexylmethyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-918 Cyclohexylmethyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-919 Cyclohexylmethyl 4-Methylphenyl W2a (m = 0) A-920 Cyclohexylmethyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-921 Cyclohexylmethyl 4-Methoxyphenyl W2a (m = 0) A-922 Cyclohexylmethyl 4-Chlorophenyl W2a (m = 0) A-923 Cyclohexylmethyl 4-Fluorophenyl W2a (m = 0) A-924 Cyclohexylmethyl 4-Trifluoromethylphenyl W2a (m = 0) A-925 Cyclohexylmethyl 4-Diethylaminophenyl W2a (m = 0) A-926 Cyclohexylmethyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-927 Cyclohexylmethyl 4-Cyanophenyl W2a (m = 0) A-928 Cyclohexylmethyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-929 Cyclohexylmethyl 4-(4-Methylpiperazin-1-yl)phenyl W2a (m = 0) A-930 Cyclohexylmethyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-931 Cyclohexylmethyl 4-(1H-lmidazol-1-yl)phenyl W2a (m = 0) A-932 Cyclohexylmethyl 4-Morpholin-4-yiphenyl W2a (m = 0) A-933 Cyclohexylmethyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-934 Cyclohexylmethyl 2,4-Difluorophenyl W2a (m = 0) A-935 Cyclohexylmethyl 2,6-Difluorophenyl W2a (m = 0) A-936 Cyclohexylmethyl 3,5-Difluorophenyl W2a (m = 0) A-937 Cyclohexylmethyl 2,4-Dichlorophenyl W2a (m = 0) A-938 Cyclohexylmethyl 2,6-Dichlorophenyl W2a (m = 0) A-939 Cyclohexylmethyl 3,5-Dichlorophenyl W2a (m = 0) A-940 Cyclohexylmethyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-941 Cyclohexylmethyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-942 Cyclohexylmethyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-943 Cyclohexylmethyl Pyridin-2-yl W2a (m = 0) A-944 Cyclohexylmethyl Pyridin-4-yl W2a (m = 0) A-945 Cyclohexylmethyl Thien-2-yl W2a (m = 0) A-946 Cyclohexylmethyl 2,3-Dihydrobenzo[b]furan-5-y W2a (m = 0) 62 No. R1 R2 W A-947 2-Thienylmethyl Phenyl W2a (m = 0) A-948 2-Thienylmethyl 2-Methylphenyl W2a (m = 0) A-949 2-Thienylmethyl 2-Methoxyphenyl W2a (m = 0) A-950 2-Thienylmethyl 2-Chlorophenyl W2a (m = 0) A-951 2-Thienylmethyl 2-Fluorophenyl W2a (m = 0) A-952 2-Thienylmethyl 2-Trifluoromethylphenyl W2a (m = 0) A-953 2-Thienylmethyl 3-Methylphenyl W2a (m = 0) A-954 2-Thienylmethyl 3-Methoxyphenyl W2a (m = 0) A-955 2-Thienylmethyl 3-Chlorophenyl W2a (m = 0) A-956 2-Thienylmethyl 3-Fluorophenyl W2a (m = 0) A-957 2-Thienylmethyl 3-Trifluoromethyl W2a (m = 0) A-958 2-Thienylmethyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-959 2-Thienylmethyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-960 2-Thienylmethyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-961 2-Thienylmethyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-962 2-Thienylmethyl 4-Methylphenyl W2a (m = 0) A-963 2-Thienylmethyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-964 2-Thienylmethyl 4-Methoxyphenyl W2a (m = 0) A-965 2-Thienylmethyl 4-Chlorophenyl W2a (m = 0) A-966 2-Thienylmethyl 4-Fluorophenyl W2a (m = 0) A-967 2-Thienylmethyl 4-Trifluoromethylphenyl W2a (m = 0) A-968 2-Thienylmethyl 4-Diethylaminophenyl W2a (m = 0) A-969 2-Thienylmethyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-970 2-Thienylmethyl 4-Cyanophenyl W2a (m = 0) A-971 2-Thienylmethyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-972 2-Thienylmethyl 4-(4-Methylpiperazin-1 -yl)phenyl W2a (m = 0) A-973 2-Thienylmethyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-974 2-Thienylmethyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-975 2-Thienylmethyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-976 2-Thienylmethyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-977 2-Thienylmethyl 2,4-Difluorophenyl W2a (m = 0) A-978 2-Thienylmethyl 2,6-Difluorophenyl W2a (m = 0) A-979 2-Thienylmethyl 3,5-Difluorophenyl W2a (m = 0) A-980 2-Thienylmethyl 2,4-Dichlorophenyl W2a (m = 0) A-981 2-Thienylmethyl 2,6-Dichlorophenyl W2a (m = 0) A-982 2-Thienylmethyl 3,5-Dichlorophenyl W2a (m = 0) A-983 2-Thienylmethyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-984 2-Thienylmethyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-985 2-Thienylmethyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) 63 No. R1 R2 W A-986 2-Thienylmethyl Pyridin-2-yl W2a (m = 0) A-987 2-Thienylmethyl Pyridin-4-yl W2a (m = 0) A-988 2-Thienylmethyl Thien-2-yl W2a (m = 0) A-989 2-Thienylmethyl 2,3-Dihydrobenzo[b]furan-5-y W2a (m = 0) A-990 Pyridin-3-ylmethyl Phenyl W2a (m = 0) A-991 Pyridin-3-ylmethyl 2-Methylphenyl W2a (m = 0) A-992 Pyridin-3-ylmethyl 2-Methoxyphenyl W2a (m = 0) A-993 Pyridin-3-ylmethyl 2-Chlorophenyl W2a (m = 0) A-994 Pyridin-3-ylmethyl 2-Fluorophenyl W2a (m = 0) A-995 Pyridin-3-ylmethyl 2-Trifluoromethylphenyl W2a (m = 0) A-996 Pyridin-3-ylmethyl 3-Methylphenyl W2a (m = 0) A-997 Pyridin-3-ylmethyl 3-Methoxyphenyl W2a (m = 0) A-998 Pyridin-3-ylmethyl 3-Chlorophenyl W2a (m = 0) A-999 Pyridin-3-ylmethyl 3-Fluorophenyl W2a (m = 0) A-1 000 Pyridin-3-ylmethyl 3-Trifluoromethyl W2a (m = 0) A-1001 Pyridin-3-ylmethyl 3-[(Phenylmethyl)oxy]phenyl W2a (m = 0) A-1 002 Pyridin-3-ylmethyl 3-Morpholin-4-ylphenyl W2a (m = 0) A-1 003 Pyridin-3-ylmethyl 3-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-1 004 Pyridin-3-ylmethyl 3-Pyrrolidin-1-ylphenyl W2a (m = 0) A-1 005 Pyridin-3-ylmethyl 4-Methylphenyl W2a (m = 0) A-1 006 Pyridin-3-ylmethyl 4-(1-Methylethyl)phenyl W2a (m = 0) A-1007 Pyridin-3-ylmethyl 4-Methoxyphenyl W2a (m = 0) A-1008 Pyridin-3-ylmethyl 4-Chlorophenyl W2a (m = 0) A-1009 Pyridin-3-ylmethyl 4-Fluorophenyl W2a (m = 0) A-1010 Pyridin-3-ylmethyl 4-Trifluoromethylphenyl W2a (m = 0) A-1 011 Pyridin-3-ylmethyl 4-Diethylaminophenyl W2a (m = 0) A-1012 Pyridin-3-ylmethyl 4-[(Diethylamino)methyl]phenyl W2a (m = 0) A-1013 Pyridin-3-ylmethyl 4-Cyanophenyl W2a (m = 0) A-1014 Pyridin-3-ylmethyl 4-(Piperidin-1-yl)phenyl W2a (m = 0) A-1015 Pyridin-3-ylmethyl 4-(4-Methylpiperazin-1-yl)pheny W2a (m = 0) A-1016 Pyridin-3-ylmethyl 4-Pyrrolidin-1-ylphenyl W2a (m = 0) A-1017 Pyridin-3-ylmethyl 4-(1H-Imidazol-1-yl)phenyl W2a (m = 0) A-1018 Pyridin-3-ylmethyl 4-Morpholin-4-ylphenyl W2a (m = 0) A-1019 Pyridin-3-ylmethyl 4-(Morpholin-4-ylmethyl)phenyl W2a (m = 0) A-1020 Pyridin-3-ylmethyl 2,4-Difluorophenyl W2a (m = 0) A-1021 Pyridin-3-ylmethyl 2,6-Difluorophenyl W2a (m = 0) A-1022 Pyridin-3-ylmethyl 3,5-Difluorophenyl W2a (m = 0) A-1023 Pyridin-3-ylmethyl 2,4-Dichlorophenyl W2a (m = 0) A-1024 Pyridin-3-ylmethyl 2,6-Dichlorophenyl W2a (m = 0) 64 No. R1 R2 W A-1 025 Pyridin-3-ylmethyl 3,5-Dichlorophenyl W2a (m = 0) A-1 026 Pyridin-3-ylmethyl 2-Chloro-4-fluorophenyl W2a (m = 0) A-1 027 Pyridin-3-ylmethyl 2-Chloro-4-morpholin-4-ylphenyl W2a (m = 0) A-1 028 Pyridin-3-ylmethyl 2-Fluoro-4-morpholin-4-ylphenyl W2a (m = 0) A-1 029 Pyridin-3-ylmethyl Pyridin-2-yl W2a (m = 0) A-1 030 Pyridin-3-ylmethyl Pyridin-4-yl W2a (m = 0) A-1031 Pyridin-3-ylmethyl Thien-2-yl W2a (m = 0) A-1 032 Pyridin-3-ylmethyl 2,3-Dihydrobenzo[b]furan-5-yl W2a (m = 0) A-1 033 n-Butyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 034 n-Butyl 1H-Indazol-1-yl A-1035 n-Butyl 2H-Indazol-2-yi A-1 036 n-Butyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 037 Isobutyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1038 Isobutyl 1H-Indazol-1-yl A-1 039 Isobutyl 2H-Indazol-2-yl A-1 040 Isobutyl Chromeno[4,3-c]pyrazol-2(4H)-yl A- 1041 Benzyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 042 Benzyl 1 H-Indazol-1-yl A-1043 Benzyl 2H-Indazol-2-yl A-1 044 Benzyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 045 4-Chlorobenzyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 046 4-Chlorobenzyl 1 H-Indazol-1 -yl A-1 047 4-Chlorobenzyl 2H-Indazol-2-yl A-1048 4-Chlorobenzyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 049 4-Methoxybenzyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 050 4-Methoxybenzyl 1H-Indazol-1-yl A-1051 4-Methoxybenzyl 2H-Indazol-2-yl A-1 052 4-Methoxybenzyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 053 Cyclohexylmethyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 054 Cyclohexylmethyl 1H-Indazol-1-yl A-1 055 Cyclohexylmethyl 2H-Indazol-2-yl A-1 056 Cyclohexylmethyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 057 2-Thienylmethyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 058 2-Thienylmethyl 1 H-Indazol-1-yl A-1 059 2-Thienylmethyl 2H-Indazol-2-yl A-1 060 2-Thienylmethyl Chromeno[4,3-c]pyrazol-2(4H)-yl A-1 061 Pyridin-3-ylmethyl 4,5-dihydro-2H-benzo[g]indazol-2-y A-1 062 Pyridin-3-ylmethyl 1H-Indazol-1-yl A-1063 Pyridin-3-ylmethyl 2H-Indazol-2-yl 65 No. R1 R2 W A-1064 Pyridin-3-ylmethyl Chromeno[4,3-c]pyrazol-2(4H)-yl The compounds of the invention of the general formula I and the starting materials used to prepare them can be prepared in analogy to known processes of organic chemistry as are described in standard works of organic chemistry, e.g. Houben-Weyl, 5 "Methoden der Organischen Chemie", Thieme-Verlag, Stuttgart, Jerry March "Advanced Organic Chemistry", 5*h edition, Wiley & Sons and the literature cited therein, and R. Larock, "Comprehensive Organic Transformations", 2nd edition, Weinheim, 1999 and the literature cited therein. The carboxamide compounds of the invention of the general formula I are advantageously prepared by the methods 10 described below and/or in the experimental section. The compounds of the formula I can be prepared in analogy to the schemes and methods described in WO 99/54305, pp. 6-10. An important access to compounds of the formula I is depicted in Scheme 1. 15 Scheme 1: R O R 1 0 R 1 Y OH + H X Y N X iD .X W HI O I HI I Y W H OH W OH W H 0 R2 '2 R2 RR 2R (I)(1) (IV)() In Scheme 1, R 1 , R 2 , W, Y and X exhibit the aforementioned meanings. 20 In a first step i), a carboxylic acid II is converted by reaction with an amino alcohol IlIl into a corresponding hydroxy amide IV. In this connection, conventional peptide coupling methods are ordinarily used, as are described for example in R. C. Larock, Comprehensive Organic Transformations, VCH Publisher, 1989, pages 972-976, or in 25 Houben-Weyl, Methoden der organischen Chemie, 4th edition, E5, Chap. V. It may be advantageous firstly to activate the carboxylic acid II. For this purpose, for example, the carboxylic acid 11 is reacted with a carbodiimide such as dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of hydroxybenzotriazole (HOBt), nitrophenol, pentafluorophenol, 2,4,5-trichlorophenol or 30 N-hydroxysuccinimide, to obtain an activated ester Ila. It may further be advantageous to prepare the activated ester Ila in the presence of a base, for example a tertiary amine. The activated ester Ila is subsequently reacted with the amino alcohol of the formula Ill or its hydrohalide salt to give the hydroxy amide IV. The reaction normally takes place in anhydrous inert solvents such as chlorinated hydrocarbons, e.g. 35 dichloromethane or dichloroethane, ethers, e.g. tetrahydrofuran or 1,4-dioxane or 66 carboxamides, e~g. N,N-dimethylformamide, N,N-dimethylacetamide or N methylpyrrolidone. Step i) is ordinarily carried out at temperatures in the range from -20'C to +25'C. 5 Subsequently, in a second step ii), the hydroxy amide compound IV is oxidized to the carboxamide compound I of the invention. Various conventional oxidation reactions are suitable for this (see R. C. Larock, Comprehensive Organic Transformations, VCH Publisher, 1989, page 604 et seq.) such as, for example, swern oxidation and swern analogous oxidations (T.T. Tidwell, Synthesis 1990, pp. 857-870) or Pfitzner-Moffatt 10 oxidation. Suitable oxidizing agents are dimethyl sulfoxide (DMSO) in combination with dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, dimethyl sulfoxide in combination with the pyridine-S03 complex or dimethyl sulfoxide in combination with oxalyl chloride, sodium hypochloride/TEMPO (S. L. Harbenson et al., J. MED: Chem. 1994, 37, 2918-2929) or the Dess-Martin reagent (J. Org. Chem. 1983, 15 48, 4155). Depending on the oxidizing agent used, the oxidation of the hydroxy amide compound IV takes place at temperatures of from -50 to +25*C. Compounds of the formula I in which X is -C(O)N(Rx4)-(CrCs-alkylene)-NRx2Rx3 or is -C(O)N(Rx 4 )NRx 2 Rx 3 in which Rx2, Rx 3 and Rx4 have the aforementioned meanings can 20 additionally be prepared by reacting compounds of the formula I in which X is COOH with hydrazine compounds of the formula NH(Rx4)NRx 2 Rx 3 or diamines of the formula NH(Rx 4 )-(Cr1Ce-alkylene)-NRx 2 Rx 3 . The reaction can be carried out in analogy to step i) in Scheme 1. 25 The amino alcohols IlIl can be obtained by purchase or can be prepared by processes disclosed in the literature (for amino hydroxy carboxylic acid derivatives, see, for example, S. L. Harbenson et al., J. Med. Chem. 1994, 37, 2918-2929 or J. P. Burkhardt et al., Tetrahedron Lett. 1988, 29, 3433-3436) or in analogy to the processes described in the preparation examples. 30 The carboxylic acid II can be prepared by hydrolyzing the carboxylic ester V with acids or bases under generally customary conditions. The hydrolysis preferably takes place with bases such as alkali metal or alkaline earth metal hydroxides, for example lithium hydroxide, sodium hydroxide or potassium hydroxide in aqueous medium or in a 35 mixture of water and organic solvents, e.g. alcohols such as methanol or ethanol, ethers such as tetrahydrofuran or dioxane, at room temperature or elevated temperature such as 25-100*C. 0 0 11I 2 11 R-W-Y-C-OR' - R-W-Y-C-OH (V) (11) 67 In formulae 11 and V, R 2 , W and Y have the aforementioned meanings. In formula V, R' is alkyl, preferably C-C 6 -alkyl. 5 The carboxylic ester of the formula V can advantageously be obtained by reacting the carboxylic ester of the general formula VI with an imidazole or pyrazole compound VII, see Scheme 2. Scheme 2: 10 0 0 '0, + R2-W-H -Y ) OR' Y OR' I W LG 12 R (VI) (V11) (V) In scheme 2, LG represents a nucleophilically displaceable leaving group. Examples of suitable nucleophilically displaceable leaving groups are halogen, e.g. chlorine or 15 bromine, or tosylate. R' is alkyl, preferably Ci-Ce-alkyl. R 2 , Y and W have the aforementioned meanings. As shown in Scheme 2, an ester VI is reacted with an appropriate imidazole or pyrazole compound of the formula VII. The reaction is ordinarily carried out under 20 conventional conditions in the presence of a base in an inert solvent at elevated temperature. It may be advantageous where appropriate to carry out the reaction in the presence of catalytically active amounts of a transition metal, in particular of a metal of group 10 or 11 in the periodic table. 25 In the case where Y is a divalent heteroaromatic radical, in particular a divalent nitrogen-containing heteroaromatic radical, the reaction is preferably carried out at elevated temperature without diluent or in an inert solvent such as an ether, e.g. tetrahydrofuran or dioxane, carboxamides such as N,N-dimethylformamide, N,N dimethylacetamide or N-methylpyrrolidone, or an aromatic hydrocarbon such as 30 benzene, toluene or o-, m- or p-xylene. The reaction takes place in the presence of inorganic or organic bases and of a crown ether. Suitable inorganic bases are alkali metal or alkaline earth metal amides such as sodium amide, alkali metal or alkaline earth metal carbonates such as potassium carbonate or cesium carbonate or alkali metal hydrides such as sodium hydride. Suitable organic bases are tertiary amines, 35 such as, for example, trimethylamine or triethylamine. A suitable crown ether is 18-crown-6. A Cu(I) salt such as, for example, Cul, CuCN, Cu20 is added where 68 appropriate as catalyst (see, for example, US 4,826,835 and WO 88/00468). In the case where Y is a divalent aromatic radical, the reaction of the carboxylic ester VI with the pyrazole or imidazole compound VII preferably takes place by transition 5 metal-catalyzed N-arylation as described for example by H.J. Cristeau et al., Eur. J. Org. Chem. 2004, pp. 695-709, and S.L. Buchwald et al.; J. Org. Chem. 2004, 69, pages 5578-5587. The reaction frequently takes place in the presence of catalytically active amounts of a metal of group 10 in the periodic table, especially in the presence of a nickel(II) compound, Ni(0) compound, Pd(II) compound or Pd(0) compound. An 10 example of a suitable method is the Buchwald cross-coupling. The Buchwald cross-coupling normally takes place in the presence of a phosphorus containing ligand, especially of a monodentate or bidentate phosphine ligand. Preferred ligands on the palladium are bulky, monodentate or bidentate phosphines such as 15 triphenylphosphine, tri(o-tolyl)phosphine, tri(cyclohexyl)phosphine, BINAP (2,2'-bis (diphenylphosphino)-1,1'-binaphthyl) or the Buchwald phosphines. The ligand may be present in the palladium compound or be added separately. Suitable palladium compounds include tris(dibenzylideneacetone)dipalladium(0), palladium(II) bis(o tolyl)phosphine chloride and palladium(II) acetate. The Buchwald cross-coupling 20 normally takes place in an organic solvent. Suitable organic solvents are aromatic hydrocarbons such as benzene or toluene, halogenated aromatic hydrocarbons such as chlorobenzene, halogenated hydrocarbons such as dichloromethane, trichloromethane, dichloroethane, ethers such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, methyl tert-butyl ether, or amides such as dimethylformamide or 25 N-methylpyrrolidone, and mixtures thereof. The Buchwald coupling reaction can be carried out under normal conditions or with use of microwaves. The imidazole or pyrazole compounds VII can be purchased or can be prepared by conventional methods, which are briefly outlined below, from precursors which can be 30 obtained by purchase. A general overview of the preparation of imidazoles is to be found in W. M. Menge, Pharmacochemistry Library 1998, 30, pages 145-158. The imidazole compounds VII used are particularly advantageously prepared by the method described by Bredereck 35 et al. (Chem. Ber. 1953, 86, pages 88-96) in which alpha-halo or alpha-hydroxy ketones are reacted with formamide - ordinarily with heating - to give the imidazoles VIl. General methods for preparing pyrazoles of the general formula VII are described for 40 example in R. Fusco in "The Chemistry of Heterocyclic Compounds: Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings", Wiley, R. H., editor; Wiley: New York, 1967; Vol. 22, pages 1-174; or J. Elguero, in "Comprehensive 69 Heterocyclic Chemistry"; Potts, K. T., Ed.; Pergamon: Oxford 1984; Vol. 5, pages 291-298. One of the most commonly used methods is cyclocondensation of 1,3 dicarbonyl compounds or correspondingly reactive analogs with hydrazine or substituted hydrazine derivatives. 5 3-Aryl- or 3-hetaryl-substituted pyrazoles VII are particularly advantageously prepared by reacting 1-aryl- or 1-hetaryl-3-dimethylamino-2-propene compounds with hydrazine in analogy to the processes described for example in M.A. Halcrow et al.; J. Chem. Soc. Dalton Trans. 1997, pages 4025-4035. The 1-aryl- or 1-hetaryl-3-dimethylamino 10 2-propenes required as starting material can easily be prepared by condensing the analogous aromatic acetyl compounds with N,N-dimethylformamide dimethyl acetal (or analogously using the corresponding diethyl acetal). The reaction is normally carried out without diluent or in an inert solvent such as, for example, dimethylformamide or toluene, at elevated temperature. It is particularly advantageous to introduce the 15 activation energy necessary for the reaction into the reaction mixture also by means of microwaves and to carry out the reaction under elevated pressure as described in A.K. Pleier, Synthesis 2001, 1, pages 55-62. Analogous 4-substituted pyrazoles of the general formula VII are prepared for example 20 starting from aryl- or hetarylacetic acids which are converted by means of the Vilsmeier reagent into the corresponding gamma-dimethylamino-2-propenals, with subsequent cyclization with hydrazine, see, for example, US 4,888,352. A further general possibility for preparing substituted pyrazoles of the formula VII is the 25 Suzuki coupling of appropriate pyrazoleboronic acids or pyrazoleboronic esters as described for example in: N. Zhe et al.; J. Med. Chem. 2005, 48 (5), pages 1569-1609; Young et al.; J. Med. Chem. 2004, 47 (6), pp. 1547-1552; C. Slee et al.; Bioorg. Med. Chem. Lett. 2001, 9, pages 3243-3253. An appropriate alternative is also Stille coupling of halogenated pyrazole derivatives with appropriate tin organyls as described 30 for example by J. Eluguero et al.; Synthesis 1997, 5, pp. 563-566. The preparation of 1,4-dihydrobenzopyranopyrazoles can be performed according to the methods described by Chandrasekhar, S. et al.; Tetrahedron Letters 2001, 42(37), 6599-6601. 35 The reaction mixtures are worked up in a conventional way, e.g. by mixing with water, separating the phases and, where appropriate, purifying the crude products by chromatography. The intermediates and final products in some cases result in the form of colorless or pale brownish, viscous oils which are freed of volatiles or purified under 40 reduced pressure and at moderately elevated temperature. If the intermediates and final products are obtained as solids, the purification can also take place by recrystallization or digestion.

70 If individual compounds I are not obtainable by the routes described above, they can be prepared by derivatization of other compounds 1. 5 The compounds of the invention exhibit extremely low Ki values in relation to the inhibition of calpain and thus permit efficient inhibition of calpain, especially calpain I, at low serum levels. The compounds of the invention ordinarily exhibit Ki values in relation to the inhibition of calpain in vitro of < 500 nM, in particular < 100 nM and specifically < 40 nM. The compounds of the invention are therefore particularly suitable for the 10 treatment of disorders associated with an elevated calpain activity. In addition, the compounds of the invention are selective calpain inhibitors, i.e. the inhibition of other cysteine proteases such as cathepsin B, cathepsin K, cathepsin L or cathepsin S takes place only at concentrations which are distinctly higher than the 15 concentrations necessary for inhibition of calpain. Accordingly, the compounds of the invention ought to show distinctly fewer side effects than the prior art compounds which are comparatively unselective in relation to inhibition of calpain and likewise inhibit other cysteine proteases. 20 Compounds preferred according to the invention accordingly have a selectivity in relation to inhibition of cathepsin B, expressed in the form of the ratio of the Ki for inhibition of cathepsin B to the Ki for inhibition of calpain of >_10, in particular >_30. Compounds preferred according to the invention accordingly have a selectivity in 25 relation to inhibition of cathepsin K, expressed in the form of the ratio of the Ki for inhibition of cathepsin K to the Ki for inhibition of calpain of >_10, in particular >_30. Compounds preferred according to the invention accordingly have a selectivity in relation to inhibition of cathepsin L, expressed in the form of the ratio of the Ki for 30 inhibition of cathepsin L to the Ki for inhibition of calpain of >_30, in particular >_50. Compounds preferred according to the invention accordingly have a selectivity in relation to inhibition of cathepsin S, expressed in the form of the ratio of the Ki for inhibition of cathepsin S to the Ki for inhibition of calpain of > 50, in particular >_100. 35 Owing to their inhibitory effect on calpain and their selectivity for calpain by comparison with other cysteine proteases, the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts are particularly suitable for the treatment of a disorder or of a condition which is associated with an elevated calpain 40 activity as are described for example in the prior art cited at the outset. Disorders associated with an elevated calpain activity are in particular 71 neurodegenerative disorders, especially those neurodegenerative disorders occuring as a result of a chronic brain supply deficit, of an ischemia (stroke) or of a trauma such as brain trauma, and the neurodegenerative disorders Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, also 5 multiple sclerosis and the damage to the nervous system associated therewith, especially damage to the optic nerve (optic neuritis) and the nerves which control the movement of the eye. Accordingly, preferred embodiments of the invention relate to the treatment of neurodegenerative disorders, especially of the aforementioned neurodegenerative disorders in humans, and to the use of the compounds of the 10 invention of the formula 1, their tautomers and their pharmaceutically suitable salts for the manufacture of a medicament for the treatment of these disorders. Disorders associated with an elevated calpain activity also include epilepsy. Accordingly, preferred embodiments of the invention relate to the treatment of epilepsy 15 in humans, and to the use of the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts for the manufacture of a medicament for the treatment of epilepsy. The disorders or conditions associated with an elevated calpain activity also include 20 pain and painful conditions. Accordingly, preferred embodiments of the invention relate to the treatment of pain and painful conditions in mammals, especially in humans, and to the use of the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts for the manufacture of a medicament for the treatment of pain and painful conditions. 25 The disorders or conditions associated with an elevated calpain activity also include damage to the heart following cardiac ischemias, damage to the kidneys following renal ischemias, skeletal muscle damage, muscular dystrophies, damage arising through proliferation of smooth muscle cells, coronary vasospasms, cerebral vasospasms, 30 macular degeneration, cataracts of the eyes, or restenosis of blood vessels following angioplasty. Accordingly, preferred embodiments of the invention relate to the treatment of diseases or conditions associated with damage to the heart following cardiac ischemias, damage to the kidneys following renal ischemias, skeletal muscle damage, muscular dystrophies, damage arising through proliferation of smooth muscle 35 cells, coronary vasospasms, cerebral vasospasms, macular degeneration, cataracts of the eyes, or restenosis of blood vessels following angioplasty in mammals, especially in humans, and to the use of the compounds of the invention of the formula I, their tautomers, prodrugs and their pharmaceutically suitable salts for the manufacture of a medicament for the treatment of these disorders. 40 It has further emerged that inhibition of calpain brings about cytotoxic effects on tumor cells. Accordingly, the compounds of the invention are suitable for the chemotherapy of 72 tumors and metastasis thereof. Preferred embodiments of the invention therefore relate to the use of the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts in the therapy of tumors and metastases, and to their use for the manufacture of a medicament for the therapy of tumors and metastases. 5 It has further been found that various impairments associated with an HIV disorder, especially nerve damage (HIV-induced neurotoxicity), are mediated by calpain and therefore inhibition of calpain allows such impairments to be treated or alleviated. Accordingly, the compounds of the invention of the formula 1, their tautomers, their 10 prodrugs and their pharmaceutically suitable salts are suitable for the treatment of HIV patients. Preferred embodiments of the invention therefore relate to the use of the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts for the treatment of HIV-infected patients, especially the treatment of those impairments caused by an HIV-induced neurotoxicity, and to their use for the 15 manufacture of a medicament for the treatment of HIV patients. It has further been found that the release of interleukin-l, TNF or beta-amyloid peptides (AB or AB-peptides) can be reduced or completely inhibited by calpain inhibitors. Accordingly, impairments or disorders associated with an elevated interleukin-1, TNF or 20 AR level can be treated by using the compounds of the invention of the formula 1, their tautomers and their pharmaceutically suitable salts. Preferred embodiments of the invention therefore relate to the use of the compounds of the invention of the formula 1, their tautomers, their produgs and their pharmaceutically acceptable salts for the treatment of impairments or disorders associated with an elevated interleukin-1, TNF or 25 A8 level such as rheumatism, rheumatoid arthritis and to their use for the manufacture of a medicament for the treatment of such impairments or disorders. The compounds of the general formula (1) are distinguished in particular also by a good metabolic stability. The metabolic stability of a compound can be measured for 30 example by incubating a solution of this compound with liver microsomes from particular species (for example rat, dog or human) and determining the half-life of the compound under these conditions (RS Obach, Curr Opin Drug Discov Devel. 2001, 4, 36-44). It is possible to conclude from larger half-lives that the metabolic stability of the compound is improved. The stability in the presence of human liver microsomes is of 35 particular interest because it makes it possible to predict the metabolic degradation of the compound in the human liver. Compounds with increased metabolic stability are therefore probably also degraded more slowly in the liver (measured in the liver microsome test). Slower metabolic degradation in the liver can lead to higher and/or longer-lasting concentrations (effective levels) of the compound in the body, so that the 40 elimination half-life of the compounds of the invention is increased. Increased and/or longer-lasting effective levels may lead to a better efficacy of the compound in the treatment or prophylaxis of various calpain-dependent diseases. An improved 73 metabolic stability may additionally lead to an increased bioavailability after oral administration, because the compound is subjected, after being absorbed in the intestine, to less metabolic degradation in the liver (termed the first pass effect). An increased oral bioavailability may, because the concentration (effective level) of the 5 compound is increased, lead to a better efficacy of the compound after oral administration. The compounds of the invention of the formula I are further distinguished by exhibiting an improved pharmacological activity, compared with the carboxamide compounds of 10 the formula I disclosed in the prior art, in patients or relevant animal models allowing prognostic statements for use in treatment. The present invention also relates to pharmaceutical compositions (i.e. medicaments) which comprise at least one compound of the invention of the formula I or a tautomer 15 or a pharmaceutically suitable salt thereof and, where appropriate, one or more suitable drug carriers. Thes drug carriers are chosen according to the pharmaceutical form and the desired mode of administration. 20 The compounds of the invention of the general formula I, their tautomers and the pharmaceutically suitable salts of these compounds can be used to manufacture pharmaceutical compositions for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, intratracheal, intranasal, transdermal or rectal administration, and 25 be administered to animals or humans in unit dose forms, mixed with conventional pharmaceutical carriers, for the prophylaxis or treatment of the above impairments or diseases. Suitable unit dose forms include forms for oral administration, such as tablets, gelatin 30 capsules, powders, granules and solutions or suspensions for oral intake, forms for sublingual, buccal, intratracheal or intranasal administration, aerosols, implants, forms of subcutaneous, intramuscular or intravenous administration and forms of rectal administration. 35 The compounds of the invention can be used in creams, ointments or lotions for topical administration. In order to achieve the desired prophylactic or therapeutic effect, the dose of the active basic ingredient may vary between 0.01 and 50 mg per kg of body weight and per day. 40 Each unit dose may comprise from 0.05 to 5000 mg, preferably 1 to 1000 mg, of the active ingredient in combination with a pharmaceutical carrier. This unit dose can be 74 administered 1 to 5 times a day, so that a daily dose of from 0.5 to 25 000 mg, preferably 1 to 5000 mg, is administered. If a solid composition is prepared in the form of tablets, the main ingredient is mixed 5 with a pharmaceutical carrier such as gelatin, starch, lactose, magnesium stearate, talc, silicon dioxide or the like. The tablets may be coated with sucrose, a cellulose derivative or another suitable substance or be treated otherwise in order to display a prolonged or delayed activity 10 and in order to release a predetermined amount of the active basic ingredient continuously. A preparation in the form of gelatin capsules is obtained by mixing the active ingredient with an extender and taking up the resulting mixture in soft or hard gelatin capsules. 15 A preparation in the form of a syrup or elixir or for administration in the form of drops may comprise active ingredients together with a sweetener, which is preferably calorie free, methylparaben or propylparaben as antiseptics, a flavoring and a suitable coloring. 20 The water-dispersible powders or granules may comprise the active ingredients mixed with dispersants, wetting agents or suspending agents such as polyvinylpyrrolidones, and sweeteners or taste improvers. 25 Rectal administration is achieved by the use of suppositories which are prepared with binders which melt at the rectal temperature, for example cocobutter or polyethylene glycols. Parenteral administration is effected by using aqueous suspensions, isotonic salt solutions or sterile and injectable solutions which comprise pharmacologically suitable dispersants and/or wetting agents, for example propylene glycol or 30 polyethylene glycol. The active basic ingredient may also be formulated as microcapsules or liposomes/centrosomes, if suitable with one or more carriers or additives. 35 In addition to the compounds of the general formula 1, their tautomers or their pharmaceutically suitable salts, the compositions of the invention may comprise further active basic ingredients which may be beneficial for the treatment of the impairments or diseases indicated above. 40 The present invention thus further relates to pharmaceutical compositions in which a plurality of active basic ingredients are present together, where at least one thereof is a compound of the invention.

75 The following examples illustrate the invention without restricting it. Depending on the management of the reaction and working up, the compounds of the general formula I result as mixtures of carbonyl form and the corresponding hydrates. Conversion into 5 the pure carbonyl compounds generally takes place by treating the substances with HCI in an inert solvent. Preparation examples 10 Example 1: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-(4-phenyl-1 H-imidazol-1 -yl)nicotinamide 1.1 Ethyl 2-(4-phenyl-1 H-imidazol-1-yl)pyridine-3-carboxylate A mixture of 5.0 g of ethyl 2-chloronicotinate (26.94 mmol), 3.4 g of 4-phenylimidazole 15 (23.58 mmol), 7.6 g of K 2

CO

3 and 80 mg of 18-crown-6 in 18 ml of N,N-dimethyl formamide was heated in a microwave at 160 0 C for about 1 hour. This was followed by concentrating, taking up the residue in dichloromethane, washing with water and sat. NaCl solution, drying over MgSO 4 , filtering and evaporating. Chromatography on silica gel (eluent: CH 2 Cl 2 /methanol 2%-5%) resulted in 2 g of a dark oil, which was 20 immediately reacted further; ESI-MS [M+H]+ = 294.15. 1.2 2-(4-Phenyl-1H-imidazol-1-yl)pyridin-3-carboxylic acid 15 m of a 2N NaOH solution were added to a solution of 2.0 g of ethyl 2-(4-phenyl-1 H imidazol-1-yl)pyridine-3-carboxylate (6.82 mmol) in 30 ml of methanol, and the mixture 25 was then stirred at room temperature for 2 hours. The reaction mixture was subsequently evaporated to dryness, mixed with 10 ml of H 2 0 and neutralized by adding 2N HCI. Filtration with suction and drying the precipitate formed resulted in 1.3 g of the acid as brown amorphous solid. ESI-MS [M+H]+ = 266.05. 30 1 H-NMR (500 MHz DMSO) S ppm: 13.99-13.45 (s broad, 1H), 8.74 (m, 1H), 8.37 (m, 1H), 8.08 (s, 1H), 8.03 (s, 1H), 7.86 (m, 1H), 7.84 (m, 1H), 7.62 (m, 1H), 7.39 (m, 2H), 7.25 (m, 1H). 1.3 N-[3-Amino-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-2-(4-phenyl-1H-imidazol-1 35 yl)pyridine-3-carboxamide 0.75 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 0.51 g of hydroxyl benzotriazole (HOBt) and 0.55 ml of triethylamine (Et 3 N) were successively added to a solution of 1.0 g of 2-(4-phenyl-1 H-imidazol-1-yl)pyridine-3-carboxylic acid (3.77 mmol) in 50 ml of dichloromethane at 0-4*C, and the mixture was stirred at 0-4*C for 1 hour. 40 0.9 g of 3-amino-2-hydroxy-4-phenylbutanamide hydrochloride (3.9 mmol) and 0.55 ml of Et 3 N were then added and, after about 5 minutes, a pH of 8-9 was adjusted by adding 0.5 ml of Et 3 N. The mixture was stirred at 0-4*C for 1 hour and then at room 76 temperature overnight. 50 ml of saturated NaHCO 3 solution were then added to the mixture, and the organic phase was separated off. Drying and evaporating the solvent resulted in 620 mg of a reddish oil, which was reacted further immediately without further purification. 5 ESI-MS [M+H]+ = 442.15. 1.4 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(4-phenyl-1H-imidazol-1-yl)nicotinamide 2.7 g of EDC and 0.5 ml of dichloroacetic acid were added to 620 mg of N-[3-amino-2 hydroxy-3-oxo-1-(phenylmethy)propyl]-2-(4-phenyl-1 H-imidazol-1-yl)pyridine-3 10 carboxamide (1.45 mmol) in 15 ml of dry dimethyl sulfoxide, and the mixture was stirred at room temperature for about 1 hour. To work up the reaction mixture it was mixed with 40 ml of NaCl solution and sat. NaHCO 3 solution (1:1), and the resulting solid was filtered off with suction, dried and stirred with methyl tert-butyl ether. The residue obtained in this way was further purified by stirring with 2N HCI and then with 15 10 ml of 1:1 acetonitrile/water. The remaining residue was filtered off with suction and dried. 50 mg of the target compound were obtained as a pale amorphous solid in this way. ESI-MS [M+H 2 O+H]+= 458.15. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.51 (d, 1H), 8.72 (dd, 2H), 8.16 (s, 1H), 8.12 (s, 20 1H), 7.93 (m, 2H), 7.88 (m, 2H), 7.70 (dd, 1H), 7.85 (m, 2H), 7.38 (m, 1H), 7.27 (m, 4H), 7.19 (m, 1H), 6.54 (m, 1H), 3.24 (dd, 1H), 2.87 (dd, 1H). Example 2: N-{1-[Amino(oxo)acetyl]pentyl}-2-(4-phenyl-1 H-imidazol-1-yl)nicotinamide 25 2.1 N-[1 -(2-Amino-1 -hydroxy-2-oxoethy)pentyl]-2-(4-phenyl-1 H-imidazol-1 yl)pyridine-3-carboxamide Preparation took place in analogy to 1.3 using 0.23 g of 3-amino-2-hydroxyheptan amide hydrochloride (1.17 mmol). During the usual workup, the target product 30 precipitated as a white solid from the aqueous phase. The solid was filtered off with suction and dried at 40'C in a vacuum drying oven. 219 mg of the title compound were obtained. ESI-MS [M+H]'= 408.15. 35 2.2 N-{1-[Amino(oxo)acetyl]pentyl)-2-(4-phenyl-1H-imidazol-1-yl)nicotinamide 200 mg of N-[1 -(2-amino-1 -hydroxy-2-oxoethyl)pentyl]-2-(4-phenyl-1 H-imidazol- 1 yl)pyridine-3-carboxamide (0.49 mmol) were oxidized in a manner analogous to Example 1.4. The crude product obtained after workup was purified by chromatography on silica gel (eluent: CH 2 Cl 2 /methanol 0%-7%). Evaporation of the solvent resulted in 40 37 mg of the title compound. ESI-MS [M+H]+= 406.15. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.15(d, 1H), 8.65 (d, 1H), 8.12 (s, 1H), 8.09 (s, 1H), 77 8.01 (dd, 1H), 7.95 (s, 1H), 7.84 (m, 3H), 7.56 (m, 1H), 7.39 (m, 2H), 7.24 (m, 1H), 5.16 (m, 1H), 1.77 and 1.50 (each m, H), 1.26 (m, 4H), 0.77 (m, 3H). Example 3: 5 N-{1-[Amino(oxo)acetyl]pentyl}-2-(4-phenyl-1 H-pyrazol-1-yl)nicotinamide 3.1 Ethyl 2-(4-phenyl-1 H-pyrazol-1-yl)pyridine-3-carboxylate A mixture of 3.6 g of ethyl 2-chloronicotinate (19.4 mmol), 1.3 g of 4-phenylpyrazole (8.12 mmol), 4.4 g of K 2

CO

3 , 40 mg of 18-crown-6 and 30 mg of KI in 30 ml of N,N 10 dimethylformamide was stirred at 130*C for 6 hours. For workup, H 2 0 was added and, after extraction with ethyl acetate, the organic phase was washed with H 2 0 and sat. NaCl solution. The crude product obtained after drying and concentration of the solution was purified by chromatography on silica gel (eluent: CH 2

CI

2 /methanol 1-10%). In total, 1.9 g of an oil were obtained, which crystallized completely on standing in a 15 refrigerator. ESI-MS [M+H]+ = 294.15. 3.2 2-(4-Phenyl-1H-pyrazol-1-yl)pyridine-3-carboxylic acid Hydrolysis of 1.0 g of ethyl 2-(4-phenyl-1 H-pyrazol-1-yl)pyridine-3-carboxylate 20 (6.48 mmol) took place in analogy to 1.2. 0.8 g of the carboxylic acid was obtained as a white amorphous solid. ESI-MS [M+H]+ = 266.1 1 H-NMR (500 MHz DMSO) 5 ppm: 8.64 (s, 1 H), 8.32 (m, 1 H), 8.06 (s, 1 H), 7.77 (m, 1H), 7.67 (m, 2H), 7.40 (m, 1H), 7.32 (m, IH), 7.24 (m, 1H). 25 3.3 N-[1-(2-Amino-1-hydroxy-2-oxoethyl)pentyl]-2-(4-phenyl-1H-pyrazol-1-yl)pyridine 3-carboxamide Preparation took place in analogy to 1.3 using 0.19 g of 3-amino-2-hydroxyheptan amide hydrochloride (1.0 mmol). Completion of the reaction was followed by 30 concentration, addition of H 2 0 and filtration of the resulting precipitate with suction and drying. Crystallization of the crude product from ethanol afforded 290 mg of the title compound as a white amorphous solid. ESI-MS [M+H]+= 408.3. 35 3.4 N-{1-[Amino(oxo)acetyl]pentyl}-2-(4-phenyl-1H-pyrazol-1-yl)nicotinamide 0.47 g of EDC and 0.08 ml of dichloroacetic acid were added to 100 mg of N-[1-(2 amino-1 -hydroxy-2-oxoethyl)pentyl]-2-(4-phenyl-1 H-pyrazol-1 -yl)pyridine-3 carboxamide (0.25 mmol) in 4 ml of dimethyl sulfoxide, and the mixture was stirred at room temperature overnight. For workup, the reaction mixture was poured into H 2 0, 40 and the resulting precipitate was filtered off with suction and dried in a vacuum drying oven at 40 0 C. 77 mg of the title compound were obtained as an amorphous white solid. ESI-MS [M+H]+= 406.2 78 1 H-NMR (500 MHz DMSO) 8 ppm: 8.87 (d, 1H), 8.68 (d, 1H), 8.60 (dd, 1H), 8.16 (s, 1H), 8.02 (s, 1H), 7.87 (dd, 1H), 7.76 (m, 3H), 7.55 (dd, 1H), 7.41 (m, 2H), 7.27 (m, 1 H), 5.11 (m, 1 H), 1.76 (m, 1 H), 1.51 (m, 1 H), 1.35-1.25 (m, 4H), 0.85-0.82 (m, 3H). 5 Example 4: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(4-phenyl-1 H-pyrazol-1 -yl)nicotinamide 4.1 N-[3-Amino-2-hydroxy-3-oxo-1 -(phenylmethyl)propyl]-2-(4-phenyl-1 H-pyrazol-1 yl)pyridine-3-carboxamide 10 0.23 g of 3-amino-2-hydroxy-4-phenylbutanamide hydrochloride (1.0 mmol) was reacted with 2-(4-phenyl-1 H-imidazol-1-yl)pyridine-3-carboxylic acid in analogy to Example 3.3, resulting in 280 mg of the title compound of a white amorphous solid. ESI-MS [M+H]*= 442.4. 15 4.2 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(4-phenyl-1H-pyrazol-1-yl)nicotinamide 250 mg of N-[3-amino-2-hydroxy-3-oxo-1 -(phenylmethyl)propyl]-2-(4-phenyl-1 H pyrazol-1-yl)pyridine-3-carboxamide (0.57 mmol) were oxidized in analogy to Example 3.4, resulting in 228 mg of the title compound as a white solid. ESI-MS [M+H]+= 440.1. 20 1 H-NMR (500 MHz DMSO) 8 ppm: 8.92 (d, 1H), 8.86 (s, 1H), 8.58 (dd, 1H), 8.05 (s, 2H), 7.82 (s, 1H), 7.75 (m, 3H), 7.49 (dd, 1H), 7.43 (m, 2H), 7.30 (m, 5H), 7.20 (m, 1H), 5.39 (m, 1H), 3.18 (dd, 1H), 2.91 (dd, 1H). Example 5: 25 N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-(3-phenyl-1 H-pyrazol-1 -yl)nicotinamide 5.1 Ethyl 2-(3-phenyl-1 H-pyrazol-1 -yl)pyridine-3-carboxylate Reaction of 4.3 g of 3-phenyl-1 H-pyrazole (29.82 mmol) in a manner analogous to Example 3.1 and chromatography of the resulting crude product on silica gel (eluent: 30 CH 2 Cl 2 ) afforded 9.7 g of the title compound as a pale oil. ESI-MS [M+H]+= 294.0. 5.2 2-(3-Phenyl-1H-pyrazol-1-yl)pyridine-3-carboxylic acid Hydrolysis took place in analogy to Example 1.2. After the reaction was complete, the 35 reaction mixture was extracted with ethyl acetate, and the aqueous phase was acidified with 2N HCI and extracted with dichloromethane. Washing with H 2 0 and sat. NaCl solution, drying and evaporation afforded 5.1 g of the acid as a pale solid. ESI-MS [M+H]+= 266.0. 1 H-NMR (500 MHz DMSO) 3 ppm: 13.2 (s broad, 1H), 8.61 (m, 1H), 8.56 (m, 1H), 8.11 40 (m, 1H), 7.92 (m, 2H), 7.52-7.39 (m, 2H), 7.39 (m, 1H), 7.08 (m, 1H). 5.3 N-[1-(2-Amino-1-hydroxy-2-oxoethyl)pentyl]-2-(3-phenyl-1H-pyrazol-1-yl)pyridine- 79 3-carboxamide Coupling and working up in a manner analgous to Example 3.3 afforded 5.1 g of the title compound as a white solid. ESI-MS [M+H]+= 442.1. 5 5.4 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(3-phenyl-1H-pyrazol-1-yl)nicotinamide Oxidation of 5.1 g of N-[1 -(2-amino-1 -hydroxy-2-oxoethyl)pentyl]-2-(3-phenyl-1 H pyrazol-1 -yl)pyridine-3-carboxamide (11.55 mmol) in a manner analogous to Example 3.4, and purification of the crude product by recrystallization from ethyl 10 acetate afforded 3.5 g of the title compound as a white solid with a melting point of 190*C. ESI-MS [M+H]+= 440.0. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.93 (d, 1H), 8.56 (dd, 1H), 8.49 (dd, 1H), 8.48 (m, 1H), 8.06 (s, 1H), 7.84 (s, 1H), 7.78 (m, 2H), 7.7.73 (dd, 1H), 7.48 (dd, 1H), 7.42-7.35 15 (m, 3H), 7.19 (m, 5H), 7.02 (d,1H), 5.58 (m, 1H), 3.15 (dd, 1H), 2.81 (dd, 1H). Example 6: N-{1-[Amino(oxo)acetyl]pentyl)-2-(3-phenyl-1 H-pyrazol-1-yl)nicotinamide Preparation in analogy to Example 5 by coupling 2-(3-phenyl-1H-pyrazol-1-yl)pyridine 20 3-carboxylic acid and 3-amino-2-hydroxyheptanamide hydrochloride and subsequent oxidation afforded 40 mg of the title compound as a white solid. ESI-MS [M+H]+= 406.1 1 H-NMR (500 MHz DMSO) 5 ppm: 8.73 (d, 1H), 8.58 (d, 1H), 8.52 (d, 1H), 8.02 (s, 1H), 7.90-7.85 (m, 3H), 7.79 (s, 1H), 7.51 (dd, 1H), 7.45 (m, 2H), 7.37 (m, 1H), 7.05 (m, 1H), 25 5.17 (m, 1H), 1.73 (m, 1H), 1.46 (m, 1H), 1.15 (m, 4H), 0.70 (m, 3H). Example 7: N-{1-[Amino(oxo)acetyl]-3-methylbutyl}-2-(4-phenyl-1 H-imidazol-1-yl)nicotinamide 7.1 N-[1 -(2-Amino-1 -hydroxy-2-oxoethyl)-3-methylbutyl]-2-(4-phenyl-1 H-imidazol-1 30 yl)pyridine-3-carboxamide Coupling of 0.39 g of 3-amino-2-hydroxy-5-methylhexanamide hydrochloride (1.0 mmol) with 2-(4-phenyl-1 H-imidazol-1 -yl)pyridine-3-carboxylic acid in a manner analogous to Example 3.3 afforded 280 mg of the title compound as a white amorphous solid. 35 ESI-MS [M+H]+= 442.4. 7.2 N-{1-[Amino(oxo)acetyl]-3-methylbutyl)-2-(4-phenyl-1H-imidazol-1-yl)nicotinamide Oxidation of 200 mg of N-[3-amino-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-2-(4 phenyl-1H-pyrazol-1-yl)pyridine-3-carboxamide (0.49 mmol) afforded 102 mg of the title 40 compound as a pale solid. ESI-MS [M+H]'= 406.24. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.18 (d, 1H), 8.69 (d, 1H), 8.13 (m, 2H), 8.01 (dd, 80 1H), 7.95 (s, 1H), 7.85 (m, 3H), 7.61 (m, 1H), 7.41 (m, 2H), 7.27 (m, 1H), 5.25 (m, 1H), 1.65 (m, 1H), 1.53 (dd, 1H), 1.44 (dd, 1H). The compounds of Examples 8 to 13 can be prepared in a manner analogous to the 5 above examples. Example 8: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-fluorophenyl)-1 H-imidazol-1 yl]nicotinamide 10 ESI-MS [M+H]*= 458.15. 1 H-NMR (500 MHz DMSO) S ppm: 9.34 (m, 1H), 8.63 (m, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 7.91-7.75 (m, 5H), 7.56 (m, IH), 7.31-7.20 (m, 7H), 5.50 (m, 1H), 3.22 (m overlapped by H 2 0), 2.83 (dd, 1H). 15 Example 9: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-chlorophenyl)-1 H-imidazol-1 yl]nicotinamide ESI-MS [M+H]*= 474.15. 1 H-NMR (500 MHz DMSO) S ppm: 9.38 (m, 1H), 8.64 (m, 1H), 8.16 (s, 1H), 8.05 (s, 20 1H), 7.94-7.91 (m, 2H), 7.83-7.81 (m, 2H), 7.76 (m, 1H), 7.56 (m, 1H), 7.45 (m, 2H), 7.31-7.21 (m, 5H), 5.45 (m, 1H), 3.23 (m overlapped by H 2 0), 2.82 (dd, 1H). Example 10: N-{1-[Amino(oxo)acetyl]pentyl}-2-[4-(4-chlorophenyl)-1H-imidazol-1-yl]nicotinamide 25 ESI-MS [M+H]+= 440.2. 1 H-NMR (500 MHz DMSO) S ppm: 9.20 (m, 1H), 8.69 (dd, 1H), 8.17 (s, 1H), 8.14 (m, 1H), 8.03 (m, 2H), 7.89 (m, 3H), 7.61 (dd, 1H), 7.48 (m, 1H), 7.46 (m, 1H), 5.18 (m, 1H), 1.78 and 1.52 (each dd, 1H), 1.26 (m, 4H), 0.79 (m, 3H). 30 Example 11: N-{1-[Amino(oxo)acetyl]pentyl}-2-[4-(4-fluorophenyl)-1 H-imidazol-1 -yl]nicotinamide ESI-MS [M+H]+= 424.2. 1 H-NMR (500 MHz DMSO) S ppm: 9.17 (m, 1H), 8.68 (m, 1 H), 8.13 (m, 1H), 8.11 (m, 1H), 8.03 (m, 1H), 7.97 (s, 1H), 7.91-7.86 (m, 3H), 7.60 (m, 1H), 7.24 (m 3H), 5.17 (m, 35 1H), 1.78 (m, 1H), 1.52 (m, 1H), 1.27 (m, 4H), 0.79 (m, 3H). Example 12: N-{1 -[Amino(oxo)acetyl]pentyl}-2-[4-(4-methoxyphenyl)-1 H-imidazol-1 -yl]nicotinamide ESI-MS [M+H]'= 436.25. 40 1 H-NMR (500 MHz DMSO) S ppm: 9.19 (m, 1 H), 8.66 (m, 1 H), 8.11 (m, 2H), 8.01 (m, 1H), 7.85 (m, 2H), 7.71 (m, 2H), 7.58 (m, 1H), 6.99 (m, 2H), 5.19 (m, 1H), 3.79 (s, 3H), 1.79 (m, 1H), 1.52 (m, 1H), 1.29 (m, 4H), 0.80 (m, 3H).

81 Example 13: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-methoxyphenyl)-1 H-imidazol-1 yl]nicotinamide 5 1 H-NMR (500 MHz DMSO) S ppm: 9.45 (d, 1H), 8.66 (dd, 1H), 8.28 (s, 1H), 8.19 (s, 1 H), 7.94 (s, 1 H), 7.87 (s, 1 H), 7.81 (m, 2H), 7.75 (m, 2H), 7.61 (m, 1 H), 7.30-7.24 (m, 5H), 7.01 (d, 1H), 5.46 (m, 1H), 3.82 (s, 3H), 3.26 (dd, 1H), 2.85 (dd, 1H). Example 14: 10 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-morpholin-4-ylphenyl)-1 H-imidazol-1 yl]nicotinamide 14.1 4-[4-(1 H-Imidazol-4-yl)phenyl]morpholine 3.0 g of 2-bromo-1-(4-morpholin-4-ylphenyl)ethanone and 8 ml of formamide were 15 heated in a microwave at 180*C for about 30 minutes. The mixture was then poured into 150 ml of H 2 0, the pH was adjusted to 10-12 by adding 2N NaOH solution, and the resulting solid was filtered off with suction and dried, resulting in 2.2 g of the title compound. ESI-MS [M+H]*= 230.1. 20 14.2 Ethyl 2-[4-(4-morpholin-4-ylphenyl)-1H-imidazol-1-yl]pyridine-3-carboxylate Starting from 0.9 g of 4-[4-(1 H-imidazol-4-yl)phenyl]morpholine (3.93 mmol) and reaction in analogy to Example 3.2 resulted in 0.6 g of the title compound as a dark oil. ESI-MS [M+H]*= 379.15. 25 Further reactions took place in a manner analogous to the above examples, resulting in 78 mg of N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-[4-(4-morpholin-4-yphenyl)-1 H imidazol-1 -yl]nicotinamide. ESI-MS [M+H 2 0+H+]= 543.2. 30 Example 15: N-{1-[Amino(oxo)acetyl]pentyl}-2-[4-(4-morpholin-4-ylphenyl)-1 H-imidazol-1 yl]nicotinamide hydrochloride The title compound was prepared in a manner analogous to the above examples.ESI 35 MS [M+H]*= 491.29. Example 16: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{4-[4-(diethylamino)phenyl]-1 H-imidazol-1 yl}nicotinamide hydrochloride 40 16.1 N,N-Diethyl-4-(1 H-imidazol-4-yl)aniline Preparation took place in a manner analogous to Example 14.1. Chromatography on silica gel (eluent: CH 2 CI2/methanol 2-7%) resulted in 1.1 g of the title compound as a 82 dark solid. ESI-MS [M+H]+= 216.15. The title compound was prepared in a manner analogous to the above examples, 5 resulting in 32 mg of N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-{4-[4 (diethylamino)phenyl]-1 H-imidazol-1 -yl}nicotinamide hydrochloride. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.43 (s, 1H), 8.64 (s, 1H), 8.21 (s, 1H), 8.04 (s, 1H), 7.95 (s, 1H), 7.75 (d, 1H), 7.68-7.52 (m, 5H), 7.35-7.17 (m, 7H), 6.72 (s broad, 2H), 5.47 (m, 1H), 3.38 and 3.28 (overlapped by H 2 0), 2.86 (dd, 1H), 1.14 (m, 6H). 10 Example 17: N-{1-[Amino(oxo)acetyl]pentyl)-2-{4-[4-(trifluoromethyl)phenyl]-1H-imidazol-1 yl}nicotinamide hydrochloride The title compound was prepared in a manner analogous to the above examples.ESI 15 MS [M+H]+= 474.21. 'H-NMR (500 MHz DMSO) S ppm: 9.24 (m, 1H), 8.74 (m, 1H), 8.63 (s, 1H), 8.31 (s, 1H), 8.15-8.12 (m, 4H), 7.88 (s, 1H), 7.90 (m, 2H), 7.71 (m, 1H), 6.13 (s broad), 5.17 (m, 1 H), 1.78 (m, 1 H), 1.52 (m, 1 H), 1.25 (m, 4H), 0.77 (m, 3H). 20 Example 18: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{4-[4-(trifluoromethyl)phenyl]-1 H-imidazol-1 yl}nicotinamide hydrochloride The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]'= 508.26. 25 1 H-NMR (500 MHz DMSO) S ppm: 9.46 (m, 1H), 8.69 (m, 1H), 8.37 (s, 1H), 8.20 (m, 2H), 8.07 (m, 2H), 7.95 (s, 1H), 7.86 (m, 3H), 7.65 (m, 1H), 7.28 (m, 4H), 7.21 (m, 1H), 5.47 (m, IH), 5.27 (s broad), 3.26 and 2.86 (each dd, 1H). Example 19: 30 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(2-chlorophenyl)-1 H-imidazol-1 yl]nicotinamide hydrochloride The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H 2 0+H+]= 492.17. 1 H-NMR (500 MHz DMSO) S ppm: 9.46 (m, 1H), 8.71 (m, 2H), 8.14 (s, 2H), 8.04 (d, 35 1H), 7.93 (dd, 1H), 7.69 (m, 1H), 7.58 (d, IH), 7.49 (m, 1H), 7.42 (m, 1H), 7.24 (m, 5H), 7.14 (m, 1H), 5.45 (m, 1H), 3.23 and 2.84 (each dd, 1H). Example 20: N-{1-[Amino(oxo)acetyl]pentyl}-2-[4-(2-chlorophenyl)-1 H-imidazol-1-yl]nicotinamide 40 hydrochloride The title compound was prepared in a manner analogous to the above examples. The crude product was purified by chromatography on silica gel (eluent: CH 2

CI

2 /methanol 83 1-10%) and lyophilized after addition of 1 equivalent of HCI to afford 50 mg of the title compound as a white solid. ESI-MS [M+H]*= 440.21. 1 H-NMR (500 MHz DMSO) 3 ppm: 9.17 (d, 1H), 8.72 (m, 1H), 8.49 (s, 1H), 8.21 (s, 5 1H), 8.15 (m, 1H), 8.08 (m, 1H), 8.06 (m, 1H), 7.85 (s, 1H), 7.67 (dd, 1H), 7.56 (d, 1H), 7.46 (m, 1H), 7.36 (m, 1H), 5.16 (m, 1H), 4.09 (s broad), 1.75 and 1.49 (each m, 1H), 1.21 (m, 4H), 0.74 (m, 3H). Example 21: 10 N-{1-[Amino(oxo)acetyl]pentyl}-2-[4-(3-chlorophenyl)-1 H-imidazol-1-yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 440.21. 1 H-NMR (500 MHz DMSO) S ppm: 9.16 (m, 1H), 8.69 (m, 1H), 8.14-8.03 (m, 4H), 7.91 7.82 (m, 3H), 7.62 (m 1H), 7.44 (m, 1H), 7.32 (m, 1H), 5.16 (m, 1H), 1.78 (m, 1H), 1.51 15 (m, 1H), 1.25 (m, 4H), 0.79 (m, 3H). Example 22: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[4-(3-chlorophenyl)-1 H-imidazol-1-yl]nicotin amide 20 The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H 3 0]*= 492.14. 1 H-NMR (500 MHz DMSO) S ppm: 9.40 (dd, IH), 8.66 (m, 1H), 8.16 (s, IH), 8.04 (m, 2H), 7.95 (s, 1H), 7.89 (s, 1H), 7.78 (m, 2H), 7.59 (m, 1H), 7.45 (m, 1H), 7.33-7.25 (m, 5H), 7.22 (m, 1H), 5.46 (m, IH), 3.26 (dd, overlapped by H 2 0), 2.84 (dd, 1H). 25 Example 23: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-5-chloro-2-(4-phenyl-1 H-imidazol-1 yl)nicotinamide hydrochloride 5.4 g of methyl 2,5-dichloronicotinate (26.2 mmol) and 2.8 g of 4-phenylimidazole were 30 reacted in a manner analogous to Example 3.1. Purification by chromatography resulted in 1.7 g of methyl 5-chloro-2-(4-phenyl-1H-imidazol-1-yl)pyridine-3-carboxylate as a dark oil. ESI-MS [M+H]+= 314.05. 35 The title compound was prepared in a manner analogous to the above examples starting from methyl 5-chloro-2-(4-phenyl-1 H-imidazol-1 -yl)pyridine-3-carboxylate. 110 mg of the title compound were obtained as a pale solid. ESI-MS [M+H 2 0+H+]= 492.11. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.54 (dd, 1H), 8.83 (s, 1H), 8.59 (s, 1H), 8.18 (s, 40 1H), 8.07 (s, 1H), 7.95 (m, 2H), 7.85 (m, 2H), 7.48 (m, 2H), 7.37 (m, 1H), 7.27 (m, 4H), 7.21 (m, IH), 5.45 (m, 1H), 4.97 (s broad), 3.26 and 2.89 (each dd, 1H).

84 Example 24: N-{1-[Amino(oxo)acetyl]pentyl}-5-chloro-2-(4-phenyl-1 H-imidazol-1-yl)nicotinamide hydrochloride The title compound was prepared in a manner analogous to the above examples.ESI 5 MS [M+H]+= 440.19. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.26 (m, 1H), 8.77 (m, 1H), 8.16 (m, IH), 8.13 (m, 2H), 7.96 (s, 1 H), 7.89-7.84 (m, 3H), 7.41 (m, 2H), 7.27 (m, 1 H), 5.19 (m, 1 H), 1.79 and 1.54 (each m, 1H), 1.28 (m, 4H), 0.80 (m, 3H). 10 Example 25: N-{1 -[Amino(oxo)acetyl]-3-methylbutyl}-5-chloro-2-(4-phenyl-1 H-imidazol-1 yl)nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 440.2. 15 1 H-NMR (500 MHz DMSO) S ppm: 9.26 (m, 1H), 8.78 (m, 1H), 8.13 (m, 3H), 7.94 (s, 1 H), 7.85 (m, 3H), 7.41 (m, 2H), 7.28 (m, 1 H), 5.26 (m, 1 H), 1.68 (m, 1 H), 1.54 (m, 1 H), 1.44 (m, 1H), 0.87 (m, 6H). Example 26: 20 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{4-[4-(morpholin-4-ylmethyl)phenyl]-1 H imidazol-1-yl}nicotinamide hydrochloride 26.1 1-[4-(Morpholin-4-ylmethyl)phenyl]ethanone 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 25 3 g of 4A molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO 3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a 30 yellowish oil were obtained. ESI-MS [M+H]+= 220.1. 26.2 4-{[4-(1H-Imidazol-4-yl)phenyl]methyl}morpholine 0.55 ml of bromine (dissolved in 5 ml of 47% HBr) was added dropwise to 1.76 g of 35 1-[4-(morpholin-4-ylmethyl)phenyl]ethanone (8.03 mmol) in 15 ml of 47% HBr at 5*C, and the mixture was stirred at room temperature for about 2 hours. Water was then added to the reaction mixture, and it was neutralized by adding NaHCO 3 and extracted with dichloromethane. The combined organic phases were washed with saturated NaCI solution, dried and evaporated. The resulting yellowish oil (2.7 g) was mixed with 8 ml 40 of formamide and heated in a microwave at 185 0 C for 30 minutes. The reaction mixture was worked up by diluting with H 2 0, adjusting the pH to 11-12 by adding 2N NaOH, extracting with dichloromethane and washing the combined organic phases anew with 85 saturated NaCl solution. Drying of the organic phase and evaporation of the solvent was followed by treating the remaining residue with methyl tert-butyl ether, resulting in 1.3 g of the title compound as a brown oil. ESI-MS [M+H]'= 244.15. 5 The title compound was prepared in a manner analogous to the above examples. 115 mg of N-(3-amino-1 -benzyl-2,3-dioxopropyl)-2-{4-[4-(morpholin-4-ylmethyl)phenyl] I H-imidazol-1 -yl}nicotinamide were obtained as hydrochloride. ESI-MS [M+H]+= 541.1. 10 Example 27: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-5-chloro-2-(3-phenyl-1 H-pyrazol-1-yl)nicotin amide The title compound was prepared in a manner analogous to the above examples.ESI 15 MS [M+H]+= 474.2. 1 H-NMR (500 MHz DMSO) 6 ppm: 9.02 (d, 1H), 8.64 (d, 1H), 8.48 (s, 1H), 8.10 (s, 1H), 7.88 (s, 1H), 7.75 (m, 2H), 7.66 (d, 1H), 7.38 (m, 3H), 7.21 (m, 6H), 5.59 (m, 1H), 3.20 (dd, 1H), 2.83 (dd, 1H). 20 Example 28: N-{1 -[Amino(oxo)acetyl]pentyl}-5-chloro-2-(3-phenyl-1 H-pyrazol-1 -yl)nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 440.2. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.84 (dd, 1H), 8.67 (s, 1H), 8.52 (s, 1H), 8.05 (s, 25 1h), 7.94 (s, 1H), 7.84 (m, 3H), 7.45 (m, 2H), 7.39 (m, IH), 7.08 (s, 1H), 5.19 (m, 1H), 1.75 (m, 1H), 1.49 (m, 1H), 1.17 (m, 4H), 0.71 (m, 3H). Example 29: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-[3-(4-morpholin-4-ylphenyl)-1 H-pyrazol-1 30 yl]nicotinamide hydrochloride 29.1 4-[4-(1H-Pyrazol-3-yl)phenyl]morpholine A mixture of 2.05 g of 4-morpholinoacetophenone (10 mmol) and N,N-dimethyl formamide dimethyl acetal was heated under reflux for 7 hours. The mixture was then mixed with 30 ml of methanol and, after addition of 0.57 ml of hydrazine hydrate, again 35 heated under reflux for about 6 hours. The solid formed on cooling the mixture was filtered off with suction and thoroughly washed with methanol, resulting in 3.8 g of the title compound. ESI-MS [M+H]'= 230.1. 40 The title compound was prepared in a manner analogous to the above examples. 82 mg of N-(3-amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-morpholin-4-yphenyl)-1

H

pyrazol-1-yl]nicotinamide hydrochloride were obtained.

86 ESI-MS [M+H]+= 525.3. 'H-NMR (500 MHz DMSO) 8 ppm: 8.93 (d, 1 H), 8.54 (d, 1 H), 8.45 (d, 1 H), 8.08 (s, 1 H), 7.86 (s, 1H), 7.70 (m, 3H), 7.46 (dd, 1H), 7.30 (m, 8H), 6.94 (d, 1H), 5.58 (m, 1H), 4.86 (s broad), 3.87 (m, 4H), 3.29 (m, 4H), 3.16 (dd, 1H), 2.81 (dd, 1H). 5 Example 30: N-{1 -[Amino(oxo)acetyl]-3-methylbutyl)-2-(3-phenyl-1 H-pyrazol-1 -yl)nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 406.02. 10 1 H-NMR (500 MHz DMSO) 8 ppm: 8.73 (d, 1H), 8.58 (dd, 1H), 8.49 (d, 1H), 8.01 (s, 1H), 7.89 (dd, 1H), 7.85 (m, 2H), 7.78 (s broad, 1H), 7.51 (dd, 1H), 7.44 (m, 2H), 7.37 (m, 1H), 7.03 (d, 1H), 5.25 (m, 1H), 1.60 (m, 1H), 1.47 (m, 1H), 1.35 (m, 1H), 0.79 and 0.76 (each d, 3H). 15 Example 31: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-5-chloro-2-[3-(4-morpholin-4-ylphenyl)-1 H pyrazol-1 -yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 559.2. 20 1 H-NMR (500 MHz DMSO) S ppm: 8.96 (d, 1H), 8.57 (d, 1H), 8.38 (d, 1H), 8.08 (s, 1H), 7.87 (s, 1H), 7.59 (dd, 1H), 7.18 (m, 5H), .89 (m, 3H), 5.57 (m, 1H), 3.74 (m, 4H), 3.14 (m, 5H), 2.81 (dd, 1H). Example 32: 25 N-{1 -[Amino(oxo)acetyl]-3-methylbutyl)-5-chloro-2-(3-phenyl-1 H-pyrazol-1 yl)nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M + H+]= 440.04. 'H-NMR (500 MHz DMSO) 8 ppm: 8.34 (d, 1H), 8.67 (s, 1H), 8.50 (s, 1H), 8.03 (s, 1H), 30 7.95 (s,1H), 7.83 (m, 3H), 7.40-7.37 (3H), 7.07 (d, 1H), 5.25 (m, 1H), 1.62 (m, 1H), 1.51 (m, 1H), 1.41 (m, 1H), 0.80 (m, 6H). Example 33: N-{1-[Amino(oxo)acetyl]pentyl}-2-[3-(4-morpholin-4-ylphenyl)-1 H-pyrazol-1 35 yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M + H+]= 491.1. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.70 (d, 1H), 8.55 (d, 1H), 8.46 (d, 1H), 8.03 (s, 1H), 7.85 (d, 1H), 7.80 (s, 1H), 7.72 (m, 2H), 7.47 (dd, 1H), 7.01 (m, 2H), 6.93 (m, 1H), 5.18 40 (m, 1H), 3.85 (s broad, overlapped by H 2 0), 3.19 (m, 4H), 1.72 (m, 1H), 1.47 (m, 1H), 1.25-1.15 (m, 4H), 0.82 (m, 3H).

87 N-{ 1 -[Am ino(oxo)acetyl]-3-methylbutyl}-2-[3-(4-morpholin-4-ylphenyl)-1 H-pyrazol-1 yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI 5 MS [M+H]+= 491.2. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.71 (d, 1H), 8.56 (d, 1H), 8.45 (d, 1H), 8.02 (s, 1H), 7.87 (d, 1H), 7.79 (s, 1H), 7.71 (m, 2H), 7.48 (dd, 1H), 7.02 (d, 1H), 6.92 (m, 1H), 5.28 (m, 1 H), 3.78 (m broad, 4H), 3.20 (m, 4H), 1.63 (m, 1 H), 1.48 (m, 1 H), 1.39 (m, 1 H), 0.81 (m, 6H). 10 Example 35: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(3-pyridin-2-yl-1 H-pyrazol-1-yl)nicotinamide The title compound was prepared in a manner analogous to the above examples.

1

H

NMR (500 MHz DMSO) S ppm: 8.97 (d, 1 H), 8.60 (m, 2H), 8.49 (m, 2H), 8.08 (s, 1 H), 15 7.85 (s, 1H), 7.80-7.69 (m, 3H), 7.51 (m, 1H), 7.35 (m, 1H), 7.19-7.13 (m, 5H), 7.04 (m, 1H), 5.55 (m, 1H), 3.15 (m, 1H), 2.79 (m, 1H). Example 36: N-{1-[Amino(oxo)acetyi]pentyl}-2-(3-pyridin-2-yl-1 H-pyrazol-1-yl)nicotinamide 20 The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 407.2. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.73 (d, 1H), 8.62 (m, 2H), 8.53 (d, 1H), 8.03 (s, 1H), 7.90 (m, 3H), 7.79 (s, 1H), 7.54 (dd, 1H), 7.38 (m, 1H), 7.08 (d, 1H), 5.18 (m, 1H), 1.71 (m, 1H), 1.44 (m, 1H), 1.11 (m, 4H), 0.67 (m, 3H). 25 Example 37: N-{1-[Amino(oxo)acetyl]pentyl}-2-[3-(4-chlorophenyl)-1 H-pyrazol-1-yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]+= 440.05. 30 1 H-NMR (500 MHz DMSO) S ppm: 8.71 (d, 1H), 8.59 (d, 1H), 8.52 (s broad, 1H), 8.04 (s, 1H), 7.98-7.88 (m, 3H), 7.81 (s, 1H), 7.51 (m, 3H), 7.08 (m, 1H), 5.17 (m, 1H), 1.70 (m, 1H), 1.44 (m, 1H), 1.12 (m, 4H), 0.69 (m, 3H). Example 38: 35 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-fluorophenyl)-1 H-pyrazol-1 yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]*= 458.1. 1 H-NMR (500 MHz DMSO) S ppm: 8.93 (d, 1H), 8.55 (dd, 1H), 8.47 (d, 1H), 8.09 (s, 40 1H), 7.87 (s, 1H), 7.78 (m, 2H), 7.71 (m, 1H), 7.48 (dd, 1H), 7.20-7.16 (m, 7H), 7.0 (m, 1H), 5.58 (m, 1 H), 3.15 (m, 1H), 2.79 (m, 1 H).

88 Example 39: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-chlorophenyl)-1 H-pyrazol-1 yl]nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI 5 MS [M+H]+= 474.05. 1 H-NMR (500 MHz DMSO) S ppm: 8.94 (dd, 1H), 8.57 (dd, 1H), 8.48 (d, 1H), 8.10 (s, 1H), 7.88 (s, 1H), 7.77 (m, 2H), 7.72 (dd, 1H), 7.48 (dd, 1H), 7.44 (m, 2H), 7.19 (m, 5H), 7.04 (m, 1H), 5.56 (m, 1H), 3.15 and 2.78 (each dd, 1H). 10 Example 40: N-[3-Amino-2,3-dioxo-1-(2-thienylmethyl)propyl]-2-(3-phenyl-1 H-pyrazol-1-yl)pyridine 3-carboxamide 40.1 Phenylmethyl [2-hydroxy-1 -(2-thienylmethyl)ethyl]carbamate 24.8 g of 3-(2-thienyl)alanine (144.8 mmol) were added in portions to 11.0 g of LiAIH 4 in 15 550 ml of tetrahydrofuran, heated to reflux. The mixture was then heated under reflux for 8 hours and subsequently stirred at room temperature overnight. 17.6 ml of 10% NaOH solution were added and then 22 ml of H 2 0 were slowly added dropwise, and the mixture was stirred for 5 minutes. Then, first 391 ml of 10% NaOH solution and subsequently, at -5*C, 22.2 g of benzyl chloroformate (130.32 mmol) were added, and 20 the mixture was stirred at room temperature for 3 hours. For workup, the mixture was extracted with dichloromethane, the organic phase was dried, the solvent was evaporated and the remaining residue was filtered through silica gel (eluent: CH2Cl2/methanol 2.5%). 36.8 g of the title compound were obtained as a yellowish oil. ESI-MS [M+H]+= 292. 25 40.2 Phenylmethyl [3-am i no-2-hyd roxy-3-oxo-1 -(2-thienylmethyl)propyl]carba mate 40.2 g of pyridine-S0 3 complex were added in portions to a mixture of 36.8 g of phenylmethyl [2-hydroxy-1-(2-thienylmethyl)ethyl]carbamate (126.3 mmol) and 51.2 g of triethylamine in 220 ml of dimethyl sulfoxide at about 160C, and the mixture was 30 stirred at room temperature for 3 hours. It was then poured into ice-water (1.5 I) and extracted with ethyl acetate, and the organic phase was washed with 1 N HCI and sat. NaCl solution, dried and evaporated. The resulting oil (38 g) was dissolved in 150 ml of tetrahydrofuran, and a solution of 44.4 g of NaCN in 225 ml of saturated NaHCO 3 solution was added dropwise. After 2 hours, the phases were separated, the aqueous 35 phase was extracted with ethyl acetate, and the combined organic phases were washed with H 2 0 and saturated NaCl solution, dried and concentrated. The residue obtained in this way was again dissolved in 400 ml of tetrahydrofuran and, over the course of 30 minutes, 65 ml of conc. HCI and 150 ml of conc. H 2

SO

4 were added dropwise in parallel while cooling in ice, and the mixture was stirred at room 40 temperature. After the reaction was complete, the reaction mixture was poured into ice water and extracted with ethyl acetate, and the organic phase was washed with 1 N NaOH and sat. NaCl solution, dried and concentrated. The remaining oily residue was 89 stirred with diethyl ether, and the resulting solid was filtered off with suction and dried, resulting in 16.3 g of the title compound as a whitish gray amorphous solid. ESI-MS [M+H]*= 335. 5 40.3 3-Amino-2-hydroxy-4-(2-thienyl)butanamide 70 ml of 30% HBr in glacial acetic acid were added to 11 g of phenylmethyl [3-amino-2 hydroxy-3-oxo-1-(2-thienylmethyl)propyl]carbamate (29.66 mmol) in 30 ml of glacial acetic acid. After about 2 hours, the mixture was concentrated and the resulting residue was stirred firstly with cyclohexane and then with dichloromethane. 7.8 g of the title 10 compound were obtained as hydrobromide. ESI-MS [M+H]*= 201. The title compound was prepared in a manner analogous to the above examples, resulting in 25 mg of N-[3-amino-2,3-dioxo-1 -(2-thienylmethyl)propyl]-2-(3-phenyl-1 H 15 pyrazol-1-yl)pyridine-3-carboxamide as a white solid. ESI-MS [M+H]+= 446.05. 1 H-NMR (500 MHz DMSO) 8 ppm: 9.01 (d, 1 H), 8.59 (m, 1 H), 8.50 (m, 1 H), 8.05 (s, 1 H), 7.84-7.78 (m, 4H), 7.50 (m, 1 H), 7.41 (m, 2H), 7.36-7.31 (m, 2H), 7.02 (m, 1 H), 6.84 (m, 2H), 5.52 (m, 1 H), 3.38 and 3.12 (each dd, 1 H). 20 Example 41: N-{1-[Amino(oxo)acetyl]pentyl)-2-[3-(4-fluorophenyl)-1 H-pyrazol-1-yl]nicotinamide The title compound was prepared in a manner analogous to the above examples. ESI-MS [M+H]*= 424.05. 25 1 H-NMR (500 MHz DMSO) 8 ppm: 8.71 (d, 1H), 8.57 (d, 1H), 8.51 (m, 1H), 8.03 (s, 1H), 7.89 (m, 2H), 7.80 (s, 1H), 7.51 (m, 1H), 7.28 (m, 1H), 7.04 (s, 1H), 5.17 (m, 1H), 1.70 (m, 1H), 1.44 (m, 1H), 1.13 (m, 4H), 0.70 (m, 3H). Example 42: 30 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[4-(diethylamino)phenyl]-1 H-pyrazol-1 yl}nicotinamide The title compound was prepared in a manner analogous to the above examples.ESI MS [M+H]'= 511.3. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.52 (d, 1H), 8.41 (d, 1H), 8.07 (s, 1H), 35 7.82 (s, 1H), 7.71 (d, 1H), 7.56 (m, 2H), 7.42 (dd, 1H), 7.21 (m, 5H), 6.82 (d, 1H), 6.66 and 6.63 (each s, 1H), 5.57 (m, 1H), 3.39 (m, 4H), 3.17 and 2.84 (each dd, 1H), 1.15 (m, 6H). Example 43: 40 N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-(3-{4-[(diethylamino)methyl]pheny)-1 H pyrazol-1-yl)nicotinamide hydrochloride 90 43.1 1-{4-[(Diethylamino)methyl]phenyl}ethanone 5.3 g of diethylamine were added to 10 g of 4-[chloromethyl]benzonitrile (65.96 mmol), 18.24 g of K 2

CO

3 and 1.1 g of KI in 150 ml of N,N-dimethylformamide at room temperature, and the mixture was stirred at room temperature until the reaction was 5 complete. The mixture was then poured into ice-water and extracted with diethyl ether, and the organic phase was washed with saturated NaCl solution, dried and evaporated, resulting in 12.1 g of 4-[diethylaminomethyl]benzonitrile as an oil. ESI-MS [M+H]+= 189.05. 10 A solution of 12.1 g of 4-[diethylaminomethyl]benzonitrile in 40 ml of toluene was added to a solution of methylmagnesium bromide (43 ml of a 3 M solution in diethyl ether) in 40 ml of toluene, and the mixture was heated to reflux. Completion of the reaction was followed by pouring into ice-water, extracting with methyl tert-butyl ether, adjusting the aqueous phase to pH 11-12 by adding NaOH, and renewed extracting with methyl tert 15 butyl ether. The organic phase was dried and the solvent was evaporated. 12.1 g of the title compound were obtained. ESI-MS [M+H]*= 206.15. It was possible in a manner analogous to the above examples to prepare N-(3-amino 20 1-benzyl-2,3-d ioxopropyl)-2-(3-{4-[(diethyla mino)methyl]phenyl}-1 H-pyrazol-1 yl)nicotinamide hydrochloride. ESI-MS [M+H]*= 525.35. 1 H-NMR (500 MHz DMSO) 8 ppm: 10.02 (s broad, 1H), 8.95 (d, 1H), 8.51 (d, 1H), 8.05 (s, 1H), 7.86-7.81 (m, 3H), 7.76 (m, 1H), 7.61 (m, 2H), 7.52 (m, 1H), 7.19-7.12 (m, 5H), 25 7.07 8m, 1H), 5.53 (m, 1H), 4.35 (d, 2H), 3.10 (m, 5H), 2.80 (dd, 1H), 1.29 (m, 6H). It was possible to prepare the compounds of Examples 44 to 105 in a manner analogous to the above examples. 30 Example 44: N-{1 -[Amino(oxo)acetyl]pentyl}-2-(3-{4-[(diethylamino)methyl]phenyl)-1 H-pyrazol-1 yl)nicotinamide ESI-MS [M+H]*= 491.35. 35 Example 45: N-{1-[Amino(oxo)acetyl]pentyl}-2-{3-[4-(morpholin-4-ylmethyl)phenyl]-1 H-pyrazol-1 yl}nicotinamide ESI-MS [M+H]*= 505.15. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.72 (d, 1 H), 8.58 (d, 1 H), 8.51 (m, 1 H), 8.02 (s, 40 1H), 7.88 (d, 1H), 7.82-7.78 (m, 3H), 7.50 (dd, 1H), 7.38-7.36 (m, 2H), 7.02 (m, 1H), 5.16 (m, 1H), 3.61 (m, 4H), 3.52 (m, 2H), 2.40 (m, 4H), 1.71 and 1.43 (each m, 1H), 1.26-1.11 (m, 4H), 0.69 (m, 1H).

91 Example 46: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[4-(morpholin-4-ylmethyl)phenyl]-1 H pyrazol-1 -yl}nicotinamide 5 ESI-MS [M+H]'= 539.35 1 H-NMR (500 MHz DMSO) S ppm: 8.92 (d, 1 H), 8.56 (dd, 1 H), 8.47 (d, 1 H), 8.05 (s, 1H), 7.83 (s, 1H), 7.73 (m, 3H), 7.47 (dd, 1H), 7.33 (s, 1H), 7.31 (s, 1H), 7.17 (m, 5H), 6.98 (d, 1H), 5.56 (m, 1H), 3.61 (m, 4H), 3.51 (s, 2H), 3.12 (m, 1H), 2.82 (m, 1H), 2.39 (m, 4H). 10 Example 47: N-{1-[Amino(oxo)acetyl]pentyl}-2-{3-[4-(diethylamino)phenyl]-1 H-pyrazol-1 yl}nicotinamide ESI-MS [M+H]'= 477.15 15 1 H-NMR (500 MHz DMSO) 6 ppm: 8.71 (d, 1 H), 8.54 (d, 1 H), 8.44 (m, 1 H), 8.03 (s, 1H), 7.84 (d, 1H), 7.78 (s, 1H), 7.63 (m, 1H), 7.44 (m, 1H), 6.84 (s, 1H), 6.69 (m, 2H), 5.18 (m, 1H), 3.40 (m, 4H), 1.74 and 1.50 (each m, 1H), 1.30-1.12 (m, 10H), 0.75 (m, 3H). 20 Example 48: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-methoxyphenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]+= 470.45. 1 H-NMR (500 MHz DMSO) S ppm: 8.92 (d, 1H), 8.54 (dd, 1H), 8.44 (d, 1H), 8.08 (s, 25 1H), 7.86 (s, 1H), 7.72-7.68 (m, 3H), 7.45 (dd, 1H), 7.21 (m, 5H), 6.96 (s, 1H), 6.93 (m, 2H), 5.59 (m, 1H), 3.82 (s, 3H), 3.16 and 2.81 (each dd, 1H). Example 49: N-{1-[Amino(oxo)acetyl]pentyl}-2-[3-(4-methoxyphenyl)-1 H-pyrazol-1-yl]nicotinamide 30 ESI-MS [M+H]*= 436.45. 1 H-NMR (500 MHz DMSO) S ppm: 8.72 (d, 1H), 8.56 (d, 1H), 8.47 (d, 1H), 8.03 (s, 1H), 7.87 (dd, 1H), 7.79-7.70 (m, 3H), 7.49 (m, 1H), 7.01 (s, 1H), 6.99 (s, 1H), 6.96 (dd, 1H), 5.18 (m, 1H), 3.83 (s, 3H), 1.73 and 1.47 (each m, 1H), 1.17 (m, 4H), 0.72 (m, 3H). 35 Example 50: N-[3-Amino-1 -(4-chlorobenzyl)-2,3-dioxopropyl]-2-(3-phenyl-1 H-pyrazol-1 yl)nicotinamide ESI-MS [M+H]+= 474.13. 'H-NMR (500 MHz DMSO) 6 ppm: 8.57 (dd, 1 H), 8.48 (d, 1 H), 8.07 (s, 1 H), 7.86 (s, 40 1H), 7.78 (dd, 1H), 7.74 (m, 2H), 7.49 (dd, 1H), 7.41-7.30 (m, 3H), 7.18 (m, 4H), 7.0 (m, 1H), 5.50 (m, 1H), 3.12 and 2.77 (each m, 1H).

92 3-Amino-4-(4-chlorophenyl)-2-hydroxybutanamide was prepared in a manner analogous to the preparation of 3-amino-2-hydroxy-4-(2-thienyl)butanamide in Example 40. 5 Example 51: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-5-fluoro-2-(3-phenyl-1 H-pyrazol-1 yl)nicotinamide ESI-MS [M+H]+= 458.6. 1 H-NMR (500 MHz DMSO) S ppm: 9.01 (d, 1H), 8.62 (d, 1H), 8.42 (d, 1H), 8.08 (s, 1H), 10 7.87 (s, 1H), 7.77 (s, 1H), 7.75 (s, 1H), 7.58 (dd, 1H), 7.42-7.32 (m, 3H), 7.23-7.17 (m, 5H), 7.02 (d, 1H), 5.58 (m, 1H), 3.17 and 2.83 (each dd, 1H). Example 52: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[3-(morpholin-4-ylmethyl)phenyl]-1 H 15 pyrazol-1-yl}nicotinamide hydrochloride ESI-MS [M+H]+= 539.35. 1 H-NMR (500 MHz DMSO) S ppm: 10.89 (s, broad, 1H), 8.96 (d, 1H), 8.58 (m, 1H), 8.49 (d, 1H), 8.08 (s, 2H), 7.84 (m, 2H), 7.76 (dd, IH), 7.58 (m, 1H), 7.52-7.48 (m, 2H), 7.15 (5H), 7.03 (d, 1H), 5.52 (m, 1H), 4.38 (s broad, 2H), 3.95 and 3.77 (each m, 2H), 20 3.26 (dd, 1H), 3.10 (m, 4H), 2.80 (dd, 1H). Example 53: N-{1 -[Amino(oxo)acetyl]pentyl}-2-{3-[3-(morpholin-4-ylmethyl)phenyl]-1 H-pyrazol-1 yl}nicotinamide hydrochloride 25 ESI-MS [M+H]+= 505.35. 1 H-NMR (500 MHz DMSO) S ppm: 11.03 (s broad, 1H), 8.72 (d, 1H), 8.60 (dd, 1H), 8.54 (d, 1H), 8.13 (s, 1H), 8.05 (s, 1H), 7.95-7.89 (m, 2H), 7.81 (m, 1 H), 7.62 (m, 1H), 7.54 (m, 2H), 7.06 (d, 1H), 5.16 (m, 1H), 4.43 (s, 2H), 3.96 and 3.81 (each m, 2H), 3.3 (m, overlapped by H 2 0), 3.15 (m, 2H), 1.67 and 1.43 (each m, 1H), 1.14 (m, 4H), 0.68 30 (m, 3H). Example 54: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(2-chlorophenyl)-1 H-pyrazol-1 yl]nicotinamide 35 ESI-MS [M+H]+= 474.06. 1 H-NMR (400 MHz DMSO) S ppm: 8.94 (d, 1H), 8.57 (d, 1H), 8.50 (d, IH), 7.98 (s, 1H), 7.80 (s, 1H), 7.70 (dd, 2H), 7.47-7.54 (m, 2H), 7.30-7.37 (m, 2H), 7.13 (s, 5H), 7.02 (s, 1H), 5.48-5.53 (m, 1H), 3.11 (dd, 1H), 2.77 (dd, 1H). 40 Example 55: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-[3-(2-thienyl)-1 H-pyrazol-1 -yl]nicotinamide ESI-MS [M+H]+= 446.0.

93 1 H-NMR (400 MHz DMSO) 6 ppm: 8.94 (d, 0.5H), 8.58 (s, 1 H), 8.43 (s, 1 H), 8.04 (s, 0.5H), 7.75-7.86 (m, 2H), 7.46-7.52 (m, 3H), 7.22-7.264 (m, 5H), 7.12 (s, 1H), 6.89 (s, 0.5H), 6.70 (s, 0.5H), 6.39 (s, 0.5H), 6.11 (s, 0.5H) 5.50-5.56 (m, 0.5H), 4.46-4.52 (m, 0.5H), 3.18 (dd, 0.5H), 3.06 (dd, 0.5H), 2.85-2.92 (m, 0.5H), 2.71-2.77 (m, 0.5H). 5 The compound is in the form of a mixture of carbonyl and hydrate forms. Example 56: N-{1 -[Amino(oxo)acetyl]pentyl}-2-(3-pyridin-4-y-1 H-pyrazol-1 -yl)nicotinamide ESI-MS [M+H]+ = 407.15. 10 1 H-NMR (500 MHz DMSO) 8 ppm: 8.75 (d, 1H), 8.65-8.58 (m, 3H), 8.03 (s, 1H), 7.93 (m, 1H), 7.80 (m, 3H), 7.56 (dd, 1H), 7.22 (d, 1H), 5.17 (m, 1H), 1.71 and 1.43 (each m, IH), 1.12 (m, 4H), 0.69 (m, 3H). Example 57: 15 N-[3-Amino-2,3-dioxo-1 -(2-thienylmethyl)propyl]-2-[3-(4-fluorophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]+= 464.45. 1 H-NMR (500 MHz DMSO) 5 ppm: 8.75 (d, 1H), 8.65-8.58 (m, 3H), 8.03 (s, 1H), 7.93 (m, 1H), 7.80 (m, 3H), 7.56 (dd, 1H), 7.22 (d, 1H), 5.17 (m, 1H), 1.71 and 1.43 (each m, 20 1H), 1.12 (m, 4H), 0.69 (m, 3H). Example 58: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(3-morpholin-4-ylphenyl)-1 H-pyrazol-1 yl]nicotinamide 25 ESI-MS [M+H]+= 525.25. 1 H-NMR (500 MHz DMSO) 6 ppm: 8.90 (d, 1H), 8.56 (dd, 1H), 8.47 (d, 1H), 8.02 (s, 1H), 7.81 (s, 1H), 7.75 (dd, 1H), 7.48 (m, 2H), 7.29 (m, 2H), 7.12 (m, 5H), 7.03 (d, 1H), 6.99 (m, 1H), 5.50 (m, 1H), 3.80 (m, 4H), 3.21 (m, 4H), 3.13 and 2.80 (each dd, 1H). 30 Example 59: N-{1 -[Amino(oxo)acetyl]pentyl}-2-[3-(3-morpholin-4-ylphenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]+= 491.25. 1 H-NMR (500 MHz DMSO) 6 ppm: 8.68 (d, 1H), 5.57 (d, 1H), 8.51 (m, 1H), 8.00 (s, 35 1H), 7.86 (m, 1H), 7.78 (d, 1H), 7.50 (m, 1H), 7.44 (s, 1H), 7.31 (m, 2H), 7.04 (m, 1H), 6.95 (d, 1H), 5.14 (m, 1H), 3.81 (m, 4H), 3.20 (m, 4H), 1.67 (m, 1H), 1.45 (m, 1H), 1.14 (m, 4H), 0.67 (m, 3H). Example 60: 40 N-(3-Aiino-1-benzyl-2,3-dioxopropyl)-2-{3-[4-(trifluoromethyl)phenyl]-1 H-pyrazol-1 yl}nicotinamide ESI-MS [M+H]+= 508.0.

94 1 H-NMR (400 MHz DMSO) 6 ppm: 8.95 (d, 1H), 8.57 (d, 1H), 8.51 (d,1H), 8.10 (s, 1H), 7.94 (d, 2H), 7.86 (s, 1H), 7.74 (d, 1H), 7.71 (d, 2H), 7.50 (dd, 1H), 7.14-7.16 (m, 4H), 7.11-7.13 (m, 2H), 5.51-5.56 (m, 1H), 3.11 (dd, 1H), 2.75 (dd, 1H). 5 Example 61: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(5-methyl-3-phenyl-1 H-pyrazol-1 yl)nicotinamide ESI-MS [M+H]*= 454.1 1 H-NMR (400 MHz DMSO) 8 ppm: 8.83 (d, 1H), 8.58 (d, 1H), 7.96 (s, 1H), 7.85 (d, 1H), 10 7.74 (s, 1H), 7.66 (d, 2H), 7.50-7.54 (m, 1H), 7.34 (dd, 2H), 7.27 (dd, 1H), 7.10-7.17 (m, 3H), 7.06 (d, 2H), 6.64 (s, 1H), 5.26-5.31 (m, 1H), 3.02 (dd, 1H), 2.67 (dd, 1H), 2.49 (s, 3H). Example 62: 15 N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-[3-(4-cyanophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]*= 465.1. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.96 (d, 1H), 8.57 (s, 1H), 8.51 (s,1H), 8.09 (s, 1H), 7.82-7.92 (m, 5H), 7.72 (d, 1H), 7.50 (dd, 1H), 7.17 (s, 5H), 7.14 (s, 1H), 5.51-5.56 (m, 20 1H), 3.12 (dd, 1H), 2.74 (dd, 1H) Example 63: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(4,5-dihydro-2H-benzo[g]indazol-2 yl)nicotinamide 25 ESI-MS [M+H]+= 466.09 1 H-NMR (400 MHz DMSO) 6 ppm: 8.94 (d, 1H), 8.51(d, 1H), 8.23 (s,1H), 8.05 (s,1H), 7.83 (s, 1H), 7.70 (d, 1H), 7.48 (d, 1H), 7.41 (dd, 1H), 7.28 (dd, 1H), 7.13-7.24 (m, 7H), 5.50-5.55 (m, 1H), 3.16 (dd, 1H), 2,90(t, 2H), 2.80 (dd, 1H), 2.73-2.79 (m, 2H). 30 Example 64: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-piperidin-1-ylphenyl)-1H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]*= 523.18. 'H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.53 (d, 1H), 8.42 (s, 1H), 8.08 (s, 1H), 35 7.85 (s, 1H), 7.70 (d, 1H), 7.60 (m, 2H), 7.43 (m, 1H), 7.20 (m, 5H), 6.91 (m, 3H), 5.58 (m, 1H), 3.23 (m, 4H), 3.15 (m overlapped, 1H), 1.66-1.60 (m, 6H). Example 65: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(3-pyridin-4-yl-1 H-pyrazol-1-yl)nicotinamide 40 ESI-MS [M+H]'= 441.16. 1 H-NMR (500 MHz DMSO) 6 ppm: 8.98 (m, 1 H), 8.62-8.53 (m, 4H), 8.09 (s, 1 H), 7.87 (m, 1H), 7.75 (m, 1H), 7.67 (m, 2H), 7.54 (m, 1H), 7.18 (m, 6H), 5.56 (m, 1H), 3.15 and 95 2.78 (each m, 1H). Example 66: N-[3-Amino-1-(cyclohexylmethyl)-2,3-dioxopropyl]-2-(3-phenyl-1 H-pyrazol-1 5 yl)nicotinamide ESI-MS [M+H]*= 446.15. 1H-NMR (500 MHz DMSO) 8 ppm: 8.77 (d, 1 H), 8.59 (m, 1 H), 8.51 (d, 1 H), 7.96 (s, 1H), 7.87 (m, 3H), 7.76 (s, 1H), 7.51 (dd, 1H), 7.43 (m, 2H), 7.37 (m, 1H), 7.05 (m, 1H), 5.22 (m, 1H), 1.65 (m, 1H), 1.54-1.24 (m, 7H), 1.01 (m, 2H), 0.89-0.68 (m, 3H). 10 Example 67: N-[3-Amino-1 -(4-chlorobenzyl)-2,3-dioxopropyl]-2-[3-(4-fluorophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]*= 492.09. 15 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1 H), 8.57 (d, 1 H), 8.48 (s, 1 H), 8.09 (s, 1 H), 7.88 (s, 1H), 7.74 (m, 3H), 7.50 (m, 1H), 7.19 (m, 6H), 6.98 (m, 1H), 5.48 (m, 1H), 3.12 (m, 1 H), 2.75 (m, 1 H). Example 68: 20 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1 H pyrazol-1 -yl}nicotinamide ESI-MS [M+H]*= 538.24. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1 H), 8.54 (m, 1 H), 8.42 (m, I H), 8.08 (s, 1H), 7.86 (s, 1H), 7.69 (dd, 1H), 7.61 (m, 2H), 7.44 (m, 1H), 7.20 (m, 5H), 6.92 (m, 3H), 25 5.58 (m, 1 H), 3.20 (m, 5H), 2.81 (m, 1 H), 2.49 (m overlapped by DMSO), 2.26 (s, 3H). Example 69: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(4-pyrrolidin-1-ylphenyl)-1 H-pyrazol-1 yl]nicotinamide 30 ESI-MS [M+H]*= 509.25. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1 H), 8.51 (m, 1 H), 8.40 (d, 1 H), 8.07 (s, 1H), 7.84 8s, 1H), 7.69 (m, 1H), 7.58 (m, 2H), 7.41 (m, 1H), 7.22 (m, 5H), 6.83 (m, 1H), 6.54 (m, 2H), 5.59 (m, 1H), 3.29 (m overlapped by H 2 0), 3.10 and 2.83 (each dd, 1H), 2.01 (m, 4H). 35 Example 70: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(3-chlorophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]*= 474.05. 40 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.58 (d, 1H), 8.50 (d, 1H), 8.01 (s, 1H), 7.84 (s, 1H), 7.81 (s, 1H), 7.73 (m, 2H), 7.49 (dd, 1H), 7.41 (m, 2H), 7.16 (m, 5H), 7.09 (m, 1H), 5.51 (m, 1H), 3.15 and 2.80 (each dd, 1H).

96 Example 71: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(2-chloro-4-fluorophenyl)-1 H-pyrazol-1 yl]nicotinamide 5 ESI-MS [M+H]+= 492.05 1 H-NMR (500 MHz DMSO) S ppm: 8.93 (d, 1H), 8.58 (d, IH), 8.52 (d, 1H), 8.06 (s, IH), 7.84 (s, 1H), 7.74 (d, 1H), 7.67 (dd, 1H), 7.51 (m, 2H), 7.19 (dd, 1H), 7.15 (m, 5H), 7.01 (d, 1H), 5.51 (m, 1H), 3.12 (dd, 1H), 2.78 (dd, 1H). 10 Example 72: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[2-(trifluoromethyl)phenyl]-1 H-pyrazol-1 yl}nicotinamide ESI-MS [M+H]+= 508.06. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.94 (d, 1H), 8.57 (d, 1H), 8.50 (d,1H), 7.98 (s, 1H), 15 7.75-7.83 (m, 3H), 7.46-7.74 (m, 4H), 7.09 (s, 5H), 6.67 (s, 1H), 5.40-5.45 (m, 1H), 3.08 (dd, 1H), 2.74-2.80 (dd, 1H). Example 73: N-[1-Benzyl-3-(ethylamino)-2,3-dioxopropyl]-2-(3-phenyl-1 H-pyrazol-1-yl)nicotinamide 20 ESI-MS [M+H]+= 468.10 1 H-NMR (400 MHz DMSO) 5 ppm: 8.92 (d, 1H), 8.70 (t, 1H), 8.54 (dd,1H), 8.47 (d, 1H), 7.75 (d, 2H), 7.71 (d, 1H), 7.76 (dd, 1H), 7.31-7.39 (m, 3H), 7.13-7.21 (m, 5H), 6.99(d, 1H), 5.56-5.61 (m, 1H), 3.10-3.20 (m, 3H), 2.76-2.81 (dd, 1H), 1.05 (t, 3H). 25 Example 74: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-[3-(3-pyrrolidin-1 -ylphenyl)-1 H-pyrazol- 1 yl]nicotinamide ESI-MS [M+H]*= 509.15. 30 Example 75: N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-[3-(2,3-dihydrobenzo[b]furan-5-yl)-1 H-pyrazol 1-yl]nicotinamide ESI-MS [M+H]'= 482.1. 1 H-NMR (400 MHz DMSO) 6 ppm: 8.87 (d, 1H), 8.52 (d, 1H), 8.44 (d,1H), 8.01 (s, 1H), 35 7.81 (s, 1H), 7.65 (s, 1H), 7.51 (d, 1H), 7.41 (dd, 1H), 7.15-7.21 (m, 6H), 6.88 (d, 1H), 6.75 (d, 1H), 5.56-5.62 (m, 1H), 4.55 (t, 2H), 3.11-3.20 (m, 3H), 2.81 (dd, 1H). Example 76: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(2-fluorophenyl)-1 H-pyrazol-1 40 yl]nicotinamide ESI-MS [M+H]*= 458.07. 1 H-NMR (400 MHz DMSO) 6 ppm: 8.91 (d, 1H), 8.57 (d,1H), 8.50 (d, 1H), 8.04 (s, 97 1H), 7.82 (s, 1H), 7.78 (d, 1H), 7.74 (d,1H), 7.49 (dd, 1H), 7.39 (dd, 1H), 7.39 (dd, 1H), 7.19 (dd, 1H), 7.15 (s, 5H ), 6.85 (dd, 1H), 5.50-5.56 (m, 1H), 3.12 (dd, 1H), 2.76 (dd, 1 H) 5 Example 77: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(1 H-indazol-1-yl)nicotinamide 77.1 Ethyl 2-(1H-indazol-1-yl)pyridine-3-carboxylate and ethyl 2-(2H-indazol-2 yl)pyridine-3-carboxylate 10 Reaction of 4.7 g of ethyl 2-chloronicotinate (25.39 mmol) with 2.5 g of indazole (21.16 mmol) afforded a mixture of the isomers which were separated by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 5-40%). Fraction 1: ethyl 2-(1 H-indazol-1-yl)pyridine-3-carboxylate about 80%, contaminated 15 with fraction 2. 'H-NMR (500 MHz DMSO) 8 ppm: 8.74 (d, 1 H), 8.41 (s, 1 H), 8.36 (d, 1 H), 8.23 (d, 1 H), 8.18 (d, 1H), 7.61 (m, 2H), 7.36 (m, 1H), 4.23 (q, 2H), 1.12 (t, 3H). Fraction 2: ethyl 2-(2 H-indazol-2-yl) pyridine-3-ca rboxylate 20 1 H-NMR (500 MHz DMSO) S ppm: 9.11 (s, 1 H), 8.75 (d, 1 h9, 8.24 (d, 1 H), 7.83 (d, 1 H), 7.67 (m, 2H), 7.36 (m, 1h), 7.15 (m, 1H), 4.26 (q, 2H), 1.05 (t, 3H). N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-(1 H-indazol-1 -yl)nicotinamide: ESI-MS [M+H]'= 414.05. 25 1 H-NMR (500 MHz DMSO) 8 ppm: 8.93 (d, 1H), 8.64 (dd, 1H), 8.30 (dd, 1H), 8.13 (s, 1H), 8.05 (s, 1H), 7.86 (m, 1H), 7.80 (m, 2H), 7.53 (m, 1H), 7.48 (m, 1H), 7.34 (m, 1H), 7.26 (m, 5H), 5.36 (m, 1H), 3.15 and 2.19 (each dd, 1H). Example 78: 30 N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-(2H-indazol-2-yl)nicotinamide ESI-MS [M + H+]= 414.05. 1 H-NMR (500 MHz DMSO) S ppm: 9.07 (d, 1H), 8.98 (s, 1H), 8.67 (m, 1H), 8.05 (s, 1H), 7.86-7.79 (m, 3H), 7.62 (m, 1H), 7.52 (d, 1H), 7.32-7.19 (m, 6H), 7.12 (m, 1H), 5.41 (m 1H), 3.18 and 2.92 (each dd, 1H). 35 Example 79: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-[3-(2,4-dichlorophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]'= 508.03 40 1 H-NMR (400 MHz DMSO) 8 ppm: 8.93 (d, 1H), 8.57 (d, 1H), 8.51 (d, 1H), 8.06 (s, 1H), 7.84 (s, 1H), 7.74 (d, 1H), 7.68 (s, 1H), 7.65 (d, 1H), 7.49 (dd, 1H), 7.36 (d, IH), 7.13 (s, 5H), 7.03 (s, 1H), 5.46-5.51 (m, 1H), 3.09 (dd, 1H), 2.75 (dd, 1H).

98 Example 80: N-[3-Amino-1 -(4-methoxybenzyl)-2,3-dioxopropyl]-2-(3-phenyl-1 H-pyrazol-1 yl)nicotinamide 5 ESI-MS [M+H]*= 470.25. 1 H-NMR (500 MHz DMSO) S ppm: 8.89 (m, 1H), 8.50 (m, 2H), 8.49 (s, 1H), 8.04 (s, 1H), 7.80-7.58 (m, 4H), 7.49 (m, 1H), 7.40-7.37 (m, 3H), 7.09 (m, 2H), 7.01 (m, 1H), 6.75 (m, 1 H), 5.52 (m, 1 H), 3.69 (s, 3H), 3.06 and 2.76 (each dd, 1 H). 10 Example 81: N-[3-Amino-1-(4-methoxybenzyl)-2,3-dioxopropyl]-2-[3-(4-fluorophenyl)-1 H-pyrazol-1 yl]nicotinamide ESI-MS [M+H]*= 488.25. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.89 (dd, 1 H), 8.56 (dd, 1 H), 8.47 (s, 1 H), 8.07 (s, 15 1H), 7.86 (s, 1H), 7.76 (m, 3H), 7.48 (dd, 1H), 7.21 (m, 2H), 7.10 (m, 2H), 7.0 (m, IH), 6.75 (m, 2H), 5.51 (m, 1H), 3.70 (s, 3H), 3.07 and 2.73 (each dd, 1H). Example 82: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-5-cyano-2-(3-phenyl-1 H-pyrazol-1 20 yl)nicotinamide ESI-MS [M+H]*= 465.3. 1 H-NMR (500 MHz DMSO) S ppm: 9.03 (s, 1 H), 8.99 (d, 1 H), 8.63 (s, 1 H), 8.09 (s, 1 H), 8.05 (s, 1H), 7.89 (s, 1H), 7.87 (m, 2H), 7.34 (m, 3H), 7.18 (m, 5H), 6.91 (m, 1H), 5.67 (m, 1 H), 3.20 (dd, 1 H), 2.86 (dd, 1 H). 25 Example 83: N-(3-Amino-1-benzyl-2,3-dioxopropyl)-2-{3-[3-(trifluoromethyl)phenyl]-1 H-pyrazol-1 yl}nicotinamide ESI-MS [M+H]*= 508.05. 30 1H-NMR (400 MHz DMSO) S ppm: 8.91 (d, 1 H), 8.57 (d, 1 H), 8.51 (d, 1 H), 8.49 (s, 1 H), 8.03 (s, 1H), 8.00 (d, 1H), 7.80 (s, 1H), 7.76 (d, 1H), 7.68 (d, 1H), 7.61 (dd, 1H), 7.50 (dd, 1H), 7.16 (dd, 1H), 7.09 (s, 5H), 5.42-5.47 (m, 1H), 3.11 (dd, 1H), 2.75 (dd, 1H). Example 84: 35 N-(3-Amino-1 -benzyl-2,3-dioxopropyl)-2-(4-methyl-3-phenyl-1 H-pyrazol-1 yl)nicotinamide ESI-MS [M+H]*= 454.08. 1H-NMR (400 MHz DMSO) S ppm: 8.88 (d, 1 H), 8.52 (d, 1 H), 8.32 (s, 1 H), 8.01 (s, 1 H), 7.80 (s, 1H), 7.69 (d, 1H), 7.64 (d, 2H), 7.33-7.43 (m, 4H), 7.15 (s, 5H), 5.50-5.55 (m, 40 1H), 3.12 (dd, 1H), 2.79 (dd, 1H), 2.29 (s, 3H). Example 85: 99 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,6-difluorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]'= 476.05. 1 H-NMR (400 MHz DMSO) 5 ppm: 8.81 (d, 1H), 8.58 (d, 1H), 8.49 (d, 1H), 7.91 (s, 1H), 5 7.78 (d, 1H), 7.73 (s, 1H), 7.51 (dd, 1H), 7.41-7.47 (m, 1H), 7.15 (d, 2H), 7.11 (s, 5H), 6.77 (s, 1H), 5.36-5.41 (m, 1H), 3.09 (dd, 1H), 2.78 (dd, 1H). Example 86: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(4-methyl-3-phenyl-1 H-pyrazol-1 10 yl)pyridine-3-carboxamide ESI-MS [M+H]'= 454.07. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.58 (s,1H), 8.52 (d, 1H), 8.02 (s, 1H), 7.79 (s, 1H), 7.70 (d, 1H), 7.54 (d, 2H ), 7.40-7.45 (m, 3H), 7.23-7.32 (m, 5H), 7.19 (dd, 1H), 5.39-5.44 (m, 1H), 3.17 (dd, 1H), 2.90 (dd, 1H), 2.23 (s, 3H). 15 Example 87: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[4-(1 -methylethyl)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 482.09 20 1 H-NMR (500 MHz DMSO) 6 ppm: 8.92 (m, 1H), 8.56 (m, IH), 8.46 (m, 1H), 8.05 (s, 1H), 7.83 (s, 1H), 7.73 (m, 1H), 7.68 (m, 2H), 7.46 (m, 1H), 7.25 (m, 2H), 7.18 (m, 5H), 6.95 (m, 1H), 5.56 (m, 1H), 3.15 (dd, 1H), 2.94 (m, 1H), 2.82 (dd, 1H), 1.26 (d, 6H). Example 88: 25 N-[3-Amino-2,3-dioxo-1 -(pyridin-3-ylmethyl)propyl]-2-(3-phenyl-1 H-pyrazol-1 yl)pyridine-3-carboxamide hydrochloride ESI-MS [M+H]+= 441.15. 1 H-NMR (500 MHz DMSO) 6 ppm: 9.16 (d, 1H), 8.69 (s, IH), 8.58 (m, 2H), 8.46 (d, 1H), 8.31 (d, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.85 (dd, 1H), 7.69 (dd, 1 H), 7.62 (m, 2H), 30 7.49 (dd, 1 H), 7.35 (m, 3H), 6.98 (d, 1 H), 5.39 (m, 1 H), 3.36 and 3.03 (each dd, 1 H). Example 89: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(3,5-dichlorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide 35 ESI-MS [M + H+]= 581.09. 1 H-NMR (500 MHz DMSO) 6 ppm: 8.90 (d, 1 H), 8.59 (m, 1 H), 8.51 (m, 1 H), 7.94 (s, 1H), 7.76 (m, 4H), 7.55 (s, 1H), 7.52 (m, 1H), 7.17-7.05 (m, 6H), 7.49 (m, 1H), 3.15 and 2.79 (each dd, 1H). 40 Example 90: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[2-(methyloxy)phenyl]-1 H-pyrazol 1 -yl}pyridine-3-carboxamide 100 ESI-MS [M+H]+= 470.13. 1 H-NMR (400 MHz DMSO) 3 ppm: 8.90 (d, 1H), 8.54 (d,1H), 8.44 (s, 1H), 8.02 (s, 1H), 7.80 (s, 1H), 7.73 (dd, 2H), 7.44 (t, 1H), 7.32 (t, 1H), 7.15 (m, 5H ), 7.10 (d, 1H), 6.96 (d, 1H), 6.92 (t, IH), 5.52-5.57 (m, 1H), 3.89 (s, 3H), 3.12 (dd, 1H), 2.79 (dd, 1H). 5 Example 91: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(3,5-difluoropheny)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 476.16. 10 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.58 (m, 1H), 8.51 (d, 1H), 7.95 (s, 1H), 7.80 (s, 1H), 7.76 (dd, 1H), 7.51 (dd, 1H), 7.45 (m, 2H), 7.14 (m, 7H), 5.47 (m, 1H), 3.14 and 2.77 (each dd, 1H). Example 92: 15 N-(3-Amino-1-{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropy)-2-[3-(2-fluorophenyl)-1 H pyrazol-1-yl]pyridine-3-carboxamide ESI-MS [M+H]+= 488.15. 1 H-NMR (500 MHz DMSO) 8 ppm: 3.86 (d, 1H), 3.58 (m, 1H), 8.51 (m, 1H), 8.02 (s, 1 H), 7.78 (m, 3H), 7.51 (m 1 H), 7.41 (m, 1 H), 7.29 (m, 1 H), 7.20 (m, 1 H), 7.05 (m, 2H), 20 6.86 (s, 1H), 6.71 (m, 2H), 5.47 (m, 1H), 3.68 (s, 3H), 3.04 and 2.72 (each dd, 1H). Example 93: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2-methylphenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide 25 ESI-MS [M+H]+= 454.10. 1 H-NMR (400 MHz DMSO) 3 ppm: 8.87 (d, 1H), 8.56 (d,1H), 8.49 (d, 1H), 7.97 (s, 1H), 7.77 (m, 2H), 7.54 (d,1H), 7.47 (t, 1H), 7.22 (m, 3H), 7.11 (m, 5H ), 6.81 (m, 1H), 5.48-5.42 (m, 1H), 3.09 (dd, 1H), 2.77 (dd, 1H), 2.36 (s, 3H). 30 Example 94: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-[3-(2,4-difluorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]*= 476.05. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.89 (d, 1H), 8.56 (d, 1H), 8.49 (d,1H), 8.06 (s, 1H), 35 7.84 (s, 1H), 7.76 (dd, 1H), 7.73 (dd, 1H), 7.49 (dd, 1H), 7.33 (dd, 1H), 7.15 (s, 5H), 7.06(dd, 1H), 6.81 (dd, 1H), 5.48-5.53 (m, 1H), 3.11 (dd, 1H), 2.73 (dd, 1H). Example 95: N-[3-Amino-2,3-dioxo-1 -(phenyl methyl)propyl]-2-[3-(2,6-dichlorophenyl)-1 H-pyrazol-1 40 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 508.05. 1 H-NMR (400 MHz DMSO) 3 ppm: 8.92 (d, 1H), 8.57 (d, 1H), 8.51 (d, 1H), 8.50 (s, 1H), 101 7.85 (s, 1H), 7.78 (d, 1H), 7.67 (s, 1H), 7.47-7.53 (m, 3H), 7.40 (dd, 1H), 7.50 (dd, 1H), 7.08 (s, 5H), 6.60 (s, 1H), 5.22-5.27 (m, 1H), 3.09 (dd, 1H), 2.85 (dd, 1H). Example 96: 5 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{3-[(phenylmethyl)oxy]phenyl}-1 H pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]*= 546.17. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.88 (d, 1 H), 8.54-8.56 (m, 1 H), 8.45 (d, 1 H), 7.97 (s, 1H), 7.73-7.78(m, 2H), 7.45-7.50 (m, 4H), 7.27-7.41 (m, 5H), 7.10-7.20 (m, 6H), 10 6.97-7.01 (d, 1H), 5.49-5.54 (m, 1H), 5.15 (s, 2H), 3.12 (dd, 1H), 2.80 (dd, 1H). Example 97: N-(3-Amino-1-{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropyl)-2-[3-(2,4-difluorophenyl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide 15 ESI-MS [M + H]'= 506.15. 1 H-NMR (500 MHz DMSO) 6 ppm: 8.85 (d, 1H), 8.58 (dd, 1H), 8.51 (m, 1H), 8.05 (s, 1H), 7.84 (s, 1H), 7.77 (m, 2H), 7.51 (dd, 1H), 7.33 (m, 1H), 7.06 (m, 3H), 6.83 (m, 1H), 6.72 (s, 1H), 6.70 (s, 1H), 5.46 (m, 1H), 3.69 (s, 3H), 3.04 and 2.70 (each dd, 1H). 20 Example 98: N-(3-Amino-1 -{[4-(methyloxy)phenyl]methyl)-2,3-dioxopropyl)-2-[3-(2,4-dichlorophenyl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 538.05. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.87 (d, IH), 8.60 (m, 1H), 8.53 (d, 1H), 8.04 (s, 25 1 H), 7.83 (s, 1 H), 7.80 (dd, 1 H), 7.69 (m, 1 H), 7.62 (d, 1 H), 7.53 (dd, 1 H), 7.36 (dd, 1H), 7.04 (m, 3H), 6.69 (s, 1H), 6.67 (s, 1H), 5.44 (m, 1H), 3.68 (s, 3H), 3.03 and 2.70 (each dd, 1H). Example 99: 30 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2-chloro-4-morpholin-4-ylphenyl) 1 H-pyrazol-1-yl]pyridine-3-carboxamide ESI-MS [M+H]+= 559.15. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.90 (d, 1H), 8.56 (m, 1H), 8.48 (m, IH), 8.05 (s, 1 H), 7.83 (s, 1 H), 7.72 (m, 1 H), 7.56 (m, 1 H), 7.47 (dd, 1 H), 7.17 (m, 5H), 7.04 (d, 1 H), 35 6.95 (d, 1H), 6.87 (dd, 1H), 5.56 (m, 1H), 3.77 (m, 4H), 3.20 (m, 4H), 3.15 and 2.81 (each dd, 1H). Example 100: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-chromeno[4,3-c]pyrazol-2(4H) 40 ylpyridine-3-carboxamide ESI-MS [M+H]+= 468.1. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.97 (d, 1 H), 8.54 (d, 1 H), 8.27 (s, 1 H), 8.05 (s, 1 H), 102 7.83 (s, 1H), 7.74 (d, 1H), 7.46 (dd, 1H), 7.40 (d, 1H), 7.24 (s, 5H), 7.18 (dd, 1H), 6.97 dd, 2H), 5.43-5.54 (m, 1H), 5.31 (s, 2H), 3.16 (dd, 1H), 2.82 (dd, 1H). Example 101: 5 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[4-(1 H-imidazol-1 -yl)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 506.1. 1 H-NMR (400 MHz DMSO) 8 ppm: 8.94 (d, 1H), 8.55 (d, 1H), 8.48 (d, IH), 8.33 (s, 1H), 8.08 (s, 1H), 7.88 (s, 2H), 7.86 (s, 1H), 7.80 (s, 1H), 7.65-7.71 (m, 3H), 7.47 (dd, 1H), 10 7.13-7.19 (m, 6H), 7.06 (d, 1H), 5.56-5.60 (m, 1H), 3.14 (dd, 1H), 2.77 (dd, 1H). Example 102: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2-fluoro-4-morpholin-4-ylphenyl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide 15 ESI-MS [M+H]+= 543.2. 1 H-NMR (500 MHz DMSO) S ppm: 8.99 (d, 1H), 8.55 (m, 1H), 8.48 (m, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.71 (m, 1H), 7.62 (m, 1H), 7.48 (m, 1H), 7.20 (m, 5H), 6.84-6.75 (m, 3H), 5.59 (m, 1H), 3.77 (m, 4H), 3.22-3.15 (m, 5H), 2.78 (dd, 1H). 20 Example 103: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(5-chloro-2-thienyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 480.5. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.55 (d, 1H), 8.45 (d, 1H), 8.01 (s, 1H), 25 7.80 (m, 1 H), 7.77 (s, 1 H), 7.49 (dd, 1 H), 7.35 (m, 1 H), 7.34 (m, 5H), 7.21 (d, 1 H), 6.91 (d, 1H), 5.51 (m, 1H), 3.17 and 2.86 (each dd, 1H). Example 104: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[4-(2-fluorophenyl)-1 H-pyrazol-1 30 yl]pyridine-3-carboxamide 4-(2-Fluorophenyl)-1 H-pyrazole 11.08 ml of N,N-dimethylformamide was slowly added dropwise to 11.03 ml of POC 3 were at 0-5*C while stirring and, after about 5 minutes a solution of 2 fluorophenylacetic acid (6 g, 38.9 mmol) in 20 ml of N,N-dimethylformamide was added 35 dropwise. The mixture was then heated at 700C for about 17 hours. The mixture was subsequently quenched with ice-water and the mixture was made alkaline by adding NaOH. The resulting solid was filtered off, the solution was extracted with dichloromethane, and the organic phase was dried and concentrated. The oil obtained in this way was directly dissolved in 50 ml of ethanol. 7.3 ml of hydrazine hydrate were 40 added, and the reaction mixture was heated at 55*C for 3 hours. After the reaction was complete, the solvent was evaporated and the remaining solid was stirred with water and then dried. 2.65 g of 4-(2-fluorophenyl)-1 H-pyrazole were obtained.

103 ESI-MS [M+H]+= 163.1. 1 H-NMR (500 MHz DMSO) S ppm: 13.07 (s, 1H), 8.10 (s broad, 2H), 7.73 (m, 1H), 7.24 (m, 3H). 5 The 4-(2-fluorophenyl)-1 H-pyrazole obtained in this way was then reacted in a manner analogous to the above examples to give N-[3-amino-2,3-dioxo-1-(phenylmethyl) propyl]-2-[4-(2-fluorophenyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide. ESI-MS [M+H]*= 458.2. 1 H-NMR (500 MHz DMSO) 8 ppm: 8.91 (d, 1H), 8.79 (s broad, 1H), 8.59 (d, 1H), 8.05 10 (m, 2H), 7.88 (m, 1H), 7.81 (s, 1H), 7.76 (d, 1H), 7.51 (m, 1H), 7.35-7.20 (m, 7H), 7.18 (m, 1H), 5.34 (m, 1H), 3.18 and 2.90 (each dd, 1H). Example 105: N-[(1 S)-1 -Formyl-2-phenylethyl]-2-(3-phenyl-1 H-pyrazol-1 -yl)pyridine-3-carboxamide 15 N-[(1 S)-2-Hydroxy-1 -(phenylmethyl)ethyl]-2-(3-pheny-1 H-pyrazol-1 -yl)pyridine-3 carboxamide Coupling of 1.0 g of 2-(3-phenyl-1 H-pyrazol-1-yl)pyridine-3-carboxylic acid (3.77 mmol) 20 with 0.63 g of L-phenylalaninol afforded 1.14 g of N-[(1S)-2-hydroxy-1-(phenylmethyl) ethyl]-2-(3-phenyl-1 H-pyrazol-1 -yl)pyridine-3-carboxamide as a white solid. ESI-MS [M+H] += 399.2. 1H-NMR (500 MHz DMSO) 8 ppm: 8.54 (dd, 1H), 8.45 (d, 1H), 8.30 (d, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.69 (d, 1H), 7.42 (m, 3H), 7.35 (m, 1H), 7.28 (m, 2H), 7.20 (m, 3H), 25 7.01 (1H), 4.70 (t, 1H), 4.09 (m, 1H), 3.49 (m, 1H), 3.35 (m, overlapped by H 2 0), 2.91 and 2.71 (each dd, 1H). Oxidation of N-[(1 S)-2-hydroxy-1 -(phenylmethyl)ethyl]-2-(3-phenyl-1 H-pyrazol-1 yl)pyridine-3-carboxamide in a manner analogous to the above examples and 30 subsequent treatment of the resulting crude product with HCI in dioxane and stirring the resulting residue with ether afforded 71 mg of the title compound as a white solid. ESI-MS [M+H]+ 1 H-NMR (500 MHz DMSO) 6 ppm: 9.58 (s, 1H), 8.99 (d, 1H), 8.58 (dd, IH), 8.51 (d, 1H), 7.83 (m, 2H), 7.80 (m, 1H), 7.48 (dd, 1H), 7.43 (m, 2H), 7.37 (m, 1H), 7.27-7.19 35 (m, 5H), 7.05 (d, 1H), 4.48 (m, 1H), 3.13 and 2.87 (each dd, 1H). Example 106: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-phenyl-1 H-pyrazol-1 -yl)benzamide ESI-MS [M+H]*= 439. 40 1 H-NMR (400 MHz DMSO) 8 ppm: 9.01 (d, 1H), 8.07 (s,1H), 7.8 (s, 1H), 7.82 (d, 1H), 7.73 (d, 2H), 7.70 (d, 1H), 7.59 (dd, 1H), 7.39-7.47 (m, 3H), 7.34 (dd, 2H ), 7.23-7.28 (m, 5H), 6.81 (d, 1H), 5.35-5.41 (m, 1H), 3.18 (dd, 1H), 2.78 (dd, 1H).

104 The compounds of Examples 107 and 108 can be prepared in a manner analogous to the Example 5 using (3S)-amino-2-(R/S)-hydroxy-4-phenyl-butyramide (e.g. prepared according to WO 98/29401 or DE 19642591): 5 Example 107: N-[(1 S)-3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-phenyl-1 H-pyrazol-1 yl)pyridine-3-carboxamide ESI-MS [M+H]+= 440.1; 10 [a ]D20: +71* (c: 1 % in DMF; freshly prepared solution) Example 108: N-[(1 S)-3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(4-fluorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide 15 ESI-MS [M+H]+= 458.2; [a ]D20: +62.5* (c: 1 % in dimethylformamide (DMF); freshly prepared solution) The following examples were prepared in a manner analogous to the above examples 20 Example 109: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-[3-(3-chloro-2-thienyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]'= 480.2 25 Example 110: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-(3-naphthalen-1-yl-lH-pyrazol-1 yl)pyridine-3-carboxamide ESI-MS [M+H]+= 490.0 1 H-NMR (400 MHz DMSO) 6 ppm: 8.90 (d, 1H), 8.75 (d, 1H), 8.60 (s, 1H), 8.59 30 (d,1H), 7.75 (dd, 3H), 7.81 (d, 1H), 7.75 (d, 1H), 7.74 (s, 1H), 7.48-7.63 (m, 4H), 6.91 6.96 (m, 2H), 6.82-6.88 (m, 4H), 5.47-5.53 (m, 1H), 3.02 (dd, 1H), 2.70 (dd, 1H). Example 111: N-(3-Amino-1 -{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropyl)-2-[3-(2-chloro-4 35 fluorophenyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 522.1 Example 112: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,5-dichlorophenyl)-1 H-pyrazol-1 40 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 508.1. 1 H-NMR (400 MHz DMSO) 6 ppm: 8.88 (d, 1H), 8.59 (d, 1H), 8.52 (d,1H), 7.94 (s, 105 1H), 7.79 (d, 1H), 7.76 (s, 1H), 7.64 (d, 1H), 7.50-7.56 (m, 2H), 7.42 (dd, 1H), 7.02-7.10 (m, 6H), 5.35-5.41 (m, 1H), 3.13 (dd, 1H), 2.77 (dd, 1H). Example 113: 5 N-[3-Amino-2,3-dioxo-1 -({4-[(phenylmethyl)oxy]phenyl}methyl)propyl]-2-[3-(2,4 dichlorophenyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 615.2 1 H-NMR (400 MHz DMSO) 6 ppm: 8.87 (d, 1H), 8.57 (dd, 1H), 8.51 (d, 1H), 8.04 (s, 1 H), 7.83 (s, 1 H), 7.77 (dd, 1 H), 7.65 (d, 1 H), 7.59 (d, 1 H), 7.50 (dd, 1 H), 7.30-7.43 (m, 10 6H), 7.04 (d, 2H), 7.02 (s, 1H), 6.75 (d, 2H), 5.39-5.45 (m, 1H), 4.97 (s, 2H), 3.01 (dd, 1H), 2.68 (dd, 1H). Example 114: N-{-3-Amino-1-[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-[3-(2,4-dichlorophenyl)-1H 15 pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 526.1 'H-NMR (400 MHz DMSO) 6 ppm: 8.91 (d, 1H), 8.58 (dd, 1H), 8.52 (d, 1H), 8.05 (s, 1H), 7.85 (s, 1H), 7.78 (d, 1H), 7.67 (d, 1H), 7.59 (d, IH), 7.51 (dd, 1H), 7.35 (dd, 1H), 7.13 (dd, 2H), 7.03 (d, 1H), 6.90 (dd, 2H), 5.38-5.44 (m, 1H), 3.06 (dd, 1H), 2.72 (dd, 20 1H). Example 115: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,3-dichlorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide 25 ESI-MS [M+H]*= 508.1 1 H-NMR (400 MHz DMSO) 5 ppm: 8.92 (d, 1H), 8.58 (dd, 1H), 8.53 (d,1H), 8.01 (s, 1H), 7.79 (s, IH), 7.76 (dd, 1H), 7.64 (dd, 1H), 7.56 (dd, 1H), 7.50 (dd, 1H), 7.33 (dd, 1H), 7.12 (s, 5H), 7.02 (d, 1H), 5.44-5.50 (m, 1H), 3.09 (dd, 1H), 2.76 (dd, 1H). 30 Example 116: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,4,6-trifluorophenyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 494.04 35 Example 117: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[2,4-bis(methyloxy)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 500.2 1 H-NMR (400 MHz DMSO) 6 ppm: 8.88 (d, 1H), 8.52 (dd, 1H), 8.41 (d, 1H), 8.04 (s, 40 1H), 7.82 (s, 1H), 7.67 (t, 2H), 7.41 (dd, 1H), 7.17 (s, 5H), 6.88 (d, 1H), 6.63 (d, 1H), 6.49 (dd, 1H), 5.54-5.59 (m, 1H), 3.87 (s, 3H), 3.80 (s, 3H), 3.16 (dd, 1H), 2.79 (dd, 1 H).

106 Example 118: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,2-difluoro-1,3-benzodioxol-5-y) 1 H-pyrazol-1-yl]pyridine-3-carboxamide 5 ESI-MS [M+H]+= 520.1 Example 119: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,2-difluoro-1,3-benzodioxol-4-yl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide 10 ESI-MS [M+H]+= 520.1 Example 120: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,3-dichloro-6-fluorophenyl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide 15 ESI-MS [M+H]'= 526.1 1 H-NMR (400 MHz DMSO) 5 ppm: 8.96 (d, 1H), 8.58 (d, 1H), 8.54 (d,1H), 7.86 (s, 1 H), 7.79 (d, 1 H), 7.69 (s, 1 H), 7.45-7.58 (m, 3H), 7.03-7.13 (m, 5H), 6.64 (d, 1 H), 5.21-5.27 (m, 1H), 3.08 (dd, 1H), 2.84 (dd, 1H). 20 Example 121: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[3,5-dimethyl-2-(methyloxy)phenyl] 1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 498.02 25 Example 122: N-{3-Amino-1 -[(4-bromophenyl)methyl]-2,3-dioxopropyl}-2-(3-phenyl-1 H-pyrazol-1 yl)pyridine-3-carboxamide ESI-MS [M+H]+= 518.1 30 Example 123: N-{3-Amino-l-[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-(3-phenyl-1H-pyrazol-1 yl)pyridine-3-carboxamide ESI-MS [M+H]+= 458.1 35 Example 124: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{2-[(trifluoromethyl)oxy]phenyl}-1 H pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]+= 524.2 40 Example 125: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[4-fluoro-2-(methyloxy)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide 107 ESI-MS [M+H]+= 488.1. Example 126: N-(3-Amino-1 -{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropyl)-2-{3-[3 5 (trifluoromethyl) phenyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 537.5 Example 127: N-[3-Amino-2,3-dioxo-1 -({4-[(phenylmethyl)oxy]phenyl}methyl)propyl]-2-(3-phenyl-1 H 10 pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]'= 546.3 Example 128: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-5-phenyl-2-(3-phenyl-1 H-pyrazol-1 15 yl)pyridine-3-carboxamide ESI-MS [M+H]'= 516.25. Example 129: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(1,3-benzoxazol-5-yl)-1 H-pyrazol-1 20 yl]pyridine-3-carboxamide ESI-MS [M+H 2 0+H]+= 499.1 Example 130: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[5-fluoro-2-(methyloxy)phenyl]-1 H 25 pyrazol-1-yl}pyridine-3-carboxamide ESI-MS [M+H]'= 488.1 Example 131: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[5-chloro-2-(methyloxy)phenyl]-1 H 30 pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 504.1 Example 132: N-[3-Amino-2,3-dioxo-1 -({4-[(trifluoromethyl)oxy]phenyl}methyl)propyl]-2-[3-(4 35 fluorophenyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 542.1 Example 133: N-[3-Amino-2,3-dioxo-1 -({4-[(trifluoromethyl)oxy]phenyl}methyl)propyl]-2-(3-phenyl-1 H 40 pyrazol-1-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 524.1 108 Example 134: N-[3-Amino-2,3-dioxo-1 -({4-[(trifluoromethyl)oxy]phenyl}methyl)propyl]-2-{3-[3 (trifluoromethyl)phenyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 592.1. 5 Example 135: N-(3-Amino-1 -{[4-(methyloxy)phenyl]methyl)-2,3-dioxopropyl)-2-(3-naphthalen-1 -yl-1 H pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]+= 520.2 10 Example 136: N-(3-Amino-1 -{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropyl)-2-{3-[4-fluoro-2 (methyloxy) phenyl]-1 H-pyrazol-1-yl}pyridine-3-carboxamide ESI-MS [M+H]'= 518.2 15 Example 137: N-(3-Amino-1-{[4-(methyloxy)phenyi]methyl}-2,3-dioxopropyl)-2-[3-(2,2-difluoro-1,3 benzodioxol-5-yl)-1 H-pyrazol-1-yl]pyridine-3-carboxamide ESI-MS [M+H]*= 550.1 20 Example 138: N-[3-Amino-2,3-dioxo-1 -({4-[(trifluoromethyl)oxy]phenyl}methyl)propyl]-2-(3-naphthalen 1 -yl-1 H-pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]*= 573.5 25 Example 139: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[4-chloro-2-(methyloxy)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]'= 504.1 30 Example 140: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(8-chlorochromeno[4,3-c]pyrazol 2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 502.2 35 Example 141: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-(4,5-dihydro-2H-[1]benzoxepino[5,4 c]pyrazol-2-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 482.1 40 Example 142: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[7-(methyloxy)chromeno[4,3-c]pyrazol- 109 2(4 H)-yl]pyridine-3-carboxamide ESI-MS [M+H]+= 498.1 Example 143: 5 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(8-chloro-9-methylchromeno[4,3 c]pyrazol-2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 516.2 Example 144: 10 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propy]-2-[8-(1 -methylethyl)chromeno[4,3 c]pyrazol-2(4H)-yl]pyridine-3-carboxamide ESI-MS [M+H]'= 510.2 Example 145: 15 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2-chloro-3-fluorophenyl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 492.1 Example 146: 20 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(4-fluoronaphthalen-1 -yl)-l H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]'= 508.1 Example 147: 25 N-{3-Amino-1-[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-{3-[3-(trifluoromethyl)phenyl] 1H-pyrazol-1-yl}pyridine-3-carboxamide ESI-MS [M+H]'= 526.2 Example 148: 30 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{4-[(diethylamino)methyl]-3-(4 fluorophenyl)-1 H-pyrazol-1 -yl}pyridine-3-carboxamide methanesulfonate ESI-MS [M+H]'= 543.20 (free base) Example 149: 35 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(4-fluorophenyl)-4-(morpholin-4 ylmethyl)-1H-pyrazol-1-yl]pyridine-3-carboxamidee Methanesulfonat ESI-MS [M+H]+= 557.2 (free base) Example 150: 40 N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-{3-[4-fluoro-2-(morpholin-4 ylmethyl)phenyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide methanesulfonate ESI-MS [M+H]'= 557.2 (free base) 110 Example 151: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-[2,5-bis(methyloxy)phenyl]-1 H pyrazol-1 -yl}pyridine-3-carboxamide 5 ESI-MS [M+H]'= 500.1 Example 152: N-{3-Amino-1 -[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-(3-{2 [(trifluoromethyl)oxy]phenyl}-1 H-pyrazol-1 -yl)pyridine-3-carboxamide 10 ESI-MS [M+H]'= 542.1 Example 153: N-(3-Aamino-1-{[4-(methyloxy)phenyl]methyl}-2,3-dioxopropyl)-2-[3-(2,3 dichlorophenyl)-1 H-pyrazol-1-yl]pyridine-3-carboxamide 15 ESI-MS [M+H]+= 538.2 Example 154: N-{3-Amino-1-[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-[3-(2-chloro-3-fluorophenyl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide 20 ESI-MS [M+H]'= 511.1 Example 155: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-{3-[2-chloro-3-(trifluoromethyl)phenyl] 1 H-pyrazol-1 -yl}pyridine-3-carboxamide 25 ESI-MS [M+H]*= 542.2 Example 156: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-isoquinolin-5-yl-1 H-pyrazol-1 yl)pyridine-3-carboxamide 30 ESI-MS [M+H]'= 491.1 Example 157: N-(3-Amino-1-{[4-(methyloxy)phenyl]methy)-2,3-dioxopropyl)-2-[3-(2-chloro-3 fluorophenyl)-1 H-pyrazol-1-yl]pyridine-3-carboxamide 35 ESI-MS [M+H]'= 522.2 Example 158: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-5-[(methylsulfonyl)amino]-2-(3-phenyl 1 H-pyrazol-1 -yl)pyridine-3-carboxamide 40 ESI-MS [M+H]'= 533.2 Example 159: 111 N-{3-Amino-1 -[(4-fluorophenyl)methyl]-2,3-dioxopropyl}-2-[3-(2,3-dichlorophenyl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 526.2 5 Example 160: N-[3-amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-(3-quinolin-8-y-1 H-pyrazol-1 yl)pyridine-3-carboxamide ESI-MS [M+H]*= 491.1 10 Example 161 N-{3-Amino-1 -[(4-fluorophenyl)methyl]-2,3-dioxopropyl)-2-[3-(2,3-dichlorophenyl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 607.2 15 Example 162: N-{3-Amino-1 -[(3-fluorophenyl)methyl]-2,3-dioxopropyl}-2-(3-{2 [(trifluoromethyl)oxy]phenyl}-1 H-pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]*= 542.2 20 Example 163: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-{3-[2-(morpholin-4-ylmethyl)-5 (trifluoromethyl) phenyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 607.25 25 Example 164: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,3-dihydro-1 -benzofuran-7-yl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 482.1 30 Example 165: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(4-fluorophenyl)-4-(2-morpholin-4 ylethyl)-1 H-pyrazol-1-yl]pyridine-3-carboxamide ESI-MS [M+H]*= 571.2 35 Example 166: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{2-[(difluoromethyl)oxy]phenyl}-1 H pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]*= 506.1 40 Example 167: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{2-[(diethylamino)methyl]-4 fluorophenyl}-1 H-pyrazol-1-yl)pyridine-3-carboxamide 112 ESI-MS [M+H]+= 543.25 Example 168: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{3-[(trifluoromethyl)oxy]phenyl}-1 H 5 pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]+= 524.15 Example 169: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-[3-(4-fluorophenyl)-4-(pyrrolidin-1 10 ylmethyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 541.25 Example 170: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-(4-fluorophenyl)-4 15 [(methyloxy)methyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]+= 502.2 Example 171: N-{3-Amino-1-[(4-bromophenyl)methyl]-2,3-dioxopropyl}-2-[3-(4-fluorophenyl)-1H 20 pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 536.1 Example 172: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-5-(dimethylamino)-2-(3-phenyl-1 H 25 pyrazol-1-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 483.25 Example 173: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-thiochromeno[4,3-c]pyrazol-2(4H) 30 ylpyridine-3-carboxamide ESI-MS [M+H]+= 484.2 Example 174: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(5,5-dioxidothiochromeno4,3 35 c]pyrazol-2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 516.2 Example 175: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(6-chlorochromeno[4,3-c]pyrazol 40 2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]+= 502.3 113 Example 176: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{4-[(dimethylamino)methyl]-3-[3 (trifluoromethyl) phenyl]- 1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 565.2 5 Example 177: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{4-(morpholin-4-ylmethyl)-3-[3 (trifluoromethyl)phenyl]- 1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 607.25 10 Example 178: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{4-(pyrrolid in-1 -ylmethyl)-3-[3 (trifluoromethyl) phenyl]-I H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 591.25 15 Example 179: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-{3-(4-fluorophenyl)-4 [(phenyloxy)methyl]-1 H-pyrazol-1 -yl}pyridine-3-carboxamide ESI-MS [M+H]*= 564.15 20 Example 180: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-{2-[(diethylamino)methyl]-3 (trifluoromethyl)phenyl}-1 H-pyrazol-1-yl)pyridine-3-carboxamide ESI-MS [M+H]*= 593.15 25 Example 181: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(8-fluorochromeno[4,3-c]pyrazol 2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]*= 486.2 30 Example 182: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[6-(ethyloxy)chromeno[4,3-c]pyrazol 2(4H)-yl]pyridine-3-carboxamide ESI-MS [M+H]*= 512.3 35 Example 183: N-[3-Aamino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[8-(methyloxy)chromeno[4,3 c]pyrazol-2(4H)-yl]pyridine-3-carboxamide ESI-MS [M+H]*= 498.2 40 Example 184: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[4-chloro-3-(4-fluorophenyl)-1 H- 114 pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 492.1 Example 185: 5 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[4-(dimethylamino)-3-(4-fluorophenyl) 1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]'= 483.55 Example 186: 10 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(8-methylchromeno[4,3-c]pyrazol 2(4H)-yl)pyridine-3-carboxamide ESI-MS [M+H]*= 482.1 Example 187: 15 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(4-fluorophenyl)-4 {[(methylsulfonyl)amino]methyl)-1 H-pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]*= 565.15. Example 188: 20 N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-5-cyano-2-[3-(2-fluorophenyl)-1 H pyrazol-1 -yl]pyridine-3-carboxamide ESI-MS [M+H]+= 483.15 Example 189: 25 Ethyl-3-[({2-[3-(4-fluorophenyl)-1 H-pyrazol-1-yl]pyridin-3-yl}carbonyl)amino]-2-oxo-4 phenylbutanoate Ethyl-3-amino-2-hydroxy-4-phenylbutanoate was prepared according to WO 2005/124673. The title compound was prepared in a manner analogous to the above 30 Examples. ESI-MS [M+H]+= 487.14 Example 190: 2-[3-(4-Fluorophenyl)-1 H-pyrazol-1 -yl]-N-[3-(methylamino)-2,3-dioxo-1 35 (phenylmethyl)propyl]pyridine-3-carboxamide ESI-MS [M+H]'= 472.15 Example 191: 2-[3-(5-Fluoropyridin-2-yl)-1 H-pyrazol-1-yl]-N-[3-(methylamino)-2,3-dioxo-1 40 (phenylmethyl)propyl]pyridine-3-carboxamide ESI-MS [M+H]*= 459.1 115 The 3-alkyl- and 3-cycloalkyl-1 H-pyrazole used in the following examples were prepared in a manner analogous to the methode described above for 3-isopropyl-1 H pyrazol (Trofimenko et al.; Inorganic Chemistry 1989, 28(6), 1091-1101). 5 Example 192: N-[3-Amino-2,3-dioxo-1-(phenylmethyl)propyl]-2-(3-cyclohexyl-1 H-pyrazol-1-yl)pyridine 3-carboxamide ESI-MS [M+H]+= 446.2 10 Example 193: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-(3-tricyclo[3.3.1.1 3 ,ldec-1 -yl-1 H pyrazol-1 -yl)pyridine-3-carboxamide ESI-MS [M+H]+= 498.2 15 Example 194: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(2,2-dimethylpropyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]+= 434.2 20 Example 195: N-[3-Amino-2,3-dioxo-1 -(phenylmethyl)propyl]-2-[3-(1, 1 -dimethylethyl)-1 H-pyrazol-1 yl]pyridine-3-carboxamide ESI-MS [M+H]'= 420.2 25 Biological investigation of inhibition of calpain and cathepsins The following solutions and buffers were employed: - HBS (for 40 ml): 800 pl 1 M HEPES; 2.16 ml 100 mM KCI; 4.8 ml 1M NaCl; 3.59 ml 5% glucose; 60 pl 1 M MgSO 4 ; 400 pl 100 mM Na pyruvate, 28.19 ml 30 water; pH 7.2-7.5. - lysis buffer (for 20 ml): 400 p 1 M Tris pH 8.2; 2.74 ml 1 M NaCl; 520 pl 0.5M EDTA; 2 ml 10% triton X-100; 0.8 ml (= 1:25) CompletePlus (1 tablet/2 ml H 2 0); 200 pl 100 mM Pefabloc; 13.34 ml water, pH 8.2. - TBST (1Ox) (for 11): 100 mM Tris (12.1 g); 1.5M NaCl (87 g); 1% Tween 20 35 (10 g), adjusted to pH 8. I Enzyme inhibition in vitro: Testing for blockade of the corresponding enzymic activities was carried out by 40 means of kinetic fluorescence assays (excitation 390 nm, emission 460 nm). Apparent Ki values were calculated from the experimentally determined IC 5 o 116 values by the Cheng-Prussoff relation assuming a reversible competitive enzyme inhibition. The Km values of the substrates used under the assay conditions indicated above were: 90 pM (Z-Phe-Arg-AMC, cathepsin B), 10 pM (Z-Gly-Pro Arg-AMC, cathepsin K), 2 pM (Z-Phe-Arg-AMC, cathepsin L), and 30 pM (Z-Val 5 Val-Arg-AMC, cathepsin S). The indicated Ki values are averages of the inhibition constants calculated on the basis of 2 to 4 independent dose-effect plots. The following assays were used: 10 1. Calpain 1: 20 nM calpain-l - isolated from human erythrocytes (Calbiochem #208713), 100 pM Suc-Leu-Tyr-AMC (Bachem #1-1355) as substrate in buffer with 62 mM imidazole, 0.3 mM CaC1 2 , 0.10% CHAPS, 0.05% BSA, 1 mM DTT at pH 7.3 and room temperature. 15 2. Cathepsin B: 0.25 nM cathepsin B - isolated from human liver (Calbiochem #219362), 100 pM Z-Phe-Arg-AMC (Bachem #1-1160) as substrate 50 mM MES, 2 mM EDTA, 0.05% Brij 35, 2.5 mM L-cysteine, pH 6.0, room temperature. 3. Cathepsin K: 20 3 nM cathepsin K - activated from recombinant human procathepsin K from E. coli (Calbiochem #342001), 10 pM Z-Gly-Pro-Arg-AMC (Biomol #P-142) as substrate in 50 mM MES, 2 mM EDTA, 0.05% Brij 35, 2.5 mM L-cysteine, pH 6.0, room temperature. 4. Cathepsin L: 25 1 nM cathepsin L - isolated from human liver (Calbiochem #219402), 2 pM Z-Phe-Arg-AMC (Bachem #1-1160) as substrate in 50 mM MES, 2 mM EDTA, 0.05% Brij 35, 2.5 mM L-cysteine, pH 6.0, room temperature. 5. Cathepsin S: 0.5 nM recombinant human cathepsin S from E. coli (Calbiochem 30 #219343), 20 pM Z-Val-Val-Arg-AMC (Bachem #1-1540) as substrate in 50 mM MES, 2 mM EDTA, 0.05% Brij 35, 2.5 mM L-cysteine, pH 6.0, room temperature. The results of the in vitro determination are indicated in Table 1. The following 35 abbreviations are used in Table 1: The the "Calpain activity" column, ++ stands for a calpain Ki (Ki(calpain)) of < 40 nM and + means: 40 nM < Ki(Calpain) < 100 nM. 40 The "Sel. cat. B" column indicates the Ki(cathepsin B)/Ki(calpain) ratio. In this connection, ++ means a Ki(cathepsin B)/Ki(calpain) ratio of > 30 and + means 10 < Ki(cathepsin B)/Ki(calpain) < 30.

117 The "Sel. cat. K" column indicates the Ki(cathepsin K)/Ki(calpain) ratio. In this connection, ++ means a Ki(cathepsin K)/Ki(calpain) ratio of > 30 and + means 10 < Ki(cathepsin K)/Ki(calpain) < 30. 5 The "Sel. cat. L" column indicates the Ki(cathepsin L)/Ki(calpain) ratio. In this connection, ++ means a Ki(cathepsin L)/Ki(calpain) ratio of > 50 and + means 30 < Ki(cathepsin L)/Ki(calpain) < 50. 10 The "Sel. cat. S" column indicates the Ki(cathepsin S)/Ki(calpain) ratio. In this connection, ++ means a Ki(cathepsin S)/Ki(calpain) ratio of > 100 and + means 50 < Ki(cathepsin S)/Ki(calpain) < 100. Table 1: 15 Example Calpain Sel cat. B Sel cat. K Sel cat. L Sel cat. S activity 2 ++ ++ 4 ++ 5 ++ + + ++ ++ 6 ++ 9 ++ + ++ 10 ++ 12 ++ 13 + ++ + 14 + ++ 15 ++ ++ + 16 + + + 17 ++ ++ + 18 ++ + ++ 19 ++ 20 ++ 21 ++ 22 ++ + ++ 23 ++ + 24 ++ + 25 ++ 26 ++ ++ 27 ++ ++ + + 28 ++ + 118 Example Calpain Sel cat. B Sel cat. K Sel cat. L Sel cat. S activity 29 ++ + ++ ++ 31 ++ ++ + + 32 ++ + 33 ++ + + 35 + +- + ++ ++ 38 + + + ++ ++4 39 + ++ 4-4 40 ++ +i ++ ++ 42 ++ ++ 43 + ++ 44 ++ + 45 ++ + 46 +- ++ 47 .H- ++ 48 + + + ++ ++ 49 + + ++-I 50 + + + + + 52 + ++ 54 + +-4 +4- +4 +4 55 +4- + + +4- 4-4 57 + ++ ++ 58 ++ + + ++ +4 59 +4- +4 + 60 + +- + +4- + 61 +++ 62 + -1-4 ++ 63 ++ + +- ++ +4 64 +4- 4- ++ 65 ++ 66 +4- + + ++4 67 + +- + +4- ++4 68 + + +4 69 + + +4- +4 70 +4- + + +4- +4 71 + ++ +4- +4 +4 72 +- +- + + +4 74 +4- 4-4 4-4 +4 75 + + +4- +4- 119 Example Calpain Sel cat. B Sel cat. K Sel cat. L Sel cat. S _________activity 76 ++ ++ + ++ ++ 77 ++ 78 + +4- + 79 + ++ ++-i- ++ 80 + ++ +I ++ ++ 81 ++ + + +i+ ++ 82 + ++ ++i ++ 83 ++ + ++ ++ ++ 84 ++ +I ++ ++ 85 +-4 + ++ +4- 4-4 86 +4- ++ 87 +4- +4- ++-i -+ ++ 88 + +- 4--i ++ ++ 89 + +- + +4- ++ 90 ++ +4- + ++ ++ 91 +4- -1-4 + +4- ++4 92 +- +4- + ++ 4-4 93 +4- ++ +- ++ +4 94 + 4-4 + +4- +4 95 ++ +4- 4-4 +4 +4 96 ++ 4--i +4- +4- 4 97 4-4 4-4 + +4- ++4 98 ++ ++4 +4- +4- 4-4 99 4-4 +4- 4-4 +4- 4 100 +4- + ++4 +4- +4 101 +4- 4-4 102 +4- + +4- +4- 4 103 ++ +- + +4- +4 104 +4- + 105 +4- +4 +4- +4 106 +4- + ++4 107 ++ + +- +4- 4-4 109 +4- +- +4- +4- +4 110 4-4 4-4 4-4 +4- +4 ill +4- +4- 4-4 +4- 4 112 +4- +4- 4-4 +4- ++ 114 +- +4- +4 +4- 4-4 115 4-4 +4- 4-4 +4- 4-4 120 Example Calpain Sel cat. B Sel cat. K Sel cat. L Sel cat. S activity 116 ++ ++ + ++ ++ 117 ++ ++ ++ ++ ++ 118 ++ ++ + ++ ++ 119 ++ 44 ++ ++ ++ 120 ++ ++ ++ + ++ 121 ++ ++ ++ ++ ++ 122 ++ ++ ++ ++ 123 ++ ++ ++ ++ ++ 124 ++ ++ ++ ++ ++ 125 ++ ++ +4 ++ ++ 126 ++ ++ ++ ++ ++ 127 ++ +4 ++ ++ ++ 129 + ++ 130 ++ ++ ++ ++ ++ 131 ++ ++ ++ ++ ++ 132 + + ++ ++ ++ 133 + ++ ++ ++ ++ 134 ++ ++ + + 135 ++ ++ ++ ++ ++ 136 ++ ++ ++ ++ ++ 137 + + + ++ ++ 138 ++ ++ ++ ++ 139 + + ++ ++ ++ 140 ++ + ++ ++ ++ 141 + ++ ++ 142 ++ + + ++ ++ 143 + ++ ++ ++ ++ 144 ++ + ++ ++ 151 + ++ ++ ++ 152 ++ ++ ++ ++ ++ 153 ++ ++ ++ ++ ++ 154 ++ ++ ++ ++ 155 + ++ ++ ++ ++ 156 + + ++ 157 ++ ++ ++ ++ ++ 158 + ++ ++ ++ ++ 160 + ++ ++ ++ ++ 161 + + ++ 121 Example Calpain Sel cat. B Sel cat. K Sel cat. L Sel cat. S activity 162 + ++ ++ ++ ++ 163 + + + + ++ 164 ++ + ++ ++ ++ 165 + ++ 166 ++ + ++ ++ ++ 168 ++ + + ++ ++ 170 + + 173 ++ + + ++ ++ 174 ++ + + ++ ++ 175 ++ ++ ++ ++ ++ 176 ++ 177 + ++ 178 + ++ 179 + ++ 183 ++ + + ++ ++ 184 + + + ++ ++ 187 + + ++ 188 + ++ ++ 192 + + ++ ++ 193 ++ ++ ++ ++ ++ 11 Spectrin molt-4 asssay to determine cellular calpain inhibition: The assay design and procedure were as disclosed by Chatterjee; BMC 1998, 6, 5 pp. 509-522; the EC 5 o values are calculated from the percentage degradation of spectrin as a function of the dose. Cell culture conditions: the molt-4 cells are maintained in RPMI 1640 + GlutamaxTM I medium (Gibco) with 10% FCS and 50 pg/ml gentamicin at 37 0 C, 10 5% C02 and split 1:15 twice a week. Preparation of the molt-4 cells: the cells are washed, counted and taken up in a concentration of 2 x 107 cells/ml in HBS buffer. 15 Dilution of the inhibitor substances: all the inhibitors are dissolved in a concentration of 10-2 M in DMSO. The stock solution is then diluted 1:15 in DMSO (= 6.67 x 104 M). Thereafter the stock solution diluted 1:15 is diluted 1:4 in DMSO in two steps (= 1.67 x 10-4 M and 4.17 x 10-5 M). Thereafter, these three solutions are further diluted 1:50 in HBS buffer to give solutions having a 122 concentration of 1.33 x 10-5 M, 3.36 x 10-6 M and 8.34 x 10-7 M. Test mixture: for each mixture, 106 cells (see above) are introduced into a 1.5 ml Eppendorf tube. To these are added in each case 150 pl of the diluted 5 substances (final conc. 10-5 M; 2.5 x 10-6 M and 6.25 x 10-7 M) and thoroughly mixed. A negative control and a positive control are used as controls. In this case, initially only 150 pl of HBS buffer is pipetted onto the cells. All the mixtures are incubated at 37*C, 5% CO 2 in an incubator for 10 min. Thereafter, except for the negative control, in each case CaC1 2 (final conc. 5 mM) and ionomycin (final 10 conc. 5 pM) are added, thoroughly mixed and incubated at 37 0 C, 5% CO 2 in an incubator for 30 min. Then centrifuge at 700 g for 5 min. The supernatants are discarded and the pellets are taken up in 20 pl of lysis buffer. The mixtures are subsequently placed on ice for 30-60 min and then centrifuged at 150OOg for 15 min. The supernatants are removed and put into new Eppendorf tubes. The 15 protein determination is then carried out thereon, e.g. with a MicroBCA assay (Pierce). SDS-PAGE electrophoresis: 10 pg of total protein from each mixture are put into a new Eppendorf tube and, after pipetting in the same volume of 2x Tris-glycine 20 SDS sample buffer (Invitrogen) and 1/10 volume of 1M DTT, thoroughly mixed and heated at 95*C for 15 min. The solutions are briefly centrifuged and loaded onto a 6% SDS gel (Invitrogen). The gel is run at 100V with 1x Tris-glycine laemmli buffer (Biomol) until the lower band of the marker has reached the base of the gel. 25 Western blotting: the gel is removed from the apparatus and blotted onto nitrocellulose in Ix Tris-glycine transfer buffer (Invitrogen) + 20% methanol with 1.5 A/cm 2 in a FastBlot chamber (Biometra) for 30 min. The nitrocellulose filter is removed, briefly washed in TBST buffer and blocked in TBST/5% milk powder for 30 1 h at RT (room temperature). The blocked nitrocellulose is then incubated with an anti-spectrin Ab (Chemicon) (1:10000 in TBST/5% milk powder) at RT for 3 h or at 4 0 C overnight. The nitrocellulose is washed 3x in TBST buffer. It is then incubated with anti-mouse IgG (POD) antibody (Sigma) (1:10000 in TBST/5% milk powder) at room temperature for 1 h. 35 The nitrocellulose is then washed 5x in TBST buffer. In the next step, 5 ml of prepared solution of the SuperSignal* West Pico chemiluminescence substrate (Pierce) are put on the filter and incubated for 5 min. The nitrocellulose is then taken out of the solution, gently dabbed dry and inserted into a development 40 folder film (Tropix). A digital image analysis system (VersaDoc, Biorad) is used to record and quantify the ECL (QuantityOne), and the percentage degradation of 123 spectrin is calculated from the data. Graph-pad prism is used to fit the percentage spectrum degradation as a function of the dose to a sigmoidal dose-effect plot (top fixed at 100% and bottom at 0%), and the EC 50% is calculated.

Claims (20)

1. A carboxamide compound of the formula I 0 R R W-Y N 3b 3a 5 H R R in which R 1 is hydrogen, C-C 1 o-alkyl, C 2 -C1o-alkenyl, C 2 -C 10 -alkynyl, where the last 3 10 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Ria, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C-C4-alkyl, where a CH 2 group in the cycloalkyl moiety of the last two radicals mentioned may be replaced by 0, NH, or S, or two adjacent C atoms may form a double bond, where the 15 cycloalkyl moiety may further have 1, 2, 3 or 4 radicals Rib, aryl, hetaryl, aryl-Ci-Ce-alkyl, aryl-C 2 -C 6 -alkenyl, hetaryl-CrC 4 -alkyl or hetaryl-C2-Ce-alkenyl, where aryl and hetaryl in the last 6 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals Ric; where 20 Ria is selected independently of one another from OH, SH, COOH, CN, OCH 2 COOH, CI-C 6 -alkoxy, Ci-Ce-halolkoxy, C 3 -C 7 -cycloalkyloxy, Ci C 6 -alkylthio, C-C 6 -haloalkylthio, COORal, CONRa 2 Ra 3 , SO 2 NRa 2 Ra 3 , -NRa 2 -SO 2 -Ra 4 , NRa 2 -CO-Ra5, SO 2 -Ra 4 , NRaeRa7, 25 Rib is selected independently of one another from OH, SH, COOH, CN, OCH 2 COOH, halogen, phenyl which optionally has 1, 2 or 3 substituents Rid, or Ci-Ce-alkyl, Ci-Ce-alkoxy, C-Ce-alkylthio, where the alkyl moieties in the last 3 substituents mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Ria, 30 COORbi, CONRb2Rb3, SO 2 NRb2Rb3, NRb2-SO 2 -Rb 4 , NRb2-CO-Rb5, SO 2 Rb4, NRb6Rb7, where in addition two Rib radicals may together form a C-C 4 -alkylene group, or 2 Rib radicals bonded to adjacent C atoms of cycloalkyl may form together with the carbon atoms to which they are bonded also a 35 benzene ring, Ric is selected independently of one another from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, O-CF 3 , O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, Ci-Ce-alkyl, Ci-Ce-alkoxy, C-C 6 -alkoxy-Ci-C4-alkyl, Ci C 6 -alkylthio, where the alkyl moieties in the last 4 substituents 125 mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Ria, C 3 -C7-cycloalkyl, C3-C7-cycloalkyl-Ci-C 4 -alkyl, C 3 -Cr-cycloalkyloxy, where the cycloalkyl moiety of the last three radicals mentioned may 5 have 1, 2, 3 or 4 Rib radicals, aryl, hetaryl, O-aryl, O-CH 2 -aryl, where the last three radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 Rid radicals, COORe1, CONRc 2 Rc 3 , SO 2 NRc 2 Rc 3 , NRc2-SO 2 -Rr4, NRc 2 -CO-Rc 5 , 10 SO 2 -R 4 , -(CH 2 )p-NRc 6 Rc 7 with p = 0, 1, 2, 3, 4, 5 or 6 and 0-(CH 2 )q-NR 6 R7 with q = 2, 3, 4, 5 or 6; where Rai, Rbi and Rci are independently of one another H, C-C 6 -alkyl, 15 Ci-C 6 -haloalkyl, CI-C6-alkyl which has 1, 2 or 3 substituents Ria, or C 2 -C 6 -alkenyl, C2-C6-alkynyl, C 3 -C7-cycloalkyl, C3-C7 cycloalkyl-Ci-C4-alkyl, C 3 -C 7 -heterocycloalkyl-Ci-C4-alkyl, Ci C 6 -alkoxy-C-C 4 -alkyl, aryl, aryl-Ci-C4-alkyl, hetaryl or hetaryl C-C4-alkyl, where aryl and hetaryl in the last 4 radicals 20 mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, Ra 2 , Rb2 and Rc2 are independently of one another H, Ci-C6-alkyl, Ci-C 6 -haloalkyl, Ci-C6-alkyl which has 1, 2 or 3 substituents Ria, or C2-C6-alkenyl, C2-C 6 -alkynyl, C 3 -C7-cycloalkyl, C3-C7 cycloalkyl-Ci-C4-alkyl, C 3 -C 7 -heterocycloalkyl-Ci-C4-alkyl, CI 25 C 6 -alkoxy-Ci-C4-alkyl, aryl, aryl-Ci-C4-alkyl, hetaryl or hetaryl CI-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, and Ra3, Rb3 and Rc3 are independently of one another H, Cr-C 6 -alkyl, 30 C-Ce-haloalkyl, Ci-C6-alkyl which has 1, 2 or 3 substituents Ria, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C3-C7 cycloalkyl-Ci-C4-alkyl, C 3 -C7-heterocycloalkyl-Ci-C4-alkyl, C C 6 -alkoxy-Ci-C 4 -alkyl, aryl, aryl-Ci-C 4 -alkyl, hetaryl or hetaryl Ci-C4-alkyl, where aryl and hetaryl in the last 4 radicals 35 mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, or the two radicals Ra2 and Ra3, or Rb2 and Rb3 or Rc2 and Rc3 form together with the N atom a 3 to 7-membered, optionally substituted nitrogen heterocycle which may optionally have 1, 2 40 or 3 further different or identical heteroatoms from the group of 0, N, S as ring members, Ra 4 , Rb4 and Rc4 are independently of one another C-C 6 -alkyl, CirC6- 126 haloalkyl, C-C6-alkyl which has 1, 2 or 3 substituents Ria, or C2-C6-alkenyl, C 2 -Ce-alkynyl, C 3 -C7-cycloalkyl, C 3 -C 7 -cycloalkyl Cr-C4-alkyl, C 3 -Cr-heterocycloalkyl-C-C 4 -alkyl, CI-Ce-alkoxy CI-C 4 -alkyl, aryl, aryl-C-C 4 -alkyl, hetaryl or hetaryl-C-C 4 -alkyl, 5 where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, and Ra5, Rb5 and Rc5 have independently of one another one of the meanings mentioned for Ral, Rbl and Rd; Ra6, Rb6 and Rc6 are independently of one another H, C-C 6 -alkyl, 10 Ci-C 6 -alkoxy, Cl-C 6 -haloalkyl, C-C6-alkyl which has 1, 2 or 3 substituents R1a, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 cycloalkyl, C3-C 7 -cycloalkyl-Ci-C 4 -alkyl, C 3 -C 7 -heterocycloalkyl C-C4-alkyl, C-C6-alkoxy-C-C4-alkyl, CO-C-C6-alkyl, CO-O-Ci C 6 -alkyl, S0 2 -C-C 6 -alkyl, aryl, hetaryl, 0-aryl, OCH 2 -aryl, aryl 15 C-C 4 -alkyl, hetaryl-C-C 4 -alkyl, CO-aryl, CO-hetaryl, CO-(aryl Ce1C4-alkyl), CO-(hetaryl-C-C4-alkyl), CO-O-aryl, CO-O-hetaryl, CO-O-(aryl-Cr-C 4 -alkyl), CO-O-(hetaryl-C-C 4 -alkyl), S02-aryl, S0 2 -hetaryl, S0 2 -(aryl-C-C 4 -alkyl) or S0 2 -(hetary-C-C4-alkyl), where aryl and hetaryl in the last 18 radicals mentioned are 20 unsubstituted or have 1, 2 or 3 substituents Rid, and Ra7, Rb7 and Rc7 are independently of one another H, C-C 6 -alkyl, Ci-Ce-haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Ria, or C2-C6-alkenyl, C 2 -C 6 -alkynyl, C 3 -C7-cycloalkyl, C 3 -C 7 cycloalkyl-Cr-C 4 -alkyl, C 3 -C 7 -heterocycloalkyl-C-C 4 -alkyl, Cr 25 C 6 -alkoxy-C-C 4 -alkyl, aryl, aryl-Ci-C4-alkyl, hetaryl or hetaryl C-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rid, or the two radicals Ra6 and Ra7, or Rb6 and Rb7 or Rc6 and Rc7 form 30 together with the N atom a 3 to 7-membered, optionally substituted nitrogen heterocycle which may optionally have 1, 2 or 3 further different or identical heteroatoms from the group of 0, N and S as ring members, or two radicals Rib and Ric bonded to adjacent C atoms form together 35 with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from the group of 0, N and S as ring members; Rid is selected from halogen, OH, SH, NO 2 , COOH, C(O)NH 2 , CHO, CN, 40 NH 2 , OCH 2 COOH, Ci-C6-alkyl, C-C 6 -haloalkyl, C-C 6 -alkoxy, C 1 -C 6 haloalkoxy, C-C 6 -alkylthio, C-C 6 -haloalkylthio, CO-C-C 6 -alkyl, CO O-Ci-C 6 -alkyl, NH-C-C 6 -alkyl, NHCHO, NH-C(O)C-C 6 -alkyl, and 127 S0 2 -C-C 6 -alkyl; R 2 is selected from aryl and hetaryl, where aryl and hetaryl may be unsubstituted or carry 1, 2, 3 or 4 identical or different R2c radicals; where 5 R2c has one of the meanings indicated for Ric; R3a and R3b are independently of one another hydroxy or C-C 4 -alkoxy, or together with the carbon atom to which they are bonded are C=0; 10 X is hydrogen or a radical of the formulae C(=O)-O-Rxl, C(=O)-NRx 2 Rx 3 , C(=0)-N(Rx4)-(CrCe-alkylene)-NRx2Rx3 or C(=0)-N(Rx 4 )NRx 2 Rx 3 , in which Rx1 is hydrogen, CI-C 6 -alkyl, Cr 1 C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 15 or 3 substituents Rxa, or C 2 -Ce-alkenyl, C 2 -C 6 -alkynyl, C3-C7 cycloalkyl, C 3 -C 7 -cycloalkyl-C-C4-alkyl, C 3 -C 7 -heterocycloalkyl-C-C4 alkyl, C-C 6 -alkoxy-Cl-C 4 -alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, heterocycloalkyl in the last 6 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxa, or aryl, aryl-C-C4 20 alkyl, hetaryl or hetaryl-C-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, Rx 2 is H, OH, CN, Cr 1 C 6 -alkyl, CrC 6 -haloalkyl, Cl-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C3-C7 25 cycloalkyl, C 3 -C 7 -cycloalkyl-Cl-C4-alkyl, C 3 -C 7 -heterocycloalkyl-Cr-C4 alkyl, Cr-C 6 -alkoxy-C-C 4 -alkyl, CO-C-C 6 -alkyl, CO-0-C-C-alkyl, S0 2 -CrC 6 -alkyl, O-C-Ce-alkyl, where alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl in the last 10 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxa, 30 aryl, O-aryl, O-CH 2 -aryl, hetaryl, O-CH 2 -hetaryl, aryl-C-C4-alkyl, hetaryl-C-C 4 -alkyl, CO-aryl, CO-hetaryl, CO-(aryl-C-C 4 -alkyl), CO (hetaryl-C-C4-alkyl), CO-0-aryl, CO-0-hetaryl, CO-O-(aryl-C-C4 alkyl), CO-O-(hetaryl-C-C4-alkyl), S0 2 -aryl, S0 2 -hetaryl, S0 2 -(aryl C-C 4 -alkyl) or S0 2 -(hetaryl-C-C4-alkyl), where aryl and hetaryl in the 35 last 19 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, and Rx 3 is H, C-C 6 -alkyl, Cl-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C3 C 7 -cycloalkyl-Ci-C 4 -alkyl, C 3 -C 7 -heterocycloalkyl-Ci-C 4 -alkyl, CrC-6 40 alkoxy-C-C4-alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, heterocycloalkyl in the last 6 radicals mentioned are unsubstituted or 128 have 1, 2 or 3 substituents Rxa, aryl, aryl-Ci-C4-alkyl, hetaryl or hetaryl-Cr-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, or 5 the two radicals Rx 2 and Rx 3 form together with the N atom a 3 to 7 membered nitrogen heterocycle which may optionally have 1, 2 or 3 further different or identical heteroatoms from the group of 0, N, S as ring members, and which may have 1, 2 or 3 substituents Rxb, Rx 4 is H, OH, CN, C-C6-alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 10 or 3 substituents Rxa, or C 2 -C 6 -alkenyl, C2-Ce-alkynyl, C3-C7 cycloalkyl, C 3 -C 7 -cycloalkyl-C-C 4 -alkyl, C 3 -C 7 -heterocycloalkyl-Ci-C4 alkyl, C-C 6 -alkoxy-C-C 4 -alkyl, CO-C-C 6 -alkyl, CO-0-C-C 6 -alkyl, SO2-Ci-C6-alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, heterocycloalkyl in the last 9 radicals mentioned are unsubstituted or 15 have 1, 2 or 3 substituents Rxa, aryl, O-aryl, O-CH2-aryl, hetaryl, aryl-C-C 4 -alkyl, hetary-C-C 4 -alkyl, CO-aryl, CO-hetaryl, CO-(aryl-C-C4-alkyl), CO-(hetaryl-C-C 4 -alkyl), CO-0-aryl, CO-0-hetaryl, CO-O-(aryl-Cl-C4-alkyl), CO-O-(hetaryl-Ci C 4 -alkyl), S02-aryl, S02-hetaryl, SO 2 -(aryl-Ci-C4-alkyl) or S02 20 (hetaryl-Ci-C 4 -alkyl), where aryl and hetaryl in the last 18 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, and where Rxa has one of the meanings indicated for Ria, Rxb has one of the meanings indicated for Rib, and Rxd has one of the meanings indicated for 25 Rid Y is a divalent, aromatic or 6-membered heteroaromatic radical which has 1 or 2 nitrogen atoms as ring members and where Y optionally has 1 or 2 identical or different substituents RY: 30 Ry is selected independently of one another from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, 0-CF 3 , O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, 0 1 -C 6 -alkyl, Oi-C 6 -alkoxy, Cl-C 6 -alkoxy-CriC4-alkyl, C C 6 -alkylthio, where the last 4 radicals mentioned may be partly or 35 completely halogenated and/or have 1, 2 or 3 substituents Rya, C 3 -C 7 -cycloalkyl, C 3 -Cr-cycloalkyl-C-C4-alkyl, C 3 -C 7 -cycloalkyl-0, where the cycloalkyl moiety in the last three radicals mentioned may have 1, 2, 3 or 4 Ryb radicals, aryl, O-aryl, CH2-aryl, O-CH2-aryl, where the last 4 radicals mentioned 40 are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals Ryd, COORYi, CONRy 2 Ry 3 , SO 2 NRy 2 Ry 3 , -NH-SO 2 -Ry 4 , 129 NH-CO-RY 5 , SO 2 -RY 4 , -(CH 2 )p-NR 6 R 7 with p = 0, 1, 2, 3, 4, 5 or 6 and 0-(CH2)-NR 6 R 7 with q = 2, 3, 4, 5 or 6; 5 or two RY radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from the group of 0, N, S as ring members, where 10 Rya has one of the meanings indicated for Ria, Ryb has one of the meanings indicated for Rib, Ryd has one of the meanings indicated for Rid, Ry1 has one of the meanings indicated for Rci, 15 Ry 2 has one of the meanings indicated for Rc2, Ry 3 has one of the meanings indicated for Rc3, RY 4 has one of the meanings indicated for Rc 4 , Ry 5 has one of the meanings indicated for Rc5, Ry 6 has one of the meanings indicated for Rc6, and 20 RY 7 has one of the meanings indicated for RC7; W is a radical of the formulae W2 which is linked via nitrogen: * N (Rw)m # (W2) in which 25 * means the linkage to Y, and # means the linkage to R 2 , m is 0, 1 or 2, and Rw is selected from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, 0-CF 3 , O-CHF 2 , O-CH 2 F, COOH, OCH 2 COOH, C1-C6-alkyl, C1-C6 30 alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -Ce-alkylthio, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents Rwa, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C1-C4-alkyl, C 3 -C 7 -cycloalkyloxy, where the cycloalkyl moiety of the last three radicals mentioned may 35 have 1, 2, 3 or 4 radicals Rwb, aryl, O-aryl, O-CH 2 -aryl, hetaryl, where the last four radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals Rwd, 130 COORWi, CONRw 2 Rw 3 , SO 2 NRw 2 Rw 3 , NRw 2 -SO 2 -Rw 4 , NRw 2 -CO-Rw 5 , SO 2 -Rw 4 , -(CH 2 )p-NRw 6 Rw 7 with p = 0, 1, 2, 3, 4, 5 or 6 and O-(CH2)q-NRw 6 R 7 with q = 2, 3, 4, 5 or 6; 5 or two Rw radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle or an optionally substituted heterocycle which has 1, 2 or 3 different or identical heteroatoms from 10 the group of 0, N, S as ring members, where Rwa has one of the meanings indicated for Ria, Rwb has one of the meanings indicated for R1b, Rwd has one of the meanings indicated for Rid, 15 Rw1 has one of the meanings indicated for Rci, Rw2 has one of the meanings indicated for Rc2, Rw3 has one of the meanings indicated for RC3, Rw4 has one of the meanings indicated for Rc4, Rw5 has one of the meanings indicated for Rc5, 20 Rw 6 has one of the meanings indicated for Rc6, Rw7 has one of the meanings indicated for Rc7, or 25 W forms together with R 2 a bi- or tricyclic radical of the formulae W3, W4, W5, W7 or W8 which is linked via nitrogen: 1 NN N R WN R m (RN )m (W3) (W4) (W5) 131 * ,N * N\ / N - (R" )m E E (Rw' 7 *)mE (W7) (W8) in which * means the linkage to Y, m is 0, 1 or 2, and 5 Rw 3 , Rw4*, Rw5*, Rw7 and Rw8* have independently of one another one of the meanings indicated for Rw, E has one of the following meanings: -CRE 2 RE 3 -, -CHRE 2 -CHRE 3 , CH 2 CH 2 -CH 2 -, -CO-, -CO-NRE 1 -, -NRE 1 -CO-, -0-, -CH 2 -0-, -0-CH 2 -, -S-, -S-CH 2 -, -CH 2 -S-, -SO-, CH 2 -SO-, -SO-CH 2 -, -SO 2 -, -CH 2 -SO 2 -, 10 -SO 2 -CH 2 -, -NRE 1 -, -NRE 1 -CH2-, -CH2-NRE 1 , -SO2-NRE 1 -, -NRE 1 -S0 2 -, -CO-0-, -O-CO-, -C(=CRE 2 RE 3 )-, -CRE 2 =CRE 3 -, where RE 1 is H, 1 -Cr-alkyl, C-Ce-haloalkyl, Cr-C 6 -alkyl which has 1, 2 or 3 substituents REla, or 02-C6-alkenyl, C 2 -C 6 -alkynyl, C 3 -C7-CyCloalkyl, C 3 -C 7 -cycloalkyl-ClC4-alkyl, C 3 -Cz-heterocycloalkyl-C-C 4 -alkyl, 15 Cl-C 6 -alkoxy-Cr-C4-alkyl, CO-Cr 1 C 6 -alkyl, CO--CrC-alkyl, S0 2 -C C 6 -alkyl, aryl, hetaryl, aryl-Ce-C4-alkyl, hetaryl-Cr-C 4 -alkyl, CO-aryl, CO-hetaryl, CO-(aryl-Cr-C 4 -alkyl), CO-(hetaryl-Cr-C4-alkyl), CO-0 aryl, CO-0-hetaryl, CO-0-(aryl-Cr-C4-alkyl), CO-0-(hetaryl-CC4 alkyl), S02-aryl, S0 2 -hetaryl, S0 2 -(aryl-Cr-C 4 -alkyl) or S0 2 -(hetaryl 20 Ce1C4-alkyl), where aryl and hetaryl in the last 16 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents RE1d, and RE 2 , RE 3 are independently of one another selected from hydrogen, C1-C6 alkyl, C 1 C 6 -alkoxy, C2-C 6 -alkenyl, C 2 -C 6 -alkynyl, where the last 4 radicals mentioned may be partly or completely halogenated and/or 25 have 1, 2 or 3 substituents REla, C3-C7-cycloalkyl, C 3 -Cz-cycloalkyl-C-C4-alkyl, C3-C7-cycloalkyl-0, where a CH 2 group in the cycloalkyl moiety of the last three radicals mentioned may be replaced by 0, NH, or S, or two adjacent C atoms may form a double bond, where the cycloalkyl moiety may further 30 have 1, 2, 3 or 4 RElb radicals, aryl, hetaryl, aryl-Ci-C6-alkyl, or hetaryl-Cr-C4-alkyl, where aryl and hetaryl in the last 4 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals REId; and where REla has one of the meanings indicated for Ria, RElb has one of the 35 meanings indicated for Rib, and REid has one of the meanings indicated for 132 Rid; wherein W is bonded to a C atom of Y which is located in the position ortho to the C atom of Y which is connected to the carbonyl group; 5 and the tautomers thereof, the prodrugs thereof and the pharmaceutically suitable salts thereof, where the prodrugs are compounds of the formula I, where R 1 , R 2 , W, X and Y are as defined above and wherein R3a and R3b together form a group O-Alk-O, S-Alk-O or S-Alk-S, where Alk is linear C2-C 5 -alkandiyl, which 10 may be unsubstituted or substituted with 1, 2, 3 or 4 radicals selected from Cr-C4 alkyl or halogen, or wherein R3a and R3b together with the carbon atom form a group C=NR 3 , where R 3 is selected from H, Cl-C6-alkyl, C-C 6 -alkoxy, C2-C6 alkenyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C-C 4 -alkyl, C2-Ce-alkenyloxy, C3-C6 cycloalkyloxy and C3-C6-cycloalkyl-Cl-C4-alkyloxy. 15

2. The carboxamide compound as claimed in claim 1, in which W is a radical of the formulae W2.

3. The carboxamide compound as claimed in claim 2, in which m is 0 or 1 and, 20 when m = 1, Rw is selected from OH, F, Cl, CN, CF 3 , Cl-C 6 -alkyl which is unsubstituted or may have 1, 2 or 3 substituents Rwa, or Cr-C 6 -haloalkyl, C1-C6 alkoxy, C-C 6 -haloalkoxy and C 3 -C7-cycloalkyl.

4. The carboxamide compound as claimed in any of the preceding claims, in which 25 X in the formula I is a C(=O)-NRx 2 Rx 3 radical in which Rx 2 and Rx 3 have one of the aforementioned meanings, in which Rx 2 is H, OH, CN, Cr 1 C 6 -alkyl, C-C 6 -haloalkyl, C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, C2-C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl, C3-C7 cycloalkyl-C-C 4 -alkyl, C3-C7-heterocycloalkyl-C-C 4 -alkyl, C1C6-alkoxy 30 CrC4-alkyl, aryl, hetaryl, aryl-C-C4-alkyl or hetaryl-Cr-C 4 -alkyl, where aryl and hetaryl in the last 4 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents Rxd, and Rx 3 is H, C-Ce-alkyl, Cl-Ce-haloalkyl or C-C 6 -alkyl which has 1, 2 or 3 substituents Rxa, or 35 NRx2Rx3 is a nitrogen heterocycle of the following formulae: Rx 5 R X -N 0 -N N-Rx -N -N -N 133 in which Rx 5 is hydrogen or has the meaning indicated in claim 1 for Rxb.

5. The carboxamide compound as claimed in claim 4, in which X is C(O)-NH 2 . 5

6. The carboxamide compound as claimed in any of the preceding claims, in which R 1 is selected from C1-C1o-alkyl which may be partly or completely halogenated and/or have 1, 2 or 3 substituents Ria, C3-C7-cycloalkyl-C1-C 4 -alkyl, where the cycloalkyl moiety may have 1, 2, 3 or 4 10 radicals R1b, phenyl-C 1 -C 4 -alkyl and hetaryl-C 1 -C 4 -alkyl, where phenyl and hetaryl in the last 2 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals Ric. 15

7. The carboxamide compound as claimed in any of the preceding claims, in which Y in the formula I is a divalent heteroaromatic radical which is selected from pyridindiyl and pyrimidindiyl and optionally has 1 or 2 identical or different substituents RY. 20

8. The carboxamide compound as claimed in any of the preceding claims, in which RY is selected from OH, F, Cl, NH 2 , CN, CF 3 , -CHF 2 , 0-CF 3 , O-CHF 2 , O-CH 2 F, Ci-C 6 -alkyl, C 3 -C7-cycloalkyl, C 1 -C 6 -alkylamino, C 1 -Ce-dialkylamino, pyrrolidinyl, piperidinyl, morpholinyl, imidazolyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, CONRy 2 Ry 3 , SO 2 NRy 2 Ry 3 , -NH-S0 2 -Ry 4 , -(CH 2 )p-NR 6 R7, NH-CO-R 5 , in which p 25 is 1, 2, 3, 4, or 5, and Ry 2 , Ry 3 , Ry 4 , Ry 5 , Ry 6 , Ry 7 are H or C 1 -C 6 -alkyl, phenyl, benzyl and O-benzyl, where the phenyl ring in the last 3 groups mentioned may have 1, 2 or 3 substituents selected from halogen, OH, SH, NO 2 , COOH, C(O)NH 2 , CHO, CN, NH 2 , OCH 2 COOH, C1-Ce-alkyl, C 1 -C 6 -haloalkyl, C1-C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, 30 CO-C 1 -C 6 -alkyl, CO-0 1 -Ce-alkyl, NH-C 1 -C 6 -Alkyl, NHCHO, NH-C(O)C1-C 6 -alkyl, and S0 2 -C 1 -C 6 -alkyl.

9. The carboxamide compound as claimed in any of the preceding claims, which corresponds to the formula I-A 35 (R') O R4 2Y N (I-A) Il3b R 3 a 3 H R R 2 Y4 W-R 134 in which X, W, R4, R 2 , R3a, R3b, RY have the aforementioned meanings, n is 0, 1 or 2, one of the variables Y 1 , Y2, Y3 and Y4 is a nitrogen atom, and the remaining variables Y1, Y2, Y 3 or Y4 are CH, the tautomers thereof, the prodrugs thereof and the pharmaceutically suitable salts thereof, where the prodrugs are as defined in 5 claim 1..

10. The carboxamide compound as claimed in any of the preceding claims, which corresponds to the formula 1-A.a, (R Y) O R4 x N (I-A. a) H 3b 3a H R R 2 10 N W-R in which X, W, R 1 , R 2 , R3a, R3b, RY have the aforementioned meanings, and n is 0, 1 or 2, the tautomers thereof, the prodrugs thereof and the pharmaceutically suitable salts thereof, where the prodrugs are as defined in claim 1. 15

11. The carboxamide compound as claimed in any of the preceding claims, which has the S configuration at the carbon atom carrying the group R 1 .

12. A medicament comprising at least one carboxamide compound as claimed in any 20 of claims 1 to 11, a tautomer, a prodrug or a pharmaceutically suitable salt thereof, where the prodrugs are as defined in claim 1.

13. The carboxamide compound as claimed in any of claims 1 to 11 for use in therapy. 25

14. The carboxamide compound as claimed in any of claims 1 to 11 for use in therapy of a disorder, an impairment or a condition which is associated with an elevated calpain activity. 30

15. The carboxamide compound as claimed in any of claims 1 to 11 for use in therapy of a disorder, an impairment or a condition, where the disorder, impairment or condition is selected from neurodegenerative disorders or impairments; epilepsy; pain; damage to the heart following cardiac ischemias; damage to the kidneys following renal ischemias; skeletal muscle damage; 35 muscular dystrophies; damage resulting from proliferation of smooth muscle cells; coronary vasospasms; cerebral vasospasms; macular degeneration; cataracts of the eyes; or restenosis of the blood vessels following angioplasty; 13b and disorder or an impairment associated with an elevated interleukin-1, TNF or AB level.

16. The carboxamide compound as claimed in any of claims 1 to 11 for use in 5 chemotherapy of tumors and metastasis thereof.

17. The carboxamide compound as claimed in any of claims 1 to 11 for use in the treatment of HIV patients. 10

18. The carboxamide compound as claimed in any of claims 1 to 11, for use in the treatment of neurodegenerative disorders or impairments, where the neurodegenerative disorder occurring as a result of a chronic brain supply deficit, an ischemia or a trauma is involved. 15

19. The carboxamide compound as claimed in any of claims 1 to 11, for use in the treatment of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis or Huntington's disease.

20. The carboxamide compound as claimed in any of claims 1 to 11, for use in the 20 treatment of multiple sclerosis and concomitant damage to the nervous system. Dated 9 January 2013 Abbott GmbH & Co. KG 25 Patent Attorneys for the ApplicantlNominated Person SPRUSON & FERGUSON