BG106392A - 2-pyrazolin-5-ones - Google Patents

Abstract

Chemical compounds having structural formula wherein the substituents have the meanings given in the description and physiologically acceptable salts thereof are inhibitors of serine/threonine and tyrosine kinase activity. Several of the tyrosine kinases, whose activity is inhibited by these chemical compounds are involved in angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyperproliferative disorders. 45 claims

Description

Technical field

The application is based on the benefits of US pre-application no. 60 / 146,563, filed July 30, 1999, the full explanations of which are incorporated herein by reference.

The invention relates to certain 2-pyrazolin-5-ones which are inhibitors of protein kinases, in particular tyrosine kinases and serine / threonine kinases, some of which are novel, to pharmaceutical compositions containing such pyrazolinones and to methods for preparing these pyrazolinones.

BACKGROUND OF THE INVENTION

There are at least 400 enzymes identified as protein kinases. These enzymes catalyze the phosphorylation of the target protein substrates, phosphorylation is usually a reaction of the transfer of a phosphate group from adenosine-5'-triphosphate (ATf) to the protein substrate. The specific structure of the target substrate to which the phosphate is transferred is a tyrosine, serine or threonine residue. Because these amino acid residues are the target structures for phosphoryl transfer, these protein kinase enzymes usually refer to tyrosine kinases or serine / threonine kinases.

Phosphorylation reactions and adverse reactions of phosphatase to the tyrosine, serine and threonine residues are involved in a number of cellular processes that underlie reactions for various intracellular signals (usually mediated by cellular receptors), regulation of cellular functions, and activation or activation of cells . Multiple protein kinases are often involved in intracellular signaling and are required for the realization of these cellular processes. Due to their comprehensive involvement in these processes, protein kinases can be detected as an integral part of the plasma membrane, or as cytoplasmic enzymes, or localized in nuclei often as components of enzyme complexes. In many cases, these protein kinases are an essential element of the enzyme and structural protein complexes and determine where and when processes occur within the cell.

Protein tyrosine kinases. Protein tyrosine kinases (PTKs) are enzymes that catalyze the phosphorylation of certain tyrosine residues in cellular proteins. Such post-sequential modification of these major proteins, often enzymes themselves, acts as a molecular switch regulating cell proliferation, activation or differentiation (for a review, see Schlessinger and Ulrich, 1992, Neuron 9: 383-391). Abnormal or excessive activity of protein tyrosine kinases has been observed in many disease states, including benign and malignant proliferative disorders, as well as diseases resulting from inappropriate activation of the immune system (eg autoimmune disorders), graft rejection and homologous graft disease (graft-versus-host reaction). In addition, specific endothelial cell receptors (RTKs), such as KDR and Tie-2, mediate the angiogenic process and thus participate in stimulating the development of cancers and other diseases that involve inappropriate vascularization (eg diabetic retinopathy, choroidal neovascularization due to age-related macular degeneration, psoriasis, arthritis, premature retinopathy, childhood hemangiomas).

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Tyrosine kinases can be of the receptor type (having extracellular, transmembrane and intracellular regions) or non-receptor type (being entirely intracellular).

Receptor tyrosine kinases (RTK). Receptor tyrosine kinases include the large family of transmembrane receptors with diverse biological activities. At least nineteen (19) individual RTK subfamilies are currently identified. the receptor tyrosine kinase (RTK) family includes receptors that are crucial for the growth and differentiation of a number of cell types (Yarden and Ullrich, Ann. Rev. Biochem. 57: 433478, 1988; Ullrich and Schlessinger, Cell 61: 243-254, 1990 ). An essential function of RTK is the activation of ligand binding, which is obtained by phosphorylation of the receptor and a number of cellular substrates and subsequently in multiple cellular responses (Ullrich & Schlessinger, 1990, Cell 61: 203-212). Thus, receptor tyrosine kinase signaling is caused by extracellular interaction with a specific growth factor (ligand), usually followed by receptor dimerization, stimulation of intrinsic protein tyrosine kinase activity, and receptor trans-phosphorylation. This creates binding sites for intracellular signaling molecules and this leads to the formation of complexes with a wide range of cytoplasmic signaling molecules that facilitate the corresponding cellular response (eg cell division, differentiation, metabolic effects, changes in the extracellular microenvironment), see Schlessinger and 1992, Neuron 9: 1-20.

Proteins with SH2 (src homology-2) or phosphotyrosine-binding (PTB) domains bind activated tyrosine kinase receptors and their substrates with strong affinity for cell signaling. Both areas recognize phosphotyrosine. (Fantl et al., 1992, Cell 69: 413423; Songyang et al., 1994, Mol. Cell. Biol. 14: 2777-2785; Songyang et al., 1993, Cell; · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ····

72: 767-778; and Koch et al., 1991, Science 252: 668 ^ 678; Shoelson, Carr. Opin. Chem. Biol. (1997), 1 (2), 227-234; Cowbum, Curr. Opin. Struct. Biol. (1997), 7 (6), 835838). Separate intracellular substrate proteins have been identified that bind to receptor tyrosine kinases (RTKs). They can be divided into two main groups: (1) substrates having a catalytic domain; and (2) substrates that lack such an area but serve as adapters and bind to catalytically active molecules (Songyang et al., 1993, Cell 12: 767-778). The specificity of interactions between receptors or proteins and the SH2 or PTB regions of their substrates binds to the amino acid residues immediately surrounding the tyrosine residue. For example, differences in binding affinity between SH2 domains and amino acid sequences surrounding phosphotyrosine residues at specific receptors are consistent with the differences observed in the phosphorylation profiles of their substrates (Songyang et al., 1993, Cell 72: 767-778). Based on the observations, it is suggested that the function of each receptor tyrosine kinase is determined not only by its expression and presence of ligands, but also by the avalanche signaling that is activated by the individual receptor, as well as by finding the appropriate moment and duration for these stimuli. Thus, phosphorylation provides an important regulatory step that determines the selectivity of signal transduction pathways enhanced by specific growth factor receptors as well as by differentiation factor receptors.

Some receptor tyrosine kinases, such as FGFR-1, PDGFR and c-Met, and growth factors that bind to them, are thought to play a role in angiogenesis, although some may indirectly stimulate angiogenesis (Mustonen and Alitalo, J. Cel I Biol 129: 895-898,1995). One such receptor tyrosine kinase, known as embryonic liver kinase 1 (FLK-1), is a member of the type III receptor tyrosine kinase subclass. Alternative designation for human • · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

FLK-1 is a receptor with an insertion kinase region (KDR) (Terman et al., Oncogene 6: 1677-83, 1991). Another indication for FLK-1 / KDR is vascular endothelial cell growth factor receptor 2 (VEGFR-2), as it binds vascular endothelial cell growth factor (VEGF) with high affinity. The mouse version of FLK-1 / VEGFR-2 is also called ΝΎΚ (Oelrichs et al, Oncogene 8 (1): 11-15, 1993). DNA encoding mouse, rat, and human FLK-1 was isolated and the nucleotide and the coding amino acid sequence reported (Matthews et al., Proc. Natl. Acad. Sci. USA, 88: 9026-30, 1991; Terman et al. , 1991, as above, · Terman et al., Biochem. Biophys. Res. Comm 187: 1579-86, 1992; Sarzani et al., As above; and Millauer et al., Cell 72: 835 -846,1993). A number of studies, such as those reported by Millauer et al., As above, suggest that VEGF and FLK-1 / KDR / VEGFR-2 are ligand-receptor pairs that play important roles in vascular endothelial proliferation and the formation and growth of blood vessels called vasculogenesis and angiogenesis respectively.

Another subclass, type III receptor tyrosine kinase, termed fms-like tyrosine kinase-1 (Fit-1), is associated with FLK-1 / KDR (DeVries et al. Science 255; 989-991, 1992; Shibuya et al., Oncogene 5 : 519-524, 1990). An alternative designation of Flt-1 is vascular endothelial cell growth factor receptor (VEGFR) receptor 1. So far, members of the FLK-1 / KDR / VEGFR-2 and Flt-1 / VEGFR-1 subfamilies have been found expressed mainly on endothelial cells. These subclass members are specifically stimulated by members of the vascular endothelial cell growth factor (VEGF) family of ligands (Klagsbum and D'Amore, Cytokine & Growth Factor Reviews 7: 259270, 1996). Vascular endothelial cell growth factor (VEGF) binds to Flt-1 with greater affinity than to FLK-1 / KDR and is mitogenic to vascular endothelial cells (Terman et al., 1992, as above; Mustonen et al. above; DeVries et al., as above).

Flt-Ι is thought to be important for endothelial organization during vessel development. Flt-Ι expression is associated with early vascular development in mouse embryos and neovascularization during wound healing (Mustonen and Alitalo, as above). Expression of Flt-Ι in adult organs such as renal glomeruli speaks of an additional function of these receptors that is unrelated to cellular growth (Mustonen and Alitalo, as above).

Recent findings suggest that VEGF plays a role in stimulating normal and pathological angiogenesis (Jakeman et al., Endocrinology 133: 848-859, 1993; Kolch et al, Breast Cancer Research and Treatment 36: 139-155,1995 ; Ferrara et aL, Endocrine Reviews 18 (1); 4-25, 1997; Ferrara et al., Regulation of Angiogenesis (ed. LD Goldberg and EM Rosen), 209-232, 1997). In addition, VEGF is involved in the control and increase of vascular permeability (Connolly, et al., J. Biol. Chem. 264: 20017-2004,1989; Brown et al., Regulation of Angiogenesis (ed. LD Goldberg and EM Rosen), 233 -269,1997).

Various forms of VEGF have been reported to occur in alternative m-ribonucleic acid splicing, including the four species described by Ferrara et al. (J. Cell. Biochem. 47: 211-218, 1991). Both types of VEGF - both hidden and predominantly cell-bound - have been identified by Ferrara et al., As above, and the protein is known to exist in the form of disulfide-linked dimers.

Some VEGF-related homologs have recently been identified. However, their role in normal physiological and disease processes has not yet been studied. In addition, members of the VEGF family are often co-expressed with VEGF in a variety of tissues and are usually capable of forming heterodimers with VEGF. This property probably alters receptor specificity and the biological effects of heterodimers and further complicates the evaluation of their specific functions, as shown below (Korpelainen and Alitalo, Korpelainen and Alitalo,

Curr. Opin. Cell Biol, 159-164, 1998 and sources cited therein).

The placenta growth factor (P1GF) has an amino acid sequence that shows significant homology to the VEGF sequence (Park et al., J. Biol. Chem. 269: 25646-54, 1994; Maglione, et al. Oncogene 8 : 925-31,1993). As with VEGF, different types of P1GF occur in alternative junction of t-ribonucleic acid and the protein is in dimeric form (Park et al., As above). P1GF1 and P1GF-2 bind to Fit-Ι with greater affinity, and P1GF-2 binds readily also to neuropilin-1 (Migdal et al, J. Biol. Chem. 273 (35): 2227222278), but does not binds to FLK-1 / KDR (Park et al., as above). P1GF has been reported to potentiate vascular permeability and mitogenic action of VEGF on endothelial cells when it attaches VEGF at low concentrations (thought to be due to heterodimer formation) (Park et al., As above).

VEGF-B is obtained as two isomeric forms (167 and 185 residues) that also appear to bind Fit-1 / VEGFR-1. It may play a role in the regulation of extracellular matrix degradation, cell adhesion and migration by modulating the expression and activity of the urokinase-type plasminogen activator and plasminogen activator inhibitor 1 (Pepper et al, Proc. Natl. Acad. Sci. USA (1998) ), 95 (20): 11709-11714).

VEGF-C is naturally cloned as a ligand for VEGFR-3 / Flt-4, which is mainly expressed by lymphatic endothelial cells. In its fully processed form, VEGF-C can also bind KDR / VEGFR-2 and stimulate endothelial cell proliferation and migration in vitro and angiogenesis in in vivo models (Lymboussaki et al, Am. J. Pathol. (1998), 153 (2): 395-403; Witzenbichler et al., Am. J. Pathol. (1998), 153 (2), 381-394). Transgenic overexpression of VEGF-C causes proliferation and enlargement of the lymphatic vessels only, while the blood vessels remain unaffected. Unlike VEGF · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · The expression of VEGF-C is not induced by hypoxia (Ristimaki et al, J. Biol. Chem. (1998), 273 (14), 8413-8418). ).

The recently discovered VEGF-D is structurally very similar to VEGF-C. VEGF-D has been reported to bind and activate at least two VEGF receptors - VEGFR-3 / FH-4 and KDR / VEGFR-2. By nature, it is cloned as a c-fos mitogen-inducing fibroblast and is most expressed in lung and skin mesenchymal cells (Achen et al, Proc. Natl. Acad. Sci. USA (1998), 95 (2), 548- 553 and the sources cited therein).

u VEGF, VEGF-C and VEGF-D have been reported to cause an increase in vascular permeability in vivo when injected into skin tissue with Mile analysis (PCT / US97 / 14696; WO98 / 07832; Witzenbichler et al, as above ), the physiological role and relevance of these ligands in modulating vascular hyperpermeability and endothelial responses in the tissues where they are expressed remain unclear.

Recently, a virus-encoded new type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), has been reported that predominantly utilizes the KDR / Flk-тор receptor and possesses strong mitogenic activity without a heparin binding region (Meyer et al, EMBO J. ( 1999), * 18 (2), 363-374; Ogawa et al., J. Biol. Chem. (1998), 273 (47), 31273-31282.).

VEGF-E sequences have about 25% homology to animal VEGF and are encoded by the parapox virus Orf virus (OV). This parapox virus, which acts on sheep and goats and in some cases in humans, leads to impaired angiogenesis. VEGF-E is a dimer of about 20 kDa with no base region and no affinity for heparin, but possesses the characteristic cysteine assembly present in all mammalian VEGFs and is surprisingly found to possess strength and bioactivity similar to the heparin binding VEGF 165 isoform of VEGF- A, ie. both factors stimulate tissue factor (TF) release, proliferation, chemotaxis, and new growth of cultured vascular endothelial cells in vitro and angiogenesis in vivo. Like VEGF 165, VEGF-E has been found to bind with high affinity for VEGF receptor-2 (KDR), resulting in autophosphorylation of the receptor and a two-phase increase in free intracellular Ca 2+ concentrations, whereas unlike VEGF 165 VEGF-E does not bind to VEGF receptor-1 (Flt-1).

Based on the newly discovered findings of other VEGF and VEGFR homologs and the precedents of ligand and receptor heterodimerization, the action of such VEGF homologs may involve the formation of VEGF ligand heterodimers and / or heterodimerization of receptors, or binding to the still undetectedRF (Witzenbichler et al., As above). Recent reports have also suggested that neuropilin-1 (Migdal et al., As above) or VEGFR-3 / Flt-4 (Witzenbichler et al., As above), or receptors other than KDR / VEGFR- 2, may be involved in inducing vascular permeability (Stacker, SA, Vitali, A., Domagala, T., Nice, E. and Wilks, A. F., Angiogenesis and Cancer Conference, Amer. Assoc. Cancer Res., Jan. 1998 , Orlando, FL; Williams, Diabetelogia 40: S118-120 (1997). To date, there is no direct evidence of a significant role for KDR in VEGF mediated vascular permeability.

Non-receptor tyrosine kinases. Non-receptor tyrosine kinases are a collection of cellular enzymes that lack extracellular and transmembrane sequences. Currently, over twenty-four distinct non-receptor tyrosine kinases have been identified, including eleven (11) subfamilies (Src, Frk, Btk, Csk, Abl, Zap70, Fes / Fps, Fak, Jak, Ack, and LIMK). Currently, the subfamily Src of non-receptor tyrosine kinases consists of the largest number of receptor tyrosine kinases and includes Src, Yes, Fyn, Lyn, Lek, Blk, Hck, Fgr, and Yrk. The Src subfamily of enzymes has been linked to oncogenesis and immune responses. A more detailed discussion of the · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Non-receptor tyrosine kinases are given in Bolen, 1993, Oncogene 8: 20252031, which source is incorporated herein by reference.

Many of the tyrosine kinases, receptor or non-receptor, have been found to be involved in cellular signaling pathways involved in a number of pathogenic conditions, including cancer, psoriasis, and other over-proliferative disorders or over-immune responses.

Development of receptor tyrosine kinase-modulating compounds. In view of the supposed importance of receptor tyrosine kinases for the control, regulation and modulation of cells in cell proliferation, diseases and disorders associated with atypical cell proliferation, many attempts are made to identify "inhibitors" of receptor and non-receptor tyrosine kinases approaches, including the use of mutant ligands (US Application No. 4,966,849), soluble receptors, and antibodies (Application No. WO 94/10202; Kendall & Thomas, 1994, Proc. Natl. Acad. Sci 90: 10705-09; Kim et al , 1993, Nature 362: 841-844), PHK ligands (Jellinek, et a 1, Biochemistry 33: 10450-56; Takano, et al., 1993, Mol. Bio. Cell 4: 358A; Kinsella, et al. 1992, Exp. Cell Res 199: 56-62; Wright, et al. , 1992,7. Cellular Phys. 152: 448-57) and tyrosine kinase inhibitors (WO 94/03427; WO 92/21660; WO 91/15495; WO 94/14808; US Patent No. 5,330,992; Mariani, et al. , 1994, Proc. Am. Assoc. Cancer Res. 35: 2268).

More recently, attempts have been made to identify small molecules that act as tyrosine kinase inhibitors. For example, bismonocyclic, bicyclic or heterocyclic aryl compounds (PCT WO 92/20642) and vinylene-azaindole derivatives (PCT WO 94/14808) are described mainly as tyrosine kinase inhibitors. Styril Compounds (US Patent No. 5,217,999), Styryl-substituted Pyridyl Compounds (US Patent No. 5,217,999)

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5,302,606), some quinazoline derivatives (European Patent Application No. 0 566 266 A1; Expert Opin. Ther. Pat. (1998), 8 (4): 475-478), selenoindoles and selenides (PCT WO 94/03427), tricyclic polyhydroxyl compounds (PCT WO 92/21660) and benzylphosphonic acid compounds (PCT WO 91/15495) are described as compounds useful as tyrosine kinase inhibitors for the treatment of cancer. Anilincinolines (PCT WO97 / 34876) and quinazoline derivatives (PCT WO97 / 22596; PCT WO97 / 42187) have been described as inhibitors of angiogenesis and vascular permeability.

In addition, attempts have been made to identify small molecules that act as serine / threonine kinase inhibitors. For example, bis (indolylmaleimide) compounds have been described as specifically inhibiting PKC serine / threonine kinase isoforms whose impaired transductive function is associated with altered vascular permeability in VEGF-related diseases (PCT WO97 / 40830; PCT WO97 / 40831).

Plk-kinase inhibitors

Plk-1 is a serine / threonine kinase, which is an important regulator of the course of the cell cycle. It plays a critical role in the overall and dynamic function of the mitotic spindle. Plk-1 and the corresponding kinases have also been shown to be closely linked to the activation and inactivation of other cell cycle regulators such as cyclin-dependent kinases. High levels of Plk-пре expression are associated with cell proliferative activities. This is often found in malignant tumors of various types. Plk-ин inhibitors are expected to block cancer cell proliferation by disrupting processes involving mitotic spindles and inappropriately activated cyclin-dependent kinases.

Cbc2 / tchklin B kinase inhibitors (Cdc2, also known as cdkl)

CClc2 / cyclin B is another serine / threonine kinase enzyme that ·· ♦ ·

belongs to the family of cyclin-dependent kinases (cdks). These enzymes are involved in the critical transitions between a number of cell cycle phases. Uncontrolled cell proliferation, which is a sure guarantee of cancer, is thought to be dependent on increased cdk activity in these cells. Inhibition of increased cdk activity in cancer cells by cbc2 / cyclin B kinase inhibitors could suppress proliferation and restore normal control of the course of the cell cycle.

Therefore, it is desirable to identify effective small compounds that specifically inhibit signal transduction and cell proliferation by modulating the activity of receptor and non-receptor tyrosine and serine / threonine kinases to regulate and modulate atypical and inappropriate cell proliferation, differentiation or metabolic. In particular, it would be advantageous to identify methods and compounds that specifically inhibit the function of tyrosine kinase, which is essential for angiogenic processes or the production of vascular hyperpermeability leading to edema, ascites, effusions, exudates and macromolecular extravasation, as well as matrix deposition, and related diseases.

SUMMARY OF THE INVENTION

The invention is directed to compounds of formula

N

I.

and physiologically acceptable salts thereof, wherein R is a substituted or unsubstituted aliphatic, aromatic, heterocyclic or aralkyl group and R ² is hydrogen, a lower alkyl group or an aryl group. R ¹ is hydrogen or -A-Z, wherein A is - (CH2) n-, - ( CH2) nNH-, - (CH2) nO-, - (CH2) nS -, - (CH2) nS (O) or - (CH 2) n S (O) 2 -; and Z is -H, lower alkyl, aralkyl, trihalomethyl, RCO-, trihalomethylcarbonyl, R ³ OC (O) -, -NR'fc ⁵ , -QOjNR ^ R ⁵ , R ³ O- or a ring system selected from the group consisting of _C3-C6 cycloalkane, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, thiophene, imidazole, furan, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole, benzothiazole, tetrahydrofuran, triazine and their applicable N-oxides, which may optionally a

are substituted by one or more halogens, lower alkyl, R Ο-, HO-, NOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CH 2, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ . In each case, R ³ is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C3C6) cycloalkyl group, heterocyclic group, aralkyl group, (C3C6) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group. In each case, R ⁴ and R ⁵ are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C _{A 3-} C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally K and R together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, ·· ♦ · · ·· H | «*« · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 14 (C ₃ -C ₆ ) cycloalkyl-alkyl group and heterocycles a l-alkyl group; The letter index η is an integer from 0 to 3.

Suitable substituents for R include halogens, lower alkyl rpynas, R ³ O-, hydroxy, NOC (O) -, R ³ OC (O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, nitro, -C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, - (CH 2) n R ⁷ , - C (O) (CH 2) _n -R ⁷ , -QO) - ( CH2) nC (O) -R ⁷ > -O (CH 2) _n R ⁷ , -C (O) NR ⁴ (CH 2) "R ⁷ , -C (O) O (CH 2)" R ⁷ , -OC (O ) (CH ₂ ) „R ⁷ ,

-NRYOXCH ^ R ⁷ , -RWE ⁵ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -RYfR ^ R'fc • -R ⁶ C (O) NR ⁴ (CH,) "R ⁷ , - R ⁶ C (O) O (CH ₂ ) „R ⁷ , ^ occoxch ^ r ⁷ ,

4 <Wc (OXCH ₂ ) _n R ⁷ -R ⁶ CH [C (O) OR ⁴ ] [NR ⁵ C (O) R ⁴ ] or a substituted aryl or aralkyl group wherein the substituent is selected from the group consisting of halogen , trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , a lower alkyl group, R ³ O-, -C (O) OR ⁴ or -OC (O) R. R is a lower alkyl group or an aryl group. R is alkoxy, haloalkyl, lower alkylpiperazine, hydroxy, R O-, R C (O) or -NR ⁴ R ⁵ .

u Suitable substituents for R ³ , R ⁴ and R ⁵ include one or more groups selected from the group consisting of halogens, lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkyl ester, trihalomethyl, preferably trifluoromethyl, nitro, phenyl , phenyl-lower alkyl, (C ₃ -C ₆ ) cycloalkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl, CN, amino, alkylamino, dialkylamino, -C (O) NH ₂ , -C (O) MH (alkyl ) and -C (O) M (alkyl) ₂ .

Aliphatic groups include straight chained or branched _Cl-C18 hydrocarbons or cyclic Q-C18 hydrocarbons which are completely saturated or which contain one or more degrees of • · ··· · · · ···· ·· «·· ·· · · · · · · · · · · · · · · · · · · · · · · · · · Insaturation. The lower alkyl groups are straight or branched C ₁ -C ₆ hydrocarbons or C ₃ -C ₆ cyclic hydrocarbons which are fully saturated.

Aromatic groups as used herein include carbocyclic ring systems (e.g. benzyl and cinnamylidene) and fused polycyclic aromatic ring systems (e.g. naphthyl). In addition, the aromatic groups include heteroaryl ring systems (e.g., pyridine, thiophene, furan, pyrrole, imidazole, oxazole, thiazole, pyrazole, triazole, pyrimidine and pyrazine) and heteroaryl ring systems in which a carbocyclic aromatic ring or carboxylic ring aromatic fused to one or more other heteroaryl rings (e.g., benzimidazole, benzothiazole, indole, tetrahydroindole, azaindole, indazole, isoxazole, isothiazole, imidazole and quinoline). Aryl groups as used herein refer to an aromatic group having 5 or 6 atoms. An aralkyl group is an aromatic substituent which is bonded to the compound by an aliphatic group having from one to six carbon atoms. The heterocyclic group as used herein refers to a mono-, bi-, or tricyclic heterocyclic group that is non-aromatic or unsaturated, and unsaturation does not make the group aromatic.

The invention includes tautomers, stereoisomers, enantiomers and mixtures of these compounds. The invention also includes pharmaceutically acceptable addition salts of these compounds.

In one embodiment, R ² is hydrogen and R is preferably substituted indole or substituted or unsubstituted imidazole, 1,2,3-triazole, 1,2,4 triazole, benzimidazole, pyrrole, pyrazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene • or • pyrazine.

In one preferred embodiment, R is hydrogen, η is zero and Ζ is a cyclopropyl, 3-pyridyl or pyrazinyl group. In another preferred embodiment, R is hydrogen, A is -Ο-, η is 0 and Ζ is ethyl, propyl or isopropyl. In another preferred embodiment, R is hydrogen, A is CH ₂ , η is 2, and Ζ is benzene, optionally substituted by halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -C (O) NR ⁴ R ⁵ , lower an alkyl group, R ³ O-, -C (O) (R ⁴ or -OC (O) R ³ .

In a preferred embodiment, the present invention is directed to a compound represented by the following formula:

and its physiologically acceptable salts, where:

R is selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole , pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O, or a ring system selected from the group consisting of a C ~ C ₆ myySh

·· · · · · · · · · ··· 9 «« • 9 · 9 · · · · 99

99999 99 999 9

999 99 99 99 9999 Cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, pyrazolidine, pyridazine, pyrazolidine The N-oxides where said ring system may be optionally substituted are one or more groups selected from the group consisting of halogens, lower alkyl, R Ο-, HO-, NOC (O) -, R OC (O) - , trihalomethyl, nitro, an aromatic group (C ₆₎ cycloalkyl group, a heterocyclic group, an aralkyl group, _(C-C6) cycloalkyl-alk hunt group, heterocyclylalkyl group, -CN, -C (O) NR ⁴ R ⁵ or - NRA;

In each case, R ³ is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ a cycloalkyl-alkyl group and a heterocyclyl-alkyl group;

In each case, R ⁴ and R ⁵ are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C 3 -C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

5 optionally K and k together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4diazepin-1-yl groups, each optionally substituted or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, an aromatic group (C ₆₎ cycloalkyl group, a heterocyclic group, an aralkyl group, _(C-C6) cycloalkyl-alkyl • · A group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3;

provided that when R is unsubstituted indol-3-yl, R is not-не ₂ .

In another preferred embodiment, the present invention is directed to a compound represented by the following structural formula:

and their physiologically acceptable salts, where:

R is selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7tetrahydroindole, benzoindole, azaindole, indazole, pyridine , quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O, or a ring system selected from the group consisting of C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyrimidazole, benzazidine , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, · * · · · * ·· ·· * · 4 · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group, heterocyclyl-alkyl group, -CN, C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

a

R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 - C6) cycloalkyl-alkyl group and heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl groups, each optionally substituted with one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, an aromatic group, (S3S ₆₎ cycloalkyl group, a heterocyclic group, an aralkyl group, (C ₃ C ₆₎ cycloalkyl-alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3;

in case that:

when R is unsubstituted indol-3-yl, R ¹ is not -ΝΗ ₂ ; and when R is substituted or unsubstituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or thiazole; then R ¹ is not lower alkyl, (C ₃ C ₆ ) cycloalkyl, benzene or -C (O) NR ⁴ R ⁵ , wherein R ⁴ and R ⁵ are each independently H, lower alkyl or carbocyclic aryl.

In another preferred embodiment, the present invention is directed to a compound represented by the following structural formula:

and their physiologically acceptable salts, where:

R is selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7tetrahydroindole, benzoindole, azaindole, indazole, pyridine , quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O, or a ring system selected from the group consisting of C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyrimidazole, benzazidine , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, C 1-6 alkyl, R ³ O-, HO-, NOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C _{A 3} -C ₆ ) cycloalkyl-alkyl group, a heterocyclyl-alkyl group, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4diazepin-1-yl groups, each optionally substituted with one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl- an alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3; in case that:

a) R is not pyrrol-3-yl or pyrrol-3-yl substituted with an alkyl or carbocyclic aryl group;

b) R is not indol-3-yl or indol-3-yl substituted with alkyl or · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 99 99 9999 Carbocyclic aryl group; and

c) R is not azaindole or azaindole substituted at the 2-position by an alkyl or carbocyclic aryl group.

In another preferred embodiment, the present invention is directed to a compound represented by the following structural formula:

and its physiologically acceptable salts, where:

R is substituted pyrrole or selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole , indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or

- (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ^ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or the ring system selected from the group consisting of C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidine , pyrazole, oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R -, NO-, NOS (O) -, • · ♦ · ·· «·« · · ♦ «« ·· · · · · · · • · · · · · · · · · · · · · 3 · · · · · · · · · · · · · · Nitro, aromatic group, (C ₃ a

R OC (O) -, trihalomethyl,

C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group, heterocyclyl-alkyl group, -CN, -C (O) NR ⁴ R ⁵ or - NRV ⁵ ;

ο

R in each case is independently selected from the group consisting of: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ a cycloalkyl-alkyl group and a heterocyclyl-alkyl group;

R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4 diazepine-tyloxy groups, each optionally substituted by one or more more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3;

in case that:

About Z about Z

a) when R is substituted pyrrole, the pyrrole is substituted with R OC (O) R, R OR7 7 trihalomethyl, trihalomethylcarbonyl, - (CH ₂ ) pR, -O (CH ₂ ) pR,

-C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH 2) p R ⁷ , -OC (O) (CH ₂ ) p R ⁷

-N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ^ R ^ -R ^ R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) _p R ⁷ , -R ⁶ OC (O) (CH 2) p R ⁷ , -R ⁶ N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ );

substituted aryl or aralkyl group wherein:

R ⁶ in each case is independently a lower alkyl group or an aryl group;

R ⁷ in each case is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxy, R ³ O-, R ³ C (O) - or NR ⁴ R ⁵ ; and p is an integer of 1-3;

and g

b) when R is indol-3-yl, the indol-3-yl is substituted with R OC (O) R,

R OR -, trihalomethyl, trihalomethylcarbonyl, - (CH ₂ ) _p -R, -O (CH ₂ ) _p R ⁷ , -C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O ( CH2) _p R ⁷ ,

-OC (CH ₂ ) _p R ⁷ , -N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , - R ^ R ^ R ⁷ ) * -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH ₂ ) p R ⁷ ,

-R ⁶ OC (O) (CH 2) p R ⁷ , -R ⁶ N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group; and

c) when R is pyrazol-3-yl, pyrazol-3-yl is substituted with

D £ O £

R OC (O) R, R OR -, trihalomethyl, trihalomethylcarbonyl, - (CH ₂ ) _p -R ⁷ , -O (CH 2) p R ⁷ , -C (O) N (R 4) (CH ₂ ) _p R ⁷ , -C (O) O (CH 2) p R ⁷ , -OC (O) - (CH 2) _p R ⁷ , -N (R ⁴ ) Q O) (CH 2) _p R ⁷ -r ^ rV ⁵ , -R ^ R ^ - R ^ R ⁷ , -R ^ -R ⁷ ), -R ⁶ Q O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ Q O) O (CH ₂ ) p R ⁷ , ^ 00 (0) (01 N, -R ⁶ N (R ⁴ ) C (O) (CH ₂ ) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or substituted aryl or an aralkyl group.

In another preferred embodiment, the present invention is directed to a compound represented by the following structural formula:

and their physiologically acceptable salts, where:

R is substituted pyrrole or selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole , indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O, or a ring system selected from the group consisting of C3-C6 cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, benzazidine, pyrazine , thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R ³ O, HO-, NOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group , heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or -NR ^ R ^5;

• · · · * · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

R is in each case independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ - C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C _{A 3-} C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4diazepin-1-yl groups, each optionally substituted with one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl- an alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3;

in case that:

a) when R is unsubstituted indol-3-yl then R ¹ is not -ΝΗ ₂ ;

b) when R is substituted or unsubstituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or thiazole; then R is not lower alkyl, (C ₃ -C ₆ ) cycloalkyl, benzene or -C (O) NR ⁴ R ⁵ , where R ⁴ and R ⁵ are each independently H, lower alkyl or carbocyclic aryl;

c) R is not pyrrol-3-yl or pyrrol-3-yl substituted with an alkyl or carbocyclic aryl group;

Μ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 9 9 · ·

999 99 99 99 9999

d) R is not indol-3-yl or indol-3-yl substituted with an alkyl or carbocyclic aryl group;

e) R is not azaindole or azaindole substituted at the 2-position by an alkyl or carbocyclic aryl group

6

f) when R is substituted pyrrole, the pyrrole is substituted by R OC (O) R,

R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, - (CH 2) p R ⁷ , -O (CH 2) _p R ⁷ , -C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH 2 ) _p R ⁷ , -OC (O) (CH 2) p R ⁷ , -N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ^ RV, -R ^ R ^ -R ^ R ⁷ , -R ^ R ⁶ R ⁷ ) 2, -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) _p R ⁷ -R ⁶ OC (O) (CH 2) pR ⁷ , -R ⁶ N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ), substituted aryl or an aralkyl group where:

R ⁶ in each case is independently a lower alkyl group or an aryl group;

R ⁷ in each case is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxy, R ³ O-, R ³ C (O) - or NR ⁴ R ⁵ ; and p is an integer from 1 to 3;

6

g) when R is indol-3-yl, the indol-3-yl is substituted with R OC (O) R,

6 7

R OR -, trihalomethyl, trihalomethylcarbonyl, - (CH ₂ ) _p -R, -O (CH ₂ ) _p R ⁷ , -C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O ( CH 2) p R ⁷ , -OC (O) (CH 2) p R ⁷ , -N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ₆ N (R ⁴ ) - R ⁶ -R ⁷ ,

-R ⁶ N (R ⁶ -R ⁷ ) 2, -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH ₂ ) p R ⁷ ,

-R ⁶ OC (O) (CH 2) p R ⁷ , -R ⁶ N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group; and

h) when R is pyrazol-3-yl, pyrazol-3-yl is substituted with R OC (O) R, R OR -, trihalomethyl, trihalomethylcarbonyl, - (CH ₂ ) _p -R ⁷ , -O (CH 2) p R ⁷ , -QO) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH,) _p R ⁷ ,

-OC (O) (CH ₂ ) _p R ⁷ , -N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) p R ⁷ ,

-R ⁶ OC (O) (CH 2) p R ⁷ , -R ⁶ N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group.

In a more preferred embodiment, the present invention is directed to any of the above compounds wherein A is -NH-, -O-, -S-, -S (O) - or -S (O) ₂ -; and Z is cyclopropyl, 3-pyridyl or pyrazinyl.

In another more preferred embodiment, the present invention is directed to any of the above compounds wherein A is -O-; and Z is ethyl, η-propyl or isopropyl.

In another more preferred embodiment, the present invention is directed to any of the above compounds wherein A is -CH ₂ -; and Z is phenyl, said phenyl being optionally substituted by one or more groups selected from the group consisting of halogens, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, -C (O) OR ⁴ and -OC (O) R ⁴

In another preferred embodiment, the present invention is directed to any of the above compounds, wherein R is substituted by one or more substituents independently independently selected from the group consisting of halogens, lower alkyl groups, R O-, hydroxy, HOC (O) - , R ³ OC (O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, nitro, -C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO -, - (CH 2) n R ⁷ , -C (O) (CH 2) _n -R ⁷ , -C (O) - (CH 2) n C (O) -R ⁷ -O (CH 2) _n R ⁷ , -C ( O) NR ⁴ (CH 2) n R ⁷ , -C (O) O (CH 2) _n R ⁷ , -OQO) (CH 2) n R ⁷ , -NR ⁴ C (O) (CH 2) _n R ⁷ , -RWR ⁵ , -R ^ R ⁴ ) R ⁶ -R ⁷ , -R ^ R ^ R ⁷ ) -R ⁶ Q O) NR ⁴ (CH 2) n R ⁷ , -R ⁶ Q O) O (CH 2) _n R ⁷ .

-R ⁶ OC (O) (CH 2) n R ⁷ , -R ⁶ NR ⁴ C (O) (CH 2) _n R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (NR ⁵ C (O) R ⁴ ), · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Can possible an aryl and optionally substituted aralkyl group. The optionally substituted aryl and optionally substituted aralkyl groups are optionally substituted by one or more substituents selected from the group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl group, R ³ O-, -C (O) OR ⁴ and -OC (O) R ³ . R ⁶ is a lower alkyl group or an aryl group. R ⁷ is alkoxy, haloalkyl, lower alkyl piperazine, hydroxy, R ³ O-, R ³ C (O) - or -NR ⁴ R ⁵ . In one aspect of this embodiment, R is pyrrolyl, indolyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydroindolyl or quinolinyl. In another aspect of this embodiment, R is pyrrol-2-yl, pyrrol-3-yl, indol-2-yl, indol-3-yl, azaindol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, thien-2-yl or quinolin-5-yl.

In another preferred embodiment, the present invention is directed to any of the above compounds wherein R ¹ is trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl, isopropyl, cyclopropyl, 2-methylcyclopropyl, 2,2,3,3 tetramethylcyclopropyl, 2-phenylcyclopropyl, 2-phenylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, - (CH ₂ ) _p -O-phenyl, - (CH ₂ ) _p -O- (4methoxyphenyl), - (CH ₂ ) _p -O- (4-chlorophenyl), - (CH ₂ ) _p- O- (4-methylphenyl), - (CH ₂ ) _p -O- (3-methylphenyl), - (CH ₂ ) _p -O- (4-phenylphenyl), - (CH ₂ ) _p -O- ( 4hydroxyphenyl), - (CH ₂ ) _p -O- (4-nitrophenyl), - (CH ₂ ) _p -O- (4-aminophenyl), - (CH ₂ ) _p -O- (4-carbamoylphenyl), - ( P _{2) p} -O- (4-methoxycarbonylphenyl), -NH-phenyl, -Y1N- (4-methoxyphenyl) -T4N- (4-chlorophenyl), -NH- (4-fluorophenyl), -NH- (4-isopropylphenyl) , isopropoxy, ethoxy, cyclopentoxy, - (CH ₂ ) _p -indolyl, - (CH ₂ ) _p -pyridyl, - (CH ₂ ) _p benzothiazolyl, - (CH ₂ ) _p- pyrrolyl, - (CH ₂ ) _p- tetrahydrofuryl , - (CH ₂ ) _p pyrazinyl, - (CH ₂ ) _p -furyl, - (CH ₂ ) _p -thienyl, - (CH ₂ ) _p -phenyl, - (CH ₂ ) _p -

· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·· isoxazolyl, - (CH ₂ ) _p - (5-methylisoxazolyl), - (CH ₂ ) _p- pyrimidinyl, - (CH ₂ ) _p -pyridazinyl, - (CH ₂ ) _n -C (O) -OMe, - (CH ₂ ) _n -C (O) -OEt or benzyl optionally substituted by one or more Cl, F, OMe, methyl or amino, p is an integer from 1 to 3. In one aspect of this embodiment, R is optionally substituted with one or more groups selected from the group consisting of Br, Cl, F, aminomethyl, N, N-dimethylaminomethyl, carboxy, carboxymethyl, carboxyethyl, carbonylmethyl, carbonylethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4m folinometil, -C (O) -O- (CH _{2) 2} -N (Me) _2, -C (O) -O- (CH _{2) 2} -N (Et) _2,

-C (O) -O-CH ₂ -N (Me) 2, -C (O) -O- (CH ₂ ) ₂ -N (Me) ₂ , -C (O) -NH- (CH ₂ ) ₂ -N (Me) ₂ , -CH ₂ -NH-C (O) -CF ₃ and an optionally substituted group selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl and phenyl, where the optionally substituted group is optionally substituted by one or more Br, Cl, F, hydroxy, nitro, amino or lower alkyl.

In another aspect, the present invention provides a pharmaceutical composition comprising any one or more compounds of the present invention as defined herein and a pharmaceutically acceptable carrier or diluent.

In another aspect, the present invention provides a method of inhibiting one or more protein kinase activities, comprising administering a compound represented by the formula:

and its physiologically acceptable salts and biologically active metabolites, where:

R is selected from the group consisting of substituted or unsubstituted:

• · · · · ·

aliphatic group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

R ¹ is hydrogen or -AZ;

R is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group a heterocyclyl-alkyl group;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R R-, HO-, NO (O) -, R OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NRV ^5;

R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group;

·· · · ·· · · · 4 <· • ♦ · ·· ·· «·· ····· · · · · · · · · · · · · · · · · · · · · · · ·· ·· ···· l 5ν *

R and R in each case are each independently hydrogen or are selected from the group consisting of substituted or unsubstituted: lower alkyl group, an aromatic group (C ₆₎ cycloalkyl group, a heterocyclic group, an aralkyl group, (S3S ₆₎ a cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally R and R together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3.

A preferred method of any of the above methods is one in which the inhibition of protein kinase is in a patient in need thereof.

A preferred method of any of the above methods is one in which the compound is a mixture of stereoisomers.

A preferred method of any of the above methods is one in which the stereoisomers are enantiomers.

A preferred method of any of the above methods is one in which the stereoisomers are E and Ζ isomers.

A preferred method of any of the above methods is one in which the compound is a mixture of structural isomers.

A preferred method of any of the above methods is one in which the structural isomers are tautomers.

A preferred method of any of the above methods is one in which said protein kinase is either receptor tyrosine kinase or non-receptor tyrosine kinase.

A preferred method of each of the above methods is one in which said tyrosine kinase is selected from the group consisting of KDR, Flt1, ΊΊΕ-2, FGFR, PDGFR, IGF-1R, c-Met, Lek, Src, fyn, Lyn, Blk and yes.

In another aspect, the present invention is directed to a method of treatment or mainly to inhibit hyperproliferative disorders or inflammatory diseases in a patient in need thereof, comprising administering to said patient any of the compounds of the present invention as defined herein.

In another aspect, the present invention is directed to a method of treating or inhibiting angiogenesis in a patient in need thereof, comprising administering to said patient any of the compounds of the present invention as defined herein.

In another aspect, the present invention is directed to a method of inducing an anti-angiogenic effect in a patient in need thereof, comprising administering to said patient any of the compounds of the present invention as defined herein.

In another aspect, the present invention is directed to a method of treating or inhibiting the development of a disease or condition in a patient in need thereof, comprising administering to said patient any of the compounds of the present invention as defined herein, such disease or condition are selected from the group consisting of cancer, arthritis, atherosclerosis, restenosis, psoriasis, hemangioma, myocardial angiogenesis, coronary and cerebral collateral, ischemic limbal angiogenesis, corneal disease, rubeosis, larva glaucoma, macular degeneration, wound healing, peptic ulcer related Helicobacter, angiogenic disorders caused by viruses, fractures, diabetic retinopathy, Crohn's disease, inflammatory bowel disorders, felinosis, retinopathy · · · · · · · · · · · · · · · · · · • · · · · · · · ·. · Premature birth, ulcers, thyroid hyperplasia, burns, trauma, acute lung damage, chronic lung disease, stroke, · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · polyps, cysts, synovitis, chronic and allergic inflammation, ovarian hyperstimulation syndrome, pulmonary and cerebral edema, keloid, fibrosis, cirrhosis, carpal tunnel syndrome, sepsis, age-related respiratory distress syndrome, polycystic syndrome, and edema.

In another aspect, the present invention is directed to a method of influencing vascular hyperpermeability or producing edema in a patient in need thereof, comprising administering to said patient any of the compounds of the present invention as defined herein. Preferred for the immediate preceding method is one in which the effect on edema production is counterintuitive.

A preferred method of any of the above methods is one wherein the protein kinase is a serine kinase.

A preferred method of any of the above methods is one wherein the protein kinase is a threonine kinase.

Particularly preferred compounds of the present invention are:

3-Cyclopropyl-N {[(33-Dimethyl-4- {4-methyl-1-piperazinylmethyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-N (1-pyrrolidinylmethyl-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-N [(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -

2- pyrazolin-5-one,

3- Cyclopropyl-4 - [(3,5-dimethyl-4-piperidinomethylsulfol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethanolaminomethyl-3,5-dimethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · »· · · · · · · ·

3-Cyclopropyl-4 - ^{[(3-dime1'ilaminometil-4,5-d} they fametilenpirol-2- yl) methylene] -2-pyrazolin-5-one,

3-1Diclopropyl-4 - [(3-morpholinomethyl-4,5-tetramethylene-11yl-2-yl) megylene] -2-pyrazolin-5-one,

3-11, Cyclohexylpyl-4 - [(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5tetramethylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-11-piperidinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-dimethylamino-4,5,6,7-tetrahydro-indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- (3,5-dibromo-4-hydroxybenzylidene) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4xo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(4-dimethylaminomethyl-5-methylphen-2-yl) methylene] -2-pyrazolin-5-one,

4- [(5-Chloropyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl 4- [4- (2-dimethylaminoethoxycarbonyl-11yl-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyano-propyl-4- [4- (2-dimethylamino-1-aminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (2-dimethylamino ^g- hydroxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclo 11ropyl-N [3- (2-dimethylaminoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-F [F (Fmorpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (Fmorpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-N [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- | (3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {(3,5-Dimethyl-4 - [(4-methyl-1-piperazinylmethyl) nyrrol-2-yl] methylene} -3 (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-DimethylA [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(N, N-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinomethyl-phenyl-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(FDiethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5-one,

4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- | (4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -

2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridyl) -

2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, • · • · · ·

4 - [(4-Chloropyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [(5-Chloropyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -

2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, • 9 • ·

4- {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-Fmorpholinomethylethyl-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one,

4 '[(4-Diekou ^d gilaminometil-3,5-dimethyl-pyrrol-2-yl) methylene] -3-isopropoxy

2- pyrazolin-5-one,

4- | (3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one,

4 - [(3-Dimetalaminome ^d Gil-4,5-te1rametilenpirol-2-yl) methylene] -3izopropoksi-2-pyrazolin-5-one,

3- Isopropoxy-4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one,

3-Isoropoxy {{3- (4-methyl-1-ylpiperazinyl) methyl-4,5-tetramethylene] pyrrole-

2-yl] metal} -2-pyrazolin-5-one,

3- Isopropoxy-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5H) n,

3- Isopropoxy-4 - [(3-piperidinomethyl4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Dime ^d gilamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-isopropoxy

2- pyrazolin-5-one,

4 - [(4-Diethylaminostyl-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3-isopropoxy-2-pyrazolin-5-one,

3- Isopropoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4'Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- Isopropoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-E ^d yuksikarbonilpirol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- (4- (2- Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-

2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one,

4- ((3-Ethoxycarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5one,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-isopropoxy-

2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3isopropoxy-2-sfazolin-5-one · · ·

3-Isopropoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-N [N (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- Isopropoxy-4- [3- (4-morpholinoethyl aminocarbonyl indol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,4-Diethoxycarbonylshol-2-yl) methylene] -3-isopropoxy-2-pyrazoline-

5- he,

4- {| 3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- | (3,5-Dimstyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[('4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3ethoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinyl methyl pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-Dietilaminome ^g 1-yl-3,5-dimethylpyrrole-2-yl) methylene] -3-ethoxy-2pirazolin-5-one,

4D (3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, ·

4 - [(3-Dimethylaminomethyl-4 _g 5-tetramethylene-pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-A [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] pyrazolin-5-one,

A [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-egoxy-2pyrazolin-5-one,

3-Egoxy-4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5-'methylmethylpyrrol-2yl] methylene} -2-pyrazolin-5-one,

3-Ethoxy-4- {[3- (E11irolidinil) ^methyl-4,5-d getrametilenpirol-2yl] methylene} -2-pyrazolin-5-one,

3- Ethoxy-4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Dime ^d gilamino-4,5,6,7-s ^d grahidroindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-isoxy-2pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3-ethoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

3- Ethoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

3- Ethoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3ethoxy-2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- (3- (2- Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- Ethoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one,

3- Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3ethoxy-2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2]

yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3- Pyrazinyl-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- | (3-Piperidinomethyl4,5-tetramethylenepyrrolyl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3- Pyrazinyl-4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [4- (2-N-Ethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [A (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one,

N- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4- [4- (FMorpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2 ······. ... · · · · ..

• · · · · ·. • · · · · ..

Pyrazolin-5-one,

T [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4- [3 - ('Tmorpholinoethylaminocarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

T [(3,5-Dimstyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dime ^d Gil-T (2; himetilaminoetilaminokarbonil) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

T [(Indol-3-yl) me ^d Guillain] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3- Pyrazinyl-4 - [(pyrrol-2-yl) methylene] -2-11-yrazolin-5-one,

4- [(Indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

N [(3,4-Diethoxycarbonylsulfol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

F [(5-Ethoxy-4-methoxycarbonylmethyl-3-methyl ^d goksikarbonilpirol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- ((4-Bromonirol-2-yl) megylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [(5-Chloropyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(5-trifluoromethoxypyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

♦ ♦ · »

3- (Imidazol-2-yl) -4 - [(4-egoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline-

The 5th,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3 (imidazol-2-yl) -2-pyrazolin-5-one,

4- [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazoline-

5- he,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3 (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4- [3- (4-morpholinoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4- [3- (4-morpholinoethylaminocarbonylindol-2yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4- ((3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3 (imidazol-2-yl) -2-pyrazolin-5-one,

4- {(3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (imidazol-2-yl) -

2- pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [(4-Bromopyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline-

5- he,

4- [(4-Chloropyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline-

5- he,

4- [(5-Chloropyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline-

5- he,

3- (1-Methylcyclopropyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4- (4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (1- • · ♦ ··· • ···

methylcyclopropyl) -2-pyrazolin-5-one,

4- (4- (2-Dimethylaminoethyl aminocarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (1methylcyclopropyl) -2-pyrazolin-5-one,

4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4- [3- (4-morpholinoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4- [3- (4-morpholinoethylaminocarbonylindole-

2-yl) methylene] -2-pyrazolin-5-one,

4- ((3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Metal cyclopropyl) -4 - ((1-methylindol-3-yl) methylene] -2-pyrazoline-

5- he,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-Methoxyindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4 - [(4,5-tetramethalen-pyrrol-2-yl) metal] -2-pyrazolin-5-one,

4- {(3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, • · ♦ · • * ·· · · · · · ·

4- {[3,5-Dimethyl-4- (2-dimethylaminoethyl aminocarbonyl) pyrrol-2yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(Pyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4- {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -

3- (2-furyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-

Furyl) -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one,

4- [(3-Diethylaminoethyl-4,5-tetramethylene-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5-one,

3- (2-Furyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-furyl) -

2- pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(4-dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Bromopyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) metal] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -

2-pyrazolin-5-one,

4- (4- (2- Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5one,

4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) -

2- pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -

2- pyrazolin-5-one,

3- (2-furyl) -4- [3- (4-morpholinoethoxycarbonylidol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -

2- pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(1-methylidol-3-yl) methylene] -2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, · · · · ·

3- (2-furyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4- ((3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (3- (2-furyl)) -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4- {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4 - [(morpholinomethylpyrrol-2-yl) methylene] -3- (2-thienyl) -

2- pyrazolin-5-one,

4 - {[(3,5-Dimethyl-4- (4-methyl-1-piperazinyl) methylpyrrol-2-yl] methylene} -

3- (2-thienyl) -2-pyrazolin-5-one,

4- ((3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene) -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -

2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - ((4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylene-11yl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- {[3- (4-Methyl-1-siperazinylmethyl) -4,5-tetramethylene-pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4- {[3- (1-Pyrrolidinylmethyl) -4,5-tetramethylenepyrrol-2-yl] methylene} -3 (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

3- (2-Thienyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2 • ·

• · · · · · · · • • • · · · thienyl) -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one,

4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one,

4 - [(1-Methylindol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- (3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - ((5-Methoxyindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - ((4,5-Tertramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(Pyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-megoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

4- [(4-Chloropyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

4D (5-Chloropyrrol-2-yl) metal] -3-cycloproxy-2-pyrazolin-5-one,

3-Cyclo [1110] oxy-4 - [(5- ^g difluoromethylpyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

3-Cyclopropoxy-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5one,

3-11, iclopropoxy-4- [4- (2-dimethylaminoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3-Cycloneroxy} to [4- (2-dimethylaminoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazoline-

The 5th,

3-Cycloropoxy-N [3- (2-dimethylaminoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyutopropoxy-4- [3- (2-dimethylaminoethyl aminocarbonylindole-2 ············

yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -

2- pyrazolin-5-one,

3- Cyclogotropoxy-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4- [3- (Fmorpholinoethoxycarbonylindol-2-yl) methylene] -

2- pyrazolin-5-one,

3- Cyclopropoxy-4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(3,5-dimethyl-ethyl-pyrrol-2-yl) methylene] -2-pyrazoline-

The 5th,

3-Cycloneropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4- [3,5-dimethyl-Aetoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) metal] -2- pyrazoline-5one,

3-Cycloneropoxy-4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - {[3,5-dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cycloneropoxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropoxy-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one,

3- Cyclopropoxy-4 - [(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

3- [2- (5-Pyrimidinylethyl)] -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -

2-pyrazolin-5-one,

4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- (3- (2-Dimethylaminoethyl aminocarbonyl indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, · · · · · · · · · · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -

2- pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2H-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(5-Methoxyindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

3- [2- (5-Pyrimidinylethyl)] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - {[3 , 5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(14dol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

3- [2- (5-Pyrimidinylethyl)] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (5 -)

pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

3- (2-phenylethyl) A [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

N- ((Fethoxycarbonylpipol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5one,

N- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

N- [4- (2-Dimethylaminoethylaminocarbonyl-11yl-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [(3Toxycarbonylindol-2-yl) methylene] A (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

A [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (Fluoro-ethoxy-carbonyl-phenyl-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (4-Morpholinostylaminocarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

N- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-Methoxyindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

3- (2-phenylethyl) -4 - [(4,5- 1 Hgramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5one,

4- {[3,5-Dimethyl-4- (2-dimethylamine-5-hydroxycarbonyl) pyrrol-2-yl] methylene} -

3- (2-phenylethyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(3,4-Distoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-Fetoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [(4-Bromopyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline-

5- he,

4- [(4-Chloropyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline-

5- he,

N - [(5-Chloropyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline-

The 5th,

3- [2- (4-Hydroxyphenyl) ethyl] -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

T (4-Ethoxycarbonylpyrrol-2-yl) megylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

T [T (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- | 4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- [2- (trihydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-Hydroxyphenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Hydroxyphenyl) ethyl] -4- [4- (4-morpholinoethylaminocarbonylpyrrole)

2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Hydroxyphenyl) ethyl] -4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Hydroxyphenyl) ethyl] -4- [3- (4-morpholinoethylaminocarbonylindole-

2-yl) methylene] -2-pyrazolin-5-one,

T [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-Hydroxyphenyl) ethyl] -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (THhydroxyphenyl) ethyl] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -

3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl -4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 {[3- (2-acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2H) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4- Aminophenyl) ethyl] -4 - [(4-bromopyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

3- [2- (4-Aminophenyl) ethyl] -4 - [(4-chloropyrrol-2-yl) methylene] -2-pyrazoline-

The 5th,

3- [2- (4-Aminophenyl) ethyl] -4 - [(5-chloropyrrol-2-yl) methylene] -2-pyrazoline-

The 5th,

3- [2- (4-Aminophenyl) ethyl] -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4- [4- (2-dimethylaminoethoxycarbonylpyrrole-

2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - [(3-ethoxycarbonyl indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4- [3- (2-dimethylaminoethoxycarbonylindole-

2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4- [3- (2-dimethylaminoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4- [3- (4-morpholinoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4- (3- (4-morpholinoethylaminocarbonylindole-

2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - ((5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, N 3- (2- (4-Aminophenyl) ethyl] - 4 - {(3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - {[3,5-dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {(3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one, "·

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-Aminophenyl) ethyl] -4 - [(5-ethoxy-4-methoxycarbonylmethyl-3methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2- (4-Aminophenyl) ethyl] -4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (4-

Imirinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -

3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinyl) methyl-4D-tetramethylenepyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

3- (4-N-pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5tramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, -

4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidinyl) pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (4-pyrimidinyl) -2-pyrazoline-

5- he,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-diethylaminomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, · · · · · · · · · · ·

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

3- (5-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-pyrimidinyl) -2-pyrazoline-

5- he,

4 - ((3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4- (1-pyrrolidinyl methyl pyrrol-2-yl) methylene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3- (4-Metal-1-piperazinyl) methyl-4,5-TCIramethyl ethylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

3- (2-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

A [(4 ~ Distillaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-pyrimidinyl) -2-pyrazolin-5one,

A [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(AOxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

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4 - [(4-Dimethylaminomethyl-5-methylgyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

N [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3 (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-N (1-pyrrolidinylmethyl) tyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4'-Dihylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-'metramethylenepyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- {| 3- (4-Methyl-1-niperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

3- (3-Pyridazinyl) -F {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

N- ((3-Psheridinometall4,5-tetramethalenpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- [(4-Dime ^d gilamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, ·· ···· • · · · · · · · · ·

4 - [(4-Diethylaminoethyl-3,5-dimethylglyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (3-pyridazinyl) -2-pyrazolin-5one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomegyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -

2- pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethyl-sulfol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -

3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

F [(3-morpholinomethyl-4,5-tetrametilenpirol-2-yl) methylene] -3- (4piridazinil) -2-pyrazolin-5-one, ^/ k [(3-Distilaminometil-4,5-tetrametilenpirol-2- yl) methylene] -3- (4pyridazinyl) -2-pyrazolin-5-one, • · · · · · · · · · · · · · · · · · · · · · · · · ··

4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

3- (4-Pyridazinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2yl] methylene} -2-pyrazolin-5-one,

N- ((3-Piperidinomethyl4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- [(FDimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

A [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (4-pyridazinyl) -2-pyrazolin-5one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(AD dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -

2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -

2-pyrazolin-5-one,

4 - [(3,5-Dime ™ 1-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

4 - [(ADiethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, · · · · · · · · · · · ·

isoxazolyl) -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylsinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (5-Isoxazolyl) A {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2yl] methylene} -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - ^{[(3-piperidinomethyl-4,5-d} getrametilenpirol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(ADimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

N (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -

2-pyrazolin-5-one,

N- ((3,5-Dimethylamorpholinomethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3 (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one ,

4 - [(3,5-Dime ^d Gil-4 - [(1-pirolidinilmetilpirol-2-yl) methylene] -3- (5-methyl-3izoksazolil) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-piperidinomegylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one,

4 - ((3-Dimethylaminomethyl4,5-tefamethylpyrrol-2-yl) methylene] -3- (5methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) 4 - [(3-morpholinomethyl4,5-tetramethylenepyrrole-

2-yl) methylene] -2-pyrazolin-5-one,

4- ^{[(3-Diethylaminomethyl-4,5-d} they fametilenpirol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) 4- {[3- (4-methyl-1-piperazinyl) methyl-4,5tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (5-Megyl-3-isoxazolyl) -4 - {[3- (1-pyrrolidinyl) methyl 4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) -4 - [(3-piperidinomethyl4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Dimethylamino4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-methyl3-isoxazolyl) -2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2yl) methylene] -2-pyrazolin-5-one,

4- ((4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3-1Diclopropyl-4- (1-3 - [(dimethylamino) methyl] -4,5,6,7-tetrahydro-1H-2indolylmethylidene) -4,5-dihydro-1H-5-pyrazolone,

3- Cyclopropyl-4- (1-4 - [(1,1-dimethylamino) methyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -4,5-dihydro-1H-5-pyrazolone, maleate

4- [1- (4 - [[2- (Dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1H-2pyrrolyl) methylidene] -3- (2-pyrazinyl) -4,5-dihydro -S-5-pyrazolone,

4- (1-4- [2- (Diethylamino) ethyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -3 (2-pyrazinyl) -4,5-dihydro-1H-5-pyrazolone,

4- 1- [4- (3-Chloropropanoyl) -3,5-dimethyl-1H-2-pyrrolyl] methylidene-3- (2-pyrazinyl) -4,5-dihydro-1H-5-pyrazolone,

4- (1-3 - [(Dimethylamino) methyl] -4,5,6,7-tetrahydro-1 H -2-indolylmethylidene) -3- (2-pyrazinyl) -4,5-dihydro-1 H-5-pyrazolone,

4- (1-4 - [(Dimethylamino) methyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) 3- (5-methyl-3-isoxazolyl) -4,5-dihydro-1H-5-pyrazolone,

3-Cyclopropyl-4 - [(4,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Benzyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methoxyphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazoline- 5on,

3-Phenyloxymethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlorophenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Benzyl-4 - {[4- (2-carboxyethyl) -3-methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Benzyl-4 - {[3- (2-carboxyethyl) -4-methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (4-Methylphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

2- Amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- Isopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, • · · · ·

3-phenylethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-phenylamino-4D (pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methylbenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methyl phenyl amino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxyphenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlorobenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlorophenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Chlorophenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Indol-3-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3,4-Dimethoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-phenylphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-phenylpropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-phenylpropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Hydroxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3- (4-Methylphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Nitrophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-fluorophenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlorophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoline-

5- he,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5one,

4 - {[1- (4-Hydroxybutyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

3-Cyclopentoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Tert-butylureido-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5one,

3-Isopropoxy-4 - [(1-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Carbamoylphenylethyl) -4 - [(3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] -

2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (4-methoxycarbonylphenylethyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-

2- pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(5-Ethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one,

3- (Ethoxycarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxyphenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, • · · ·

· · · · • · ♦ · • · · • f ·

99

999999

4- {[3- (2-Carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-isopropyl-2pyrazolin-5-one,

3-Cyclopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclobutyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- 1Dclopropyl-4 - [[1- (3,5-dichlorophenyl) pyrrol-2-yl] methylene] -2-pyrazoline-

5- he,

4- [(Pyrrol-2-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazoline-

5- he,

3-Cyclopropyl-4 - [(3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopentyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5one,

3- (2-Methylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- (Benzothiazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4,5-Dimethylpyrrol-2-yl) methylene] -4- (3-pyridyl)] -2-pyrazolin-5-one,

3-CyclopropylA [(3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] -2-1Pfazolin-5one,

3- (Pyrrol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Benzothiazol-2-yl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 '[(3,5-Dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [(3,5-Dmethyl-4-ethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3- Cyclopropyl-N [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(5-Methylpyrrol-2-yl) methylene] -3 - (- 3-pyridyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-ethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

• «

3-Propyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Methyl A [(pyrrol-2-yl) metal] -2-pyrazolin-5-one,

3- (4-Isopropyl phenyl amino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - {[1- (4-hidroksibugil) pyrrol-2-yl] me ^d Guillain} -2-pyrazolin

The 5th,

4- {[4- (2-Carboxyethyl) -3-methylpyrrol-2-yl] methylene} -3-isopropoxy-2pyrazolin-5-one,

4- [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- Isopropoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, N [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3 -isopropoxy-2-pyrazolin-5-one,

4 {(3,5-Dimethyl-4-dimethylaminomethyl-1H-2-yl) methylene] -3-isopropoxy-

2- pyrazolin-5-one,

A [(4-Acetyl-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoline-

5- he,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5one,

4 - [(5-Carboxypyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- (AHProphenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-D ^ ethyl-4-ethylpol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-

• ·

pyrazolin-5-one,

4 - [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-cyclopropyl-2pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(3,5-dimethyl-4-morpholinomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

4- [(3,4-Dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Carboxyethyl) -3-methylpyrrol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

3-Cyclopropyl-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazoline-

The 5th,

3- (2-Methoxycarbonylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxycarbonyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Trans-2-phenylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5one,

3-Cyclohexyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropylamino-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5- he,

3- Cyclopropyl-4 - [(5-morpholinomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(5-Carboxypyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

4 - [(4-Chloropyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, -

4 - ((4-Bromopyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(5-Chloropyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 [(4-Chloropyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one ₅

4 - [(4-Bromopyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3-Pyrazinyl-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5one,

3- (3-Pyridyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methyl] -2-pyrazolin-5-one,

4- [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

3- Cyclopropyl-4 - {[3,5-dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethyl aminoethyloxycarbonyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, maleate,

4- {(3,5-Dimethyl-4- (2-morpholinoethylaminocarbonyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - ((3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4- ((3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazoline-

5- he,

4 - ((4,5-Tetramethylenepyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5one,

4 - ((3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, • · a · · ·

«4

4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline-

5- he,

3-Pdclopropyl-4 - [(3,5-dimethyl-Trifluoroacetamidomethylphenol-2yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-U [(4-aminomethyl-3,5-dimetalpirol-2-yl) methyl ^l Guillain] -2pirazolin-5-one,

3- (Benz (Liazol-2-yl) -F [(33-Dimethyl-phenol-2-yl) methylene] -2-pyrazolin-5one,

3- (Benzothiazol-2-yl) -4 - [(3,5-dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, N [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl -2-pyrazolin-5-one,

4 - [(4-Carboxypyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, T [(3,5-Dimethyl-4-diethanolaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl -

2- pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-trifluoroacetamidomethylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(4-ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

T [(3,5-Dimethyl-adimethylaminomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridyl) 2-pyrazolin-5-one, · · · • 9 • · 9 · • "

4 - ((3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-ylpyrrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - ((3,4-Di (ethoxycarbonyl) pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5one,

3- Ethoxy-4 - ((4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 ((3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-pyridylethyl) -

2- pyrazolin-5-one,

4- ((3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methyl-2-phenylethyl) -2-pyrazolin-5-one,

4 - ((4Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5one,

3- Ethoxy-4 - [(5-nitropyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- Ethoxy-4 - ((4-nitropyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(4-Carboxypyrrol-2-yl) metal] -3-ethoxy-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl) methylene} -3-ethoxy-2-pyrazolin-5-one,

4 - [(5-Chloro-3-methoxycarbonyl-4-methoxycarbonylmethylpyrrol-2yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- {[3- (2-Carboxyethyl) -4-methylphenol-2-yl] methylene} -3-ethoxy-2-pyrazoline-

5- he,

4 [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

3- Ethoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- ((3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3gluoromethyl-2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

......... ·· ......

3- (3-Aminophenyl) -4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

3- Ethoxy-4 - {[2- (4-morpholinoethyl) aminocarbonylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- [(4-Ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (4-Methyl-Epiperazinylmethyl) -3,5-dimethylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-

2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one,

4- | (5-Methyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-dimethyl-4- [N- (2-dimethylaminoethyl) -N-methylaminomethylpyrrole-

2-yl} methylene} -3-pyrazinyl-2ylshrazolin-5-one,

3- Cyanopropyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenepyrrol-2 'yl) methylene] -2-pyrazolin-5-one,

4- [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, maleate,

4- {[4- (3-Chloropropionyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · ·

♦ · • «

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-methyl-

3- isoxazolyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (4-hydroxypiperidinomethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - ((4- Aminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, maleate,

4 - {[4- (4-Benzylpiperidino) methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- (2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3,5-dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -2-pyrazolin-5-one,

3- Cyclopropyl-4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- {(3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-

2-pyrazolin-5-one,

4 - {[4- (3-Diethylaminopropyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (3-hydroxypropyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, hydrochloride,

4 - ((3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, · · · · · · · · · ·

3- Cyclopropyl-4 - {[(2-diethylaminoethyl) -3,5-dimethyl-4-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-dimethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (4-hydroxybutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-

2- pyrazolin-5-one,

4- {| 4- (4-Diethylaminobutyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl-N-oxide) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4,11-pyrrolidinylacetyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Diethylaminoacetyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [(3-Isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoline-

5- he,

4 - {[3,5-Dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(Dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-ethoxyxalyl) pyrrol-2-yl] methylene} -3-pyrazinyl-

2- pyrazolin-5-one,

3- Benzyl-4 - [(ivol-3-yl) methylene] -2-pyrazolin-5-one,

3- Benzyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5one,

4 - [(Indol-3-yl) methylene] -3-phenyloxymethyl-2-pyrazolin-5-one,

3- (4-Chlorophenyloxymethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylphenyloxymethyl) - 2-Pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-isopropoxy- 2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-phenylamino-2-pyrazoline- 5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylphenylamino) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4 -methoxyphenylamino) -2-pyrazolin-5-one,

3- (4-Chlorobenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- {[1- (4-Hydroxybugyl) indol-3-yl] methylene) -3- (4-methoxybenzyl) -2-pyrazolin-5-one,

3- (4-Chlorophenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (3-methoxybenzyl) -2-pyrazolin-5-one, 3- (3,4-dimethoxybenzyl) -4 - [(indol-3-yl) methylene ] -2-Pyrazolin-5-one, 3- (4-Hydroxybenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (3-Chlorophenyloxymethyl) -4- [ (indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (Indol-3-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methoxyphenylethyl) -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-phenylphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-phenylpropyl) - 2-Pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (3-phenylpropyl) -2-pyrazolin-5-one,

3- (4-Hydroxyphenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methylphenylethyl) -2-pyrazolin-5-one, 3-Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-4-yl] 5-one, ·· ····

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

4- {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-phenylethyl-2-pyrazoline-

5- he,

4 - [(Indol-3-yl) methylene] -3- (4-nitrophenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-propoxy-2-pyrazoline- 5-one, 3- (4-fluorophenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(2-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

3- Isopropoxy-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(7-Methylindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3-Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- Isopropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methoxycarbonylphenylethyl) -2-pyrazoline-

5- he,

3-Isopropoxy-4 - [(1-isopropylindol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(1-methylindol-3-yl) methylene] - 2-pyrazolin5-one,

3-Isopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-chlorophenylaminocarbonylmethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5- he,

3- Ethoxycarbonylmethyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (4-methoxyphenylaminocarbonylmethyl) -2pyrazolin-5-one,

3- Cyclopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3- (2-Aminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, ·

· · · · · ·

3-Cyclobutyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (2- Dimethylaminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4- [(P1ndol-3-yl) methylene] -3- (4-pyridyl) -2-pyrazolin-5-one,

3- Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (2-methylcyclopropyl) -2-pyrazolin-5-one,

3- Cyclohexyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4- {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3- (4-pyridyl) -2-pyrazolin-5-one,

3- (Benzothiazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

3- Dimethylamino-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (pyrrol-2-yl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (6-methoxybenzothiazole -2-yl) -2-pyrazolin-5one,

3-Cyclopropyl-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(1-Methylindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one ······

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-methyl-2-pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-trifluoromethyl-2pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3- (1-butyl) -2-pyrazoline-

5- he,

3- Ethoxycarbonyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (2-methoxycarbonylethyl) -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3- (trans-2-phenyl-1-cyclopropyl) -2-pyrazoline-

5- he,

3- Cyclobutyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4- [(6-Carboxy-1-methylindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(1,7-dimethylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(1-Methylindol-3-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-

5- he,

3- Cyclopropylamino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(6-Carboxy-1-methylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [(1,7-Dimethylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazoline-

5- he,

3- (4-fluorophenylamino) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

·· ····

4 - [(1-Methylindol-3-yl) methylene] -3-trifluoroacetamido-2-pyrazolin-5one,

3- (4-Aminophenylethyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5one,

3-Amino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlorophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [(1-Methylindol-3-yl) methylene] -3-1-tert-butyl-2-pyrazolin-5-one,

4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5one,

4- {{1-Methyl-6- [2- (4-morpholino) ethyl] aminocarbonylindol-3-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- [(Indol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- (4-Hydroxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxycarbonylphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazoline-

5- he,

3- (4-Carbamoylphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one _! ,

3- Cyclopropyl-4 - [(3-dimethylaminomethylindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

3- Isopropoxy-4 - [(1-methylindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(Ivdol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one,

• · · ·

3- Cyclopropyl-4 - [(5-nitroindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-2-yl) methylene] -3-isopropylamino-2-pyrazolin-5-one,

3- (4-Carboxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4- [(Indol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(3-methylindol-2-yl) methylene] -2-sfazolin-5-one,

3-Isopropoxy-4 - {[3- (2-methoxycarbonyl-2-acetamidoethyl) indol-2yl] methylene} -2-pyrazolin-5-one,

3-Ethoxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2 -pyrazoline-5one,

3- Cyclopropyl-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one,

4- [(5-Methoxyindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-Methoxyindol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Chloro-6,7-dihydroindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- [(4-Chloro-6,7-dihydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazoline-

5- he,

4 - [(4-Oxo-1,5,6,7-dihydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5one,

4 - [(7-Azaindol-3-yl) methylene] -3-benzyl-2-pyrazolin-5-one,

3- Benzyl-4 - {[1- (4-hydroxybutyl) -7-azaindol-3-yl] methylene} -2-pyrazolin-5-one,

4- [(7-Azaindol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Amino-4 - [(7-azaindol-3-yl) methylene] -2-pyrazolin-5-one, · · · · · · · · · · · · · · · · · · · · · · · · · · · · 91 * ·· *

4 - [(7-Azaindol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5one,

4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl] methylene} -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-isopropyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-cyclobutyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (4-fluorophenylamino) -2-pyrazolin-5one,

4 - [(7-Azaindol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one,

4 - [(7-Azaindole-3-yl) me ^d Guillain] -3-methyl-2-pyrazoline-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-1rifluoromethyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (tert-boogyl) -2-pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl] methylene} -3-1rifluoromethyl-2pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (4-isopropylphenylamino) -2-pyrazolin-5one,

4 - [(7-Azaindol-3-yl) methylene] -3- (3-metal phenyl amino) -2-pyrazolin-5-one, A {[1- (4-Hydroxybutyl) -7-azaindol-3- yl] methylene} -3- (3methyl phenyl amino) -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3-Benzyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, · · · · · · · · · · · · · · · · ·

• ·

N - ((dimethylaminophenyl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-dimethylaminophenyl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-cyclopropyl 1-4- [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyl-N [ (3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one, N [(Imidazol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-cyclopropyl-4- [(imidazol-2-yl) methylene] -2-pyrazolin-5-one, A [(imidazol-4-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- Cyclopropyl-A [(thien-2-yl) metal] -2-pyrazolin-5-one,

4- [(Indol-3-yl) methylene] -3-isopropyl-1-methyl-2-pyrazolin-5-one,

3- Isopropyloxy-4 - [(pyrrol-3-yl) methylene] -2-pyrazolin-5-one, A [(8-Hydroxyquinolin-5-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one ,

4- {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2pirazolin-5-one, 4 - {[4- (2-Die ^d 1L1laminoetil) -3,5-dimethylpyrrole-2-yl] methylene} -3- (2-thienyl ) -

2- pyrazolin-5-one,

A {[A (2-Diethylaminoethyl) -3,5-dimethylglyrol-2-yl] methylene} -3- (4-shrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

3- Cyclopropyl-4 - [(3f-dimethyl ™ -4- (1-pyrrolidinylmethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, ·· ♦ ··· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 9 · · · · · · · ·

3-Cyclopropyl [A [(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -

2- pyrazolin-5-one,

3- Cyanoyl-11-yl-4 - {[4- (2-cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-phenylaminoethyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one,

3- Cyclopropyl-4 - {{3,5-dimethyl4- [2- (4-pyridylmethylamino) ethyl] pyrrole-

2-yl} methylene} -2-pyrazolin-5-one,

4- {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one,

3- Cyclohexyl] -4 - [(4-diethylaminomethyl-3-isopropyl-5-methyl-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclo [11] propyl-4 - {[4- (1-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2yl] megylene} -2-pyrazolin-5-one,

3-Cyclo11ropyl {{3-isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrole-

2-yl} methylene} -2-pyrazolin-5-one,

3- Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylgyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl N- (4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl) methylene} -2-pyrazolin-5-one,

3-PdclopropylA- [[3-isopropyl-5-metal-N (piperidine (yutyl) pyrrol-2yl] methylene) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{A [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-N - {[4- (Fdimethylaminobenzyl) -3-isopropyl-5-methylpyrrole-

2-yl] methylene} -2-pyrazolin-5-one,

3- Cyclo7-propyl-4 - [(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2yl) methylene] -2-pyrazolin-5-one,

·· · · • · · · • · «• · · • 4 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 94 · ·

3-Cyclohexyl-4 - {[3-cyclopropyl-4- (1-pyrrolidinylmethyl) -5methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4- {{3-cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -

5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyano-10R11yl-4 - {[3-cyclopropylA (3-daetylaminopropyl) -5methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-4- [3- (2,5-dimethylgly- ¹ -pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl4 - {{3-cyclopropyl-5-methyl-4- [4- (1pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (4 ~ cyclobutylaminobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5H) n,

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-nirazinyl-2pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3- Pyrazinyl-4- {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[3-Isopropyl-5-metal-N (4-pyridinobugyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3- Pyrazinyl-N {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomegyl-5-methylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (me1Pksietil) amino- ^d Gill] -5-methylpyrrole-2-yl} methylene} -2-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

N- {{3-Cyclopropyl4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 {[3- Cyclopropyl-5-methyl4- (3-phenylmethylamino-phenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N - {[3-cyclopropyl- 5-metal-4- (4-11-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, ·

4 - [(3,5-Dimethyl-4- (1-pyrrolidinyl methyl pyrrol-2-yl) methylene] -3- (2-furyl) -

2- pyrazolin-5-one,

T [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (2-Tsiklopropilaminsh-Gill) -3,5-dimethylpyrrole-2-yl] me ^d Guillain} -3- (2furil) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

N {{3,5-Dmethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3 (2-furyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -

3- (2-furyl) -2-pyrazolin-5-one,

4- {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3- (2-furyl) -4 - {[3-isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one,

3- (2-furyl) -4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, ·

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (2-furyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5- he,

4- {13-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopolyIyl) Ilipol-2yl | methylene} -3- (2-phenyl) -2-pipazolin-5-one.

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4- {[3-Cycle O11ropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -

2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-thienyl) -

2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -

3- (2-thienyl) -2-iirazolin-5-one,

4 {[4 (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 [(4-Diethylaminomethyl-3-isoropropyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4 (1-Pyrrolidinylmethyl) -3-isopropyl-5-methyl-pyrrol-2-yl] methylene} -3 (2-thienyl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylirol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobugyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4 (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3 (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopr (N-yl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 {{3-Cyclopropyl-4 [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -3- (2-thienyl) -2-fphazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminonropyl) -5-methylpyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3-CyclopropylA [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) yl-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3-Cyclohero-11-yl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Cylo-N-yl] -yl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (2-thienyl) -2-pphazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (N-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclohexylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -

3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropyl aminoethyl) -3-iso-phenyl-methyl-pyrrol-3-yl] ethylene-3- (3-pyrimidinyl) -cyrazolin-one,

3- (4-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methyl-1-yl-methyl} methyl} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4D3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5- he,

4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - ((3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3XDimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4 - (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -

3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Isopropyl-5-metal-4- [2- (1-pyrrolidinyl ethyl)] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

3- (5-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (4- Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, • »· · · · · • · · · · · · · · · · · · · · · · · ·

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (5-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cycloneropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5- he,

4- {[3-Cyclopropyl-5-methyl-4- (3-phenyl methyl aminopropyl) schrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

A {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

Μ · · · · · · • • • · · · ·

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl) -5-methylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -

3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

3- (2-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclo [pyrrolidin-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} megylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5- he, • · a • · • · ·· • ·

·· »9

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-metal-4- (4-phthobutylaminobutyl) 11 Hyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- ((4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3H-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- {{3,5-Dime ^d Gil-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3 (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

3- (3-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (3-pyridazinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-5-metal-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylamino-pyrrolyl) -5-methyl-pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4f (3,5-Dimethyl-4D1 chrolidinyl methyl pyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminostyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, ······ ..

? ......

J »· · · · · · · ·

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- {| 3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -

3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpropyl-2-yl] methylene} -

3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- {[4- (2-Cyclopropyl aminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

3- (4-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-ylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -

3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (4-pyridazinyl) -2-pyrazolin-5-one, ······

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5- one, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylamino-propyl) pyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4D4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-D imethyl-4- (1-pyrrolidinyl methyl pyrrol-2-yl) methylene] -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one,

4- {{3,5-Dimethyl-4- [2- (4-pyridyl methyl amino) ethyl] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline -5-he,

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one, 1 H • ···

• · · · · · · ·

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-1riazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- The 5th,

4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4- {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- The 5th,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one ,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (1,2,4-1 triazin-3-yl) -2-pyrazoline- The 5th,

4- {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (1,2,4-1riazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (1,2,4-1riazin-3-yl) -2-pyrazoline -5-he,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5 -one,

4- {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4- {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (1,2,4-triazin-3-yl ) -2-pyrazolin-5-one,

4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

····

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline -5-he,

4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (1,2,4-1 triazin-3-yl) -2-pyrazolin-5- he,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-4- [2- (1-pyrrolidinylethyl)] -3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-4- [2- (4-pyridylmethylaminoethyl)] -3trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-1rifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-1rifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3-1-butylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-4- [2- (1-pyrrolidinylethyl)] -3-1-tert-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (4-pyridylmethylaminoethyl)] - 3-tert-bushpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-yl-butylpyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Aminoethyl) -5-methyl-3-1ret-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, ·· ♦ ···

· · · · · · · · · · · · · · · · · · · · · ·

4 - {[4- (2-Diethylaminoethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Egyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[3-Ethyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-ethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[3-Cyclobutyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{3-Cyclobutyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} metal} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclobutyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclobugyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclobutylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclobutylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[3-Cyclopentyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one ········ · · · · · · · · · · · · ♦ · · · · · ·

4 - {[3-Cyclopentyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] metal} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-imidazoyl) ethyl] -5-methyl-3-cyclopentylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

A {{3-Cyclohexyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclohexyl-N (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

A {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylamino-1-yl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclohexylpyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[A (2-Aminoethyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-N [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

A {[4- (2-Ethylaminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, ······ · · · · · · · · 4 · · · · · · · · · · · ·

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {| 4- (2-Aminoethyl) -5-me ^d Gil-3-fenilg1irol-2-yl] methylene} -3-pyrazinyl-2pirazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Metal-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{5-Megyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrole-

2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4 [2- (1-Imidazoyl) ethyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3- (4-methoxyphenyl) sulfol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-11ridyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4 (2-Ethylaminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[A (2-Aminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 {[4- (2-Diethylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] megylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-11-iresinyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4 (2-Ethylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Metct-3-irazinyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4D {4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-pyrazinylpyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-imidazoyl) pyrrol-2yl} methyl en} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-yirazolin-5-one,

4 - {(5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, ·

4 - {[A (2-Ethylaminoethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{5-Metal-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} mesplen} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4 ~ [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[A (2-Cyclopropylaminoethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -311irazinyl-2-11irazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-metal-3- (3-isoxazolyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-E (cycloropropylaminoethyl) -5-megyl-3- (3-isoxazolyl) pyrrol-2yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one,

A {[N (2-Diethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-nirazolin-5-one, ·

• · · · · · · · · ·

4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

A {[4- (2-Cyclopropylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

A {[4- (2-Diethylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Egylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Hydroxymetal-3-isopropyl-4- [2- (4-iridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-hydroxymethyl-3-isopropylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dicyclopropylgyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dicyclo 11ropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminoethyl) -3,5-dicyclopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dicyclopropyl-4- [2- (4-piridilmetilaminoe ^d Gill)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- (2- (1-Imidazoyl) ethyl] -3,5-dicyclopropyl pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminosutal) -3,5-dichloropropylphenyl-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one,

• ·

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-dimethylaminoethoxy ^d pi1) -5-methyl-3-trifluorometilpirol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {(5-Methyl-4- [2- (1-pyrrolidinyl methyl)] -3-trifluoromethyl pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminomethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] -3trifluoromethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Diethylaminomethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Dimethylaminomethyl) -5-methyl-3-tert-butyl ^d gilpirol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (1-pyrrolidinylmethyl)] -3-tert-butylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] -3-tert-butyl pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-tert-butylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, * · • "

4 - {[4- (2-Diethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - ((4- (2-Dimethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Ethyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-ethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclobutyl-N (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[3-Cyclobutyl-4- (2-dimethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclobutal-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cisobutyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{3-Cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (EImidazoil) me ^d Gill] -5-methyl-3-tsiklobutilpirol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclobutylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[3-Cyclopentyl-4- (2-dimethylaminoethoxy ^d Gill) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclopental-5-methyl-4- [2- (1-pyrrolidinylmethyl) yl] -yl-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclops ^d Gil-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3pirazinil-2-pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-cyclopental-schrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {| 3-Cyclohexyl-4- (2-dimethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclohexyl-5-methyl ^d p4l-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {(3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

N {{4- [2- (1-Imidazoyl) metal] -5-metal-3-cyclohexylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminostyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

119

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -311yrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Dimethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

N- {{5-Metal-3-phenyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{N [2- (1-Imidazoyl) methyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Aminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Diethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {| 4- (2-Dimethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Aminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one,

4

444

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {(4- (2-Dimethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-3- (2-pyridyl) -F [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- (2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyridyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Diethylaminomethyl) -5-methyl-3-11-yrazinylpyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Dimethylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-3-pyrazinyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {| 4- (2-Ethylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- (2- (1-Imidazoyl) methyl] -5-methyl-3-pyrazinylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {(4- (2-Cyclopropylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, ·

121

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Metal-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrole-

2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-imidazoyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Cyclopropyl aminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-11 pyrimidinyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {(4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

· · · · · · · · · · · · · · · ·

122

4- {[4- (2-Diethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

N - {[4- (2-Dimethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Ethylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -

3- pyrazinyl-2-pyrazolin-5-one,

4- {{5-Methyl-3- (2-furyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3 ~ (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

Μ

123

4 {[4- (2-Die ^d gilaminometil) -5-hydroxymethyl-3-isopropylpyrrolo-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4 (2-Dimethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Egylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} megylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {{4- [2- (1-Imidazoyl) methyl] -5-hydroxymethyl-3-isopropylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 {| 4 (2-Cyclopropylaminomethyl) -5-hydroxymethyl-3-isopropylgyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 {[4- (2-Dimethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Di-cyclopropyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4 (2-Ethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 {{4 [2- (Eimidazoyl) methyl] -3,5-; cyclopropylpyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 [(4cyclohexylaminomethyl-3,5-dicyclopropyl [irol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one,

A {[3-Tsiklo11rs) 11ilaminometil-5-methyl-4- (2-diethyl ^g gilaminoetil) g1irol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-hydroxyethyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Dimegylaminomethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, and

4 - {[3-Hydroxymethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one.

The compounds of formula I may exist in the form of salts with pharmaceutically acceptable acids. These salts are included in the present invention. Examples of such salts include hydrochlorides, hydrobromides, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, tartrates [eg (+) tartrates, (-) - tartrates or mixtures thereof, including racemic mixtures, succates, succates benzoates and salts with amino acids such as glutamic acid. These salts can be prepared by methods known to one skilled in the art.

Certain compounds of formula I that contain acid substituents may exist in the form of salts with pharmaceutically acceptable bases. These salts are included in the present invention. Examples of such salts include sodium salts, potassium salts, lysine salts and arginine salts. These salts can be prepared by methods known to one skilled in the art.

Some compounds of formula I and their salts may exist in more than one crystalline form and the present invention includes all crystalline forms and mixtures thereof.

Some compounds of formula I and their salts may also exist in the form of solvates, for example hydrates, and the present invention includes each solvate and mixtures thereof.

* · · · ·

• · · · · · · · ·

125

Some compounds of formula I may contain one or more chiral centers and exist in different optically active forms. When compounds of formula I contain a single chiral center, the compounds exist in two enantiomeric forms and the present invention includes both enantiomers and mixtures of enantiomers. The enantiomers may be separated by methods known to one skilled in the art, for example, by producing diastereoisomeric salts, which may be separated, for example, by recrystallization, formation of diastereoisomeric derivatives or complexes, which may be separated, for example, by recrystallization, gas-liquid or liquid chromatography; selective reaction of an enantiomer with an enantiomerically specific reagent, for example enzymatic esterification; or gas or liquid chromatography in a chiral medium, for example on a chiral support, for example silica gel with a bound chiral ligand, or in the presence of a chiral solvent. It is apparent that when the desired enantiomer is converted to another chemical unit by one of the methods described above, a further step of releasing the desired enantiomeric form is required.

Alternatively, certain enantiomers may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents or by converting one enantiomer into another by asymmetric transformations.

When a compound of formula I contains more than one chiral center, it may exist in diastereoisomeric forms. The diastereomeric pairs may be separated by methods known to one skilled in the art, such as chromatography or recrystallization, and the individual enantiomers of each pair may be separated as described above. The present invention includes any diastereoisomer of compounds of formula I and its compounds

126 mixtures.

Some compounds of formula I may exist in different tautomeric forms or as different geometric isomers and the present invention includes each tautomer and / or geometric isomer of compounds of formula I and mixtures thereof.

Some compounds of formula I may exist in different stable conformational forms which may be separable. Torsional asymmetry due to the limited rotation around an asymmetric single bond, for example due to ethereal obstruction or ring tension, may allow different conformers to be separated. The present invention includes any conformational isomer of compounds of formula I and mixtures thereof.

Some compounds of formula I may exist in amphoteric form and the present invention includes any amphoteric form of compounds of formula I and mixtures thereof.

The compounds of this invention are useful as inhibitors of serine / threonine- and tyrosine kinases. More specifically, the compounds of this invention are useful as tyrosine kinase inhibitors that are important in hyperproliferative diseases, especially in the process of angiogenesis. For example, some of these compounds are inhibitors of such receptor kinases as KDR, Flt-1, FGFR, PDGFR, c-Met, or IGF-1-R. Because these compounds are anti-angiogenic, they are important substances for inhibiting progressive disease states in which angiogenesis is important. Some compounds of the invention are effective as inhibitors of such serine / threonine kinases as erk, MAP kinases, cdks, Plk-1 or Raf-1. These compounds are useful in the treatment of cancer and hyperproliferative diseases. In addition, some compounds are effective inhibitors of non-receptor kinases such as sr, lyn, lek, fyn, blk, hck. These compounds are useful in the treatment of cancer,

127

hyperproliferative diseases and immunological diseases.

The present invention provides a method of inhibiting the kinase activity of tyrosine kinases and serine / threonine kinases, comprising administering a compound of formula I to said kinase at a concentration sufficient to inhibit the enzymatic activity of that kinase.

The present invention further includes the use of these compounds in pharmaceutical compositions with a pharmaceutically effective amount of the compounds described above and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be administered to patients for the attenuation or retardation of the angiogenesis process in diseases promoted by angiogenesis, or for the treatment of edema, effusion, exudates or ascites, and other conditions associated with vascular permeability. Some pharmaceutical compositions may be administered to patients for the treatment of cancer and hyperproliferative diseases by inhibiting serine / threonine kinases such as cdk, Plk-1, erk, and the like. Detailed description of the invention

The compounds of this invention have antiangiogenic properties. These anti-angiogenic properties are due at least in part to the inhibition of protein tyrosine kinases important for the antigenic processes. For this reason, such compounds can be used as active agents against conditions such as arthritis, atherosclerosis, psoriasis, hemangiomas, myocardial angiogenesis, coronary or cerebral collateral, ischemic limb angiogenesis, wound healing, peptic ulcer, peptic acid from angiogenic disorders, fractures, Crow-Fukase syndrome (POEMS), pre-eclampsia, menometrology, felinosis, rubose, neovascular glaucoma and retinopathies such as those associated with diabetic retinopathy, retinopathy in yarn premature birth or age-related macular degeneration. In addition, some of these compounds may be

128 used as active agents against solid tumors, malignant ascites, hematopoietic carcinomas and hyperproliferative diseases such as thyroid hyperplasia (in particular Grave's disease) and cysts (such as ovarian stroma hypervascularity characteristic of polycystic syndrome) ), since such diseases require proliferation of blood vessels for growth and / or metastasis.

In addition, some of these compounds can be used as active agents for burns, chronic lung disease, stroke, polyps, anaphylaxis, chronic and allergic inflammation, delayed type of hypersensitivity, ovarian hyperstimulation syndrome, cerebral edema associated with brain tumor, high disease caused by trauma or hypoxia cerebral or pulmonary edema, ocular or macular edema, ascites and other diseases in which the disease manifests in vascular superconductivity, effusion, exudates, extravasation of protein or edema. The compounds are useful for the treatment of disorders in which protein extravasation results in the deposition of fibrin and extracellular matrix, promoting stromal proliferation (eg keloid, fibrosis, cirrhosis and carpal tunnel syndrome). Increased production of VEGF enhances inflammatory processes such as the repair and activation of monocytes. The compounds of this invention are also useful for the treatment of inflammatory disorders such as inflammatory bowel disease (IBD) and Crohn's disease.

VEGFs are unique in that they are the only known angiogenic growth factors that contribute to vascular hyperpermeability and edema formation. Of course, vascular hyperpermeability and edema that is associated with the expression or application of many other growth factors appear to be mediated by the production of VEGF. Inflammatory cytokines stimulate VEGF production. Hypoxia leads to a clear regulation of VEGF in a number of tissues ·· ·· ♦ ·

129, and consequently to conditions including infarction, blockage, ischemia, anemia, or circulation damage, usually eliciting VEGF / VPF mediated responses. Vascular hyper-permeability associated with edema, changing intermittent exchange and macromolecular extravasation, often accompanied by diapedesis, can lead to excessive matrix deposition, abnormal stromal proliferation, fibrosis, etc. Therefore, VEGF mediated hyperpermeability can significantly contribute to disorders with these etiological characteristics.

The disorders listed above are thought to be largely mediated by the action of protein tyrosine kinases, including the KDR / VEGFR-2 tyrosine kinases and / or Flt-1 / VEGFR-1. By inhibiting the activity of these tyrosine kinases, the development of the listed disorders is inhibited, since the angiogenic or vascular hyperpermeability component of the disease state is significantly reduced. The action of some of the compounds of this invention by their selectivity for certain tyrosine kinases leads to a reduction in the side effects that would occur if less selective tyrosine kinase inhibitors were used. Some compounds of the invention are also effective inhibitors of FGFR, PDGFR, c-Met, and IGF-1-R. These receptor kinases can directly or indirectly potentiate angiogenic and hyperproliferative responses in a number of diseases, which means that their inhibition may delay the development of the disease.

The compounds of this invention have inhibitory activity against protein kinases. This is to say that these compounds modulate signaling by protein kinases. The compounds of the invention inhibit serine / threonine tyrosine kinase protein kinases. More specifically, these compounds selectively inhibit the activity of KDR / FLK-1 / VEGFR-2 tyrosine kinases. Some compounds

• of this invention also inhibit the activity of additional tyrosine kinases such as Flt-1 / VEGFR-1, FGFR, PDGFR, IGF-1R, c-Met, Src subfamilies kinases such as Lek, Src, fyn, yes, etc. In addition, some compounds of this invention significantly inhibit serine / threonine kinases such as PKC, MAP kinases, erk, CDKs, Plk-1, or Raf-1, which play important roles in cell proliferation and cell cycle progression. The potency and specificity of the generic compounds of this invention with respect to a particular protein kinase can often be modified and optimized by changes in the nature, number and arrangement of the substituents (i.e., R _h R ₂ , R ₃ , R ₄ , R 5, R g and R ₇ ) and conformational constraints. In addition, the metabolites of some compounds may also have significant protein kinase inhibitory activity.

The compounds of this invention, when administered to patients in need of such compounds, inhibit vascular hypersensitivity and edema formation in these patients. Such compounds are believed to act by inhibiting the activity of KDR tyrosine kinase, which is involved in the process of vascular hyperpermeability and edema formation. Tyrosine kinase KDR may also be referred to as FLK-1 tyrosine kinase, Ν YK tyrosine kinase, or VEGFR-2 tyrosine kinase. KDR tyrosine kinase is activated when the vascular endothelial cell growth factor (VEGF) or other activating ligand (such as VEGF-C, VEGF-D, VEGF-E or HIV Tat protein) binds to the KDR tyrosine kinase receptor that lies on the surface of the vascular endothelial cells. As a result of such activation of KDR tyrosine kinase, blood vessels are permeable and the fluid flowing from the blood stream passes through the walls of the blood vessels into the interstitial spaces, thus forming a region of drainage. This response is also often accompanied by diapedesis. Like this, the ultimate vascular

hyperpermeability can disrupt normal molecular metabolism through the endothelium in critical tissues and organs (eg, lung and kidney), thereby causing macromolecular extravasation and deposition. Following this acute response to KDR stimulation, which is thought to facilitate the subsequent angiogenic process, prolonged stimulation of KDR tyrosine kinase leads to vascular endothelial cell proliferation and chemotaxis and the formation of new vessels. By inhibiting KDR tyrosine kinase activity or by blocking the production of an activating ligand, by blocking the binding of the activating ligand to the KDR tyrosine kinase receptor, by preventing receptor dimerization and transphosphorylation, by inhibiting the enzymatic activity of tyrosine kinases by tyrosine kinase enzyme), or by any other mechanism that interrupts its avalanche signaling (D. Mukhopedhyay et al., Cancer Res. 58: 1278-1284 (1998) and the sources included), may be IBIR and minimized hyperpermeability, as well as associated extravasation, subsequent preparation of the swelling and matrix deposition, and angiogenic responses.

One group of preferred compounds of this invention has the property of inhibiting KDR tyrosine kinase activity without significantly inhibiting Flt-Ι tyrosine kinase activity (Flt-1 tyrosine kinase also refers to VEGFR-1 tyrosine kinase). Both kinases - both KDR tyrosine kinase and Flt-γ tyrosine kinase are activated by binding VEGF to KDR tyrosine kinase receptors and to Flt-γ tyrosine kinase receptors, respectively. Because Flt-Ι tyrosine kinase activity can mediate important events in endothelial maintenance and vascular function, inhibition of this enzyme activity can lead to toxic or adverse effects.

• · ····

132

At least such inhibition is not necessary to block angiogenic responses, to induce vascular hyperpermeability and to produce edema, so that it is unnecessary and irrelevant to the patient. Some preferred compounds of this invention are unique in that they inhibit the activity of one VEGF receptor tyrosine kinase (KDR) activated by activating ligands but do not inhibit other receptor tyrosine kinases, such as Fit--, which are also activated by some activating ligands. Preferred compounds of this invention are therefore selective in their tyrosine kinase inhibitory activity.

The compounds of the present invention are also useful for treating ulcers - bacterial, fungal, Moogep ulcer and ulcerative colitis.

The compounds of the present invention are also useful in the treatment of conditions in which unwanted angiogenesis, edema or stromal deposition occurs in viral infections such as herpes simplex, herpes zoster, AIDS, parapoxvirus, psoriasis, Kaposi's sarcoma, protozoic disease, endometriosis, ovarian hyperstimulation syndrome, preeclampsia, menometrology, systemic lupus, sarcoidosis, synovitis, inflammatory bowel disease, Crohn's disease, sickle cell anemia, Lyme disease, pemphigoid, Paget's disease, syndrome hyperviscosity, Osler-Weber-Rendu disease, chronic inflammation, chronic occlusive pulmonary disease, asthma, rheumatoid arthritis and osteoarthritis, and edema resulting from burns, trauma, radiation or stroke.

The compounds of the present invention are also useful in the treatment of ocular conditions such as eye or macular edema, ocular neovascular disease, scleritis, radial keratotomy, uveitis, vitritis, myopia, optic pits, chronic retinal detachment, ίιί ^ ϊ, ^ όϋ

133 complication after treatment with laser, conjunctivitis, Stargardt disease and Eales disease in addition to retinopathy and macular degeneration.

The compounds of the present invention are also useful in the treatment of cardiovascular conditions such as atherosclerosis, restenosis, vessel obstruction, and obstructive carotid artery disease.

The compounds of the present invention are also useful in the treatment of indications related to cancer such as solid tumors, sarcomas (especially Ewing sarcoma and osteosarcoma), retinoblastoma, rhabdomyosarcoma, neuroblastoma, haematopoietic malignancies, including leukemia, lymphoma, and lymphoma. from pleural or pericardial effusion and malignant ascites.

The compounds of the present invention are also useful in the treatment of Crow-Fukase Syndrome (POEMS) and diabetic conditions such as glaucoma, diabetic retinopathy and microangiopathy.

It is apparent that the disorders listed above are largely mediated by protein tyrosine kinase activity, including VEGF receptors (eg, KDR and Flt-Ι). By inhibiting the activity of these receptor tyrosine kinases, the development of the listed disorders is inhibited, since the angiogenic component of the disease state is greatly reduced. The action of the compounds of this invention by their selectivity to specific tyrosine kinases leads to a reduction in the side effects that would occur if less selective tyrosine kinase inhibitors were used.

In another aspect, the present invention provides compounds of formula I, as defined above (including conditional), for use as medicaments, in particular as inhibitors of protein kinase activity, for example tyrosine kinase activity, serine kinase activity and threonine kinase activity. In another aspect · · · · · · · · · · · · · · · ·

134 The present invention provides the use of compounds of formula I, as defined above (including conditional), for the manufacture of a medicament useful for inhibiting protein kinase activity.

The following definitions are adopted in the invention:

physiologically acceptable salts refer to those salts which retain the biological efficiency and free base properties and which are obtained by reacting with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or organic acids, such as sulfonic acid acid, carboxylic acid, organophosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, lactic acid, tartaric acid and the like.

Alkyl refers to a saturated aliphatic hydrocarbon comprising straight- and branched-chain groups having 1 to 6 carbon atoms or cyclic hydrocarbons having 3 to 6 carbons.

Alkoxy refers to an O-alkyl group where alkyl is defined as described above.

pharmaceutical compositions

The compounds of this invention may be administered to human patients either as the compounds themselves or in pharmaceutical compositions in which they are mixed with suitable carriers or excipient (s) in dosages for the treatment or reduction of vascular hyperpermeability, edema and related disorders. Mixtures of these compounds may also be administered to the patient in the form of a simple mixture or as suitably formulated pharmaceutical compositions. An effective dose refers to that amount of compound or compounds sufficient to prevent or mitigate adverse neovascularization, the development of hyperproliferative diseases, edema associated with VEGF hyperpermeability · · · · · · · · · · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · • · · · · · · ·

135 and / or VEGF-related hypotension. Methods for formulating and administering the compounds of this application can be found in 'Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, latest edition.

The ways of drawing

Suitable routes of administration may include, for example, oral, ophthalmic, rectal, transmucosal, topical or internal administration; parenteral administration, including intramuscular, subcutaneous, intramedullary injection, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal and intraocular injection.

On the other hand, the compound may be administered topically instead of systemically, for example by injecting it directly into the swelling site, often in a depot or sustained release form.

In addition, the drug may be administered in a suitable drug delivery system, such as a liposome coated with an endothelial-specific antibody.

Composition / formulation The pharmaceutical compositions of the present invention can be produced in a manner which is itself known, for example by conventional methods of mixing, dissolving, granulating, making dragees, suspending, emulsifying, encapsulating, retaining or lyophilizing.

Pharmaceutical compositions for use in accordance with the present invention may be formulated in a conventional manner using one or more physiologically acceptable carriers containing excipients and excipients that facilitate the conversion of the active compounds into preparations useful for the preparation of the compounds of the present invention. *

• 4 · · 4 · • 4 · • 4 4 4 4 • ·· • 4 ·

44 ··· Pharmaceutical purposes. The appropriate form depends on the input path selected.

For injection, the compounds of the invention can be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution or saline buffer. Transmucosal formulations use penetrating agents suitable to cross the barrier. Such penetrants are generally known in the art.

For oral administration, the compounds can be formulated readily by mixing the active compounds with pharmaceutically acceptable carriers known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, mash, suspensions, etc., for oral administration by the treated patient, pharmaceutical preparations for oral administration can be prepared by mixing of the active compound with a solid excipient, optionally grinding the resulting mixture and treating the granule mixture after the addition of suitable excipients, if necessary, to obtain the core of the tablets or dragees. Suitable excipients are in particular fillers such as sugars, including lactose, sucrose, mannitol or sorbitol; cellulosic preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth resin, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). If necessary, disintegrating agents such as cross-linked polyvinylpyrrolidone, agar or alginic acid or a salt thereof as sodium alginate may be added.

The cores of the dragees are provided with suitable coatings. Concentrated sugar syrups, which may optionally contain gum arabic, talc, polyvinylpyrrolidone, carbopol-gel, polyethylene glycol and / or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. Dyes or pigments may be added to the coatings for tablets or dragees to identify or characterize different combinations of doses of the active compound.

pharmaceutical compositions that can be administered orally include adjustable capsules made of gelatin as well as soft sealed capsules made of gelatin and a plasticizer such as glycerol or sorbitol. Adjustable capsules may include the active ingredients in admixture with a filler such as lactose, binders such as starch and / or lubricants such as talc or magnesium stearate and optionally stabilizers. In the soft capsules, the active compounds can be dissolved or suspended in suitable liquids, such as saturated oils, liquid paraffin or liquid polyethylene glycols. In addition, stabilizers may be added. All oral administration forms should be in appropriate doses for such administration.

Compositions for buccal administration may be in the form of tablets or candies prepared in the conventional manner.

For administration by inhalation, the compounds of the present invention are generally delivered in the form of an aerosol spray, delivered from a pressurized vial or nebulizer, the use of a suitable propellant, e.g. In the case of a pressurized aerosol, a unit dose can be determined by providing a valve to supply a metered amount. From a powder mixture of the compound and a suitable powder base such as lactose or starch, capsules and cartridges can be formulated - for example, from • · · · • ·

gelatin for use in an inhaler or insufflator.

For parenteral administration by injection, the compounds may be formulated, for example, for single injection of the entire amount or for continuous infusion, the injection forms may be presented in unit dosage form, for example in ampoules or in multiple dose containers with added preservative. The compositions may be in the form of a suspension, solutions or emulsions in oil or aqueous solutions and may contain excipients such as suspending, stabilizing and / or dispersing agents.

The pharmaceutical compositions for parenteral administration include aqueous solutions of the active compounds in water-soluble form. In addition, suspensions of the active compounds may be formulated as injectable suspensions in oil. Suitable lipophilic solvents or diluents include fatty oils, such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes.

Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. The suspension may optionally also contain suitable stabilizers or agents that increase the solubility of the compounds, allowing the preparation of highly concentrated solutions.

On the other hand, the active ingredient may be in powder form and before use included in a suitable diluent, for example sterile non-pyrogenic water.

The compounds may also be formulated in rectal compositions such as suppositories or retention enemas containing, for example, conventional suppository bases such as cocoa butter or other glycerides.

• · · · • · • · · · e

In addition to the forms described above, the compounds can be formulated in the form of depot preparations. Such long acting forms can be administered by implantation (for example, subcutaneous or intramuscular or intramuscular injection). For example, the compounds may be formulated with suitable polymeric or hydrophobic compounds (eg emulsion in acceptable oil) or ion exchange resins or as derivatives of limited solubility, for example as a salt with limited solubility.

An example of a pharmaceutical carrier for the hydrophobic compounds of the invention is a co-solvent system comprising benzyl alcohol, a non-polar surfactant miscible with an organic water polymer and an aqueous phase. The co-solvent system may be a VPD co-solvent system. VPD is a solution of 3% w / v benzyl alcohol, 8% w / v nonpolar surfactant polysorbate 80 and 65% w / v polyethylene glycol 300, adjusted to the corresponding volume with absolute ethanol. The VPD co-solvent system (VPD: 5W) consists of a VPD diluted 1: 1 with 5% aqueous dextrose. This co-solvent system dissolves hydrophobic compounds well, and itself causes low toxicity when administered systemically. Naturally, the ratios in the co-solvent system can vary significantly without impairing its solubility and toxicity characteristics. In addition, the appearance of the co-solubilizing components may vary: for example, other low-toxic non-polar surfactants may be used in place of polysorbate 80; the size of the polyethylene glycol fraction may be varied; polyethylene glycol can be replaced by other biocompatible polymers, for example polyvinylpyrrolidone; and dextrose can be replaced by other sugars or polysaccharides.

Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be used. Liposomes and emulsions are known examples of providing diluents or carriers for hydrophobic drugs. Some organic solvents such as dimethyl sulfoxide may also be used, although at the cost of greater toxicity. In addition, the compounds can be delivered using sustained release systems, for example as semipermeable matrices of solid hydrophobic polymers including the therapeutic agent. A number of sustained release agents have been evaluated and are known to those skilled in the art. Depending on their chemical nature, sustained release capsules can release the compounds for several weeks to over 100 days. Depending on the chemical nature and biological stability of the drug, additional protein stabilization strategies may be employed.

the pharmaceutical compositions may also contain carriers or excipients in a suitable solid or liquid phase. Examples of such carriers or excipients include, but are not limited to, calcium carbonate, calcium phosphate, a number of sugars, starches, cellulose derivatives, gelatin and polymers such as polyethylene glycols.

Many of the organic compounds of the invention can be provided as salts with pharmaceutically compatible counterions. pharmaceutically compatible salts may be prepared with many acids, including, but not limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, maleic, succinic and the like. Salts tend to be more soluble in aqueous or other protic solvents than their corresponding free base forms.

• · · · ·

Effective Dosage Pharmaceutical compositions suitable for use according to the present invention include compositions in which the active ingredients are contained in an effective amount to achieve the desired goal. More specifically, a therapeutically effective amount means an amount effective to prevent the development or to alleviate existing symptoms of the patient being treated. Determination of effective amounts is within the skill of the person skilled in the art.

For each compound used in the method of the invention, the therapeutically effective dose can initially be determined by cellular analysis. For example, a single dose can be formulated in a cell and animal model to obtain a circulating concentration range that includes IC ₅₀ values as determined in cellular analysis (e.g., the concentration of test compound that achieves half of the maximum inhibition of protein kinase activity). In some cases, it is appropriate to determine IC ₅₀ values in the presence of 3 to 5% serum albumin, since such determination is almost consistent with the effects of plasma protein binding to the compound. This information can be used to more accurately determine useful human doses. In addition, the most preferred compounds for systemic administration effectively inhibit whole-cell signaling protein kinase at levels attained safely in plasma.

A therapeutically effective dose refers to that amount of the compound which leads to the relief of symptoms in a patient. The toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical methods in cell cultures or experimental animals, for example to determine

• ·

· Maximum tolerated dose (MTD) and ED ₅₀ (effective dose for 50% of maximum response). The toxicity / therapeutic effects ratio represents the therapeutic index and can be expressed as the ratio between MTD and ED ₅₀ . Compounds having a higher therapeutic index are preferred. The data from cell culture assays and animal studies can be used to formulate the dose range applicable to humans. Preferably, the dosage of such compounds is within the range of circulating concentrations that include ED ₅₀ values with little or no toxicity. The dosage may vary within these limits depending on the dosage form used and the route of administration. The exact formulation, route of administration and dosage may be selected by the individual physician in view of the patient's condition. (See, for example, Fingl et al., 1975, The Pharmacological Basis of Therapeutics, Ch. 1, 1). In the treatment of crises, achieving a rapid response may require the administration of a strong dose or infusion with a maximum tolerability dose.

The dosage amount and interval can be adjusted individually to provide plasma levels of the active group that are sufficient to maintain kinase modulating effects or minimum effective concentration (MEC). The minimum effective concentration is different for each compound, but can be determined from the in vitro data, for example, the concentration required to achieve 50-90% inhibition of protein kinase using the assay described herein.

The doses required to achieve the minimum effective concentration depend on the individual characteristics and the route of administration. However, high performance thin layer chromatographic (HPLC) analysis or bioanalysis can be used to determine plasma concentrations.

Dosing intervals can also be determined using the values for the minimum effective concentration. The compounds should be administered using a regimen that maintains plasma levels above the minimum effective concentration at 1090% of the time, preferably between 30 and 90%, and most preferably between 50 and 90% of the time, until the desired symptom relief is achieved. In the case of topical administration or selective absorption, the effective local concentration of the drug may not be related to the plasma concentration.

The amount of composition administered, of course, depends on the patient being treated, on their weight, on the severity of the suffering, on the route of administration, and on the judgment of the treating physician.

Package

If desired, the compositions may be presented in a package or dispenser that may contain one or more unit dosage forms comprising the active ingredient. The package may consist of, for example, metal or plastic foil, such as a blister. The package or distribution device may be accompanied by an instruction manual. Compositions may also be prepared containing a compound of the invention formulated in a compatible pharmaceutical carrier, placed in a suitable container and labeled for the treatment of a particular condition.

In some embodiments, it may be advantageous to use the compounds of the present invention in the form of very small particle sizes, for example, as obtained by grinding in a liquid medium.

The use of compounds of the present invention for the manufacture of pharmaceutical compositions is shown in the following description. In this specification, the term active compound means any compound of the invention, and in particular any compound that is · · · · · · · · · · · · ·

end product from one of the preceding examples.

a) Capsules

In the preparation of capsules, 10 parts by weight of the active compound and 240 parts by weight of lactose can be disaggregated and mixed. The mixture can be filled into hard gelatin capsules, each capsule containing a single dose or part of a single dose of the active compound.

b) Tablets

Tablets can be obtained from the following components.

Parts by weight

The active compound 10 Lactose 190 Cornstarch 22 Polyvinylpyrrolidone 10 Magnesium stearate 3

The active compound, lactose and part of the starch can be disaggregated, mixed and the resulting mixture granulated with a solution of polyvinylpyrrolidone in ethanol. The dry granulate can be mixed with magnesium stearate and starch residue. The mixture is then compressed on a tablet machine to produce tablets, each containing a single dose or part of a single dose of the active compound.

c) enteric coated tablets

The tablets may be prepared by the method described above in (b). They can be applied enteric coated in a conventional manner using a solution of 20% cellulose acetate phthalate and 3% diethyl phthalate in ethanol: dichloromethane (1: 1).

d) Candles

Upon receipt of the suppositories, 100 parts by weight of the active ingredient

• · · · · · · ·

compound can be incorporated into 1300 parts by weight triglyceride base for suppositories and the mixture is formed into suppositories, each of which contains a therapeutically effective amount of the active ingredient

In the compositions of the present invention, the active compound can optionally be combined with other compatible pharmacologically active components. For example, the compounds of this invention may be administered in combination with one or more additional pharmaceutical agents that inhibit or prevent VEGF production, attenuate intracellular responses to VEGF, block intracellular signaling, inhibit vascular hyperpermeability, reduce inflammation or inhibit inflammation or edema formation or neovascularization. The compounds of the invention may be administered before, after, or simultaneously with the additional pharmaceutical agent - which course of administration is more appropriate. Additional pharmaceutical agents include, but are not limited to, antiemetic steroids, non-steroidal anti-inflammatory drugs, ras inhibitors, anti-TNF agents, anti-IL-1 agents, antihistamines, PAF antagonists, COX-1 inhibitors, COX-2 inhibitors, COX-2 inhibitors, of nitric oxide synthase, PKC inhibitors and PI3 kinase inhibitors. The compounds of the invention and the additional pharmaceutical agents act either additively or synergistically. Thus, the administration of such a combination of substances that inhibit angiogenesis, vascular hyperpermeability and / or inhibit edema formation may provide greater relief for the deleterious effects of hyperproliferative disorder, angiogenesis, vascular hyperpermeability, or edema, or self-permeability. In the treatment of malignancies, combinations with antiproliferative or cytotoxic chemotherapy or radiation are contemplated.

• ·

The present invention also includes the use of a compound of formula I as a medicament.

Both Src and Syk kinases play a major role in the regulation of immune function, the Src family currently includes Fyn, Lek, Fgr, Fes, Lyn, Src, Yes, Hck and Blk. The Syk family is now considered to include only Zap and Syk. the Janus family of kinases is involved in the transmission of growth factor signals and proinflammatory cytokines through a number of receptors. Although VTK and GGC, members of the Tess kinase family play a less understood role in immunology, their modulation by an inhibitor may prove their therapeutic benefit. The RIP, IRAK-1, IRAK-2, NIK, TPL-2 / COT, IKK-1 and ΙΚΚ-2 kinases are involved in signaling pathways for key TNF and IL-1 pro-inflammatory cytokines. Due to their tendency to inhibit one or more of these kinases, the compounds of formula I can act as immunomodulatory agents useful for the maintenance of allografts and for the treatment of autoimmune diseases. Due to their ability to regulate T-cell activity or potentiation of an inflammatory process, these compounds can be used to treat such autoimmune diseases. Due to the phenomenon of rejection - either a solid organ transplant or a bone marrow host transplant, the transplants are limited because of the toxicity of the currently available immunosuppressants and an effective drug with an improved therapeutic index would be beneficial. Labeled gene experiments show the important role of Src in the biology of osteoclasts, the cells responsible for bone resorption. Because of their ability to regulate Src, the compounds of formula I may also be useful in the treatment of osteoporosis, osteopetrosis, Paget's disease caused by tumor hypercalcemia, and in the treatment of bone metastases.

• · · · · · · · · · · · · · · · · · · · · · · · ·

Chromosomal rupture (at Itk kinase

A number of protein kinases that are proto-oncogenes.

chromosome cleavage site 5), translocation, as in the case of the AB1 gene with BCR (Philadelphia chromosome), interruption, as in cases such as c-Kit or

EGFR, or a mutation (eg Met), results in the formation of uncontrolled proteins, transforming them from proto-oncogenic to oncogenic products. In other tumors, oncogenesis is managed by

interactions between autocrine or paracrine ligand and growth factor receptor. Members of the src kinase family typically participate in avalanche signaling, thereby enhancing oncogenesis and can themselves become oncogenic by overexpression or mutation. By inhibiting the protein kinase activity of these proteins, disease development can be interrupted. Vascular restenosis may involve processes of FGF-enhanced and / or PDGF proliferation of smooth muscle and endothelial cells. Stimulation by ligands of FGFR, PDGFR, IGF1-R and c-Met in vivo is proangiogenic and potentiates angiogenesis-dependent diseases. Inhibition of FGFr, PDGFr, c-Met, or IGF1-R kinase activity may be an effective strategy for inhibiting these phenomena. Thus, compounds of formula I that inhibit the kinase activity of normal or atypical members of the c-kit, c-met, c-fms, src-families, EGFr, erbB2, erbB4, BCR-Abl, PDGFr, FGFr, IGF1-R and other receptor or cytosolic tyrosine kinases may be important in the treatment of benign and neoplastic proliferative diseases.

In a number of pathological conditions (eg solid primary tumors and metastases, Kaposi's sarcoma, rheumatoid arthritis, blindness due to inappropriate ocular neovascularization, psoriasis and atherosclerosis), the development of the disease results from persistent angiogenesis. Polypeptide growth factors often produced by diseased tissue or related inflammatory cells and · · · · · · · · ·

their corresponding endothelial cell receptor tyrosine kinases (e.g., KDR / VEGFR-2, Flt-1 / VEGFR-1, Tie-2 / Tek and Tie) are essential for stimulating endothelial cell growth, migration, organization, differentiation and establishment of the necessary new functional vasculature. As a result of VEGF mediated vascular permeability factor activity, VEGF stimulation of VEGFR kinase is also thought to play an important role in the production of tumor ascites, cerebral and pulmonary edema, pleural and pericardial effusions, delayed effusion hypersensitivity, tissue swelling and organ dysfunction due to trauma, burns, ischemia, complications of diabetes, endometriosis, respiratory distress syndrome in adults (ARDS), hypotension and hypersensitivity due to cardiopulmonary ypas and ocular edema leading to glaucoma or blindness due to inappropriate neovascularization. In addition to VEGF, recently identified VEGF-C and VEGF-D and virus-encoded VEGF-E or HTV-Tat protein can also elicit vascular hyperpermeability by stimulating VEGFR kinase. Tie-2 is also expressed in a select population of hematopoietic stem cells, where it may play a role in their repair, adhesion, regulation and differentiation (Blood, 4317-4326 (1997)); this Tie-2 expressing population may serve as circulating angiogenic endothelial progenitors. Certain agents of Formula I capable of blocking the kinase activity of specific endothelial cell kinases may therefore inhibit the development of a disease involving these positions.

The compounds of formula I, or salts thereof, or pharmaceutical compositions containing a therapeutically effective amount thereof, can be used in the treatment of benign and neoplastic proliferative diseases and diseases of the immune system. Such • · 4 4 4 4 • 9 • 9 99 • 9

diseases include autoimmune diseases, such as rheumatoid arthritis, thyroiditis, type 1 diabetes, multiple sclerosis, sarcoidosis, inflammatory bowel disease, Crohn's disease, myasthenia gravis and systemic lupus erythematosus; psoriasis, transplant rejection (eg kidney rejection, homologous disease), benign and neoplastic proliferative diseases, various cancers in humans such as lung, breast, stomach, bladder, colon, pancreatic, ovarian, prostate and rectum and hematopoietic malignancies (leukemia and lymphoma), diseases involving inappropriate vascularization, such as diabetic retinopathy, retinopathy in preterm birth, choroidal neovascularization due to in age-related macular degeneration and childhood hemangiomas in humans. In addition, such inhibitors may be useful in the treatment of diseases including VEGF-mediated edema, ascites, effusion and exudates, including, for example, macular edema, cerebral edema, acute pulmonary injury, and adult respiratory distress syndrome (ARDS).

The compounds of the present invention can also be used for the prevention of the above diseases.

In another aspect, the present invention provides the use of a compound of formula I or salts thereof for the manufacture of a medicament for the treatment of vascular hypersensitivity, angiogenesis-dependent diseases, proliferative diseases and / or immune system diseases in mammals and in particular humans.

The present invention also provides a method of treating vascular hyperpermeability, inappropriate neovascularization, proliferative diseases and / or diseases of the immune system, comprising administering a therapeutically effective amount of a compound of formula I to a mammal, in particular a human in need of • · · · · · · · · · · · · · · · ·

this.

The efficacy of compounds in vitro to inhibit these protein kinases can be determined by the methods described below.

The efficacy of the compounds can be determined by the amount of inhibition of phosphorylation of an exogenous substrate (e.g., synthetic peptide (Z. Songyang et al., Nature. 373: 536-539) by the test compound with respect to control. Preparation of KDR tyrosine kinase using of baculovirus system:

The coding sequence for the human KDR intracellular region (aa789-1354) was obtained by PCR using complementary deoxyribonucleic acids (cDNAs) isolated from HUVEC cells. A polyHis6 sequence is also inserted at the N-terminus of this protein. This fragment was cloned into transfection vector pVL1393 at sites Xba 1 and Not 1. Recombinant baculovirus was obtained (BV) by co-transfection using a BaculoGold transfection reagent (PharMingen). Recombinant BV was purified from plaques and verified by Western analysis. SF-9 protein was grown in SF-900-II medium at 2 x 10 6 / ml and infected with 0.5 plate-forming units (MOI). 48 hours after infection, cells were harvested.

Purification of KDR

SF-9 cells expressing (His) ₆ KDR (aa789-1354) were lysed by adding 50 ml of Triton X-100 lysis buffer (20 mM Tris, pH 8.0,137 mM Nad, 10% glycerol, 1% Triton X -100, 1 mM PMSF, 10 pg / ml aprotinin, 1 pg / ml leipeptin) to the cell pellets of 1L cell culture. The lysate was centrifuged at 19,000 rpm in a Sorval SS-34 centrifuge for 30 minutes at 4 ° C. The cell lysate was added to a 5 ml NiQ ₂ chelating sepharose column equilibrated with 50 mM HEPES, pH 7.5, 0.3 M NaCl. KDR is eluted with

using the same buffer contains 0.25 M imidazole. Column fractions were analyzed using SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and ELISA (enzyme-linked immunosorbent assay) (below), which account for kinase activity. Purified KDR was exchanged in 25 mM HEPES, pH 7.5.25 mM NaCl, 5 mM DTT buffer and stored at -80 ° C.

Preparation and purification of human Tie-2 kinase

The coding sequence for the human Pe-2 intracellular region (aa775-1124) was obtained by PCR using complementary deoxyribonucleic acids derived from human placenta as a template. Also inserted into the N-terminus of the polypeptide is the ii (uiM-His ₆ sequence. This fragment is cloned into the transfection vector pVL1393 at sites Xba 1 and Not 1. Recombinant baculovirus (BV) is prepared by co-transfection using a BaculoGold transfecting reagent Recombinant BV was purified from plaques and verified by Western analysis To obtain protein SF-9, insect cells were grown in SF-900-II medium at 2 x 10 6 / ml and infected with 0.5 plaque units per cell. (MOI) Purification of His kinase contaminants is analogous to that described for KDR.

Preparation and purification of the human Fit-1 tyrosine kinase

The baculovirus expression vector used was pVL1393 (Phar Mingen, Los Angeles, CA). The nucleotide sequence encoding nojiM-His6 is inserted in the 5 'to the nucleotide region encoding the entire intracellular kinase region of human Flt-Ι (amino acids 786-1338). The nucleotide sequence encoding the kinase region is obtained by polymerase chain reaction (PCR) using libraries of complementary deoxyribonucleic acid isolated from HUVEC cells. The histidine residues make it possible to affinity purify the protein in a manner similar to that for KDR and ZAP70. SF-9 insect cells become infected at 0.5 · · · · · · · · · · · · · · · · · · · · · · · ·

• ♦ ·

multiplicity and are harvested 48 hours after infection.

Source of EGFR tyrosine kinase

EGFR was purchased from Sigma (Cat # E-3641; 500 units / 50 μΐ) and EGF ligand was obtained from Oncogene Research Products / Calbiochem (Cat # PF011-100).

ZAP70 expression

The baculovirus expression vector used is pVL1393. (Pharmingen, Los Angeles, CA). The nucleotide sequence encoding amino acids M (H) 6 of LVPR ₉ S is inserted at 5 'to the region encoding entirely ZAP70 (amino acids).

1-619). The nucleotide sequence encoding the ZAP70 coding region was obtained by PCR using a library of complementary deoxyribonucleic acids isolated from Jurkat killed T cells. Histidine residues allow affinity purification of the protein (see below). The LVPR ₉ S bridge is a recognition sequence for proteolytic cleavage by thrombin allowing removal of the affinity end of the enzyme. SF-9 insect cells were infected by repeated infection with 0.5 and harvested 48 hours after infection.

Extraction and purification of ZAP70

SF-9 cells were lysed in buffer containing 20 mM Tris, pH 8.0, 137 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM PMSF, 1 pg / ml leipeptin, 10 pg / ml aprotinin and 1 mM sodium orthovandate. The soluble lysate was applied to a column of HiTrap chelating Sepharose (Pharmacia) equilibrated with 50 mM HEPES, pH 7.5, 0.3 M NaCl. The fusion protein was eluted with 250 mM imidazole. The enzyme is stored in a buffer containing 50 mM HEPES, pH 7.5, 50 mM NaCl and 5 mM DTT.

· · · · · ·

· · · · · · · · · · · · · · · · · ·

Source of I c

Lek or truncated Lek forms may be commercially available (for example, Upstate Biotechnology Inc. (Sarnac Lake, NY) and Santa Cruz Biotechnology Inc. (Santa Cruz, CA) or from known natural or recombinant sources by standard purification methods

Enzyme-linked immunosorbent assay (ELISA) for receptor tyrosine kinase (PTK)

Enzyme-linked immunosorbent assays (ELISA) are used to detect and determine the presence of tyrosine kinase activity. ELISAs were performed according to known protocols described, for example, in Voller, et al., 1980, Enzyme-Linked Immunosorbent Assay, In: Manual of Clinical Immunology, 2d ed., Edited by Rose and Friedman, pp. 359-371 Am. Soc. of Microbiology, Washington, D.C.

The protocol described is adapted to determine activity against a particular RTK. For example, the following are preferred protocols for conducting ELISA experiments. Adaptation of these protocols to determine the activity of the compound with respect to other members of the receptor tyrosine kinase family as well as to non-receptor tyrosine kinases is within the skill of the art. In order to determine the inhibitory selectivity, a PTK substrate (e.g., an arbitrary copolymer of (Glu ₄ Tyr), molecular weight 20,000-50,000) is used together with adenosine-5'-triphosphate (usually 5 μΜ) at concentrations approximately twice as high. larger than the true Km in the analysis.

The following procedure was used to analyze the inhibitory effect of compounds of this invention on KDR, Flt-1, Flt-4 / VEGFR-3, Tie-2, EGFR, FGFR, PDGFR, IGF-1R, c-Met, and ZAP70 tyrosine kinase activity. :

· · · · · · · · · · · · · · · · · · · ·

Buffers and solutions:

PGT: Poly (O1i, Tug) 4: 1

The powder was stored at -20 ° C. The powder was dissolved in phosphate-buffered saline (PBS) at a concentration of 50 mg / ml solution. Equal portions of 1 ml were stored at -20 ° C. When preparing the plates, dilute to 250 pg / ml in Gibco PBS.

Reaction buffer: 100 mM Hepes, 20 mM MgQ ^ 4 mM MnCl ^ 5 mM DTT, 0.02% BSA, 200 μ MNaVO ₄ , pH 7.10

ATP: Equal sections of 100 mM were stored at -20 ° C. Dilute with water to 20 μΜ.

Wash Buffer: PBS with 0.1% Tween 20

Antibody dilution buffer: 0.1% bovine serum albumin (BSA) bPBS

TMB substrate: Immediately before use, TMB substrate is mixed with 9: 1 peroxide solutions or K-blue substrate is used from Neogen

Stop solution: 1M phosphoric acid • Method

1. Preparation of the plate:

Stock solution of PGT (50 mg / ml, frozen) was diluted with PBS to 250 pg / ml. 125 μΐ were added to each well of Coming-modified flat bottom plates for high affinity ELISA (Coming # 25805-96). 125 μΐ PBS was added to the empty wells. Cover with sealing tapes and incubate overnight at 37 ° C. They were washed once with 250 μΐ wash buffer and dried for 2 hours at 37 ° C in a dry incubator. The coated plates are stored in a sealed bag at 4 ° C until used.

·· ····

• · · • »· ♦ · ···· • A 4« • · ·

2. Tyrosine kinase reaction:

- Prepare solutions with 4 concentrations of enzyme in 20% dimethyl sulfoxide in water.

- Prepare a reaction buffer.

- An enzyme solution is prepared so that the desired units are in 50 μΐ, for example for KDR is made at 1 ng / μΙ for a total of 50 ng per well of reaction. It is stored in ice.

- Prepare 4 ATP solutions in water up to 20 μΜ from 100 mM stock solution. They are stored in ice.

- Add 50 μΙ of the enzyme solution per well (usually 5-50 ng enzyme / well depending on the kinase specific activity).

- Add 25 μΐ (4 x) inhibitor.

- Add 25 μΐ (4 x) ATP for inhibitor analysis.

- Incubate for 10 minutes at room temperature.

- The reaction is quenched by the addition of 50 μΐ 0.05 N HCl per well.

- The plate is washed.

** Reaction final concentrations: 5 μΜ ATP, 5% dimethyl sulfoxide

3. Binding of the antibody

- A 1 mg / ml aliquot of PY20-HRP antibody (Pierce) (phosphotyrosine antibody) was diluted to 50 ng / ml in 0.1% BSA in PBS in 2 dilution steps (100 x, then 200 x).

- Add 100 μί Ab per well. Incubate for 1 hour at room temperature. Incubate for 1 hour at 4 ° C.

- Wash the plate (4 x).

4. Color reaction · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- Prepare a TMB substrate and add 100 μΐ per well

- Monitor OD at 650 nm to reach 0.6

- Interrupted with 1M phosphoric acid. Shake on the reading device.

- Immediately read OD at 450 nm.

The optimum incubation times and enzyme reaction conditions vary slightly with the enzyme preparations and are determined empirically for each sample. The reaction buffer used for Lek is 100 mM 3-morpholino-2-hydroxypropanesulfonic acid (MOPSO), pH 6.5, 4 mM MnCl ₂ , 20 mM MgCl ₂ , 5 mM 1,4-digio-OE-triitol (DTT), 0.2% bovine serum albumin (BSA), 200 mM NaVO ₄ under similar assay conditions.

Compounds of formula I may be of therapeutic benefit in the treatment of diseases including both those identified, including those not mentioned herein, and unidentified protein tyrosine kinases, which are inhibited by compounds of formula I. All compounds tested here significantly inhibit KDR kinase at concentrations of 50 micromoles or lower. Some of the compounds of this invention also significantly inhibit other receptor tyrosine kinases as drugs at concentrations of 50 micromoles or lower.

Source of Cdc2

Human recombinant enzyme and assay buffer can be obtained commercially (New England Biolabs, Beverly, MA, SATTT) or by purification of known or recombinant sources using conventional methods.

Analysis of Cdc2

The protocol used is provided by the procurement of reagents with • ·

minimal changes. Briefly, the reaction is carried out in a buffer consisting of 50 mM Tris pH 7.5, 100 mM Nad, 1 mM ethylene glycol, O'-bis (2-aminoethyl) -N, N, N, N-tetraacetic acid (EGTA), 2 cm

1,4-dithiothreitol, 0.01% Brij, 5% DMSO and 10 mM MgCl ₂ (commercially available buffer) supplemented with 300 μΜ ATP (31 pCi / ml) and final concentrations of 30 pg / ml Hiss type histone. A reaction volume of 80 µL containing enzyme units was treated for 20 minutes at 25 ° C in the presence and absence of an inhibitor. The reaction was quenched by the addition of 120 µL of 10% acetic acid. The substrate was removed from the unlabeled marker by dropping the mixture on phosphocellulose paper, followed by 3 washes every 5 minutes with 75 mM phosphoric acid. The pulses are counted on a beta counter in the presence of liquid scintillant.

Some compounds of this invention significantly inhibit cdc2 at concentrations lower than 50 μΜ.

Source of PKC kinase

The catalytic subunit of PKC can be obtained commercially (Calbiochem).

Analysis of PKC kinase

Radioactive kinase analysis is used following the published method (Yasuda, I., Kirshimoto, A, Tanaka, S., Tominaga, M., Sakurai, A, Nishizuka, Y. Biochemical and Biophysical Research Communication 5: 166,1220 -1227 (1990)). Briefly, all reactions were performed in buffer containing 50 mM Tris-HQ pH 7.5.10 mM MgCl ₂ , 2 mM DTT, 1 mM EGTA, 100 μΜ ATP, 8 μΜ peptide, 5% DMSO, and ³³ P ATP (8 Ci / mM). The compound and the enzyme are mixed in a reaction vessel and the reaction is started by adding a mixture of ATP and substrate. The reaction was terminated by the addition of 10 µL of interrupt buffer (5 µM ATP in 75 mM phosphoric acid) and a portion of the mixture was added to phosphorous cellulose filters. The collected samples were washed three times in 75 µM phosphoric acid at room temperature for 5 to 15 minutes. The inclusion

• ·

of a radioactive marker is quantified by liquid scintillation counting.

Source of Erk2 enzyme

The recombinant murine enzyme and assay buffer can be obtained commercially (New England Biolabs, Beverly, MA, USA) or by purification of known or recombinant sources using conventional methods.

Erk2 enzyme assay

Briefly, the reaction was carried out in a buffer consisting of 50 mM Tris pH 7.5.1 mM EGTA, 2 mM DTT, 0.01% Brij, 5% DMSO and 10 mM MgCl ₂ (commercially available buffer) supplemented with fresh 100 μΜ ATP ( 31 pCi / ml) and 30 μΜ myelin based protein under conditions recommended by the supplier. The reaction volumes and the method for analyzing the radioactivity involved are as described for PKC analysis (see above).

In Vitro models for T-cell activation

When activated with a mitogen or antigen, T cells are induced to secrete IL-2, a growth factor that promotes their subsequent proliferative phase. Therefore, the production of IL-2 from T cells, or cell proliferation of primary T cells, or suitable T cell lines as witnesses for T cell activation can be measured. Both assays are described in the literature and their parameters are documented (in Current Protocols in Immunology, Vol 2, 7.10.1-7.11.2).

In short, T cells can be activated by coculture with allogeneic stimulating cells, a process that is defined as a unidirectional lymphocyte response. Responding and stimulating peripheral blood mononuclear cells were purified using a Ficoll-Hypaque (Pharmacia) gradient according to the manufacturer's instructions. The stimulating cells are mitotically deactivated by treatment with mitomycin C (Sigma) or by gamma irradiation. Responding and stimulating cells are • ·

····

cocultured in a 2: 1 ratio in the presence or absence of test compound. Typically, 10 ⁵ responders are mixed with 5 x 10 ⁴ stimuli and placed (200 μ (volume) in microtiter plates with a U-shaped bottom (Costar Scientific). The cells were cultured in RPMI 1640 to which either heat-deactivated fetal bovine serum (Hyclone, Laboratories) or pooled AB donor serum, 5 x 10 &apos; ⁵ M 2-mercaptoethanol and 0.5% dimethyl sulfoxide were added. The cultures were irradiated with 0.5 pCi H thymidine (Amersham) one day before harvest (usually on the third day). The cultures were harvested (Betaplate harvester, Wallac) and isotope uptake evaluated by liquid scintillation (Betaplate, Wallac).

The same culture system can be used to evaluate T-cell activation by measuring IL-2 production. Eighteen to twenty-four hours after the start of cultivation, the supernatant is removed and the IL-2 concentration is measured by ELISA (R and D systems) according to the manufacturer's instructions.

In-vivo models of T-cell activation

The efficacy of the compounds in vivo can be tested in animal models known to directly measure T-cell activation or for which T-cells have been shown to cause the effect. T cells can be activated in vivo by binding the permanent portion of the T cell receptor to a monoclonal anti-CD3 antibody (Ab). In this model, BALB / c mice were administered intraperitoneally 10 pg of anti-CD3Ab two hours before bleeding. Animals receiving the test drug were pre-treated with a single dose of the compound one hour before the administration of anti-POPs Ab. Serum levels of proinflammatory cytokines enteroferon-γ (IFNγ) and tumor necrosis factor-axis (TNF-α), indicators of T cell activation, are determined by ELISA. A similar model uses in vivo T cells treated with • · • · ··

a specific antigen such as the hemocyanin of the mussel diodora aspera (keyhole limpet hyacinin (KLH)) and the subsequent in vitro stimulation of the leakage of cells from the lymph nodes with the same antigen. As before, determination of cytokine production was used to evaluate the activation status of cultured cells. Briefly, C57BL / 6 mice were immunized subcutaneously with 100 µg of KLH emulsified in complete Freund's adjuvant (CFA) at zero day. Animals were pretreated with the compound one day before immunization and sequentially on the first, second and third days after immunization. The flowing lymph nodes were harvested on the fourth day and their cells were cultured at 6 x 10 ⁶ per ml in tissue culture medium (RPMI 1640, to which heat-inactivated fetal bovine serum (Hyclone, was added at twenty-four and forty-eighth hours). Laboratories) 5 x 10 &apos; ⁵ M 2-mercaptoethanol and 0.5% dimethyl sulfoxide). Subsequently, the culture supernatants were analyzed by ELISA for autocrine T cell growth factor interleukin-2 (IL-2) and / or IFN-γ.

The lead compounds can also be tested in animal models in terms of human disease. They are tested for experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). Models with experimental autoimmune encephalomyelitis that mimic aspects of multiple sclerosis in humans have been described in rats as well as mice (review of FASEB J. 5: 2560-2566, 1991; mouse model: Lab. Invest. 4 (3 ): 278, 1981; rodent model: J. Immunol 146 (4): 1163-8,1991). Briefly, mice and rats are immunized with a myelin-based protein (MBP) emulsion or its neurogenic peptide derivatives and CFA. Acute disease is caused by the addition of bacterial toxins such as bordetella pertussis. Recurrent / attenuating disease is caused by the digestible transfer of T cells from animals immunized with a myelin-based protein / peptide.

• · • • • ·

Collagen-induced arthritis (CIA) can be induced in DBA / 1 mice by immunization with type II collagen (J. Immunol: 142 (7): 2237-2243). Mice acquire an arthritic appearance earlier than ten days after collagen infection and can be noted 90 days after immunization. In both models, the EAE and CIA can be administered either prophylactically or at the onset of the disease. Effective drugs would reduce the severity and / or spread of the disease.

Certain compounds of this invention that inhibit one or more angiogenic receptor protein tyrosine kinases and / or protein kinase as drugs involved in mediating inflammatory responses may reduce the severity and spread of arthritis in these models.

The compounds can also be tested in mouse or skin allograft models (review of Ann. Rev. Immunol., 10: 333-58,1992; Transplantation: 57 (12): 1701-17D6,1994), or on the heart (Am.J.Anat .: 113: 273, 1963). Briefly, full thickness skin grafts were transplanted from C57BL / 6 mice to BALB / c mice. The grafts can be examined daily starting on day six to determine rejection. In a neonatal mouse heart transplant model, neonatal hearts are transplanted ethopically from C57BL / 6 mice into the earlobes of adult CBA / J mice. Hearts start beating four to seven days after transplantation and rejection can be assessed visually using a dissecting microscope to monitor the break in beating.

RTK assays of cellular receptors

The following cellular assay was used to determine the activity level and effect of the various compounds of the present invention on KDR / VEGFR2. Similar receptor RTK assays using specific ligand stimulants can be performed along the same lines for other tyrosine kinases using

• V methods known in the art.

VEGF-induced KDR phosphorylation in human umbilical vein endothelial cells (HUVEC), as measured by Western Blot:

1. HUVEC cells (from donor pools) were purchased from Clonetics (San Diego, CA) and cultured according to the manufacturer's instructions. Only early passages (3-8) are used for this analysis. Cells were cultured in 100 mm diameter dishes (Falcon for tissue cultures; Becton Dickinson; Plymouth, England) using a complete computer medium (Clonetics).

2. To evaluate the inhibitory activity of the compounds, cells were trypsinized and seeded at 0.5-1.0 x 10 ⁵ cells / well in each well of plates whose wells were grouped by 6 (Costar; Cambridge, MA).

3. 3-4 days after sowing merges in 90-100% of the plates. The media from all wells were removed, the cells were washed with 5-10 ml of PBS and incubated for 18-24 hours with 5ml of EBM stock medium without additional additives (ie serum starvation).

4. Serial dilutions of inhibitors were added to the cells in 1 ml of ECM medium (25 μΜ, 5 μΜ or 1 μΜ final concentration and incubated for 1 hour at 37 ° C. Human recombinant VEGF ₁₆₅ was then added to all wells. (R&D systems) in 2 ml of ECM medium at a final concentration of 50 ng / ml and incubated for 10 minutes at 37 ° C. Control cells untreated or treated with VEGF are used only to evaluate basic phosphorylation and phosphorylation, subsequently, all wells were washed with 5-10 ml cold PBS containing 1 mM n. tritium orthovanadate (Sigma) and cells lysed and scraped in 200 μΐ RIPA buffer (50 mM Tris-HCl) pH 7, 150 mM NaCl, 1% NP-40,0.25% sodium deoxycholate, 1 mM ethylenediaminetetraacetic acid) containing protease inhibitors (PMSF 1 mM, aprotinin 1 pg / ml, pepstatin 1 pg / ml, leipeptin 1 pg / ml, sodium vanadate 1 μΜ,

sodium fluoride 1 μΜ) and 1 pg / ml Dnase (all chemicals are from Sigma Chemical Company, St. Louis, Montana). The lysate was centrifuged at 14,000 rpm for 30 minutes to remove nuclei.

Subsequently, equal amounts of protein were precipitated by the addition of (-20 ° C) ethanol (2 volumes) for a minimum of 1 hour or a maximum of overnight. The pellets were mixed with Laemli assay buffer containing 5% β-mercaptoethanol (BioRad; Huckleuse, CA) and heated at reflux for 5 minutes. Proteins were redissolved by polyacrylamide gel electrophoresis (6%, 1.5 mm Novex, San Diego, CA) and transferred to a nitrocellulose membrane using the Novex system. After blocking with bovine serum albumin (3%), proteins were probed overnight with anti-KDR polyclonal antibody (C20, Santa Cruz Biotechnology; Santa Cruz, CA) or with anti-phosphotyrosine monoclonal antibody (4G10, Upstate Biotechnology, Lake Placid, Hugh York) at 4 ° C. After washing and incubating for 1 hour with HRP-conjugated F (ab) ₂ of goat anti-rabbit or goat anti-mouse IgG bands were visualized using an emulsion chemiluminescent (ECL) system (Amersham Life Sciences, Erlington High, IL ). Some exemplary compounds of the present invention substantially inhibit cellular VEGF KDR tyrosine kinase phosphorylation at concentrations less than 50 μΜ.

Model of uterine edema in vivo

This assay determines the ability of the compounds to inhibit the acute uterine weight gain of a mouse that occurs within the first few hours after estrogen stimulation. This state of early uterine weight gain is known to be due to swelling caused by increased permeability of the uterine blood vessels. Cullinan-Bove and Koss (Endocrinology (1993), / 33: 829837) show a close relationship between estrogen-stimulated uterine edema and increased expression of VEGF mRNA in the uterus. These results are

is confirmed by the administration of a neutralizing monoclonal antibody to VEGF, which significantly reduces the acute uterine weight gain resulting from estrogen stimulation (WO 97/42187). Therefore, this system can serve as a model for the in vivo inhibition of VEGF signaling and its associated permeability and edema.

Materials'. All hormones were purchased from Sigma (St. Louis, Montana) or Cal Biochem (La Jolla, CA) as lyophilized powders and prepared according to the manufacturer's instructions.

Solvent Components · (Dimethylsulfoxide, Cremaphor EL) purchased from Sigma (St. Louis, Montana).

Mice (Balb / c, ages 8-12 weeks) were purchased from Taconic (Jumantown, NY) and housed in non-pathogenic animals according to the instructions of the Animal Care and Use Committee.

Method:

Day 1: Intraperitoneal injection of 12.5 units of serum gonadotropin (PMSG) from a pregnant mare was administered to Balb / c mice.

Day 3: Mice received intraperitoneally 15 units of human chorionic (outer outer zipper) gonadotropin (hCG).

Day 4: Mice were randomized (randomized) into groups of 5-10. The test compounds are administered by intraperitoneal, intravenous or oral route, depending on the solubility and diluent at a dose range of 1-100 mg / kg. The control group received only a diluent and two of the groups were left untreated.

Thirty minutes later, the experimental group, the diluent-only group, and 1 of the untreated groups were injected

intraperitoneally 17-estradiol (500 pg / kg). After 2-3 hours, the animals are killed by CO ₂ inhalation. After a central incision, each uterus is removed and removed by shearing just below the cervix and at the uterine connections with the fallopian tubes. Carefully remove fat and connective tissue so that the integrity of the uterus is not disturbed before weighing (wet weight). The uterus is absorbed to remove fluid by squeezing between two sheets of filter paper with a one-liter bottle filled with water. Inquiries of the uterus are weighed (weight after watering). Differences between the two weights - that after watering and wetting - are taken as fluid content of the uterus. The mean fluid content of the treated groups was compared with that of the untreated or diluent groups. Significance is determined using the Student test. The unstimulated control group is used to monitor the estradiol response.

The results show that some compounds of the present invention inhibit edema formation when administered systemically in different ways.

Some compounds of this invention, which are inhibitors of angiogenic receptor tyrosine kinases, may also be active in a Matrigel implant neovascularization model. The Matrigel neovascularization model involves the formation of new blood vessels inside the neat extracellular matrix marble surface implanted subcutaneously, which is caused by the presence of a pro-angiogenic factor producing tumor cells (for examples see: Passaniti, A., et al. Lab. Investig. (1992), 67 (4), 519-528; Anat. Rec. (1997), 249 (1), 63-73; Int. J. Cancer (1995), 63 (5), 694- 701; Vase. Biol. (1995), 15 (11), 18576). It is preferable for the model to act 3-4 days, with endpoints including macroscopic visual / neovascularization results, microscopic determination of micro vessel density and quantification of hemoglobin (Drabkin method) and subsequent removal of the implant against controls from untreated inhibitors animals. The model may alternatively use bFGF or stimulants

· · · · · · · · · ·

HGF.

Some compounds of this invention that inhibit one or more oncogenic, proto-oncogenic or proliferatively dependent protein kinases or angiogenic receptor PTK also inhibit the growth of primary mice, rats or human xenograft tumors in mice or inhibit metastasis in models.

Examples of carrying out the invention

The basic structure of the compounds of the invention is synthesized by a base-catalyzed aldol condensation followed by an elimination reaction. Scheme I is a general representation of this reaction. Suitable starting materials II and III for the preparation of the compounds of general formula IV of the present invention, synthesized according to general scheme I, are commercially available and / or can be prepared by methods known in the art and / or possible as provided herein description.

II.

III.

IV.

Scheme I: General synthesis of 4 - [(substituted) methylene] -2-pyrazoline-5one,

1.4 - [(Pyrrol-2-yl) methylene] -2-pyrazolin-5one (V).

Example 1. 3-Cyclopropyl-4 - [(4,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one.

• 4 • ·

A reaction mixture of 3-cyclopropyl-2-pyrazolin-5-one (790 mg, 6.3 mmol), 4,5-dimethylpyrrole-2-carboxaldehyde (800 mg, 6.5 mmol) and piperidine 100 mg in ethanol 50 mL was stirred at 90 mL. ° C for 3.5 hours. The solvent was removed under reduced pressure. The solid residue was purified by flash column chromatography using ethyl acetate: hexane (3: 7) as the mobile phase, then further purified by recrystallization in toluene.

Example 40: 3-Tert-Butylureido-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5one.

A reaction mixture of 3-amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one (1.7 mmol) and pem-butylisocyanate (1 mL) in ethyl acetate 5 mL was stirred at 80 ° C. 2:00. The resultant was collected by filtration and recrystallized in ethanol. Example 88: 4 - {[4- (2-Dimethylaminoethoxycarbonyl) -3,5-dimethylpyrrole-

2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one.

A mixture of 4 - [(4-carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one (200 mg, 0.68 mmol) in dichloromethane (20 ml) and one drop of dimethylformamide were added. treated with oxalyldichloride (0.2 ml). Stirring was continued for 24 hours and a solution of dimethylaminoethanol (0.6 g, 6.7 mmol) in dichloromethane (5 ml) was added. Stirring is continued for 24 hours. The solvent was evaporated to dryness, the solid was treated with NaHCO ₃ (5%) and extracted with dichloromethane. The resulting solid phase, after removal of the solvent, was recrystallized from n-heptane.

Example 194: N - oxide of 4 - {[4- (2-diethylaminoethyl) -3,5-dimethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one

A mixture of the compound of Example 176 (0.2 g, 0.54 mmol) and perchlorobenzoic acid (0.2 g, 1.1 mmol) in chloroform (50 ml) was stirred for 48 hours at room temperature. The solvent was removed to dryness and the residue was purified by flash chromatography (dichloromethane / ethanol 9: 1). Yield 30%, mp 192 ° C (ethanol) ·· ♦ ·

Λ Λ> - -

Table 1: Other synthesized compounds having structural formula V.

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 1 4,5-dimethyl cyclopropyl toluene 30 see Example 1 2 no benzyl toluene: heptane 64 see Example 1 3 no 4-Methoxyphenyloxy methyl methanol 36 see Example 1 4 no phenyloxymethyl ΝΑ 33 see Example 1 5 no 4-chlorophenyloxymethyl ethanol 33 see Example 1 6 no 4-methoxybenzyl ethanol 21 see Example 1 7 4- (2-carboxyethyl) - 3-methyl benzyl ΝΑ see Example 1 8 3- (2-carboxyethyl) - 4-methyl benzyl isopropanol see Example 1 9 no 4-methylphenyloxymethyl methanol 42 see Example 1 10 no amino isopropanol 90 see Example 1 11 no isopropoxy isopropanol 52 see Example 1 12 no phenylethyl ΝΑ 86 see Example 1 13 no phenyl amino isopropanol 86 see Example 1 14 no 4-methylbenzyl methanol 60 see Example 1 15 no 4-methylphenylamino methanol 86 see Example 1 16 no 4-Methoxyphenyl amino DMF: water 92 see Example 1 17 no 4-chlorobenzyl ethanol 56 see Example 1 18 no 4-chlorophenylamino ethanol 90 see Example 1 19 no 3-chlorophenyloxymethyl ΝΑ 50 see Example 1 20 no indol-3-yl ethanol 90 see Example 1 21 no 3-methoxybenzyl methanol 21 see Example 1

• · ·

22 no 3,4-dimethoxybenzyl ethanol 83 see Example 1 23 no 4-methoxy- phenylethyl ethanol 91 see Example 1 24 no . 4-Phenylphenyloxymethyl methanol 72 see Example 1 25 no 2-phenylpropyl heptane 10 see Example 1 26 no 3-phenylpropyl toluene: heptane 60 see Example 1 27 no 4-hydroxyphenylethyl methanol 76 see Example 1 28 3,5-dimethyl phenylethyl methanol 51 see Example 1 29 no 4-methylphenylethyl ethanol 53 see Example 1 30 3,5-dimethyl isopropoxy heptane 55 see Example 1 31 no ethoxy ethanol 76 see Example 1 32 no 4-nitrophenylethyl toluene 48 see Example 1 33 no 4-fluorophenylamino isopropanol 66 see Example 1 34 no 4-chlorophenylethyl ethanol 60 see Example 1 35 4,5-dimethyl isopropoxy methanol 55 see Example 1 36 3,5-dimethyl-4-ethyl isopropoxy toluene 47 see Example 1 37 3,5-dimethyl-4-ethyl phenylethyl heptane 49 see Example 1 38 1- (4-hydroxybutyl) isopropoxy NA 80 see Example 1 39 no cyclopentyloxy methanol 75 see Example 1 40 no tertbutylureido ethanol 87 see Example 40 41 4-methyl isopropoxy toluene 34 see Example 1 42 4-methyl 4-aminophenylethyl NA 27 see Example 1 43 1-methyl isopropoxy toluene 55 see Example 1 44 5-methyl isopropoxy methanol: water 30 see Example 1 45 3,5-dimethyl-4-ethyl 4-aminophenyl- ethyl toluene 50 see Example 1 46 5-methyl ethoxy methanol 58 see Example 1

• · ·

47 3,5-dimethyl-4-ethyl 4-carbamoylphenylethyl DMF: water 82 see Example 1 48 3,5-dimethyl-4-ethyl 4-methoxy carbonylphenylethyl methanol 70 see Example 1 49 3,5-dimethyl-4-ethoxycarbonyl isopropoxy ethanol 81 see Example 1 50 3,5-dimethyl-4-ethoxycarbonyl 4-aminophenylethyl ethanol 62 see Example 1 51 5-ethyl isopropoxy heptane 48 see Example 1 52 3,5-dimethyl-4-ethyl 4-hydroxyphenylethyl isopropanol 35 see Example 1 53 no ethoxycarbonylmethyl ethanol 35 see Example 1 54 no 4-methoxyphenylaminocarbonylmethyl methanol 46 see Example 1 55 3 (2-carboxyethyl) -4- methyl isopropyl ethanol 32 see Example 1 56 no cyclopropyl ethanol 50 see Example 1 57 no cyclobutyl ethanol 65 see Example 1 58 no 3-Pyridyl ethanol 50 see Example 1 59 1- (3,5-dichlorophenyl) cyclopropyl ethanol 30 see Example 1 60 no 2,2,3,3tetramethylcyclopropyl toluene 55 see Example 1 61 3,5-dimethyl cyclopropyl toluene 33 see Example 1 62 no cyclopentyl toluene 66 see Example 1 63 no 2-methylcyclopropyl hexane 44 see Example 1 64 no benzothiazol-2-yl DMF: water 60 see Example 1 65 4,5-dimethyl 3-Pyridyl ethanol 35 see Example 1 66 3,5-dimethyl-4-ethyl cyclopropyl ethanol 50 see Example 1 67 no pyrrol-2-yl methanol 88 see Example 1 68 4-methyl cyclopropyl ethanol 35 see Example 1 69 4-methyl benzothiazol-2-yl ethanol 48 see Example 1 70 3,5-dimethyl 3-Pyridyl ethanol 24 see Example 1 71 3,5-dimethyl-4-ethyl 3-Pyridyl ethanol 51 see Example 1

72 5-methyl cyclopropyl ethanol 50 see Example 1 73 5-methyl 3-Pyridyl ethanol 47 see Example 1 74 5-ethyl cyclopropyl ethanol: water 21 see Example 1 75 3,5-dimethyl-4-ethoxycarbonyl cyclopropyl ethanol 83 see Example 1 76 5-phenyl isopropoxy methanol 66 see Example 1 77 no wasted NA 49 see Example 1 78 no methyl NA 6 see Example 1 79 no 4-Isopropylphenyl amino NA 50 see Example 1 80 no 3-phenylamino NA 80 see Example 1 81 1- (4-hydroxybutyl) cyclopropyl ethanol 34 see Example 1 82 4- (2-carboxyethyl) - 3-methyl isopropoxy ethanol 46 see Example 1 83 4-carboxy-3,5- dimethyl isopropoxy NA 41 see Example 1 84 4,5-tetramethylene isopropoxy ethanol 77 see Example 1 85 3,4-dimethyl-4 morpholinomethyl isopropoxy NA 30 see Example 1 86 3,5-dimethyl-4-dimethylaminomethyl isopropoxy heptane 30 see Example 1 87 4-acetyl-3,5-dimethyl isopropoxy ethanol 62 see Example 1 88 3,5-dimethyl-4- (2-dimethylaminoethyloxycarbonyl) isopropoxy heptane 40 See Example 88 89 3,5-dimethyl-4- (2-dimethylaminoethylaminocarbonyl) isopropoxy toluene: heptane 41 See Example 88 90 5-ethoxycarbonyl isopropoxy methanol 79 see Example 1 91 5-carboxy isopropoxy toluene 83 see Example 1 92 no 4-chlorophenylaminocarbonylmethyl DMF / water 50 see Example 1 93 5-phenyl cyclopropyl ethanol 72 see Example 1 94 3,5-dimethyl-4-ethyl tetrahydrofuran-3-yl toluene 44 see Example 1 95 4-carboxy-3,5dimethyl cyclopropyl ethanol 69 see Example 1

·· ····

96 3,5-dimethyl-4-ethoxycarbonyl 3-Pyridyl ethanol 86 see Example 1 97 3,5-dimethyl-4 morpholinomethyl cyclopropyl NA 34 see Example 1 98 3,4-dimethyl pyrazinyl methanol 60 see Example 1 99 4- (2-carboxyethyl) -3- methyl cyclopropyl methanol 51 see Example 1 100 3,5-dimethyl-4-dimethylaminomethyl cyclopropyl NA 67 see Example 1 101 5-ethoxycarbonyl cyclopropyl ethanol 91 see Example 1 102 4,5-tetramethylene cyclopropyl ethanol 84 see Example 1 103 no 2-methoxycarbonylethyl ethanol 56 see Example 1 104 no ethoxycarbonyl NA 40 see Example 1 105 no isopropyl NA 44 see Example 1 106 no trans-2-phenylcyclopropyl toluene 46 see Example 1 107 no cyclohexyl toluene 32 see Example 1 108 4,5-tetramethylene cyclopropylamino ethanol 50 see Example 1 109 5-morpholinomethyl cyclopropyl ethyl acetate 72 see Example 1 110 5-carboxy cyclopropyl ethanol 50 see Example 1 111 4-chloro ethoxy ethanol 88 see Example 1 112 4-bromo ethoxy ethanol 70 see Example 1 113 5-chloro ethoxy NA 37 see Example 1 114 4-chloro cyclopropyl ethanol 42 see Example 1 115 4-bromo cyclopropyl ethanol 50 see Example 1 116 4,5-tetramethylene pyrazinyl ethanol 85 see Example 1 117 4,5-tetramethylene 3-Pyridyl ethanol 84 see Example 1 118 4-carboxy-3,5- dimethyl pyrazinyl DMF 66 see Example 1 119 3,5-dimethyl-4- (2-dimethylaminoethyloxycarbonyl) cyclopropyl NA 71 see Example 88 120 3,5-dimethyl-4- (2-dimethylaminoethaloxycarbonyl) pyrazinyl NA 20 see Example 88

a a

121 3,5-dimethyl-4-dimethylaminomethyl pyrazinyl toluene 76 see Example 1 122 3,5-dimethyl-4-dimethylamino methyl maleate pyrazinyl ethanol 98 Maleate salt obtained from the free base of Example 121 (see note) 123 3,5-dimethyl-4- (2-morpholinoethylaminocarbonyl) pyrazinyl toluene 20 see Example 1 124 3,5-dimethyl 2-pyridyl ethanol 36 see Example 1 125 3,5-dimethyl 4-ethyl 2-pyridyl ethanol 50 see Example 1 126 4,5-tetramethylene 2-pyridyl ethanol 58 see Example 1 127 3,5-dimethyl 2-furyl ethanol 51 see Example 1 128 3,5-dimethyl-4 morpholinomethyl pyrazinyl NA 28 see Example 1 129 3,5-dimethyl 2-thienyl ethanol 25 see Example 1 130 4-ethoxycarbonyl cyclopropyl ethanol 68 see Example 1 131 3,5-dimethyl-4trifluoroacetamidomethyl cyclopropyl ethanol 70 see Example 1 132 4-Aminomethyl-3-dimethyl cyclopropyl ethanol 30 see Example 1 133 3,5-dimethyl benzothiazol-2yl ethanol 40 see Example 1 134 3,5-dimethyl-4 morpholinomethyl benzothiazol-2-yl ethanol 40 see Example 1 135 3,5-dimethyl-4-ethyl pyrazinyl ethanol 74 see Example 1 136 4-ethoxycarbonyl pyrazinyl toluene 26 see Example 1 137 4-carboxy pyrazinyl methanol 70 see Example 1 138 3,5-dimethyl-4-diethanolaminomethyl pyrazinyl ethanol 50 see Example 1 139 3,5-dimethyl-4trifluoroacetamidomethyl pyrazinyl NA 78 see Example 1 140 4-ethoxycarbonyl-3-phenyl cyclopropyl ethanol 68 see example!

· · · · · · · · · · · · · · ·

141 3,5-dimethyl-4- (1-pyrrolidinylmethyl) pyrazinyl toluene 23 see Example 1 142 3,5-dimethyl-4-dimethylaminomethyl 2-furyl toluene 20 see Example 1 143 3,5-dimethyl-4-dimethylaminomethyl 2-thienyl toluene 48 see Example 1 144 3,5-dimethyl-4-dimethylaminomethyl 3-Pyridyl toluene 51 see Example 1 145 3,5-dimethyl-4-ethoxycarbonyl phenyl ethanol 89 see Example 1 146 3,5-dimethyl-4-ethyl phenyl methanol 34 see Example 1 147 3,4-di (ethoxycarbonyl) ethoxy ethanol 54 see Example 1 148 4-ethoxycarbonyl ethoxy methanol 30 see Example 1 149 3,5-dimethyl-4-ethoxycarbonyl 2- (3-Pyridyl) ethyl ethanol 81 see Example 1 150 3,5-dimethyl-4-ethoxycarbonyl 1-methyl-2-phenylethyl ethanol 52 see Example 1 151 4-carboxy-3,5- dimethyl ethoxy DMF: water 81 see Example 1 152 5 nitro ethoxy ethanol 64 see Example 1 153 4 nitro ethoxy toluene 95 see Example 1 154 4-carboxy ethoxy NA 40 see Example 1 155 3,5-dimethyl-4- (2-dimethylaminoethyl aminocarbonyl) ethoxy heptane 86 see Example 88 156 5-chloro-methoxycarbonyl-4methoxycarbonylmethyl ethoxy ethanol 46 see Example 1 157 3- (2-carboxyethyl) - 4-methyl ethoxy NA 54 see Example 1 158 3,5-dimethyl-4-ethoxycarbonyl ethoxy ethanol 82 see Example 1 159 4,5-tetramethylene ethoxy heptane 80 see Example 1 160 3,5-dimethyl-4-ethoxycarbonyl trifluoromethyl ethanol 45 see Example 1 161 3,5-dimethyl-4-ethoxycarbonyl 5-isoxazolyl DMF: water 74 see Example 1 162 3,5-dimethyl-4-ethoxycarbonyl 3-aminophenyl ethanol 76 see Example 1

• · · · · ·

175 ·

163 4-morpholinoethylaminocarbonyl ethoxy NA 30 see Example 88 164 4-Ethoxycarbonyl-phenyl pyrazinyl toluene 70 see Example 1 165 4- (4-methyl-1-piperazinylmethyl) -3,5-dimethyl pyrazinyl DMF 58 see Example 1 166 4-diethylaminomethyl-3,5-dimethyl pyrazinyl NA 20 see Example 1 167 3,5-dimethyl-4-piperidinomethyl pyrazinyl toluene 25 see Example 1 168 3,5-dimethyl-4-piperidinomethyl 5-isoxazolyl NA 35 see Example 1 169 3,5-dimethyl-4-dimethylaminomethyl 5-isoxazolyl NA 30 see Example 1 170 5-methyl-4-dimethylaminomethyl pyrazinyl toluene-heptane 75 see Example 1 171 3,5-dimethyl-4-p- (2-dimethylaminoethyl) -methylaminomethyl] pyrazinyl methanol 40 see Example 1 172 3-dimethylaminomethyl-4,5tetramethylene cyclopropyl NA 30 see Example 1 173 3-dimethylaminomethyl-4,5tetramethylene pyrazinyl NA 30 see Example 1 174 3,5-dimethyl-4-dimethylaminomethyl maleate cyclopropyl ethanol 90 Free base maleate salt from Example 100 (see note) 175 4- (3-chloropropionyl) -3,5 dimethyl pyrazinyl toluene 88 see Example 1 176 4- (2-diethylamino- ethyl) -3,5-dimethyl pyrazinyl ethanol 95 see Example 1 177 3,5-dimethyl-4 (dimethylaminomethyl) 5-methyl-isoxazolyl toluene / heptane 40 see Example 1

• · · · • ·

178 3,5-dimethyl-4- (4hydroxypiperidinomethyl) pyrazinyl methanol 40 see Example 1 179 4-Aminomethyl-3,5-dimethylmaleate pyrazinyl methanol 76 see Example 1 180 4- (4-Benzylpiperidinomethyl) 3,5-dimethyl pyrazinyl toluene 80 see Example 1 181 3,5-dimethyl-4- (2hydroxyethyl) pyrazinyl NA 80 see Example 1 182 3,5-dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrazinyl toluene 67 see Example 1 183 3,5-dimethyl-4- [2- (1-pyrrolidinylethyl)] cyclopropyl toluene 20 see Example 1 184 3,5-dimethyl-4- (2hydroxyethyl) cyclopropyl NA 23 see Example 1 185 3,5-dimethyl-4- (2-ethylaminoethyl) pyrazinyl NA 35 see Example 1 186 4- (3-diethylaminopropyl) -3,5 dimethyl pyrazinyl ethanol 52 see Example 1 187 3,5-dimethyl-4- (3hydroxypropyl) pyrazinyl ethanol 82 see Example 1 188 3,5-Dimethyl-4-dimethylaminoacetylhydrochloride pyrazinyl ethanol / ethyl ether 51 see Example 1 189 3-3-Dimethyl-4-dimethylaminoacetyl ethoxy ethanol / ethyl ether 44 see Example 1 190 4- (2-diethylaminoethyl) -3,5-dimethyl cyclopropyl heptane 54 see Example 1 191 3,5-dimethyl-4- (2-dimethylaminoethyl) pyrazinyl toluene 48 see Example 1 192 3,5-dimethyl-4- (4hydroxybugyl) pyrazinyl methanol 58 see Example 1 193 4- (4-diethylamino- butyl) -3,5-dimethyl pyrazinyl toluene 60 see Example 1 194 4- (2-diethylaminoethyl-L1-oxide) -3,5 dimethyl pyrazinyl ethanol 30 See Example 194 195 3,5-dimethyl-4- (1-pyrrolidinylacetyl) pyrazinyl NA 57 see Example 1

• · · ·

196 4-Diethylaminoacetyl-3,5-dimethyl pyrazinyl NA 52 see Example 1 197 3-isopropyl-5-methyl pyrazinyl ethanol 44 see Example 1 198 3,5-dimethyl-4- [3- (1pyrrolidinylpropyl)] pyrazinyl ethanol 30 see Example 1 199 4-dimethylaminomethyl-3-isopropyl-5-methyl pyrazinyl toluene 40 see Example 1 200 4-dimethylaminomethyl-3-isopropyl-5-methyl cyclopropyl toluene 40 see Example 1 201 3,5-dimethyl-4- (2ethoxyoxalyl) pyrazinyl ethanol 40 see Example 1 202 3,5-dimethyl-4- (2-ethylaminoethyl) cyclopropyl NA 60 see Example 1 203 3,5-dimethyl-4- (2cyclopropylaminoethyl) pyrazinyl toluene 40 see Example 1 204 3,5-dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrazinyl NA 40 see Example 1 205 3,5-dimethyl-4- (2cyclopropylaminoethyl) cyclopropyl toluene 36 see Example 1 206 3,5-dimethyl-4- (2-diethylaminoethyl) 2-pyrimidinyl toluene 35 see Example 1 207 3,5-dimethyl-4- (2-diethylaminoethyl) 3-pyridazinyl toluene 40 see Example 1 208 3,5-dimethyl-4- (2-diethylaminoethyl) 4-pyrimidinyl toluene 50 see Example 1 209 3.5-dimethyl-4- (2diigylaminoethyl) 4-pyridazinyl toluene 30 see Example 1

Table 1 A: Physical data for the synthesized compounds having structural formula V.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculation- flax Received Calculated Semi- cheno Calculated Received 1 220-222 68.10 68.27 6.59 6.61 18.32 18.30

2 182-184 71.69 72.00 5.21 5.40 16.72 16.47 3 177-180 64.63 64.06 5.08 5.02 14.13 14.00 4 163-165 67.40 66.88 4.90 4.88 15.72 15.53 5 218-222 59.71 59.87 4.00 4.24 13.92 13.85 6 179-180 68.53 68.45 5.03 5.44 14.99 14.99 7 270-272 67.64 67.17 5.67 5.82 12.45 12.38 8 (0.3H ₂ O) * 226-228 66.58 66.10 5.72 5.65 12.26 12.27 9 207-210 68.31 68.20 5.37 5.44 14.93 14.96 10 265-270 54.53 55.07 4.57 4.47 31.80 31.98 11 172-174 60.26 60.37 5.97 5.80 19.16 18.97 12 145-147 72.43 72.29 5.69 5.70 15.83 16.17 13 285-287 66.65 66.66 4.79 4.71 22.20 22.12 14 254-255 72.43 72.36 5.69 5.53 15.83 15.84 15 256-258 67.65 67.31 5.29 5.12 21.03 20.96 16 288-290 63.81 63.90 4.99 4.53 19.84 19.75 17 178-180 63.05 63.26 4.23 4.10 14.70 14.59 18 (0.25 N ₂ O) * 245-247 57.74 57.69 3.97 3.81 19.23 18.95 19 165-167 59.71 59.69 4.00 4.05 13.92 13.80 20 300-305 69.55 69.67 4.37 4.61 20.27 20.39 21 169-171 68.31 68.27 5.37 5.36 14.93 14.92 22 164-165 65.58 65.58 5.50 5.63 13.49 13.44 23 137-139 69.13 69.15 5.80 5.69 14.22 2.30pm 24 (0.25 N ₂ O) * 192-194 72.50 72.56 5.07 5.36 12.07 12.02 25 130-131 73.09 73.16 6.13 6.25 15.04 14.83 26 169-170 73.09 73.46 6.13 6.32 15.04 14.42 27 253-255 68.31 68.48 5.37 5.01 14.93 14.74 28 186-187 73.69 73.89 6.52 6.49 14.32 14.25 29 153-154 73.09 73.38 6.13 5.95 15.04 14.85 30 176-177 63.14 63.20 6.93 6.77 16.99 16.98 31 211-213 58.53 58.81 5.40 5.27 20.48 20.52 32 224-226 61.92 62.02 4.54 4.75 18.05 18.31 33 272-273 62.21 62.45 4.10 4.33 20.73 20.81 34 193-194 64.11 64.27 4.71 4.85 14.02 14.07

<·

35 195-197 63.14 63.26 6.93 6.76 16.99 17.04 36 188-190 65.43 65.59 7.68 7.00 15.26 15.29 37 168-170 74.73 74.40 7.21 7.10 13.07 13.11 38 138-140 61.84 61.87 7.27 7.17 14.42 14.31 39 201-203 63.65 63.65 6.16 6.19 17.13 17.24 40 266-268 56.71 57.04 6.22 6.06 25.43 25.69 41 215-217 61.78 61.77 6.48 6.40 18.01 17.96 42 (0.75 N ₂ O) * 178-180 66.32 66.78 6.33 6.01 18.19 17.85 43 199-201 61.78 61.97 6.48 6.36 18.01 17.91 44 128-130 61.78 61.42 6.48 6.32 18.01 17.78 45 183-185 71.40 71.38 7.19 7.28 16.65 16.62 46 197-199 64.35 64.69 7.33 6.96 16.08 16.03 47 297-299 69.21 69.08 6.64 6.68 15.37 15.31 48 177-179 69.64 69.70 6.64 6.57 11.07 11.10 49 226-228 60.18 60.06 6.63 6.46 13.16 13.02 50 186-188 66.30 66.20 6.36 6.25 14.73 14.68 51 119-121 63.14 63.14 6.93 6.95 16.99 17.00 52 260-262 71.19 71.01 6.87 6.96 12.45 12.36 53 124-126 58.29 58.49 5.29 5.04 16.99 16.99 54 240-242 62.95 62.96 4.97 5.00 17.27 17.11 55 229-231 62.26 62.20 6.62 6.37 14.52 14.36 56 158-160 65.65 65.78 5.51 5.50 20.88 20.78 57 150-152 66.95 67.09 6.08 5.76 19.52 19.45 58 222-224 65.53 65.57 4.23 4.29 25.51 23.62 59 188-190 58.97 59.06 3.78 3.92 12.13 11.98 60 160-162 70.01 70.28 7.44 7.35 16.33 16.22 61 193-195 68.09 68.34 6.59 6.39 18.32 18.18 62 (0.2 toluene) * 127-129 69.82 69.73 6.75 6.64 16.96 17.20 63 132-133 66.95 67.11 6.08 6.03 19.52 19.73 64 340-342 61.20 61.38 3.42 3.70 19.03 19.19 65 220 (d) 67.65 67.47 5.29 5.30 21.04 20.94 66 206-210 70.01 69.65 7.44 7.46 16.33 16.23

• · · · · · · ·

67 245-247 63.70 63.76 4.45 4.64 24.76 24.64 68 212-215 66.95 66.72 6.08 5.63 19.52 19.29 69 (0.5 N ₂ O) * 327-329 60.55 60.90 4.12 4.09 17.65 17.42 70 235-238 67.65 67.66 5.29 5.40 21.04 20.98 71 270-272 69.36 69.41 6.16 6.21 19.03 18.98 72 170-172 66.95 67.05 6.05 6.08 19.52 19.42 73 210-212 66.65 66.73 4.79 4.82 22.21 22.10 74 163-165 68.10 68.15 6.59 6.63 18.32 18.27 75 240-242 63.77 63.77 6.35 6.35 13.94 13.90 76. 212-214 69.14 69.27 5.80 5.88 14.23 14.20 77-80 the ¹³ C and Ή NMR data and analytical LC / MS are consistent with the indicated structure 81 134-136 65.91 65.60 7.00 6.99 15.37 15.03 82 267-269 59.01 59.12 6.27 6.22 13.76 13.66 83 > 300 57.72 57.81 5.88 5.84 14.42 14.25 84 206-207 65.91 66.04 7.01 6.78 15.37 15.34 85 162-164 62.41 62.36 7.56 7.46 16.17 15.94 86 173-175 63.13 63.27 7.95 7.73 18.41 18.34 87 209-210 62.27 61.86 6.62 6.58 14.52 14.25 88 165-167 59.65 59.82 7.23 7.05 15.46 15.34 89 192-194 59.82 59.92 7.53 7.26 19.38 19.21 90 205-207 57.72 57.96 5.88 5.62 14.42 14.43 91 235-237 51.24 51.78 5.38 5.49 14.94 14.95 92 240-242 58.45 58.07 3.98 3.96 17.04 16.64 93 208-210 73.62 73.60 5.45 5.62 15.15 15.14 94 163-165 66.87 66.70 7.36 7.10 14.62 14.59 95 312 (d) 61.53 61.08 5.53 5.38 15.37 15.11 96 247-249 63.89 64.05 5.36 5.48 16.56 16.70 97 175-177 65.82 65.62 7.36 7.43 17.06 16.75 98 245-250 62.91 63.30 4.90 5.10 26.20 26.29 99 290 (d) 62.70 62.66 5.96 5.83 14.62 14.47 100 176-178 67.10 67.21 7.74 7.49 19.56 19.53 101 250-152 61.52 61.73 5.53 5.46 15.37 15.40 102 227-230 70.56 70.62 6.71 6.61 16.46 16.52

• «· · · · · · · · · · · · · · · · · · · · · · · ·

· · · · · · · ·

103 134-136 58.29 58.71 5.29 5.44 16.99 17.03 104 177-179 56.64 56.85 4.75 4.56 18.01 17.56 105 120-122 65.01 65.12 6.44 6.44 20.67 20.59 106 173-175 74.42 74.20 5.60 5.77 14.46 14.77 107 176-178 69.11 69.21 7.04 7.08 17.27 17.24 108 240-243 66.64 66.62 6.71 6.39 20.72 20.80 109 184-136 63.98 64.21 6.71 6.69 18.65 18.74 110 220 (d) 54.75 55.17 4.97 4.90 15.96 16.21 111 237-239 50.12 50.54 4.21 3.90 17.53 17.59 112 242-244 42.28 42.45 3.55 3.39 14.79 14.58 113 170-172 50.12 49.98 4.21 4.21 17.53 18.10 114 220 (d) 56.06 56.46 4.27 4.37 17.83 17.54 115 210 (d) 47.16 47.60 3.59 3.85 15.00 14.57 116 253-255 65.51 65.83 5.15 5.25 23.87 23.86 117 264-267 69.84 69.61 5.51 5.53 19.16 19.13 118 225-228 56.71 56.59 4.94 4.79 22.00 21.94 119 172-174 62.77 62.61 7.02 6.71 16.26 16.06 120 223-225 58.30 58.79 5.92 6.10 21.47 20.89 121 220-222 63.50 63.57 6.26 6.25 25.39 25.55 122 206-210 55.01 54.51 5.71 5.64 18.32 18.30 123 178-180 59.56 60.03 5.95 5.82 23.15 22.87 124 228-230 67.65 68.00 5.29 5.46 21.04 21.12 125 184-186 69.36 69.19 6.16 6.09 19.03 19.33 126 214-216 69.84 69.94 5.51 5.41 19.16 19.33 127 235-237 65.87 65.88 5.13 5.24 16.46 16.51 128 274-277 62.28 62.26 6.05 5.90 22.93 22.94 129 235-237 61.96 62.01 4.82 4.91 15.48 15.44 130 192-194 61.52 61.73 5.53 5.53 15.37 15.43 131 278-280 54.23 54.40 4.83 4.92 15.81 15.68 132 217-219 63.61 63.84 7.11 6.90 21.19 21.22 133 295-297 63.33 63.55 4.37 4.45 17.38 17.44 134 285 (d) 62.15 62.03 5.54 6.02 16.47 16.91 135 264-267 65.06 65.10 5.80 5.71 23.71 23.51 136 155-157 59.74 59.30 4.46 4.40 21.24 21.20

137 230-232 54.26 54.58 3.77 3.34 24.34 23.99 138 242-244 58.44 58.81 6.36 6.28 21.52 21.84 139 302-305 51.45 51.30 3.93 4.26 21.17 20.88 140 218-220 68.75 69.07 5.48 5.53 12.02 11.96 141 235-237 64.02 64.11 6.41 6.54 23.58 23.01 142 209-211 65.36 65.37 6.45 6.89 17.93 16.53 143 208-210 61.32 61.43 6.20 6.18 16.83 16.64 144 220-224 66.85 67.24 6.54 6.54 21.65 21.11 145 216-217 67.64 67.71 5.68 5.80 12.45 12.53 146 274-275 73.70 73.80 6.53 6.53 14.32 14.39 147 132-134 55.01 55.24 5.48 5.32 12.03 12.03 148 212-216 56.31 56.25 5.45 5.20 15.15 15.02 149 180-182 65.56 65.10 6.05 5.96 15.29 15.20 150 168-170 69.64 69.91 6.64 6.43 11.07 11.10 151 310-312 56.31 56.30 5.45 5.15 15.15 15.17 152 208-210 48.00 48.37 4.03 4.19 22.39 22.65 153 287-289 48.00 48.37 4.03 4.04 22.39 22.64 154 290-293 53.01 52.63 4.45 4.47 16.86 16.59 155 158-160 58.61 58.82 6.94 6.48 16.08 16.05 156 225-227 48.72 49.00 4.36 4.18 11.36 11.35 157 255-257 57.72 57.65 5.88 5.97 14.42 14.32 158 232-234 59.01 59.06 6.27 6.30 13.76 13.68 159 178-180 64.85 64.61 6.61 6.95 16.20 15.99 160 252-254 51.07 51.17 4.29 4.34 12.76 12.60 161 255-257 58.53 58.63 4.91 5.08 17.06 16.96 162 214-216 64.76 64.91 5.72 5.74 15.90 15.74 163 197-199 56.50 56.22 6.41 6.37 19.38 18.96 164 255-257 65.11 65.37 4.42 4.49 18.08 18.11 165 295-297 63.31 63.62 6.64 6.66 25.84 25.96 166 242-244 64.75 64.66 6.86 6.73 23.85 23.74 167 240-242 65.91 65.61 6.64 6.74 23.06 22.69 168 215-217 63.79 63.57 6.44 6.56 19.38 19.82 169 161-163 56.45 56.96 6.51 6.45 20.57 20.29 170 193-195 61.92 62.18 5.85 5.74 27.08 26.80

171 205-207 62.96 62.48 7.13 6.73 25.70 25.40 172 182-185 69.20 69.21 7.74 7.82 17.93 17.41 173 210-212 65.12 64.66 6.33 6.02 23.98 23.50 174 199-201 59.68 59.31 6.51 6.37 13.92 14.42 175 213 (d) 57.92 58.32 4.61 4.82 19.08 19.26 176 210-212 65.55 65.24 7.15 7.18 22.93 22.94 177 242-244 62.37 61.87 6.47 6.55 21.39 21.06 178 (0.5 H ₂ O) * 255-57 61.68 61.48 6.47 6.45 21.58 21.68 179 (0.5 H ₂ O) 205-8 54.15 54.27 5.02 4.97 19.94 19.63 180 (0.25) 211-14 70.64 70.56 6.69 7.06 18.30 17.93 181 306-8 61.72 61.64 5.50 5.45 22.49 22.41 182 (0.17 N ₂ O) 190-92 65.36 64.97 6.67 6.55 22.86 23.20 183 197-200 69.90 69.87 8.02 8.12 17.16 16.86 184 244-46 65.91 65.52 7.00 6.98 15.37 15.05 185 192-94 the HRMN and EM data correspond to the specified structure 186 (3H ₂ O) 208.10 58.05 58.21 7.88 7.39 19.73 19.47 187 273-75 62.75 63.01 5.88 5.76 21.52 21.33 188 (S1N.2 H ₂ O) > 300 (d) 50.83 51.14 5.88 5.70 19.76 20.10 189 198 60.36 59.86 6.97 6.90 17.60 17.36 190 133 69.48 69.19 8.59 8.47 17.06 16.74 191 216 60.60 60.43 6.73 6.32 23.56 23.14 192 222 63.70 63.85 6.24 6.23 20.63 20.53 193 184 66.98 66.70 7.66 7.40 21.30 20.85 194 192 62.75 62.46 6.79 6.73 21.96 21.64 195 (0.5 N ₂ O) 220 61.94 61.66 5.93 5.72 21.68 21.54 196 (0.5 N ₂ O) 199 61.62 61.78 6.41 6.13 21.56 22.06 197 244 65.07 65.02 5.80 5.79 23.71 23.99 198 202-04 66.64 66.24 6.92 6.99 22.20 22.00

·· ····

199 227 64.75 64.90 6.86 6.99 23.85 23.88 200 190-92 68.75 68.86 8.33 8.46 17.82 17.51 201 223 58.85 58.96 4.66 4.73 19.06 19.03 202 (0.4 N ₂ O) 150 66.37 66.46 8.12 7.90 18.21 17.80 203 210-218 63.81 63.95 6.42 6.45 23.50 23.12 204 (0.2 N ₂ O) 203-205 65.23 65.05 5.82 5.84 24.20 23.77 205 (0.4 N ₂ O) 158-160 67.64 67.93 7.81 7.74 17.53 17.40 206 (0.2 N ₂ O) 144-146 64.91 64.87 7.19 7.30 22.71 22.53 207 (0.2 N ₂ O) 218-220 64.91 64.79 7.19 7.00 22.71 22.78 208 220 65.55 65.45 7.15 7.13 22.93 22.53 209 212-216 65.55 65.49 7.15 7.38 22.93 22.31

* The molecular weight calculated from the elemental analysis includes the solvent in the indicated amount.

Note: Maleate salts are obtained by the addition of an ethanol solution of maleic acid to the free base in ethanol at room temperature and subsequent cooling and filtration of the crystalline product.

II. 4 - [(Indol-3-yl) methylene] -2-pyrazolin-5-ones (VI).

Example 210: 3-Benzyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one.

Reaction mixture of 3-benzyl-2-pyrazolin-5-one (905 mg, 5.2 mmol) · · · · · ·

3-Indolecarboxaldehyde (800 mg, 5.6 mmol) and piperidine (100 mg) in ethanol (50 mL) were stirred for 3 hours at 90 ° C. After cooling overnight, the resultant was collected by filtration and then purified by recrystallization in ethanol.

Table 2: Other synthesized compounds having structural formula VI.

An example Deputy Prindole R ¹ Recrystallization solvent % Yield Method 210 no benzyl ethanol 76 see Example 210 211 1- (4hydroxybugyl) benzyl methanol 51 see Example 210 212 no 4-methoxyphenyloxymethyl isopropanol 67 see Example 210 213 no phenyloxymethyl isopropanol 94 see Example 210 214 no 4-chlorophenyloxymethyl ethanol 65 see Example 210 215 no 4-methoxybenzyl ethanol 90 see Example 210 216 no 4-methylphenyloxymethyl ethanol 93 see Example 210 217 no phenylethyl ethanol 84 see Example 210 218 no isopropoxy methanol 81 see Example 210 219 no 4-methylbenzyl ethanol 95 see Example 210 220 no phenylamino isopropanol 52 see Example 210 221 no 4-methylphenylamino methanol 60 see Example 210 222 no 4-methoxyphenylamino ethanol 96 see Example 210 223 no 4-chlorobenzyl ethanol 77 see Example 210 224 1- (4hydroxybutyl) 4-methoxybenzyl DMF: water 89 see Example 210 225 no 4-chlorophenylamino DMF: water 86 see Example 210 226 no 3-methoxybenzyl DMF: water 99 see Example 210 227 no 3,4-dimethoxybenzyl DMF: water 88 see Example 210 228 no 4-hydroxybenzyl DMF: water 56 see Example 210 229 no 3-chlorophenyloxymethyl isopropanol 89 see Example 210 230 no indol-3-yl methanol 58 see Example 210 231 no 4-methoxyphenylethyl isopropanol 88 see Example 210

232 no 4-Phenylphenyloxymethyl NA 91 see Example 210 233 no 2-phenylpropyl methanol 60 see Example 210 234 no 3-phenylpropyl ethanol 76 see Example 210 235 no 4-hydroxyphenylethyl methanol 51 see Example 210 236 no 4-methylphenylethyl ethanol 86 see Example 210 237 no ethoxy ethanol 90 see Example 210 238 1- (4hydroxybutyl) isopropoxy toluene: heptane 43 see Example 210 239 1- (4hydroxybutyl) phenylethyl methanol 80 see Example 210 240 no 4-nitrophenylethyl isopropanol 83 see Example 210 241 no propoxy DMF: water 43 see Example 210 242 no 4-fluorophenyl amino ethyl acetate 65 see Example 210 243 no 4-aminophenylethyl methanol: water 74 see Example 210 244 2-methyl isopropoxy methanol 40 see Example 210 245 7-methyl isopropoxy ethanol 98 see Example 210 246 7-methyl phenylethyl DMF: water 97 see Example 210 247 no cyclopentyl ethanol 56 see Example 210 248 1-methyl isopropoxy ethanol 81 see Example 210 249 no 4-methoxycarbonylphenylethyl ethanol 77 see Example 210 250 1-isopropyl isopropoxy toluene: heptane 71 see Example 210 251 1-methyl 4-hydroxyphenylethyl ethanol 50 see Example 210 252 no isopropyl ethanol 76 see Example 210 253 no 4-chlorophenyl aminocarbonylmethyl DMF: water 40 see Example 210 254 no ethoxycarbonylmethyl methanol 40 see Example 210 255 no 4-methoxyphenylaminocarbonylmethyl DMF: water 40 see Example 210 256 no cyclopropyl DMF: water 50 see Example 210 257 no 3-Pyridyl ethanol 50 see Example 210 258 no 2-Aminocarbonylethyl methanol 55 see Example 210 259 no cyclobutyl ethanol 79 see Example 210 260 no 2- (dimethyl amino carbonyl) ethyl ethanol 97 see Example 210

·· ····

261 1- (4-hydroxy butyl) cyclopropyl ethanol 80 see Example 210 262 no 4-Pyridyl ethanol 91 see Example 210 263 no cyclopentyl ethanol 75 see Example 210 264 no 2,2,3,3tetramethylcyclopropyl ethanol 32 see Example 210 265 no 2-methylcyclopropyl ethanol 34 see Example 210 266 1- (4hydroxybutyl) cyclohexyl toluene 41 see Example 210 267 1- (4hydroxybutyl) 4-Pyridyl ethanol 50 see Example 210 268 no benzothiazol-2-yl ethanol 50 see Example 210 269 no 2-pyridyl 67 see Example 210 270 no dimethylamino ethanol 77 see Example 210 271 no pyrrol-2-yl ethanol 83 see Example 210 272 no 6-Methoxybenzothiazol-2-yl ethanol 60 see Example 210 273 1-methyl cyclopropyl ethanol 76 see Example 210 274 7-methyl cyclopropyl ethanol 60 see Example 210 275 1-mash 3-Pyridyl ethanol 64 see Example 210 276 no wasted NA 63 see Example 210 277 no methyl NA 68 see Example 210 278 no trifluoromethyl NA 14 see Example 210 279 1- (4-hydroxybutyl) hydrogen NA 62 see Example 210 280 1- (4hydroxybutyl) methyl NA 36 see Example 210 281 1- (F hydroxybutyl) trifluoromethyl NA 7 see Example 210 282 1 <4hydroxybutyl) tert-butyl NA 50 see Example 210 283 no ethoxycarbonyl ethanol 74 see Example 210 284 no 2-methoxy carbonylethyl ethanol 79 see Example 210 285 no trans-2-phenyl-1-cyclopropyl ethanol 92 see Example 210 286 1- (4-hydroxy butyl) cyclobutyl ethanol 26 see Example 210 287 6-carboxy- 1-methyl cyclopropyl ethanol 26 see Example 210 288 5-methoxy-1methyl cyclopropyl ethanol 75 see Example 210 289 1-methyl pyrazinyl ethanol 82 see Example 210

:: :::.: /

...... really ·· ...: ..

290 1,7-dimethyl cyclopropyl ethanol 97 see Example 210 291 1-methyl tetrahydrofuran- 3-il ethanol 78 see Example 210 292 1-methyl cyclopropylamino ethanol 54 see Example 210 293 6-carboxy-methyl isopropoxy DMF: water 45 see Example 210 294 1,7-dimethyl isopropoxy methanol 53 see Example 210 295 5-methoxy-1methyl isopropoxy ethanol 72 see Example 210 296 1-methyl 4-fluorophenylamino methanol 80 see Example 210 297 1-methyl trifluoroacetamido methanol 70 see Example 210 298 1-methyl 4-aminophenyl- ethyl toluene 64 see Example 210 299 1-methyl amino ethanol 80 see Example 210 300 no 4-chlorophenyl- ethyl ethanol 85 see Example 210 301 1-methyl ethoxy ethanol 80 see Example 210 302 1-methyl 5-isoxazalil DMF: water 83 see Example 210 303 1-methyl tert-bugil ethanol 92 see Example 210 304 6-carboxy-1- methyl pyrazinyl DMF 98 see Example 210 305 1-methyl-6- [2 (4-morpholino) ethyl] aminocarbonyl pyrazinyl NA 20 see Example 210

Table 2A: Physical data for the synthesized compounds having structural formula VI.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculate -but Get it -but Calculated Received Calculated Get it -but 210 292-295 75.73 75.74 5.02 5.28 13.94 13.85 211 217-220 73.97 73.93 6.20 6.14 11.25 11.18 212 266-268 69.35 69.23 4.65 5.05 12.13 12.03 213 284-286 71.91 71.86 4.76 4.78 13.24 13.34 214 264-267 64.87 64.78 4.01 4.12 11.94 11.93 215 265-270 72.49 72.64 5.17 5.21 12.68 12.72 216 288-291 72.49 72.52 5.17 5.36 12.68 12.74 217 268-270 76.17 76.12 5.43 5.55 13.32 13.59

• · · · · · · · · · · · · · · ·

218 263-265 66.90 66.75 5.61 5.46 15.60 15.48 219 280-282 76.17 76.34 5.43 5.23 13.32 13.30 220 265-267 71.50 71.48 4.66 4.62 18.53 18.35 221 (0.75 N ₂ O) * 255-257 69.11 69.30 5.30 5.07 16.98 16.99 222 265-267 68.66 68.65 4.85 4.98 16.85 16.67 223 274-277 67.96 67.77 4.20 4.39 12.51 12.33 224 204-206 71.44 71.39 6.24 6.14 10.41 10.32 225 248-250 64.19 64.01 3.89 4.15 16.63 16.59 226 288-290 7249 72.46 5.17 5.16 12.68 12.81 227 282-284 69.79 69.68 5.29 5.29 11.62 11.75 228 295-300 71.91 71.20 4.76 4.76 13.24 13.44 229 265-268 64.87 64.91 4.01 4.16 11.94 11.92 230 (0.5 CH ₃ OH) * 288-292 71.91 71.45 4.71 4.69 16.36 13.36 231 266-268 73.02 72.78 5.54 5.70 12.16 12.09 232 (0.75 N ₂ O) * 295-296 73.78 73.58 5.07 5.21 10.32 10.20 233 253-255 76.57 76.06 5.81 6.09 12.75 12.60 234 218-220 76.57 76.52 5.81 5.93 12.75 12.62 235 (1.0 CH ₃ OH) * 271-275 69.40 69.40 5.82 5.72 11.56 11.38 236 244-245 76.57 76.73 5.81 5.72 12.75 12.64 237 248-250 65.87 65.94 5.13 5.01 16.46 16.45 238 210-212 66.84 66.76 6.79 6.83 1230 12.21 239 205-207 74.39 74.32 6.50 658 10.84 10.92 240 295-297 66.65 66.65 4.47 4.85 15.54 15.75 241 246-247 66.90 66.95 5.61 5.56 15.60 15.61 242 (0.75 ethyl acetate) * 251-252 65.28 64.88 4.92 4.91 14.50 14.53 243 244-246 72.70 72.45 5.49 5.67 16.95 16.71 244 (0.25 CH ₃ OH) * 262-264 66.99 66.78 6.22 6.09 14.42 14.46 245 254-256 67.82 67.78 6.04 5.76 14.83 14.82 246 302-304 76.57 75.96 5.81 5.59 12.75 12.84

··. ..........

247 277-279 69.13 68.95 5.80 5.79 14.22 14.36 248 239-240 67.82 67.75 6.04 6.10 14.83 14.77 249 259-260 70.76 70.62 5.13 5.43 11.25 11.24 250 161-163 69.43 69.40 6.75 6.80 13.49 13.48 251 255-257 73.04 72.89 5.50 5.72 1217 12.11 252 264-266 71.12 71.17 5.96 5.87 16.58 16.65 253 305-307 63.41 63.17 3.99 4.07 14.79 14.57 254 235-237 64.63 64.81 5.08 5.04 14.13 14.22 255 (0.5 N ₂ O) * > 300 65.78 65.64 4.99 4.81 14.61 14.61 256 300-305 71.69 71.39 5.21 5.22 16.72 16.75 257 305-307 70.82 70.71 4.36 4.36 19.43 19.50 258 280-281 61.58 61.86 5.29 5.44 18.36 18.12 259 > 300 72.43 72.30 5.69 5.71 15.84 15.85 260 258-260 65.79 65.66 5.84 5.50 18.05 17.82 261 215-216 70.56 70.29 6.54 6.45 12.99 12.99 262 > 300 70.82 70.76 4.19 4.78 19.43 19.29 263 300-304 73.09 72.79 6.13 6.06 15.04 14.98 264 (0.25 N ₂ O) * 296-298 73.16 73.43 6.86 6.89 13.47 13.36 265 294-296 72.43 72.57 5.69 5.73 15.84 15.85 266 226-227 72.29 72.10 7.44 7.56 11.49 11.54 267 224-225 68.27 68.65 5.73 5.91 15.16 15.25 268 > 300 66.26 65.96 3.51 3.64 16.27 16.25 269 278-280 70.82 71.07 4.19 4.35 19.43 19.53 270 258-260 66.12 66.26 554 5.50 22.03 21.87 271 300-302 69.55 68.91 4.37 4.54 20.28 20.23 272 > 300 64.16 64.20 3.77 3.94 14.96 14.69 273 245-247 72.43 72.34 5.69 5.72 15.83 15.78 274 286-288 72.73 72.14 5.69 5.91 15.83 15.60 275 (0.5 N ₂ O) * 230-232 69.44 69.89 4.85 4.84 17.99 18.10 276-282 the data from ^both C and Ή NMR and analytical LC / MS correspond to the indicated structure 283 250 (d) 63.59 63.42 4.62 5.00 14.83 14.83

·· ····

284 267-269 64.63 64.58 5.08 5.29 14.13 14.14 285 280-282 75.99 76.11 5.31 5.32 12.66 12.65 286 220-222 71.19 71.16 6.87 6.85 12.45 12.46 287 237-240 (d) 66.00 66.00 4.88 4.85 13.58 13.43 288 236-238 67.09 67.48 5.96 6.00 13.80 13.76 289 263-265 67.31 67.58 4.32 4.48 23.09 23.31 290 258-260 72.15 72.33 6.22 6.06 14.85 15.11 291 208-210 69.13 69.18 5.80 5.85 14.23 14.25 292 160464 (d) 68.55 68.25 5.75 5.86 19.98 19.71 293 330-332 62.38 62.37 5.23 5.31 12.84 12.87 294 245-247 68.67 68.86 6.44 6.21 14.13 14.14 295 238-239 65.16 65.31 6.11 6.10 13.41 13.46 296 218-219 67.09 66.65 4.82 4.99 16.12 16.10 297 252-253 53.58 53.80 3.30 3.51 16.66 16.67 298 192-193 74.29 74.26 5.98 5.85 15.27 15.38 299 246-247 63.73 63.51 5.10 5.32 22.88 22.54 300 271-272 68.67 68.59 4.61 5.04 12.01 11.81 301 194-196 66.90 66.94 5.61 5.72 15.60 15.62 302 271-272 65.75 66.02 4.14 4.34 19.17 7 pm 303 201-203 70.28 70.02 7.44 7.41 13.29 13.17 304 > 300 60.47 60.96 4.54 4.33 20.02 19.85 305 240-241 61.52 61.67 559 5.67 20.92 20.91

* The molecular weight calculated from the elemental analysis includes the solvent in the indicated amount.

Note '. The maleate salts are obtained by the addition of ethanol solution of maleic acid to the free base in ethanol at room temperature and subsequent cooling and filtration of the crystalline product.

III. 4 - [(Indol-2-yl) methylene] -2-pyrazolin-5-one (VII).

·· ····

·· ·· • · · e • · · • · · • · · · · ····

Table 3: Synthesized compounds having structural formula VII.

An example Deputy Prindole R ¹ Recrystallization solvent % Yield Method 306 no isopropoxy ethanol 81 see Example 210 307 no 4-hydroxyphenylethyl ethanol 45 see Example 210 308 no 4-aminophenylethyl NA 20 see Example 210 309 no 4-methoxycarbonylphenylethyl toluene 75 see Example 210 310 no 4-carbamoylphenylethyl DMF: water 90 see Example 210 311 no cyclopropyl ethanol 35 see Example 210 312 3-dimethylaminomethyl cyclopropyl NA 20 see Example 210 313 no 3-Pyridyl ethanol 62 see Example 210 314 5-methoxy isopropoxy methanol 78 see Example 210 315 1-meg isopropoxy DMF: water 89 see Example 210 316 no tetrahydrofuran-3-yl ethyl acetate 30 see Example 210 317 5-methoxy cyclopropyl ethanol 33 see Example 210 318 5 nitro cyclopropyl DMF 84 see Example 210 319 no isopropylamino methanol 80 see Example 210 320 no 4-carboxyphenylethyl DMF: water 65 see Example 210 321 no phenyl ethanol 55 see Example 210 322 3-methyl isopropoxy methanol 76 see Example 210

· · · · · · · · · ·

323 3- (2-methoxycarbonyl-2acetamidoethyl) isopropoxy toluene: heptane 40 see Example 210 324 no ethoxy ethanol 55 see Example 210 325 3- (4morpholinomethyl) ethoxy ethanol 65 see Example 210 326 3- (4morpholinomethyl) cyclopropyl ethyl acetate 46 see Example 210 327 5-methoxy pyrazinyl NA 91 see Example 210 328 5-methoxy 2-pyridyl NA 90 see Example 210 329 4-chloro-6,7 dihydro ethoxy ethanol 54 see Example 210 330 4-chloro-6,7 dihydro pyrazinyl toluene 83 see Example 210 331 4-oxo-1,5,6,7tetrahydro pyrazinyl toluene 40 see Example 210 332 3-dimethylaminomethyl ethoxy toluene-heptane 41 see Example 210

Table 3A: Physical data for the synthesized compounds having the structural formula VIL

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 306 221-223 66.90 67.11 5.61 5.53 15.60 15.68 307 242-245 72.49 72.34 5.17 5.15 12.68 12.36 308 187-189 72.71 72.99 5.49 5.48 16.96 16.35 309 210-212 70.76 70.99 5.13 5.00 11.25 11.11 310 (0.25 N ₂ O) * 263-265 69.44 69.51 5.09 5.05 15.43 15.21 311 (0.75 N ₂ O) * 238-240 68.04 67.68 5.55 5.11 15.87 15.75 312 (0.25 N ₂ O) * 202 (d) 69.10 69.13 6.60 6.46 17.91 17.56 313 (0.5 N ₇ O) * 155-157 68.67 68.68 4.40 4.48 18.84 18.56 314 219-220 64.20 64.48 5.72 5.76 14.04 14.08 315 254-255 67.83 67.89 6.05 6.09 14.83 14.83 316 180-183 68.31 68.49 5.37 5.57 14.94 14.80 317 221-224 68.31 68.34 5.37 5.35 14.94 14.82

• · · · · · · ·

• · ·

318 316-320 60.80 60.70 4.08 4.35 18.91 19.01 319 245-247 67.14 67.08 6.01 6.03 20.88 20.94 320 > 300 70.18 69.87 4.77 4.87 11.69 11.76 321 210-211 75.25 75.17 4.56 4.75 14.62 14.62 322 241-243 67.83 67.97 6.05 6.05 14.83 14.89 323 205-206 61.16 61.51 5.87 5.93 13.58 13.27 324 265-267 65.87 65.91 5.13 5.27 16.46 16.52 325 205-206 64.39 64.64 6.26 6.35 15.81 15.82 326 203-180 68.55 68.53 6.32 6.31 15.99 15.80 327 272-274 63.94 64.29 4.10 4.00 21.93 22.10 328 170-172 67.91 68.06 4.43 4.43 17.60 17.74 329 177-203 57.64 57.87 4.84 4.79 14.40 14.35 330 (0.4 toluene) * 206-209 62.27 62.20 4.22 447 19.31 19.27 331 (0.1 toluene) * 300-303 63.36 63.49 4.36 4.41 22.12 21.96 332 185-187 65.37 65.13 6.45 6.35 17.94 17.70

* The molecular weight calculated from the elemental analysis includes the solvent in the indicated amount.

IV. 4 - [(7-Azaindol-3-yl) methylene] -2-pyrazolin-5-ones (VIII).

VIII.

Table 4: Synthesized compounds having structural formula VIII.

An example Azaindole substituent R ¹ Recrystallization solvent % Yield Method 333 no benzyl DMF: water 71 see Example 210 334 1- (4hydroxybutyl) benzyl ethyl acetate 30 see Example 210 335 no 4-methoxyphenyloxymethyl DMF: water 80 see Example 210 336 no isopropoxy methanol 61 see Example 210 337 no amino DMF: water 92 see Example 210

• ·

338 no 4-methoxybenzyl DMF: water 96 see Example 210 339 no phenyl amino DMF: water 77 see Example 210 340 no 4-methylbenzyl ethanol 95 see Example 210 341 no 4-hydroxyphenylethyl ethanol 84 see Example 210 342 1- (4hydroxybutyl) 4-hydroxyphenylethyl methanol 80 see Example 210 343 no isopropyl ethanol 30 see Example 210 344 no cyclopropyl ethanol 50 see Example 210 345 no cyclobutyl ethanol 74 see Example 210 346 no 3-Pyridyl ethanol 40 see Example 210 347 no phenyl NA 56 see Example 210 348 no 4-fluorophenyl amino NA 14 see Example 210 349 no wasted NA 24 see Example 210 350 no methyl NA 77 see Example 210 351 no trifluoromethyl NA 17 see Example 210 352 no tert-butyl NA 80 see Example 210 353 1- (4hydroxybutyl) trifluoromethyl NA 6 see Example 210 354 no 4-Isopropylphenyl amino NA 30 see Example 210 355 no 3-methyl phenylamino NA 70 see Example 210 356 1- (4hydroxybutyl) 3-methylphenylamino NA 30 see Example 210 357 no phenylethyl DMF: water 63 see Example 210

Table 4A: Physical data for the synthesized compounds having structural formula VHI.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 333 274-277 71.50 71.63 4.66 4.88 18.53 18.17 334 176-179 70.56 70.67 5.92 5.87 14.96 14.78 335 300-302 65.69 65.62 4.35 4.85 16.12 15.77 336 258-260 62.21 61.57 5.22 5.12 20.72 20.57 337 (1H ₂ O) * > 300 53.82 53.92 4.48 4.34 28.54 28.22 338 273-276 68.66 68.05 4.85 4.89 16.85 16.67 339 (1 H ₂ O) * 249-252 63.54 63.45 4.70 4.75 21.79 21.68 340 (0.5 N ₇ O) * > 300 70.07 70.54 5.22 5.07 17.21 17.24 341 270-272 68.66 68.25 4.85 5.04 16.86 16.71

• · · · · · · · · · ·

• · · ·

342 211-212 68.30 67.97 5.98 6.11 13.85 13.80 343 300 (d) 66.12 65.91 5.54 5.57 22.03 21.89 344 (0.25 N ₂ O) * 245-246 65.48 65.20 4.90 4.76 21.82 21.47 345 300-302 66.52 66.51 5.39 5.22 20.69 20.88 346 212-215 66.50 65.84 3.83 4.07 24.20 23.93 347 280-282 70.80 70.50 4.20 4.10 19.40 19.10 348-356 ¹³ C and Ή 'data 4MR and analytical LC / MS respond to the indicated structure 357 317-319 72.13 71.69 5.09 5.04 17.70 17.65

* The molecular weight calculated from the elemental analysis includes the solvent in the indicated amount.

Note '. The maleate salts are obtained by the addition of ethanol solution of maleic acid to the free base in ethanol at room temperature and subsequent cooling and filtration of the crystalline product.

V. 4- (Phenylmethylene) -2-pyrazolin-5-ones (IX).

Table 5: Synthesized compounds having the structural formula

IX.

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 358 4-dimethylamino benzyl ethanol 32 see Example 210 359 4-dimethylamino isopropoxy toluene: heptane 51 see Example 210 360 4-dimethylamino phenylethyl ΝΑ 45 see Example 210 361 4-dimethylamino cyclopropyl ethanol 77 see Example 210

Table 5A: Physical data for the synthesized compounds having structural formula IX.

· · · · · · · · · · · ·

157.

• · · · · · · · ·

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 358 253-255 74.73 74.20 6.27 6.13 13.75 13.34 359 197-198 65.91 66.33 7.01 6.86 15.37 15.27 360 224-225 75.20 75.08 6.62 6.56 13.15 13.19 361 280-289 70.56 70.33 6.71 6.80 16.46 16.20

VI. 4 - [(Pyrazol-1-yl) methylene] -2-pyrazolin-5one (X).

Table 6: Synthesized compounds having the structural formula

X.

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 362 3-methyl isopropoxy ethyl acetate 80 see Example 210 363 3-methyl cyclopropyl toluene 51 see Example 210

Table 6A: Physical data for synthesized compounds having structural formula X.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 362 228-230 56.39 56.06 6.02 5.91 23.91 23.77 363 265-267 61.09 61.30 5.59 5.83 25.91 25.71

· · · · · · ·

...... : ::

^{: 1 <J} 8 ^·:::

· · · · · · · · · · ·.

VII. 4 - [(Imidazol-2-yl) methylene] -2-pyrazolin-5-ones (XI).

XI.

Table 7: Synthesized compounds having structural formula

XI.

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 364 no isopropoxy toluene 45 see Example 210 365 no cyclopropyl ethanol 42 see Example 210

Table 7A: Physical data for the synthesized compounds having structural formula XI.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 364 212-214 54.53 54.96 5.49 4.61 25.43 25.67 365 264-266 59.39 59.52 4.98 5.00 27.71 27.37

VIII. 4 - [(Imidazol-4-yl) methylene] -2-pyrazolin-5-ones (XII)

Table 8: Synthesized compounds having the structural formula

XII.

·· ····

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 366 no isopropoxy ethanol 81 see Example 210

Table 8A: Physical data for the synthesized compounds having structural formula XII.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 366 259-260 54.53 54.84 5.49 5.68 25.43 25.37

IX. 4 - [(Thien-2-yl) methylene] -2-pyrazolin-5-ones (XIII).

XIII.

Table 9: Synthesized compounds having the structural formula

XIII.

An example Substitute in ring A R ¹ Recrystallization solvent % Yield Method 367 no cyclopropyl ethanol 20 see Example 210

Table 9A: Physical data for the synthesized compounds having structural formula XIII.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 367 275-277 60.53 60.68 4.61 4.74 12.83 12.50

X. 4 - [(Indol-3-yl) methylene] -1-methyl-2-pyrazolin-5-ones (XIV).

Table 10: Synthesized compounds having structural formula XIV.

An example Indole substituent R ¹ Recrystallization solvent % Yield Method 368 no isopropyl ethanol 54 see Example 210

Table 10A: Physical data for the synthesized compounds having structural formula XIV.

An example M.P. (° C) Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 368 241-242 71.88 71.73 6.41 6.47 15.72 15.71

XI. 4 - [(Pyrrol-3-yl) methylene] -2-pyrazolin-5-ones (XV)

Table 11: Synthesized compounds having structural formula XV.

An example Substitute for propirol R ¹ Recrystallization solvent % Yield Method 369 no isopropoxy methanol 70 see Example 210

Table 11A: Physical data for the synthesized compounds having structural formula XV.

An example M.p., ° C Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 369 252-255 60.26 60.35 5.98 5.82 19.17 19.13

XII. 4 - [(Quinolin-5-yl) methylene] -2-pyrazolin-5-ones (XVI)

Table 12. Synthesized compounds having structural formula

XVI.

An example Quinoline substitute R ¹ Recrystallization solvent % Yield Method 370 8-hydroxy isopropoxy methanol 40 see Example 210

Table 12A: Physical data for the synthesized compounds having structural formula XVI.

An example M.p., ° C Elemental analysis Carbon Hydrogen Nitrogen Calculated Received Calculated Received Calculated Received 370 > 300 64.64 64.43 5.09 5.01 14.13 13.98

X. Synthesis of starting materials

A. Synthesis of 3-ketoesters (XIX).

The general method used to synthesize 3-ketoesters is shown in the scheme P ·· ····

XVII.

XVIII.

1st base

2. 3% HCI

3. anhydrous ethanol y and heating

Scheme II: Synthesis of 3-ketoesters

Example 371: Ethyl 3- (2,2,3,3-tetramethylcyclopropyl) -3-oxopropionate.

Pyridine (5 g, 0.063 mol) and 2 were added to an ice-cold solution of 2,2-dimethyl-1,3-dioxane-4,7-dione (4.7 g, 0.032 mol) in anhydrous dichloromethane (37 mL) under nitrogen. , 2,3,3-tetramethylcyclopropyl carbonyl chloride (5 g, 0.031 mol). The temperature was maintained at 0 ° C for 1 hour, then allowed to rise to room temperature overnight. The mixture was transferred to a separatory funnel, washed twice with 3% hydrochloric acid and twice with water. The organic layer was dried over magnesium sulphate, then filtered and concentrated under reduced pressure to give 5 g of a dark red oil. The oil was heated at reflux for 3 hours in anhydrous ethanol (60 mL). The solvent was evaporated and the resulting substance was purified by distillation.

Example 377: Ethyl 3- (6-methoxybenzothiazol-2-yl) -3-oxopropionate.

Ethyl acetate (7.2 g, 0.082 mol) was added to sodium hydride (1.5 g, 50% dispersion in oil, 0.032 mol), keeping the temperature below.

25 ° C. 2-Ethoxycarbonyl-2- (6-methoxy) benzothiazole (5.25 g, 0.022 mol) was added. The mixture was gently heated to reflux and then stirred at room temperature overnight. The reaction mixture was quenched with ice water (50 mL) and the pH was adjusted to 7.7 is concentrated hydrochloric acid. The resulting precipitate was collected by filtration, washed with water and then dried.

Example 378: Ethyl 4- (4-phenylphenyloxy) -3-oxobutanoate.

Sodium hydride (5.0 g, 0.114 mol) and 4-phenylphenol (15.3 g, 0.09 mol) were stirred at 0 ° C in 75 mL of dimethylformamide (hereinafter referred to as 'DMF') for 2 hours. Ethyl 4 chloroacetoacetate (5.0 g, 0.03 mol) in DMF (75 mL) was added. The mixture was stirred for 1 hour at 0 ° C and for 12 hours at room temperature, then neutralized with 50% phosphoric acid and extracted with dichloromethane. The resulting substance was purified by chromatography on silica gel using (8: 2) toluene: ethanol as the mobile phase.

Table 13: Synthesized compounds having structural formula XIX.

An example R ¹ % Yield since (° C) mp (° C) Method 371 2,2,3,3-tetramethylcyclopropyl 67 68 (0.2mmHg) NA see Example 371 372 2-methylcyclopropyl 50 62-4 (0.2mmHg) NA see Example 371 373 trans-2-phenylcyclopropyl 64 138-40 (0.2mmHg) NA see Example 371 374 tetrahydrofuran-3-yl 60 82-6 (0.2mmHg) NA see Example 371 375 3-methoxyphenylmethyl 62 132 (0.2mmHg) NA see Example 371 376 phenylethyl 55 110 (0.2mmHg) NA see Example 371 377 6-Methoxybenzothiazol-2-yl 65 NA 160 see Example 377 378 4-phenylphenoxy- methyl 33 NA 83 see Example 378 379 3-chlorophenoxymethyl 32 147 (8mmHg) NA see Example 378 380 pyrazinyl 71 NA 82 see Example 377

· · · · · ·

B. Synthesis of ethylcyclopentyloxythiocarbonyl acetate.

Fr.

XX.

BUT-R ⁹

XXI.

Scheme III: Synthesis of ethyl alkyloxy or aryloxy carbonimidoyl acetate hydrochloride (R ⁹ is a substituted or unsubstituted aliphatic or aromatic group).

Example 381: Synthesis of ethylcyclopentyloxycarbonimidoyl acetate hydrochloride (XXII).

A mixture of dry ethyl cyanoacetate (14 g, 0.12 mol) and dry cyclopentanol (12 g, 0.15 mol) was saturated at 0 ° C with hydrogen chloride gas for 3 hours, kept overnight at 0 ° C, then diluted with diethyl ether. The resulting precipitate was collected by filtration and washed with ether.

Yield 22.4 g, (77%), mp 110-112 ° C.

XXII.

XXIV.

Scheme IV: Synthesis of ethylalkyloxythio or aryloxythiocarbonyl acetate.

Example 382: Ethylcyclopentyloxythiocarbonyl acetate (XXIV)

A mixture of ethylcyclopentyloxycarbonimidoyl acetate hydrochloride (22 g, 0.09 mol) in anhydrous pyridine (150 ml) was treated with hydrogen sulfide for 8 hours and kept at room temperature for 48 hours. The reaction mixture was acidified with concentrated hydrochloric acid and the mixture was acidified.

···· Extraction with diethyl ether. The ether phase is washed with water, dried and purified by distillation.

Yield 15 g (75%), boiling point 140-142 ° C (15 mm Hg).

C. Synthesis of 2-pyrazolin-5-ones.

2-Pyrazolin-5-ones were synthesized by the following four methods.

XXV.

h ₂ n - nh ₂

------ ►

Scheme V: Method 1 for the synthesis of 2-pyrazolin-5-ones.

s about

XXVII.

h ₂ n - nh ₂

------>

XXVIII.

Scheme VI: Method 2 for the synthesis of 2-pyrazolin-5-ones.

Scheme VII: Method 3 for the synthesis of 2-pyrazolin-5-ones.

XXIX.

XXX.

XXXI.

XXXII.

XXXIII.

Scheme VIII: Method 4 for the synthesis of 2-pyrazolin-5-ones.

Example 383: 3- (2,2,3,3-Tetramethylcyclopropyl) -2-pyrazolin-5-one.

Hydrazine hydrate (1.1 g, 0.024 mol) was added to a solution of ethyl-3- (2,2,3,3-tetramethylcyclopropyl-3-oxopropionate (4.41 g, 0.020 mol) in anhydrous ethanol (60 ml). After cooling, the solvent was evaporated and the residue triturated with hexane to give a white solid.

Example 411: 3- (4-Hydroxybenzyl) -2-pyrazolin-5-one

A stirred suspension of 3- (4-methoxybenzyl) -2-pyrazolin-5-one 2.5 mmol in dichloromethane 100 ml cooled to -78 ° C was treated with boron tribromide 7.5 ml (1M in dichloromethane). After standing for 1 hour at -78 ° C, the reaction mixture was stirred at room temperature for 12 hours. Quench with 50 ml of water. The aqueous phase was separated and basified with 5% sodium bicarbonate solution. The resulting precipitate was filtered off and recrystallized from methanol.

Example 413: 3- (4-Carbamoylphenylethyl) -2-pyrazolin-5-one

A mixture of 3- (4-methoxycarbonylphenylethyl) -2-pyrazolin-5-one (7.7 mmol) in ammonium hydroxide 25% (30 ml) was stirred at room temperature for 12 hours. The solvent was concentrated in vacuo and the resulting solid was filtered off and dried.

Example 414: 3- (2-Aminocarbonylethyl) -2-pyrazolin-5-one

4 • · · · · · · · · · · 4 • · · «·

A mixture of 3- (ethoxycarbonylmethyl) -2-pyrazolin-5-one (1 g, 5.8 mmol) and NaCN (28 mg, 0.58 mmol) in 30 ml of 9M ammonia in MeOH was heated to 45 ° C for 3 days. tightly sealed tube. After cooling, the solvent was evaporated and the residue was suspended in water. The precipitated solid was collected by filtration.

Example 416: 3- (4-Methoxyphenylamino) -2-pyrazolin-5-one

A mixture of 3-amino-2-pyrazolin-5-one (20 mmol), 4-methoxyaniline (25 mol) in 50 ml of acetic acid was refluxed for 4 hours. The solvent was evaporated and the residue was suspended in water. The solid was filtered off and recrystallized from methanol.

Table 14: Synthesized compounds having structural formula XXVI.

An example R ¹ % Yield M.P. (° C) Recrystallization solvent Method 383 2,2,3,3-tetramethylcyclopropyl 44 195-7 NA see Example 383 384 ethoxycarbonylmethyl 44 115-6 toluene see Example 383 385 pyrrol-2-yl 30 205-8 NA see Example 383 386 indol-3-yl 69 250-3 NA see Example 383 387 6-methoxybenzothiazole- 2-il 40 269-70 NA see Example 383 388 2-methylcyclopropyl 70 196-7 water see Example 383 389 trans-2-phenylcyclopropyl 65 194-5 ethanol see Example 383 390 tetrahydrofuran-3-yl 36 204-5 ethanol see Example 383 391 4-methoxybenzyl 73 192-5 NA see Example 383 392 4-methylbenzyl 80 212-4 ethanol: water see Example 383 393 4-chlorobenzyl 67 206-8 ethanol see Example 383 394 3-methoxybenzyl 72 163-5 NA see Example 383 395 3,4-dimethoxybenzyl 69 193-5 NA see Example 383 396 phenyl ethyl 72 204-7 NA see Example 383

• · ····

397 2-phenylpropyl 72 215 NA see Example 383 398 3-phenylpropyl 76 200-1 ethanol see Example 383 399 4-methoxyphenylethyl 85 230 ethanol see Example 383 400 4-methylphenylethyl 90 251-2 NA see Example 383 401 4 - chlorophenylethyl 63 243 NA see Example 383 402 4-nitrophenylethyl 69 247 DMF: water see Example 383 403 4-aminophenylethyl 61 220-2 NA see Example 383 404 4-methoxy- carbonylphenilegyl 77 259-60 ethanol see Example 383 405 4-phenylphenyloxy- methyl 50 250 ethanol see Example 383 406 4-methoxyphenyloxymethyl 70 216-8 ethanol see Example 383 407 4-chlorophenyloxymethyl 38 224-6 ethanol see Example 383 408 3-chlorophenyloxymethyl 40 232-4 ethanol see Example 383 409 4- methylphenyloxymethyl 77 207-10 methanol see Example 383 410 cyclopentyloxy 75 180-1 toluene see Example 383 411 4-hydroxybenzyl 75 233 methanol see Example 411 412 4-hydroxyphenylethyl 70 205-6 water see Example 411 413 4-carbamoylphenylethyl 90 > 270 DMF: water see Example 413 414 2-Aminocarbonylethyl 66 193-6 NA see Example 414 415 2-dimethylaminocarbonylethyl 38 203-9 NA see Example 414 416 4- methoxyphenylamino 30 232-4 methanol see Example 416 417 4-chlorophenyl amino 28 262-4 ethanol see Example 416 418 4-fluorophenylamino 35 259-60 NA see Example 416 419 cyclopropyl amino 82 155-158 NA see Example 383 420 pyrazinyl 86 193 (d) ethanol see Example 383 421 isopropylamino 20 123-25 ethanol see Example 383 422 2-pyrimidinyl 55 278-80 ethanol see Example 383 423 3-pyridazinyl 83 294-95 ethanol see Example 383

• · · ·

424 4-pyrimidinyl 72 290-300 ethanol see Example 383 425 4-pyrimidinyl 60 288-291 ethanol see Example 383

D. Synthesis of aldehydes

Example 426: 1- (4-Acetoxybutyl) -azaindole-3-carboxaldehyde

A solution of 7-azaindole-3-carboxaldehyde (4.19 g, 28 mmol) was added dropwise to a stirred suspension of 60% sodium hydride (oil dispersion) (1.2 g, 30 mmol) in dry dimethylformamide (65 ml) in a nitrogen atmosphere. dry Ν, мети dimethylformamide (50 ml) while maintaining the temperature at 5-10 ° C. After the addition is complete, stirring is continued at the same temperature for another 30 minutes, after which a solution of 4-bromobutyl acetate (6.16 g, 31 mmol) in dry, dimethylformamide (15 ml) is added dropwise and the mixture is allowed to warm to room temperature. temperature. The reaction mixture was stirred at room temperature for 137 hours, water (100 ml) was added and the mixture was extracted with dichloromethane (2 x 100 ml). The organic phase was washed with water (3 x 100 ml), dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure to give an oil (6.8 g, 93%) which was used without further purification.

Example 427: 1- (4-Hydroxybutyl) -7-azaindole-3-carboxaldehyde

To a solution of 1- (4-acetoxybutyl) -7-azaindole-3-carboxaldehyde (2.3 g, 8.8 mmol) in methanol (40 ml) was added a solution of sodium hydroxide (0.2 g, 17.5 mmol) in water (35 ml). . The mixture was heated at 60 ° C for 0.5 hours, after which the solvent was evaporated to dryness. The residue was dissolved in a mixture of ethyl acetate and water (50 ml: 50 ml) and the aqueous layer was separated. The organic phase was washed with water, dried over magnesium sulfate, filtered and evaporated to dryness. The residue was used without further purification. Yield 78%, mp 90 ° C.

Example 428: 1- (4-Hydroxybutyl) pyrrole-2-carboxaldehyde

• · ···

• ·

The compound was prepared by the method of Example 51 except that pyrrole-2-carboxaldehyde was used instead of 7-azaindole-3-carboxaldehyde. The resulting substance was purified by chromatography on silica gel using (5: 5) ethyl acetate: hexane. Yield 67%.

Example 429: 3-Isopropyl-5-methylpyrrole-2-carboxaldehyde

POQ ₃ (2.1 ml, 23 mmol) was added dropwise to a solution of anhydrous dimethylformamide (2.1 ml, 27 mmol) in anhydrous dichloroethane (50 ml) at 0 ° C under nitrogen. The solution was allowed to warm to room temperature for 1 hour. The suspension was then cooled to 0 ° C and a solution of 3-isopropyl-5-methylpyrrole (2 g, 16 mmol) in dichloroethane (20 ml) was added dropwise over 20 minutes. After stirring for 24 hours at room temperature, water was added followed by NaOH to pH 8. The organic layer was extracted, dried and the solvent was removed to dryness. The residue was purified by flash chromatography. Yield 67%, mp 90-93 ° C.

Example 430: 3,5-Dimethyl-4-morpholinomethylpyrrole-2-carboxaldehyde

To a solution of morpholine (0.35 g, 4 mmol), formaldehyde 37% (0.32 g, 4 mmol) and acetic acid (2 ml) was added 3,5-dimethylpyrrole-2carboxaldehyde (0.5 g, 4 mmol). The mixture was stirred overnight at room temperature under nitrogen, then the reaction mixture was diluted with NaHCO ₃ to pH 8. The aqueous solution was extracted with ethyl acetate and the organic layer was dried over Mg SO ₄ . The ethyl acetate was evaporated in vacuo to give 0.4 g of pure solid.

The following compounds were synthesized by a method analogous to that described in Example 430:

3.5- Dimethyl-4-dimethylaminomethylpyrrole-2-carboxaldehyde,

3- (4-morpholino) methyl-indole-2-carboxaldehyde,

3.5-dimethyl-4-diethylaminomethylpyrrole-2-carboxaldehyde, · ·

3,5-dimethyl-4-piperidinomethylpyrrole-2-carboxaldehyde,

3,5-dimethyl-4 - [(4-methyl-1-piperazinyl) methyl] pyrrole-2-carboxaldehyde,

3,5-dimethyl-4- (1-pyrrolidinylmethyl) pyrrole-2-carboxaldehyde,

5-methyl-4-dimethylaminomethylpyrrole-2-carboxaldehyde,

3.5-dimethyl-4- [X-methyl-N- (2-dimethylaminoethyl) aminomethyl] pyrrole-2carboxaldehyde,

3,5-dimethyl-4-diethanolaminomethylpyrrole-2-carboxaldehyde, 4- (4-benzylpiperidinomethyl) -3,5-dimethylpyrrole-2-carboxaldehyde,

4-dimethylaminomethyl-3-isopropyl-5-methylpyrrole-2-carboxaldehyde,

3.5-dimethyl-4- (4-hydroxypiperidinomethyl) pyrrole-2-carboxaldehyde, and

3-dimethylaminomethyl-4,5-tetramethylenepyrrole-2-carboxaldehyde.

Example 431: 3,5-Dimethyl-4-trifluoroacetamidomethylpyrrole-2carboxaldehyde

A mixture of 3,5-dimethylpyrrole-2-carboxaldehyde (2.6 g, 0.02 mol) and N (hydroxymethyl) trifluoroacetamide (3 g, 0.02 mol) was added portionwise to sulfuric acid (15 ml) while maintaining the temperature below 10 ° S. The reaction mixture was allowed to warm to room temperature for 4 hours. Pour into ice-water (100 ml), remove the precipitated solid by filtration and wash with water. The resulting white solid (yield 78%) was used without further purification. Melting point 200 ° C.

Example 432: 4-Aminomethyl-3,5-dimethylpyrrole-2-carboxaldehyde

A mixture of 3,5-dimethyl-4-trifluoroacetamidomethylpyrrole-2carboxaldehyde (3.9 g, 15.7 mmol), NaOH 10% (19 ml) and methanol (100 ml) was refluxed for 1 hour. The solution was concentrated under reduced pressure to half its volume. Water was added and the precipitated solid was filtered off. Yield 72%, mp 210-20 ° C (decomposition).

Example 433: 3-Acetyl-4-oxopentyl acetate

Mechanically stirred mixture of pentane-2,4-dione (60 g, 0.6 mol), 2 bromoethyl acetate (100 g, 0.6 mol), anhydrous potassium carbonate (83 g, 0.6 mol), IK (99.6 g, 0.6 mol) and dry acetone (500 ml) was refluxed for 24 hours. The mixture was concentrated under reduced pressure and poured into hydrochloric acid (1.7 M, 400 ml). The resulting substance was isolated by sequential extraction with ether, ethyl acetate and dichloromethane. The combined organic extracts were washed with brine, the solvent removed to dryness and the residue distilled to give 38 g of acetate, reflux temperature 75-80 ° C (0.1 mm Hg).

4-acetyl-5-oxohexyl acetate [yield 60%, boiling point 110 ° C (0.2 mm Hg)] and 5-acetyl-6-oxoheptyl acetate [yield 77%, boiling point 102 ° C (0.2 mm Hg)] were obtained by the method described in Example 433.

Example 434: tert-Butyl 4- (2-acetoxyethyl) -3,5-dimethylpyrrole-2carboxylate

A stirred solution of tert-butyl acetoacetate (26 g, 0.165 mol) in acetic acid (48 ml) was treated at a temperature below 20 ° C by the dropwise addition of sodium nitrite (11.3 g, 0.165 mol) in water (17 ml) and left to stand overnight.

A solution of 3-acetyl-4-oxopentyl acetate (30 g, 0.161 mol) in acetic acid (56 ml) was heated to 80 ° C. A mixture of zinc powder (26.2 g, 0.40 mol) and sodium acetate (26.3 g, 0.32 mol) was then added dropwise, while the above hydroxyimin derivative (97 ml, 0.165 mol) was added dropwise. The reaction mixture was stirred vigorously during the addition, which was adjusted so that the zinc was always in excess and the temperature remained between 90 and 100 ° C. When the addition is complete, the mixture is heated for 15 minutes under gentle boiling and stirred overnight at room temperature. The reaction mixture was poured into an ice-water mixture and allowed to stand for more than 2 hours. The solid is

• e

It is filtered off, washed with water and recrystallized in aqueous ethanol. Yield 78%, mp 92 ° C.

tert-Butyl-4- (3-acetoxypropyl) -3,5-dimethylpyrrole-2-carboxylate [60% yield, melting point 73 ° C (hexane)] and tert-boogyl 4- (4-acetoxybutyl) -3,5- dimethylpyrrole-2-carboxylate [yield 52%, mp 62 ° C (hexane)] were prepared by the method described in Example 434. Example 435: 3,5-Dimethyl-4- (2-hydroxyethyl) pyrrole-2- carboxaldehyde.

tert-Butyl-4- (2-acetoxyethyl) -3,5-dimethylpyrrole-2-carboxylate (15 g, 53 mmol) was dissolved in trifluoroacetic acid (40 ml) and the solution was stirred at 40 ° C under nitrogen for 2 hours. 10 minutes. The reaction mixture was allowed to cool to 0 ° C and triethylorthoformate (9.6 ml, 58 mmol) was added dropwise. The mixture was allowed to warm to 20 ° C and stirred for 1 hour before being poured into ice water. The mixture was extracted with dichloromethane and the extracts were washed sequentially with 10% aqueous ammonia and water and dried over MgSO ₄ . 4- (2-Acetoxyethyl) -3,5-dimethylpyrrole-2-carboxaldehyde was purified by chromatography on silica gel using (7: 3) ethyl acetate: hexane. Yield 45%, mp 125-27 ° C (water).

To a solution of the above compound (5 g, 23 mmol) in ethanol (20 ml) was added 10% NaOH (10 ml). The mixture was stirred for 30 minutes at room temperature and the final solution was concentrated, diluted with water and extracted with dichloromethane. The organic extracts were dried and the solvent was removed to dryness. Yield 98%, mp 100 ° C (ethyl acetate).

3,5-Dimethyl-4- (3-hydroxypropyl) pyrrole-2-carboxaldehyde [yield 60%, mp 85 ° C (ethyl acetate / hexane)] and 3,5-dimethyl-4 (4-hydroxybutyl) pyrrole- 2-carboxaldehyde [38% yield, melting point 99 ° C (hexane)] was prepared by the method described in Example 435.

Example 436: 4- (2-Diethylaminoethyl) -3,5-dimethylpyrrole-2carboxaldehyde.

To a stirred solution of 3,5-dimethyl-4- (2-hydroxyethyl) pyrrole 2-carboxaldehyde (4.3 g, 25.7 mmol) and triethylamine (5.2 g, 51 mmol) in anhydrous tetrahydrofuran (60 ml) at 0-5 ° C. methanesulfonyl chloride (4 ml, 51 mmol) in anhydrous tetrahydrofuran (4 ml) was added and the mixture was stirred for 1 hour at room temperature. Water was then added to the mixture and the precipitated solid was removed by filtration. Yield 89%, mp 142-44 ° C.

A mixture of the above mesylate (23 mmol), K ₂ CO ₃ (23 mmol), diethylamine (90 mmol) and 2-propanol (70 ml) was heated for 0.5 hours to 100 ° C. The solvent was removed to dry residue and the residue was treated with water and extracted with methylene chloride. The organic extracts were dried and the solvent was evaporated to dryness. Yield 70%, mp 70 ° C (n-heptane).

3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrole-2-carboxaldehyde,

3,5-dimethyl-4- (2-ethylaminoethyl) pyrrole-2-carboxaldehyde, 4- (3-diethylaminopropyl) -3,5-dimethylpyrrole-2-carboxaldehyde, 4- (4-diethylaminobutyl) -3,5-dimethylpyrrole -2-carboxaldehyde, 3,5-dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrole-2-carboxaldehyde was isolated in the form of oils and obtained by a method analogous to that described in Example 436.

Example 437: 4- (2-Chloroacetyl) -3,5-dimethylpyrrole-2-carboxaldehyde

To a solution of 3,5-dimethylpyrrole-2-carboxaldehyde (5 g, 40 mmol) in 1,2-dichloroethane (50 ml), anhydrous aluminum chloride (42 g, 315 mmol) was added portionwise at room temperature under nitrogen for 30 minutes. ). After stirring for 15 minutes, chloroacetyl chloride (17 g, 150 mmol) was added dropwise over 1 hour. After the addition was complete, the mixture was stirred for 16 hours at room temperature. The mixture was poured onto crushed ice and the organic layer separated, dried over

• · ····

anhydrous sodium sulfate and the solvent is removed under reduced pressure. Yield 57%, mp 205-09 ° C (toluene).

Example 438: 3,5-Dimethyl-4- (2-diethylaminoacetyl) pyrrole-2carboxaldehyde

To a solution of 4- (2-chloroacetyl) -3,5-dimethylpyrrole-2carboxaldehyde (1 g, 5 mmol) in tetrahydrofuran (20 ml) was added diethylamine (5 ml). The mixture was stirred for 24 hours at room temperature. The solvent was removed under reduced pressure and the residue was treated with water and NaHCO ₃ (5%) and extracted with dichloromethane. After drying and filtration, the solvent is removed and the residue is used without further purification.

3,5-Dimethyl-4- (2-dimethylaminoacetyl) pyrrole-2-carboxaldehyde and

3,5-Dimethyl-4- [2- (1-pyrrolidinyl) acetyl] pyrrole-2-carboxaldehyde were synthesized by a method analogous to that described in Example 438. Example 439: 3,5-Dimethyl-4-ethoxyoxylpyrrole- 2-carboxaldehyde

Anhydrous aluminum chloride (37 g, 277 mmol) was added portionwise over 30 minutes under nitrogen to a solution at room temperature of 3,5-dimethylpyrrole-2-carboxaldehyde (7.6 g, 62 mmol) in 1,2-dichloroethane (140 ml). After stirring for 30 minutes, nitromethane (11.2 ml, 179 mmol) was added. The mixture was cooled to 0 ° C and ethylchlorooxoacetate (12.8 g, 94 mmol) was added dropwise over 1 hour. After the addition is complete, the mixture is stirred for 4 hours at room temperature. It is poured into crushed ice and the organic layer is separated, dried and evaporated to give a white solid. Yield 45%, mp 125-127 ° C (toluene).

All compounds of the above examples have NMR spectral data that correspond to the respective chemical structures.

Although the invention is in fact shown and described with respect to its preferred embodiments, it will be apparent to one skilled in the art that different changes in form and detail can be made without departing from the spirit and scope of the invention as defined. in the appended claims.

Claims (42)

Patent Claims A method of inhibiting one or more protein kinase activities, comprising administering a compound represented by the formula and its physiologically acceptable salts and biologically active metabolites, wherein: R is selected from the group consisting of substituted or unsubstituted: aliphatic group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C 3 -C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group ; R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) ·· cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazine, pyrimidazine, pyrazine , pyrazole, oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R ³ O-, NO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NRV ⁵ ; a R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 C 6) a cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3. 2. * · ··· »• 99 • ···· • · 9 • ·· ·· 99 9 ·· ♦ · • · • 9« V.. Method according to claim 1, wherein the inhibition of said protein kinase is in a patient in need thereof. The method of claim 2, wherein the compound is a mixture of stereoisomers. The method of claim 3, wherein the stereoisomers are enantiomers. The method of claim 3, wherein the stereoisomers are E and Z isomers. The method of claim 2, wherein the compound is a mixture of structural isomers. The method of claim 6, wherein the structural isomers are tautomers. The method of claim 2, wherein said protein kinase is either receptor tyrosine kinase or non-receptor tyrosine kinase. The method of claim 8, wherein said tyrosine kinase is selected from the group consisting of KDR, Fit-Ι, ΊΊΕ-2, FGFR, PDGFR, IGF-1R, c-Met, Lek, Src, fyn, Lyn, Blk and yes. A method of treating, or principally inhibiting, hyperproliferative disorders or inflammatory diseases in a patient in need thereof, comprising administering to said patient a compound represented by the formula O and its physiologically acceptable salts and biologically active metabolites, where: R is selected from the group consisting of substituted or unsubstituted: aliphatic group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl a group; R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C 3 -C 6) cycloalkyl-alkyl group and heterocyclyl -alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower qq alkyl, R Ο-, HO-, H OC (O) -, R OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NrA; q R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 C 6) a cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3. A method of treating or inhibiting angiogenesis in a patient in need thereof, comprising administering to said patient a compound represented by the formula and its physiologically acceptable salts and biologically active metabolites, wherein: R is selected from the group consisting of substituted or unsubstituted: aliphatic group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl a group; R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted is one or more groups selected from the group consisting of halogens, lower alkyl, R R-, NO-, NO (O) -, R OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NRV; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ - C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 C 6) a cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3. 12. A method of inducing an anti-angiogenic effect in a patient in need thereof, comprising administering to said patient a compound represented by the formula and its physiologically acceptable salts and biologically active metabolites, wherein: R is selected from the group consisting of substituted or unsubstituted: aliphatic, aromatic, (C ₃ -C 6 cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R R-, HO-, NO (O) -, R OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR ^ ^5; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C ₆ ) cycloalkyl, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C 3 -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3. A method for treating or inhibiting the development of a disease or condition in a patient in need thereof, comprising administering to said patient a compound represented by the formula and its physiologically acceptable salts and biologically active metabolites, wherein: R is selected from the group consisting of substituted or unsubstituted: aliphatic, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl and heterocyclyl-alkyl; ·· ·· * «• & R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R R-, HO-, NO (O) -, R OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR ^ R ^5; R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ -C 8) cycloalkyl group, heterocyclic group, aralkyl group, ( C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl- an alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3 wherein said disease or condition is selected from the group consisting of cancer, arthritis, atherosclerosis, restenosis, psoriasis, hemangioma, myocardial angiogenesis, coronary and cerebral collateral, ischemic limbic angiogenesis, angiogenesis, rubeosis, neovascular glaucoma, macular degeneration, wound healing, peptic ulcer diseases related to Helicobacter caused by viruses angiogenic disorders, fractures, diabetic retinopathy, Crohn's disease, inflammatory bowel disorders, felinosis, felinosis concomitant birth, ulcers, thyroid hyperplasia, burns, trauma, acute pulmonary injury, chronic lung disease, stroke, polyps, cysts, synovitis, chronic and allergic inflammation, ovarian hyperstimulation syndrome, pulmonary and cerebral edema, fibrotic, cerebral edema, , carpal tunnel syndrome, sepsis, age-related respiratory distress syndrome, multiorgan dysfunction syndrome, ascites and tumor-related effusions and edema. 14. A method of responding to vascular hyperpermeability or producing edema in a patient in need thereof, comprising administering to said patient a compound represented by the formula and its physiologically acceptable salts and biologically active metabolites, wherein: R is selected from the group consisting of substituted or unsubstituted: aliphatic group, aromatic group, (C ₃ -C) cycloalkyl group, a heterocyclic group, an aralkyl group, (C ₃ -C ₆₎ cycloalkyl-alkyl group and a heterocyclyl-alkyl a group; R ¹ is hydrogen or -AZ; R ² is hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl a group and a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ O or a ring system selected from the group consisting of (C ₃ -C ₆ ) cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridaline, pyridaline , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R ³ O -, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR 4 R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, ( C ₃ C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; optionally K and R together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl groups, each optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ C 6) cycloalkyl-alkyl group and heterocyclyl- an alkyl group; and η is an integer from 0 to 3. The method of claim 14, wherein the effect on the production of edema is antiemetic. The method of claim 2, wherein said protein kinase is a serine kinase. The method of claim 2, wherein said protein kinase is threonine kinase. · · · · · · · · · · · · · · · · A compound represented by the following structural formula and its physiologically acceptable salts, wherein: R is selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole , pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole; R ¹ is hydrogen or -AZ; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O, or a ring system selected from the group consisting of C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyrimidazole, benzazidine , oxazole, thiazole and their N-oxides, wherein said ring system may be optionally substituted by one or more groups selected from the group consisting of halogens, lower alkyl, R Ο-, H0-, NOC (O) -, R OC (O) -, trihalomethyl, nitro, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl, heterocyclylalkyl group, -CN, -C (O) NR ⁴ R ⁵ or - NR ^ R ^5; · · · · · · · · · · · · · · · · · · · · · · · · · · · R is in each case independently selected from the group consisting of substituted or unsubstituted: lower alkyl group, lower alkoxy lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ - C ₆ ) cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl group, aromatic group, (C ₃ C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C _{A 3-} C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; optionally R and R together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, pipercino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4diazepin-1-yl groups, each optionally substituted by more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl group, heterocyclic group, aralkyl group, (C ₃ -C ₆ ) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; and η is an integer from 0 to 3; provided that when R is unsubstituted indol-3-yl, R ¹ is not-не ₂ . The compound of claim 18, wherein A is -ΝΗ-, -O-, -S-, -S (O) - or -S (O) ₂ -; and Z is cyclopropyl, 3-pyridyl or pyrazinyl. The compound of claim 18, wherein A is -O-; and Z is ethyl, η-propyl or isopropyl. ·· »··· The compound of claim 18, wherein A is -CH ₂ -; and Z is phenyl, said phenyl optionally substituted by one or more groups selected from the group consisting of halogens, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl group, R ³ O -, -C (O) OR ⁴ and -OC (O) R ⁴ . 22. A compound selected from the group consisting of 3-11 cyclopropyl4 - {[(3R-dimethyl4- (4-methyl-1-piperazinylmethyl) pyrrol-2yl] methylene} -2-11irazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl ^g Gil-4- (1-pirolidinilmetilpirol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] - 2- pyrazolin-5-one, 3- Tsiklonropil-A [(3,5-dimethyl-4-piperidinol ^d tlpirol-2-yl) methylene] -2pirazolin-5-one, 3-Cyclopropyl4 - [(4-diethanolaminomethyl-3,5-dimethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-dimethylaminomethyl4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclo-1-phenyl-4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-diethylaminomethylA5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5tetramethylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-methylsopropyl-4 - {[3- ( 1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-niperidinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-N [(4-dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cycle: 1O-pyrrol-F [(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- (3,5-dibromo-4-hydroxybenzylidene) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2 © pyrazolin-5-one, E [(5-Chloropyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-trifluoromethanol-2-yl) methylene] -2-pyrazolin-5one, 3-Cyclopropyl-4- [4- (2-dimethylaminooxycarbonylpyrrol-2yl) methylene] -2-1razolin-5-one, 3-Cyclopropyl-4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Tsiklo11ropil-4 - [(3-e'GOksikarbonilindol-2-yl) me ^d Guillain] -2-pyrazolin-5-one ©, 3-Cy (saopronyl-4- [3- (2-dimethylaminoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [3- (2-dimethylaminoethylaminocarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [3- (4-morpholinoethylaminocarbonylindol-2yl) methylene] -2-11irazolin-5-one, 3- Cyclopropyl-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclo [11] propyl-N - [(5-ethoxy-methoxycarbonylmethyl-3 msoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- CyclopropylA [(5-chloro-4-methoxycarbonylmethyl-3methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, A [(3,5-Dimethyl-Fmorpholinomethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- {(3,5-Dimetka-4 - [(tetramethyl-1-piperazinyl ^d Gill) pyrrol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 ~ [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-Morpholinometall-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one ···· 234 4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5-one, 4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,6,6-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) - 2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridyl) - 2- pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [(5-Chloropyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazoline- 5- he, 4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) - 2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one, 4 - ((3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene) -3isopropoxy-2-pyrazolin-5-one, • · · · 9 ·:: * ^:: .:: ..... · .. ·· .. · · .. · 236 4 - [(PDH-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-isopropoxy- 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-N (piperidanomethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- | (4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one, 3- 14 isopropoxy-4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - {[3- (4-methyl-1-piperazinyl) methyl 4,5,5-tetramethylenepyrrole- 2-yl] methylene} -2-pyrazolin-5-one, 3-Isogropoxy-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-11-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- Isopropoxy-4 - [(3-piperidinomethyl4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one, '4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2- yl) methylene] -3-isopropoxy- 2- pyrazolin-5-one, 4- [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-isopropoxy-2-pyrazolin-5-one, 3- Isopropoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, · · · · · · · · · · · · · · · · 4 · 4 [(4-Chloropyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- Isopropoxy-4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, N [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5one, 4- | 4- (2-Dime ^d gilaminoetoksikarbonil11irol-2-yl) methylene] -3-isopropoxy 2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-isopropoxy- 2- pyrazolin-5-one, E [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3isopropoxy-2-pyrazolin-5-one, 3- Isopropoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyloxy-4- [4- (4-morpholinoethyl aminocarbonyl pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4- [3- (4 ~ morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- Isopropoxy-4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoline- 5- he, 4 '{[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxy-Fmethoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-1shrazolin-5-one, N- ((5-Chloro-Phenoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3-Dimetilaminometil4 _{g of} 5-tetrametilenprfol-2-yl) methylene] ^-3-d is goksi-2pirazolin-5-one, Zacksi-4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -pyrazolin-5-one, 4 - [(3-Dietilaminome ^d Gil-4,5-tezrametilenpirol-2-yl) methylene] -3-ethoxy-2pirazolin-5-one, 3-Ethoxy-4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Ethoxy-4 - [(3-11-hyperidinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one · · · · 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-ethoxy-2 pyrazolin-5-one, A [(ADIETHYLAMINOETAL-3,5-DIMETHYLGYROL-2-YL) METHYLENE] -3-ethoxy-2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-ethoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 3- Ethoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5one, 4- [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 3- Ethoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3ethoxy-2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, · · · · 4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3-ethoxy-2-pyrazopin-5-one, 3- Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3ethoxy-2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- | (3-Morpholinometall-4,5-tetramethylenepyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3- N -razinyl-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3- Pyrazinyl-4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5one, 4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, N- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4- [4 ~ (4-Morpholinoethyl ethyl aminocarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - ^{[(3,5-Dimethyl-4-d} is goksikarbonilpirol-2-yl) methylene] -3-pyrazinyl-2pirazolin-5-one, 4 - {[3,5-Dimethyl-N (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, A [(Indol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Pyrazinyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, - • · · · · 4 - ((Indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - ((3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5one, 4 - {(3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(5-Chloro-4-me ^d goksikarbonilmetil-3-metoksikarbonilpirol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- [(5-Chloropyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-yl] 5- he, 3- (Imidazol-2-yl) -4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline- The 5th, 4- (4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- (4- (2- Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3 (imidazol-2-yl) -2-pyrazolin-5-one, 4- [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin- 5- he, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3 (imidazol-2-yl) -2-pyrazolin-5-one · · · · · 243 3- (Imidazol-2-yl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [3- (4-morpholinoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [3- (4-morpholinoethylaminocarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3 (imidazol-2-yl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (imidazol-2-yl) · · · · 2- pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- [(4-Bromopyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline- 5- he, 4- | (4-Chloropyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline- 5- he, 4- [(5-Chloropyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazoline- 5- he, 3- (1-Methylpropionyl) -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (1methylcyclopropyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylshol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (1methylcyclopropyl) -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, · · · · • *. ·· «« 3- (1-Methylcyclopropyl) -4- [3- (4-morpholinoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4- [3- (4-morpholinoethylaminocarbonylindole- 2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazoline- 5- he, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1methylcyclopropyl) -2-pyrazolin-5-one, 4D (5-Methoxyind ol-2-yl) methylene] -3- (1-methyl cyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Pyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -3- (1 -methylcyclopropyl) -2-pyrazolin-5-one, 4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2 ····· yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4- | (5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} - 3- (2-furyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(3-Diethylaminoethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2yl] methylene} -2-pyrazolin-5-one, 3- (2-Furyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-furyl) - 2-Pyrazolin-5-one · · · · · · · · 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(4-dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Bromopyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) - 2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) - 2- pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] 2-pyrazolin-5-one, 3- (2-furyl) -4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] - 2- pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (3- (2-furyl)) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, ···· 249 4 - [(3,5-Dimethyl-4 - [(morpholinomethylpyrrol-2-yl) methylene] -3- (2-thienyl) - 2- pyrazolin-5-one, 4 - {[(3,5-Dimethyl-4- (4-methyl-1-piperazinyl) methylpyrrol-2-yl] methylene} - 3- (2-thienyl) -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) - 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethyleneglyrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (1-Pyrrolidinylmethyl) -4,5-tetramethylenepyrrol-2-yl] methylene} -3 (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, ······ 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - ((4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 3- (2-Thienyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5one, 4- ((4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- (4- (2- Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one, 4- (3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- (4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, ······ 4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-fluazolin-5one, 4 - [(1-Methylindol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylsulfol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-Methoxyindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoylaminocarbonyl) pyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(Pyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylsulfol-2yl) methylene] -3- (2-thienyl) -2-pyrazolin-5un, 4 - [(5-Chloro-4-megoksikarbonilmetil-3-me ^d goksikarbonilpirol-2yl) mstilen] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazoline-5h) n, · · · · · · · · · · · · · ♦ · · 252 4 - [(4-Chloropyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 4- [(5-Chloropyrrol-2-yl) methylene] -3-1Sklopropoxy-2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(5-1 trifluoromethyl-11-pyrrol-2-yl) methylene] -2-pyrazoline- 5- he, 3-Cyclopropoxy-N [(4-exypicarbonylpyrrol-2-yl) megylene] -2-pyrazolin-5one, 3-Cyclohexoxy-4- [4- (2-dimethylaminoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy 4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazoline- The 5th, 3-Cyclopropoxy-4- [3- (2-dimethylaminoethoxycarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3-Cycloproxyoxy- [3- (2-dimethylaminoethylaminocarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] - 2- pyrazolin-5-one, 3- Cyclopropoxy-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] - 2- pyrazolin-5-one, 3- Cyclopropoxy-4- [3- (4-morpholinoethylaminocarbonylindol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] -2-pyrazoline- The 5th, 3-Cyclopropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4- [3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2 ········ · ··· Pyrazolin-5-one, 3-Cyclopropoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-N [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazoline -5on, 3-Cyclopropyl-4 - {[3,5-dimethylA (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropoxy-N {[3,5-dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5h) n, ZL (cyclopropoxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropoxy-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -31-cyclopropoxy-2-pyrazolin-5-one, A {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one, 3- Cslopropoxy-4 - [(5-ethoxy-4-methoxycarbonylmethyl-3methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 3- [2- (5-Pyrimidinylethyl)] -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] 254 2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(ZADimethyl-4-ethylgyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - [(1-Methyl indol-3-yl) metal] -3- [2- (5-pyrimidinyl ethyl)] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(5-Methoxyindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2 pyrazolin-5-one · · ···· 255 3- [2- (5-Pyrimidinylethyl)] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 3- | 2- (5-Pyrimidinylstyl)] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - [(3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, N - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, N - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) metal] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, A [(5-Chloro-Fmethoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- [2- (5-pyrimidinylethyl)] -2-pyrazolin-5-one, 4 - [(ABromopyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 3- (2-phenylethyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Egoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, N- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 9 9 • 9 • 9 4- (4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - ((3-Ethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- (4- (4-Morpholinoethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [4- (4-Morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (4-Morpholinoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylstyl) -2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Methoxyindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 3- (2-phenylethyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylamino ^g hydroxycarbonyl) pyrrol-2-yl] methylene} - 3- (2-phenylethyl) -2-pyrazolin-5H) n, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - ((3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl ^d Gil-3-metoksikarbonilpirol-2yl) mstilen] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [(4-Bromopyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline- 5- he, 4- [(4-Chloropyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline- 5- he, 4- [(5-Chloropyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazoline- 5- he, 3- [2- (4-Hydroxyphenyl) ethyl] -4 - [(5-1rifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- (4- (2-Dimethylaminooxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethoxycarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- (3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -F [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -F [A (Amorpholinoethylaminocarbonylpyrrole- 2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -F [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -4- [3- (4-morpholinoethylaminocarbonylindole- 2-yl) methylene] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-N-toxicarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Hydroxyphenyl) ethyl] -4 - [(43-tetramethylene-phenyl-2-yl) methylene] -2-pyrazolin-5-one, E {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} - 3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimetilaminshg ^d gilaminokarbonil) pyrrol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(3Dethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- {3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (D-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonyl-11yl-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, · · · · · · · · 3- [2- (4-Aminophenyl) ethyl] -4 - [(4-bromopyrrol-2-yl) methylene] -2-pyrazoline- The 5th, 3- [2- (4-Aminophenyl) ethyl] -4 - [(4-chloropyrrol-2-yl) methylene] -2-pyrazoline- The 5th, 3- [2- (4-Aminophenyl) ethyl] -4 - ((5-chloropyrrol-2-yl) methylene] -2-pyrazoline- The 5th, 3- [2- (4-Aminophenyl) ethyl] -4 - ((5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4- [4- (2-dimethylaminoethoxycarbonylpyrrole- 2-yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4 - ((3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4- (3- (2-dimethylaminoethoxycarbonylindole- 2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4- [3- (2-dimethylaminoethylaminocarbonyl-indol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4- [4- (4-morpholinoethylaminocarbonylpyrrole) 2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4- [3- (4-morpholinoethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4- (3- (4-morpholinoethylaminocarbonylindole- 2-yl) methylene] -2-pyrazolin-5-one, • 4 3- [2- (4-Aminophenyl) ethyl] -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4 - ((4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2- (4-Aminophenyl) ethyl] -4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4 - {[3,5-dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- [ 2- (4-Aminophenyl) ethyl] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(indole- 2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4 - [(3,4-diethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4 - [(5-ethoxy-4-methoxycarbonylmethyl-3methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-Aminophenyl) ethyl] -4 - [(5-chloro-4-methoxycarbonylmethyl-3methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4 - {((4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} - 3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene) -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- {[3- (4-Methyl 1-11iperazinil) ^methyl-4,5-d they grametilenpirol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 3- (4-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- ((3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidinyl) pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (4-pyrimidinyl) -2-pyrazoline- 5- he, 4 - ((3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one ·········· · · · · · · · · · 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4-diethylaminomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {(3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 3- (5-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, • ft 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-pyrimidinyl) -2-pyrazoline- 5- he, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-1-spherazinylmethyl) pyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - ^{[(3-Dimethylaminomethyl-4,5-d} they grametilenpirol-2-yl) methylene] -3- (2pirimvdinil) -2-pyrazolin-5-one, 4 - [(3-Morpholinometall-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] metal} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 3- (2-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- [(3-Piperidinomethyl-4,5-tetramethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diepshaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-pyrimidinyl) -2-pyrazolin-5one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, N- (3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3 (3-11-iridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-A (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimegylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-Dimegylaminomethyl4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, A [(3-Morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - ^{[(3-Diethylaminomethyl-4,5-d} ge1rametilenpirol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 3- (3-Pyridazinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2yl] methylene} -2-pyrazolin-5-one, 4- [(3-Piperidinomethyl-4,5-tefamethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(FDimethylamines> 4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (3-pyridazinyl) -2-pyrazolin-5one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) - 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} - 3- (4-pyridazinyl) -2-pyrazolin-5-one, · · · · · · 9 «· · · · · · · · · · · · · · · · · · · · · · · · · · · · · *.« * ··· * * ··? 6 ^ ·· * * ·· * ···· 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - ^[(4-t Dietilaminomea yl-3,5-dimethylpyrrole-2-yl) methylene] -3- (4piridazinil) -2-pyrazolin-5-one, 4D (3,5-Dimethyl-N (piperidinomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-Dime ^{d gilaminometil-4,5-d} ge1rame ^d gilenpirol-2-yl) methylene] -3- (4piridazinil) -2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5- ^g gearamethylenepyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -3- (Fluidazinyl) -2-pyrazolin-5-one, 3- (4-Pyridazinyl) -F {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- ^{[(3-piperidinomethyl-4,5-d} ge1rametilenpirol-2-yl) methylene] -3- (4piridazinil) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tertrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Distylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3 - (4-pyridazinyl) -2-pyrazolin-5one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, ······ · 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) - 2-pyrazolin-5-one, A [(3,5-Dimethyl-4-morphol-N-methyl-1-phen-2-yl) methylene] -3- (5-isoxazolyl) - 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl N - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-Diethanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 4 [(3-Dimethylaminomethyl4 _g, 5 ^{g of} 1-methylene-11-pyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3-Diethylaminomethyl4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 3- (5-14 isoxazolyl) -4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5-heteromethylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-Isoxazolyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2yl] methylene} -2-pyrazolin-5-one, 3- (5-14 isoxazolyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, ♦ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ···· 4 - [(PDethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, A [(DDimeadaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) - 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3 (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one , 4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, A [(ADethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, A [(3,5-Dimethyl-4-piperidinomethylethyl-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, A [(ADiethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5- ^g plramethylene-pyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenepyrrole- 2-yl) methylene] -2-pyrazolin-5-one, 4- [(3-D ^and ethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5methyl-3-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) 4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-Metal-3-isoxazolyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-Metal-3-isoxazolyl) -4 - [(3-peridinomethyl-4D-tetramethylene-pyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-methyl3-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2yl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-methyl-3isoxazolyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4- (1-3 - [(dimethylamino) methyl] -4,5,6,7-tetrahydro-1 H -2-indolylmethylidene) -4,5-dihydro-1 H -5-pyrazolone, 3- Cyclopropyl-4- (1-4 - [(1,1-dimethylamino) methyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -4,5-dihydro-1-5-pyrazolone, maleate 4- [1- (4 - [[2- (Dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-N-pyrrolyl) methylidene] -3- (2-pyrazinyl) -4,5-dihydro -S-5-pyrazolone, 4- (1-4- [2- (Diethylamino) ethyl] -3,5-dimethyl-1H-2-pyrrolyl methyl indene) -3 (2-pyrazinyl) -4,5-dihydro-1H-5-pyrazolone , 4-1 "[4- (3-Chloropropanoyl) -3,5-dimethyl-1H-2-pyrrolyl] methylidene-3- (2-pyrazinyl) -4,5-dihydro-1-5-pyrazolone, 4- (1-3 - [(Dimethylamino) methyl] -4,5,6,7-tetrahydro-1 H -2-indolylmethylidene) -3- (2-pyrazinyl) -4,5-dihydro-1 H-5-pyrazolone, 4- (1-4 - [(Dimethylamino) methyl] -3 D-dimethyl-1H-2-pyrrolylmethylidene) 3- (5-methyl-3-isoxazolyl) -4,5-dihydro-1H-5-pyrazolone, • · · · · · · · 3-Cyclopropyl-4 - [(4,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Benzyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxyphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5one, 3-Phenyloxymethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlorophenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Benzyl-4 - {[4- (2-carboxyethyl) -3-methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Benzyl-4 - {[3- (2-carboxyethyl) -4-methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (4-Methylphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 2- Amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- Isopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-phenylethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-phenylamino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methylbenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methyl phenyl amino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxyphenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlorobenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlorophenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Chlorophenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Indol-3-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3,4-Dimethoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Phenylphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, • · · · · · · · · · · · 3- (2-phenylpropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-phenylpropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3- (4-Methylphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Nitrophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-fluorophenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlorophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethyl-11-pyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoline- 5- he, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5one, 4 - {[1- (4-Hydroxybutyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 3-Cyclopentoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Tert-butylureido-N [(methyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Aminophenylethyl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5one, 3-Isopropoxy-4 - [(1-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethylsulfon-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, · · · · · · 3- (4-Carbamoylphenylethyl) -4 - [(3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] - 2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (4-methoxycarbonylphenylethyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy- 2- pyrazolin-5-one, 3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(5-Ethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dime ^d Gil-4-etiliirol-2-yl) methylene] -3- (4-hidroksifeniletil) -2pirazolin-5-one, 3- (Ethoxycarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxyphenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3- (2-Carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-isopropyl-2pyrazolin-5-one, 3-Cyclopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclobutyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclo [11] propyl-4 - [[1- (3,5-dichlorophenyl) 11-orol-2-yl] methylene] -2-pyrazoline- 5- he, N [(Pyrrol-2-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopentyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Methylcyclopropyl) -F [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- (Benzothiazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4,5-Dimethylpyrrol-2-yl) methylene] -4- (3-pyridyl)] - 2-pyrazolin-5-one, · · · · · · · · · · · · 3-Cyclopropyl-4 - ((3,5-dimethyl-4-ethylpyrrol-2-yl) methylene] -2-pyrazolin-5one, 3- (Pyrrol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-methylpyrrole-2-yl) me ^d 1li1en] -2-g1irazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- ((3,5-Dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5one, 3-Cyclopropyl-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4D (5-Methylpyrrol-2-yl) methylene] -3 - (- 3-pyridyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-ethylpyrrolo-2-yl) me ^d Guillain] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - (((3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene) -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Propyl-4 [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Methyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Isopropyl phenyl amino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - {[1- (4-hydroxybutyl) pyrrol-2-yl] methylene} -2-pyrazoline- 5- he, 4- {[4- (2-Carboxyethyl) -3-methylpyrrol-2-yl] methylene} -3-isopropoxy-2pyrazolin-5-one, 4 - ((4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one, 3-Isopropoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-isopropoxy-2pyrazolin-5-one, 4 [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-isopropoxy- 2- pyrazolin-5-one, 4- [(4-Acetyl-3,5-dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoline- 5- he, A {[3,5-Dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, A {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2yl] methylene} -3-izo1fopoksi-2-pyrazolin-5-one, 4 - [(5-ethoxycarbonylpyrrol-2yl) me ^d Guillain ] -3-isopropoxy-2-pyrazolin-5one, 4 - [(5-Carboxypyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- (4-Chlorophenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, A [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- ( tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 4- [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(3,5-dimethyl-4-morpholinomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(3,4-Dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Carboxyethyl) -3-metalpyrrol-2-yl] methylene} -3-cylopropyl-2pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline 5- he, ·· ···· ·· ···· 3-Cyclopropyl-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Methoxycarbonylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxycarbonyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Trans-2-phenylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5one, 3-Cyclohexyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropylamino-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5- he, 3- Cyclopropyl-4 - [(5-morpholinomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(5-Carboxypyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(4-Chloropyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(5-Chloropyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 [(4-Chloropyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-pyrazinyl-4 - [(4,5-tetramethylethyl-2-yl) methylene] -2- pyrazoline-5one, 3- (3-Pyridyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 3- Cyclopropyl-4 - {[3,5-domethal-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, maleate, 4- {[3,5-Dimethyl-4- (2-morpholinoethylaminocarbonyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazoline- 5- he, 4 - [(4,5-Tetramethylenepyrrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5one, 4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazoline- 5- he, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-trifluoroacetamidomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-aminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5one, 3- (Benzothiazol-2-yl) A [(3,5-dimethyl-4-morpholinomethylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Carboxypyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one · · · ·: 2:%: N- (3,5-Dimethyl-4-diethanolaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl- 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-trifluoroacetamidomethylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(4-ethylpicarbonyl-3-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-D-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylphenyl ^l ilpirol-2-yl) methylene] -3- (3-pyridyl) - 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-e ^, hydroxycarbonylpyrrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 4 - [(3,4-Di (ethoxycarbonyl) pyrrol-2-yl] ) methylene] -3-ethoxy-2-pyrazolin-5one, 3- Ethoxy-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-pyridylethyl) - 2- pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methyl-2-phenylethyl) -2-pyrazolin-5-one, 4 - [(4Carboxy-3,5-dimethylsulfol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5one, 3- Ethoxy-4 - [(5-nitropyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(4-nitropyrrol-2-yl) methylene] -2-pyrazolin-5-one, • · · · · · · · · · · · · · · · · · · · · · · · · · · · · 4 - [(4-Carboxypyrrol-2-yl) methylene] -3-ethoxy-2-pyrazoline-5H) n, A {[3,5-Dimethyl-4- (2-dimethylamino ^, gilaminocarbonyl) pyrrol-2yl) methylene} -3-ethoxy-2-pyrazolin-5-one, N (5-Chloro-3-methoxycarbonyl-4-methoxycarbonylmethylpyrrol-2yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- {[3- (2-Carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-ethoxy-2-pyrazoline- 5- he, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 3- Ethoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3trifluoromethyl-2-girazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 3- (3-Aminophenyl) -4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2yl) methylene] -2-pyrazolin-5-one, 3- Ethoxy-4 - {[2- (4-morpholinoethyl) aminocarbonylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- [(4-Ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (4-Methyl-1-piperazinylmethyl) -3,5-dimethylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl- 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-yl-hyperidinomethylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 279 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5isoxazolyl) -2-pyrazolin-5-one, 4 - [(5-Methyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [N- (2-dimethylaminoethyl) -N-methylaminomethylpyrrole- 2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3- Cyclo [11] propyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3- Cyclofopyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, maleate, 4- {[4- (3-Chloropropionyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethyl aminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-adimethylaminomethylpyrrol-2-yl) methylene] -3- (5-methyl- 3- isoxazolyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (4-hydroxypiperidinomethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Aminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, maleate, 4 - {[4- (4 "Benzylsheridino) methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) 1-schrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · · 3-Cyclopropyl-4 - {{3,5-dimethyl-4- (2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -2-pyrazolin-5-one, 3- Cyclopropyl-4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4- {(3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl- 2- pyrazolin-5-one, 4 - {(4- (3-Diethylaminopropyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(3,5-Dimethyl-4- (3-hydroxypropyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - ((3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, hydrochloride, 4 - ((3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3- Cyclopropyl-4- {[(2-diethylaminoethyl) -3,5-dimethyl-4-pyrrol-2yl] methylene} -2-pyrazolin-5-one, 4- {| 3,5-Dimethyl-4- (2-dimethylamino ^d gilaminoetil) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(3,5-Dimethyl-4- (4-hydroxybutyl) pyrrol-2-yl] methylene} -3-pyrazinyl- 2-pyrazolin-5-one, 4- {[4- (4-Diethylaminobutyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl-N-oxide) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (1-pyrrolidinylacetyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - ((4- Diethylaminoacetyl-3,5-dimethylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, · · · · · 4- [(3-Isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoline- 5- he, 4 - {[3,5-Dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3- Cyuopropyl-4 - [(dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-ethoxyxalyl) pyrrol-2-yl] methylene} -3-pyrazinyl- 2- pyrazolin-5-one, 3- Benzyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- Benzyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one 4- [(Indol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-phenyloxymethyl-2-pyrazolin-5-one, 3- (4-Chlorophenyloxymethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylphenylamino) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenylamino) -2-pyrazolin-5-one, 3- (4-Chlorobenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- {| 1- (4-Hydroxybutyl) indol-3-yl] methylene) -3- (4-methoxybenzyl) -2-pyrazolin-5-one, · 3- (4-Chlorophenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (3-methoxybenzyl) -2-pyrazolin-5-one, 3- (3,4-dimethoxybenzyl) -4 - [(indol-3-yl) methylene ] -2-Pyrazolin-5-one, 3- (4-Hydroxybenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (3-Chlorophenyloxymethyl) -4- [ (indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (Indol-3-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-methoxyphenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-phenylphenyloxymethyl) - 2-Pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-phenylpropyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] - 3- (3-phenylpropyl) -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-methylphenylethyl) -2-pyrazolin-5-one, 3- Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- {[1- (4-Hydroxybugyl) indol-3-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4- {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-phenylethyl-2-pyrazoline- 5- he, 4 - [(Indol-3-yl) methylene] -3- (4-nitrophenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-propoxy-2-pyrazoline- 5-one, 3- (4-fluorophenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-Aminophenylethyl) -4 - [(indol-3-yl) ) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(2-methylindol-3-yl) methylene] -2-pyrazolyl-5-one, 3- Isopropoxy-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(7-Methylindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5- he, 3- Isopropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-methoxycarbonylphenylethyl) -2-pyrazoline- · · · · · · · · · · · · · · · · · · · · · 283 «· The 5th, 3-Isopropoxy-4 - [(1-isopropylindol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chloro-phenylaminocarbonylmethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- Ethoxycarbonylmethyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-methoxyphenylaminocarbonylmethyl) -2pyrazolin-5-one, 3- Cyclopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3- (2-Aminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Cyclobutyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (2-Dimethylaminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (4-pyridyl) -2-pyrazolin-5-one, 3- Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-methylcyclopropyl) -2-pyrazolin-5-one, 3- Cyclohexyl-4 - {[1- (4-hydroxybugyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4- {[1- (4-Hydroxybugyl) indol-3-yl] methylene} -3- (4-pyridyl) -2-pyrazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, • · • · · 284 • · 4 - [(Indol-3-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 3- Dimethylamino-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (pyrrol-2-yl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (6-methoxybenzothiazol-2-yl) -2-pyrazolin-5one, 3-Cyclopropyl-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3- Cyclo [11] propyl-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(1-Methylindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-methyl-2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-1rifluoromethyl-2pyrazolin-5-one, 4- {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3- (tert-butyl) -2-pyrazoline- 5- he, 3- Ethoxycarbonyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (2-methoxycarbonylethyl) -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3- (trans-2-phenyl-1-cyclopropyl) -2-pyrazoline- 5- he, 3 "Cyclobugyl-4 - {[1- (4-hydroxybugyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(1,7-dimethylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(1-Methylindol-3-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin- 5- he, 3- Cyclopropylamino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(6-Carboxy-1-methylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- [(1,7-Dimethylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazoline- 5- he, 3- (4-fluorophenylamino) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazoline- The 5th, 4- [(1-Methylindol-3-yl) methylene] -3-trifluoroacetamido-2-pyrazolin-5-one, 3- (4-Aminophenylethyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5one, 3-Amino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlorophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3- (5-Isoxazolyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(1-Metallivol-3-yl) methyl] -3-tert-butyl-2-pyrazolin-5-one, 4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5one, 4- {{1-Methyl-6- [2- (4-morpholino) ethyl] aminocarbonylindol-3-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, · · · · 4 · 3- (4-Aminophenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxycarbonylphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Carbamoylphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(3-dimethylaminomethylindol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- 14 isopropoxy-4 - [(1-methylindol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(5- ^{grams of} Groindol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-2-yl) methylene] -3-isopropylamino-2-pyrazolin-5-one, 3- (4-Carboxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(3-methylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - {[3- (2-methoxycarbonyl-2-acetamidoethyl) indol-2yl] methylene} -2-pyrazolin-5-one, 3-Ethoxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2 -pyrazoline-5one, 3- Cyclopropyl-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one, 4- [(5-Methoxyindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(5-Methoxyindol-2-yl) methylene] -3- (2-pyridyl) -2-1razolin-5-one, 4 - [(4-Chloro-6,7-dihydroindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- [(4-Chloro-6,7-dihydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazoline- 5- he, 4- ((4-Oxo-1,5,6,7-dihydroindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5one, 4 - [(7-Azaindol-3-yl) methylene] -3-benzyl-2-pyrazolin-5-one, 3- Benzyl-4 - {[1- (4-hydroxybugyl) -7-azaindol-3-yl] methylene} -2-pyrazolin-5-one, 4- [(7-Azaindol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- Amino-4 - [(7-azaindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(7-Azaindol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5one, 4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl] methylene} -3- (4 hydroxyphenylethyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-isopropyl-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) metal] -3-cyclobutyl-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-fluorophenylamino) -2-pyrazolin-5one, 4 - [(7-Azaindol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one, · 4 - [(7-Azaindol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one, 4 - [(7-azaindol-3-yl) methylene] -3-1rifluoromethyl-2-pyrazoline- 5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (tert-butyl) -2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybugyl) -7-azaindole -3-yl] methylene} -3-trifluoromethyl-2pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-isopropylphenylamino) -2-pyrazolin-5one, 4 - [(7-Azaindol-3-yl) methylene] -3- (3-methylphenylamino) -2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl ] methylene} -3- (3methylphenylamino) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3- Benzyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, 4- [(4-Dimethylaminophenyl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- | (4-dimethylaminophenyl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-cyclopropyl- 4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, 3-Isoproponecin-4 - [(3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one, 4- [(Imidazol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(imidazol-2-yl) methylene] -2-nirazolin-5-one, 4- [(1-imidazol-4-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- Cyclopropyl-4 - [(thien-2-yl) methylene] -2-pyrazolin-5-one, 4- [(Indol-3-yl) methylene] -3-isopropyl-1-methyl-2-pyrazolin-5-one, 3- Isonropoxy-4 - [(pyrrol-3-yl) methylene] -2-pyrazolin-5-one, 4- [(8-Hydroxyquinolin-5-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethyl-1-nyrrol-2-yl ] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3- • · ·· Pyridazinyl) -2-sfazolin-5-one, N- [4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylsinoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) - 2- pyrazolin-5-one, 4- {| 4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 3- Cycloheroyl-4 - [(3,5-dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] - 2- pyrazolin-5-one, 3- Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-phenylaminoethyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one, 3- Cyulopropyl-4 - {{3,5-dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrole- 2-yl} methylene} -2-pyrazolin-5-one, 4- {[4- (2-carboxyethyl) -3,5-dimethylpyrrole-2-yl] me ^d Guillain} -3-cyclopropyl-2-pyrazolin-5-one, 3- CyclopropylA - [(4-diethylaminomethyl-11-3-isopropyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cycloheropyl-4 - {[4- (1-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -2-pyrazolin-5-one, 3-Cyclohexyl (N, N) -4 - {{3-isopropyl-5-methyl-4- [2- (1-pyrrolidanylethyl)] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, • 9 ··· · • · 3-Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5methylpyrrol-2-yl] methylene} -2-pyrazolin-5h) n, 3-Cyclopropyl-4 - {(4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl) methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-N - {[3-isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one, 3-Circlopropyl-4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (4-dimethylaminobutyl) -3-isopropyl-5-methylpyrrole- 2-yl] methylene} -2-pyrazolin-5-one, 3- Cyclopropyl-N - [(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3-cyclopropyl-4- (1-pyrrolidinylmethyl) -5methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4- {{3-cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3-cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] - 5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclo [1111] yl-4 - {[3-cyclopropyl-4- (3-diethylaminopropyl) -5methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyulopropyl-4 - {{3-cyclopropyl- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-cyclopropyl- 4 - {[3-cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4- {{3-cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4- {[3-cyclopropyl-5-methyl-4- (4cyclobutylaminobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, · · · · ··· · 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -311yrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Adiel ^d gilaminometil-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3 pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3- Pyrazinyl-4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-pyridinobutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3- Pyrazinyl-4 - {{A [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methyl-2-yl} methylene} -2-pyrazolin-5-one, 4- {[4- (4-Dimethylaminobugyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, A [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-11cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, ······: :.::. . · ..... '2'92' · '* ·· * · ^: ·· 4 - {{3-14dclopropyl-4- [2-da (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -2-pyrazinyl-2-pyrazolin-5-one, A {[3-Cyclopropyl-4- (3-diethylamino ^- propyl) -5-methyl-tyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N- [[3-Cyclopropyl-5-methyl4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {| 3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- | (3,5-Dimethyl-4- (1-11 pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-furyl) - 2- pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3 (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} - 3- (2-furyl) -2-pyrazolin-5-one ······ 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4- {[4- (2-Cyclopropyl aminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3- (2-furyl) -4 - {[3-isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2yl] methylene} -2-pyrazolin-5-one, 3- (2-furyl) -4 - {{4- [3- (4-pyridylme ^, pylamino) N) Opyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5- he, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (2-furyl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5- he, 4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, · 4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) - 2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-thienyl) - 2- pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-iridylmethylamino) ethyl] pyrrol-2-yl} methylene} - 3- (2-thienyl) -2-pyrazolin-5-one, 4- {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-metalpyrrol-2-yl] methylene} -3 (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4- {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, ······ 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylphenol-2-yl] methylene} -3 (2-thienyl) -2-yl] pyrazolin-5-one, N- [(3-Cyclopropyl-4-diethylaminomethyl-5-methylphen-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-1Diclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-Cyclooropropyl-N [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} mstylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3-Cycloheropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-11-duo-propyl-N [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methyl-pyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one , 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pipol-2yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) boogyl] pyrrol-2yl} metal} -3- (2 "Thienyl) -2-pyrazolin-5h) n, 4 - {[3-Cyclo-1-propyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methyl} -3- (2-thienyl) -2-11-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-fluazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-N (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} - 3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 3- (4-Pyrimidanyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- | (3-cyclopropyl-4 -diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylCH} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-cyclopropyl- 4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3- Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-D imethyl-4- (2-ethyl aminoethyl) -pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4- (2-phenyl aminoethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4 - (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} 3- (5-pyrimidinyl) -2-pyrazolin-5-one, · · · · · · · · ···· · - ·· • ♦ 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 3- (5-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-Pyridylmethylamino) 11ropyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-1razolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (5-pyrimidinyl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] ms ^g Guillain} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5- he, 4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethyl aminopropyl) pyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one ····· * · · · • · · · · ·. . • · · · · · · · · · · 4 - ((3,5-Dimethyl-4- (1-pyrrolidinyl methyl pyrrol-2-yl) methylene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-1] cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- (2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - ((4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} - 3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4- {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 3- (2-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{4- (3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, • * 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-cyclopropyl-4-diethylaminomethyl) -5-methyl-pyrrol-2-yl) methylene] -3 (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-4 (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-cyclopropyl-4 [ 3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-cyclopropyl-5 -methyl-4 (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4 [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 {[3-Cyclopropyl-5-methyl-4 (4cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4 (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4 (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- {[3,5-Dimethyl-4 (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, • 9 • · 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4 - (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3 (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- {[4- (2-Cyclopropyl aminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 3- (3-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- | (3-cyclopropyl-4 -diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, ··· ······ · · · · · · · · · · · · · · · F * ···· 9 9 · ······ « 99 ··· ·· ·· · ····· 302 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5- he, 4- {[3-Cyclopropyl-5-methyl-4- (3-phenylmethyl aminopropyl) pyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) boogyl] trifol-2yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] propol-2-yl} methylene} - 3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- [(4-Diethylaminomethyl-3-isophenyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} - 3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, • · • · · · · · 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 3- (4-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4- {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobugyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} - 3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Tsiklog1ro11il-5-me ^d Gil-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- {[3-Cyclopropyl-4- (3-diethyl aminopropyl) -5-methylpyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylpyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5- he, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylsulfonyl} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methyl en} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (1,2,41riazin-3-yl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (1,2,4 triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5 -one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (1,2,41iazin-3-yl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4- {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- The 5th, 4- {[4- (2-Cyclopropyl aminoethyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- The 5th, 4 - {[3-Isopropyl-5-methyl-4D4-piperidinobutyl) pyrrol-2-yl] methylene} -3 (1,2,4-1riazin-3-yl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- The 5th, 4- {[4D4-Dimethyl aminobutyl) -3-isopropyl-5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3 (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline -5-he, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2yl} methylene} -3- (1,2,4-1 triazin-3-yl) -2-pyrazolin-5 -one, 4- {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5methylnerol-2-yl} methylene} -3- (1,2,4-triazin-3-yl ) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2yl] methylene} -3- (1,2,4-1riazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2yl} methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline -5-he, 4- {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (1-pyrrolidinylethyl)] -3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Ethylaminoethyl) -5-methyl-3-trifluoromethyl pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Megyl-4- [2- (4-pyridylmethylaminoethyl)] - 3 trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · · · 306 • · · · · · 4- {[4- (2-Diethylaminoethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-4- [2- (1-pyrrolidinyl) -1] -3-tert-butylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Ethylaminoethyl) -5-methyl-3-1-butyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-4- [2- (4-pyridylmethylaminoethyl)] - 3-tert-butylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-tert-butylpyrrol-2-yl} methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Aminoethyl) -5-methyl-3-1ret-butylylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Ethyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethal-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-ethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[3-Cyclobutyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{3-Cyclobutyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[3-Cyclobutyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3- · ♦ · ·· 4 • · 307 pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclobutylpyrrol-2yl} methylsulfonyl} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclobutyl ^d gilpirol-2-yl] methylene} -3pirazinil-2-pyrazolin-5-one, 4- {[3-Cyclopentyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclopentyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclopentylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, N- [3-Cyclohexyl-4- (2-diethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, N {{3-Cyclohexyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-ethylamino) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclohexylpyrrol-2-yl} methylene} 3-pyrazinyl-2-pyrazolin-5-one, • · · · · · · • < • · · · · · • · 9 · · • · · · · · · · · · · · · 308 4 - {[N (2-Amine (Hggyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[A (2-diethylaminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methyl} ^d vertebrae -3pirazinil-2-pyrazolin-5-one, 4 - {{5-Metal-3-phenyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, N- {{5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-brazolin-5-one, 4 - {{4- (2- (1-Imidazoyl) ethyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminosulfonyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrole- 2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N - {{4- (2- (1-Imidazoyl) ethyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Metal-3- (2-pyridyl) -4- [2- (1-sulfidinylethyl)] pyrrol-2 ·· · · · · · 309 ти · пи · · · · * * *}}}} methylene} -3-pyrazinyl-2-pyrazolin-5-one , 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[E (2-Aminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, N - {[4- (2-Diethylaminoethyl) ) -5-methyl-3-pyrazinyl-11-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Mesyl-3-pyrazinyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Ethylaminoethyl) -5-methyl-3-pyrazinyl-11-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-pyrazinylpyrrol-2-yl} methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Cyclopropylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · · · · · · · · · · · · · · · · · · · 310 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-imidazoyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Tsikloiropilaminoe ^d Gill) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N - {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-pyridinyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{5-Metal-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4D2- (1-14midazoyl) ethyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {| 4- (2-Diethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Megyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {[4- (2-Cycloropropylaminoethyl) -5-methyl-3- (3-isoxazolyl) nyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3 ♦ · ···· • A pyrazinyl-2-pyrazolin-5-one , 4- {{5-Methyl-3- (2-furyl) -4- [2- (Pyrrolidinylethyl)] pyrrol-2-yl} methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2- ^D- gylaminesulfonyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, Φ {[4- (2ΈΊΊΈΊΊΐ3ΜΗΗθ6τ ^) - 5-ΧΗΗροκθΗΜεττυι-3-Η3θπροιπϋΐπΗροπ-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N {{4- [2- (1-Imidazoyl) ethyl] -5-hydroxymethyl-3-isopropylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dicyclopentyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclopropyl-N [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Ethylaminoethyl) -3,5-dicyclopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, ·· 44 ·· ······· · · • · · · 4444 4 4 444 44444 * · · 4444444 ·· 444 44 44 ·· 4444 312 4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -3,5-dicyclopropyl-pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[A (2-Cyclopropylaminoethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminomethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-dimethylaminoethoxy ^d Gill) -5-methyl-3-drifluorometilpirol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(5-Methyl-4- [2- (1-pyrrolidinylmethyl)] - 3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-trifluoromethylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 31rifluoromethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-trifluoromethylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethyl aminomethyl) -5-methyl-3-tert-butyl} -rol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethyl aminomethyl) -5-methyl-3- ^d Gret-butilpirol-2- yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (1-pyrrolidinylmethyl)] -3-tert-butylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-tert-butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · · 4- {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] -3-tert-butylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- (2- (1-Imidazoyl) methyl] -5-methyl-3-tert-butylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Aminomethyl) -5-methyl-3-tert-butylylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(4- (2-Diethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-N [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Ethyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- (2- (1-Imidazoyl) methyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-ethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[3-Cyclobugyl-4- (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[3-Cyclo-butyl-4- (2-dimethylaminomethyl) -5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclobutyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclobutyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one, ······ · 4 - {{3-Cyclobutyl-5-methyl-N [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-11-yrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-cyclobutylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N - {[N (2-Aminomethyl) -5-metal-3-ylblobylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[3-CyclopentylA (2-dimethylaminomethyl) -5-methylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {{3-Cyclops ^d Gil-5-methyl [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclops ^d Gil-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3pirazinil-2-pyrazolin-5-one, A {{3-Cyclopentyl-5-metal-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2H} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 {{A [2- (1-Imidazoyl) methyl] -1-methyl-5-methyl-3-cyclopentyl-pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5un, 4 - {[3-Cyclohexyl-4- (2-diethylaminomethyl) -5-methylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[3-Cyclohexyl-4- (2-dimethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {[3-Cyclohexyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · · 4 - {(3-Cyclohexyl-5-methyl-N [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, '4 - {{4- [2 - (1-Imidazoyl) methyl] -5-methyl-3-cyclohexylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[A (2-Aminomethyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Die ^d gilaminometil) -5-methyl-3-phenylpyrrol-2yl] methylene} -3pirazinil-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3-phenyl-A [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-phenylnyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4-H5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one ······ 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyridyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4D2-Diethylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethyl aminomethyl) -5-methyl-3-pyrazinyl pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3-pyrazinyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-pyrazinylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Cyclopropylaminomethyl) -5-methyl-3-pyrazinylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] metal} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrole- 2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-imidazoyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {| 4- (2-Diethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, · · ······ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 318 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {(4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[A (2-Dimethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Ethylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} - 3- pyrazinyl-2-pyrazolin-5-one, 4- {{5-Methyl-3- (2-furyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one ········ • · · · · · · · · · · · · · · · · · · · · · · · · · · · 9 · • · · · · · · 319 • ·· • · * «• · 9 • 999 9 99 ·· ···· 4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, N {{N [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {[4- (2-Cycloheropylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[N (2-Dimethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinyl ^d Gill)] pyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-hydroxymethyl-3-isopropylpyrrol-2yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylacetomethyl) -3,5-dichloro-propyl-11-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclo-11-yl-N [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, A {[4- (2-Ethylaminomethyl) -3,5-dicyclopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrole-2 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 320 • Methyl} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{A [2- (1-imidazoyl) methyl] -3,5-dicyclopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Acyclopropylaminomethyl-3,5-dicyclopropylpyrrol-2-yl) methylene] -3pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-hydroxyethyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Dimethylaminomethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2yl] methylene} -3-pyrazinyl-2-pyrazolin-5un, and 4 - {[3-Hydroxymethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one. The compound of claim 18, wherein the compound is a mixture of stereoisomers. The compound of claim 23, wherein the stereoisomers are enantiomers. The compound of claim 24, wherein the stereoisomers are E and Z isomers. The compound of claim 18, wherein the compound is a mixture of structural isomers. The compound of claim 26, wherein the structural isomers are tautomers. A method of inhibiting the activity of one or more protein kinases, comprising administering a compound of claim 18. The method of claim 28, wherein said compound is administered to a patient in need of inhibition of one or more protein kinases. • · · · The method of claim 29, wherein the compound is a mixture of stereoisomers. The method of claim 30, wherein the stereoisomers are enantiomers. The method of claim 30, wherein the stereoisomers are E and Z isomers. The method of claim 29, wherein the compound is a mixture of structural isomers. 34. The method according to claim 29, where structural isomers are tautomers. 35. The method according to claim 29, where mentioned protein kinase is a tyrosine kinase. 36. The method according to claim 35, where mentioned tyrosine kinase is selected from the group consisting of KDR, Flt-1, Lek, Src, fyn, Lyn, Blk and yes. A method for responding to hyperproliferative disorders in a patient, comprising administering to said patient a compound of claim 18. A method of responding to angiogenesis in a patient comprising administering to said patient a compound of claim 18. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable carrier or diluent. A pharmaceutical composition comprising a compound of claim 22 and a pharmaceutically acceptable carrier or diluent. The compound of claim 18, wherein R is substituted with one or more substituents independently independently selected from the group consisting of halogens, lower alkyl groups, R ³ O-, hydroxy, NOC (O) -, R ³ OC (O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, nitro, - C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, - (CH 2) n R ⁷ , -C (O) (CH 2) _n -R ⁷ , -C (O) - (CH 2) n C (O) -R ⁷ , -O (CH 2) _n R ⁷ , -QO) NR ⁴ (CH 2) n R ⁷ -C (O) O (CH 2) _n R ⁷ , -OC (O) (CH 2) n R ⁷ , -NR ⁴ QO) (CH 2) _n R ⁷ , -R ^ R ^ ⁵ , -R ^ R ⁴ ) R ⁶ -R ⁷ , -R ^^ - R ⁷ ) * -R ⁶ QO) NR ⁴ (CH 2) nR ⁷ -R ⁶ QO) O (CH 2) _n R ⁷ , -R ⁶ OQO) (CH 2) n R ⁷ , -R ⁶ NR ⁴ C (O) (CH 2) _n R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (NR ⁵ C (O) R ⁴ ), optionally substituted aryl and optionally substituted aralkyl; wherein the optionally substituted aryl and optionally substituted aralkyl groups are optionally substituted by one or more substituents selected from the group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁵ , lower alkyl group, R ³ O ~, -C (O) OR ^4, and -OC (O) R ^3; R ⁶ is a lower alkyl group or an aryl group; and 7 3 R is alkoxy, haloalkyl, lower alkyl piperazine, hydroxy, R O-, R ³ C (O) - or -NR ⁴ R ⁵ . The compound of claim 41, wherein R is pyrrolyl, indolyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7tetrahydroindolyl or quinolinyl. The compound of claim 42, wherein R is pyrrol-2-yl, pyrrol-3-yl, indol-2-yl, indol-3-yl, azaindol-3-yl, pyrazol-4-yl, imidazol-2- yl, imidazol-4-yl, thien-2-yl or quinolin-5-yl. The compound of claim 18 or 43, wherein R ¹ is trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl, isopropyl, cyclopropyl, 2-methylcyclopropyl, 2,2,3,3tetramethylcyclopropyl, 2-phenylcyclopropyl, cyclobutyl, III «· · · · · · · · · · · · · · · · · · · · · · · · · · · · · ♦ · · · · · · cyclopentyl, cyclohexyl, - (CH ₂ ) _p -O-phenyl, - (CH ₂ ) _p -O- (4methoxyphenyl), - ( CH ₂ ) _p -O- (4-chlorophenyl), - (CH ₂ ) _p -O- (4-methylphenyl), - (CH ₂ ) _p -O- (3-methylphenyl), - (CH ₂ ) _p - O- (4-phenylphenyl), - (CH ₂ ) _p -O- (4hydroxyphenyl), - (CH ₂ ) _p -O- (4-nitrophenyl), - (CH ₂ ) _p -O- (4-aminophenyl) , - (CH ₂ ) _p -O- (4-carbamoylphenyl), - (CH ₂ ) _p -O- (4-methoxycarbonylphenyl), -NH-phenyl, -N- (4-methoxyphenyl), -HH- (4 -chlorophenyl) fluorophenyl), -NH- (4-H3onponwi phenyl), isopropoxy, cyclopentoxy, - (CH _{2) p-indolyl,} - (CH _{2) q} -pyridyl, bin otiazolil, - (CH _{2) p-pyrrolyl,} - (CH _{2) p-tetrahydrofuryl,} pyrazinyl, - _{(CH2) p-furyl,} - (CH _{2) p-thienyl,} - (CH _{2) p} -phenyl, isoxazolyl , - (CH ₂ ) _p - (5-methylisoxazolyl), - (CH ₂ ) _p- pyrimidinyl, - (CH ₂ ) _p -pyridazinyl, - (CH ₂ ) _n -C (O) -OMe, - (CH ₂ ) _n -C (O) -OEt and -NH- (4ethoxy, - (CH ₂ ) _P - (CH ₂ ) _p - (CIS, benzyl, optionally substituted by one or more Cl, F, OMe, methyl or amino, wherein p is an integer from 1 to 3. The compound of claim 44, wherein R is optionally substituted by one or more groups selected from the group consisting of Br, Cl, F, aminomethyl, N, N-dimethylaminomethyl, carboxy, carboxymethyl, carboxyethyl, carbonylmethyl, carbonylethyl, methoxycarbonyl , ethoxycarbonyl, phenyl, 4morpholinomethyl, -C (O) -O- (CH ₂ ) ₂ -N (Me) ₂ , -C (O) -O- (CH ₂ ) ₂ -N (Et) ₂ , -C (O) -O-CH ₂ -N (Me) ₂ , -C (O) -O- (CH ₂ ) ₂ -N (Me) ₂ , -C (O) -NH- (CH ₂ ) ₂ -N (Me) ₂ , -CH ₂ -NH-C (O) -CF ₃ and an optionally substituted group selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl and phenyl, where the optionally substituted group is optionally substituted by one or more Br, Cl, F, hydroxy, nitro, amino or lower alkyl.