CN1377346A - Z-pyrazoline-5-ones - Google Patents

Z-pyrazoline-5-ones Download PDF

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CN1377346A
CN1377346A CN00813682A CN00813682A CN1377346A CN 1377346 A CN1377346 A CN 1377346A CN 00813682 A CN00813682 A CN 00813682A CN 00813682 A CN00813682 A CN 00813682A CN 1377346 A CN1377346 A CN 1377346A
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pyrazolin
methylene radical
pyrroles
methyl
pyrazinyl
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CN1193026C (en
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M·M·莫塞特
J·M·C·贝尔兰加
I·F·菲尔南德茨
D·J·卡尔伍德
P·拉菲蒂
L·阿诺
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Abert & Co KG GmbH
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BASF SE
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Abstract

Chemical compounds having structural formula (I) 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.

Description

The 2-pyrazolin-5-one
Related application
The application requires the interests of the U.S. Provisional Application 60/146,563 of submission on July 30th, 1999, and the full content combination of this provisional application in the present invention as a reference.
The present invention relates to some 2-pyrazolin-5-ones, they are inhibitor of protein kinase, particularly Tyrosylprotein kinase and serine/threonine kinase, some of them are new compounds, the invention still further relates to the pharmaceutical composition that contains these pyrazolones and the preparation method of these pyrazolones.
Background of invention
The protein kinase of having discerned has 400 kinds at least.The phosphorylation of these enzyme catalysis target protein substrates.Phosphorylation normally phosphate by the shift reaction of ATP to protein substrate.The ad hoc structure that shifts the target substrate of phosphoric acid on it is tyrosine, Serine or threonine residues.Because these amino-acid residues are target substrates that phosphoryl shifts, these protein kinases are commonly referred to as Tyrosylprotein kinase or serine/threonine kinase.
Phosphorylation reaction that carries out on tyrosine, Serine or threonine residues and the phosphatase reaction that contends with relate to countless cell processes, these cell processes relate to the adjusting of cell function and the activation or the deactivation of cell processes based on reply (normally by cell receptor-mediated) to signal in the different cells.The cascade of protein kinase often participates in the conduction of signal in the cell, and for realizing that these cell processes are necessary.Because their ubiquities in these processes, can find that protein kinase exists or is positioned in the nuclear as the integral part of plasma membrane or as the tenuigenin enzyme, often as the component of enzyme title complex.In many cases, these protein kinases are fundamental elements of enzyme and structural protein title complex, and it has determined whether or when to take place cell processes in cell.
Protein tyrosine kinase.Protein tyrosine kinase (PTKs) is the enzyme of tyrosine residues phosphorylation specific in the catalysis cell protein.The back translation of these substrate proteins is modified, and often is enzyme itself, plays a part the molecule transmodulator (the relevant summary, referring to Schlessinger and Ulrich, 1992, Neuron 9:383-391) of control cell proliferation, activation or differentiation.Numerous disease, comprise optimum and malignant proliferation disease and the disease (for example autoimmune disease), homograft rejection and the graft that cause by unsuitable immunity system activation to the host repel all observed superstition in the disease or over-drastic PTKs activity.In addition, therefore endothelial cell specific acceptor PTKs such as KDR and Tie-2 have mediated angiogenesis, and relate to the carrying out of supporting cancer and other and unsuitable vascularization diseases related (for example diabetic retinopathy, the choroidal neovascularization, psoriasis, sacroiliitis, retinopathy of prematurity, the infantile hemangioma that cause because of the spot shape degeneration of wearing out).
Tyrosylprotein kinase can be receptor type (have the extracellular, stride film and intracellular region) or non-receptor type (being intracellular fully).
Receptor tyrosine kinase (RTKs).RTKs comprises the transmembrane receptor of very big gang, and they have multiple biological activity.At present, 19 different RTK subtribes have been identified at least.Receptor tyrosine kinase (RTK) family comprises various cell type growths and breaks up acceptor (Yarden and Ullrich, Ann.Rev.Biochem.57:433-478,1988 with decisive role; Ullrich and Schlessinger, Cell 61:243-254,1990).In case combine with part, RTKs inherent function promptly is activated, and causes acceptor and many cells substrate phosphorylation, causes various kinds of cell to reply (Ullrich ﹠amp afterwards; Schlessinger, 1990, Cell 61:203-212).Therefore, the signal conduction of receptor tyrosine kinase mediation is interacted by the extracellular with the particular growth factor (part) and begins, and is the dimerisation of acceptor thereafter usually, stimulates the activity and the acceptor transphosphorylation of intrinsic protein tyrosine kinase.Produced the binding site of signal transduction molecule in the cell thus, and caused being beneficial to suitable cell response with a series of kytoplasm signal transduction molecules formation title complexs.(for example cell fission, differentiation, metabolism, the change in the subenvironment of extracellular), referring to Schlessinger and Ullrich, 1992, Neuron 9:1-20.
Have SH2 (src homology-2) or Tyrosine O-phosphate in conjunction with albumen and the activatory tyrosine kinase receptor in (PTB) district and have highly that the substrate of affinity combines, so that signal is transmitted to cell.Above-mentioned two districts all discern Tyrosine O-phosphate. (Fantl etc., 1992, Cell 69:413-423; Songyang etc., 1994, Mol.Cell.Biol.14:2777-2785; Songyang etc., 1993, Cell 72:767-778; With Koch etc., 1991, Science 252:668-678; Shoelson, Curr.Opin.Chem.Biol. (1997), 1 (2), 227-234; Cowburn, Curr.Opin.Struct.Biol. (1997), 7 (6), 835-838).Identified substrate protein in several cells relevant with receptor tyrosine kinase (RTKs).They can be divided into two main groups: (1) has the substrate of catalytic domain; (2) lack catalytic domain but as shifting coupling and the substrate (Songyang etc., 1993, Cell 72:767-778) relevant with the catalytic activity molecule.The interactional specificity of the acceptor of its substrate or albumen and SH2 or PTB district is to be determined by the amino-acid residue that directly centers on the phosphorylated tyrosine residue.For example, different relevant (Songyang etc., 1993, the Cell 72:767-778) in the SH2 district on the special receptor with the difference that centers on the binding affinity between the aminoacid sequence of Tyrosine O-phosphate residue and its substrate phosphorylation action characteristic.These functions of observing each receptor tyrosine kinase of hint are not only by its expression pattern and the decision of part validity, also by being determined by the timing of the arrangement of the downstream signal conducting path of specific receptor activation, those stimulations and time length.Therefore, phosphorylation provides important regulation and control step, and this has determined the selectivity of the signal conducting path that replenished by specific growth factor receptors and differentiation factor receptors.
Existing prompting, several receptor tyrosine kinases such as FGFR-1, PDGFR and c-Met, and in vasculogenesis, play effect with their bonded somatomedins, although some may be to promote vasculogenesis (Mustonen and Alitalo, J Cell Biol.129:895-898,1995) indirectly.A kind of being known as " fetal livers kinases 1 " receptor tyrosine kinase (FLK-1) is a member in the III type RTKs subclass.Perhaps " contain the acceptor that kinases inserts the district " (KDR) (Terman etc., Oncogene 6:1677-83,1991) for people FLK-1 called after.Another called after of FLK-1/KDR " vascular endothelial growth factor receptor 2 " (VEGFR-2) because it with combining of VEGF have the height affinity.The FLK-1/VEGFR-2 of mouse is known as NYK (Oelrichs etc., Oncogene 8 (1): 11-15,1993) again.Isolate mouse, rat and the people FLK-1 of dna encoding, and reported Nucleotide and encoding amino acid sequence (Matthews etc., Proc.Natl.Acad.Sci.USA, 88:9026-30,1991; Terman etc., 1991, above; Terman etc., Biochem.Biophys.Res.Comm.187:1579-86,1992; Sarzani etc., supra; With Millauer etc., Cell 72:835-846,1993).Many researchs are that ligand-receptor is right as pointed out VEGF and FLK-1/KDR/VEGFR-2 in the report of Millauer etc. above, they play an important role in the propagation and the vascularization of vascular endothelial cell and in sprouting, vascular endothelial cell proliferation and vascularization and sprout and be known as blood vessel respectively and take place and vasculogenesis.
Another kind be named as " fin sample Tyrosylprotein kinase-1 " III type RTK (Flt1) relevant with FLK-1/KDR (DeVries etc., Science 255; 989-991,1992; Shibuya etc., Oncogene 5:519-524,1990).The another kind of appellation of Flt-1 is " vascular endothelial growth factor receptor 1 ＂ (VEGFR-1).Up to now, many FLK-1/KDR/VEGFR-2 and Flt-1/VEGFR-1 subtribes of mainly on endotheliocyte, expressing have been had been found that.These subtribes member specifically is subjected to stimulation (Klagsburn and D ' Amore, the Cytokine ﹠amp of many vascular endothelial growth factors (VEGF) part; Growth Factor Reviews 7:259-270,1996).Compare with FLK-1/KDR, vascular endothelial growth factor (VEGF) and combining of Flt-1 have the height affinity, and make vascular endothelial cell mitotic division (Terman etc., 1992, above; Mustonen etc. above; DeVries etc., above).It is believed that Flt-1 is essential to endothelial tissue in vascular development.It is relevant with early stage blood vessel development in the mice embryonic that Flt-1 expresses, and relevant with the neovascularity generation in the wound healing process (Mustonen and Alitalo, above).The expression of Flt-1 in ripe organ such as renal glomerulus hinted the function that this receptor is other, the growth of these functions and cell irrelevant (Mustonen and Alitalo, above).
As mentioned above, up-to-date evidence show VEGF stimulate normal and the pathological angiogenesis generation in play an important role (Jakeman etc., Endocrinology 133:848-859,1993; Kolch etc., Breast Cancer Research and Treatment 36:139-155,1995; Ferrara etc., Endocrine Reviews 18 (1); 4-25,1997; Ferrara etc., Regulation ofAngiogenesis (ed.L.D.Goldberg and E.M.Rosen), 209-232,1997).In addition, VEGF and control and strengthen the perviousness of blood vessel relevant (Connolly, etc., J.Biol.Chem.264:20017-20024,1989; Brown etc., Regulation of Angiogenesis (ed.L.D.Goldberg and E.M.Rosen), 233-269,1997).
Report the multi-form VEGF that produces by another kind of mRNA montage, comprised described four kinds such as Ferrara (J.Cell.Biochem.47:211-218,1991).Ferrara etc. (above) have discerned and secretion property and the main relevant VEGF of cell, and known this albumen exists with the dipolymer form that disulphide connects.
Several relevant VEGF homologues have recently been discerned.But its effect in normal physiological and lysis is still undeclared.In addition, the many members among the VEGF together express with VEGF in many tissues of being everlasting, and can form heterodimer with VEGF usually.This character has perhaps changed the specificity of acceptor and the biological action of heterodimer, and further make and illustrate its specific function as described below complicated (Korpelainen and Alitalo, Curr.Opin.Cell Biol., 159-164,1998, this reference is incorporated herein by reference).
The aminoacid sequence that placenta growth factor (P1GF) is had demonstrates the homology important with the VEGF sequence (Park etc., J.Biol.Chem.269:25646-54,1994; Oncogene 8:925-31 such as Maglione, 1993).The same with VEGF, different types of P1GF is produced by the montage of another kind of mRNA, and this protein with the form of dipolymer exist (Park etc., above).P1GF-1 and P1GF-2 and Flt-1 height affinity ground combines, and P1GF-2 also combine with neuropilin-1 solicitously (Migdal etc., J.Biol.Chem.273 (35): 22272-22278), still do not combine with FLK-1/KDR (Park etc., above).Existing report, when having lower concentration VEGF, P1GF to the mitogenetic effect of VEGF on the perviousness of blood vessel and the endotheliocyte have booster action (it is said it is) because due to the formation of heterodimer (Park etc., above).
The generation of VEGF-B has two kinds of isotypes (167 and 185 residue), and they also combine with Flt-1/VEGFR-1.Their (Pepper etc. that can in the degraded of regulating cell epimatrix, cell adhesion and expression by regulating urokinase type plasminogen activator and Type 1 plasminogen activator inhibitor 1 and active dividing a word with a hyphen at the end of a line, work, Proc.Natl.Acad.Sci.U.S.A. (1998), 95 (20): 11709-11714).
VEGF-C clones as the part of VEGFR-3/Flt-4, and they are mainly expressed by the lymph endotheliocyte.In its complete action mode, VEGF-C can also combine with KDR/VEGFR-2, and in the propagation that stimulates external endotheliocyte with divide a word with a hyphen at the end of a line and vasculogenesis (Lymboussaki etc., Am.J.Pathol. (1998), 153 (2): 395-403 in the model in vivo; Witzenbichler etc., Am.J.Pathol. (1998), 153 (2), 381-394).The undue expression of the transgenosis of TheVEGF-C only causes vasculolymphatic propagation and increase, and to not influence of blood vessel.Different with VEGF, the expression of VEGF-C not by hypoxgia cause (Ristimaki etc., J.Biol.Chem. (1998), 273 (14), 8413-8418).
The VEGF-D of recent findings is structurally very similar with VEGF-C.It is reported that VEGF-D combines and make its activation with at least two kinds of VEGFRs, VEGFR-3/Flt-4 and KDR/VEGFR-2.It induces the mitogen clone as fibroblastic c-fos at first, and the most outstanding is to express (Achen etc., Proc.Natl.Acad.Sci.U.S.A. (1998), 95 (2) in the mesenchymal cell of lung and skin, 548-553, the document is incorporated herein by reference).
As VEGF, claim that when skin histology was injected, VEGF-C and VEGF-D caused that in Miles analyzes the blood vessel perviousness increases (PCT/US97/14696; W098/07832, Witzenbichler etc., above).These parts are uncertain regulating the physiological role and the importance of the too high and endothelium of vascular permeability aspect replying in its tissue of being expressed.
Recently reported vascular endothelial growth factor VEGF-E encoding viral, new (NZ-7VEGF), it preferentially utilizes the KDR/Flk-1 acceptor and has effective mitogen activation and non-heparin land (Meyer etc., EMBO J. (1999), 18 (2), 363-374; Ogawa etc., J.Biol.Chem. (1998), 273 (47), 31273-31282.).The VEGF-E sequence has the homology with Mammals VEGF about 25%, and is encoded by parapoxvirus Orf virus (OV).This parapoxvirus influences sheep and goat, and influences the people occasionally, thereby causes the infringement with vasculogenesis.VEGF-E had not only had basic region, but also heparin had not been had the dipolymer of about 20kDa of affinity, but has the feature cystine knot primitive that is present among all Mammals VEGF, and finding unexpectedly that it has combines similar usefulness of VEGF165 isotype and biological activity with the VEGF-A heparin, i.e. two kinds of releases that the factor all stimulates tissue factor (TF), the propagation of cultured vascular endothelial cells, chemotaxis and sprout and body in vasculogenesis.The same with VEGF165, find that VEGF-E highly combines with vegf receptor-2 (KDR) affinity, cause Ca2+ concentration two phasic properties rising in acceptor autophosphorylation and the free cell, simultaneously opposite with VEGF165, VEGF-E does not combine with vegf receptor-1 (Flt-1).
According to the discovery of existing other VEGF and VEGFRs homologue and the precedent of part and the assorted dimerisation of acceptor, the effect of this VEGF homologue can comprise form VEGF part heterodimer, and/or the assorted dimerisation of acceptor or combine with undiscovered VEGFR still (Witzenbichler etc., above).Equally, and up-to-date report prompting neuropilin-1 (Migdal etc., above) or VEGFR-3/Flt-4 (Witzenbichler etc., above) or the acceptor except that KDR/VEGFR-2 may with cause blood vessel perviousness relevant (Stacker, S.A., Vitali, A., Domagala, T., Nice, E. and Wilks, A.F., " Angiogenesis andCancer " Conference, Amer.Assoc.Cancer Res., Jan.1998, Orlando, FL; Williams, Diabetelogia 40:S 118-120 (1997)).Up to now, still unexposed KDR has the direct evidence of vital role in the vascular permeability of VEGF mediation is too high.
Nonreceptor tyrosine kinase.The nonreceptor tyrosine kinase representative lacks the extracellular and strides the set of the cellular enzymes of film sequence.At present, identified, comprised 11 subtribes (Src, Frk, Btk, Csk, Abl, Zap70, Fes/Fps, Fak, Jak, Ack and LIMK) above 24 kinds of one nonreceptor tyrosine kinases.Src subtribe nonreceptor tyrosine kinase is made up of the PTK of maximum at present, and comprises Src, Yes, Fyn, Lyn, Lck, Blk, Hck, Fgr and Yrk.The enzyme of Src subtribe links together with tumorigenesis and immunne response.At Bolen, 1993, more going through of relevant nonreceptor tyrosine kinase is provided among the Oncogene 8:2025-2031, the document is incorporated herein by reference.
Having been found that many Tyrosylprotein kinases, is that RTK or nonreceptor tyrosine kinase all comprise that with a lot of situations of causing a disease the cell signaling path that cancer, psoriasis and other hyperproliferation diseases or hyperimmunization relate in replying is relevant.
Regulate the exploitation of PTKs compound.Consider supposition the PTKs on cell proliferation, with the importance of control, adjusting and the adjustment of abnormal cell proliferation diseases related and imbalance, adopted various approach successfully to discern acceptor and nonreceptor tyrosine kinase " inhibitor ", described approach comprises use mutant part (U.S.A.4,966,849), soluble receptors and antibody (WO94/10202; Kendall ﹠amp; Thomas, 1994, Proc.Natl.Acad.Sci 90:10705-09; Kim etc., 1993, Nature 362:841-844), (Jellinek is etc., Biochemistry 33:10450-56 for the RNA part; Takano, etc., 1993, Mol.Bio.Cell 4:358A; Kinsella waits 1992, Exp.Cell Res.199:56-62; Wright is etc., 1992, J.Cellular Phys.152:448-57) and tyrosine kinase inhibitor (WO 94/03427; WO92/21660; WO 91/15495; WO 94/14808; U.S.P.5,330,992; Mariani, etc., 1994, Proc.Am.Assoc.Cancer Res.35:2268).
Recently, successfully discerned the small molecules that is used as tyrosine kinase inhibitor.For example, usually two monocycles, dicyclo or heterocyclic aryl compound (PCT WO 92/20642) and vinylidene 7-azaindole derivatives (PCT WO 94/14808) are described as tyrosine kinase inhibitor.Also described compound of styryl (U.S.P.5,217,999), styryl-replacement pyridinyl compounds (U.S.P.5,302,606), (EP applies for 0 566 266 A1 to some quinazoline derivant; ExpertOpin.Ther.Pat. (1998), 8 (4): 475-478), seleno indoles and selenide (PCT WO94/03427), three ring polyols (PCT WO 92/21660) and benzylphosphonic acid compound (PCT WO 91/15495) be used as tyrosine kinase inhibitor compound, is used for the treatment of cancer.Existing description, phenylamino cinnolines (PCT WO97/34876) and quinazoline derivant compound (PCTWO97/22596; PCT WO97/42187) as vasculogenesis and blood vessel perviousness inhibitor.
In addition, successfully discerned the small molecules that is used as the serine/threonine kinase inhibitor.For example, described two (Indolylmaleimide) compound and suppressed specific PKC serine/threonine kinase isotype, the signal conduction function of this isotype in the VEGF-diseases associated with relevant (the PCT WO97/40830 of blood vessel perviousness that changes; PCTWO97/40831).The Plk-1 kinase inhibitor
Plk-1 is a serine/threonine kinase, and it is the conditioning agent that carries out the important cell cycle.It is decisive role in the assembling of mitotic spindle device and power function.Plk-1 also demonstrates with the activation and the deactivation of other Cycle Regulation agent such as cell cycle protein dependent kinase closely related with relevant kinases.High level Plk-1 expresses relevant with cell-proliferation activity.It often is found in the malignant tumour of various origins.
Expection Plk-1 inhibitor is blocked cancer cell multiplication by the process of interruption and mitotic spindle and inappropriate activatory cell cycle protein dependent kinase.Cdc2/ cell periodic protein B kinase inhibitor (Cdc2 is also referred to as cdkl)
The Cdc2/ cell periodic protein B is another kind of serine/threonine kinase, and it belongs to cell cycle protein dependent kinase (cdks).These enzymes relate to the cell cycle and carry out conclusive transformation between each phase.It is believed that uncontrolled cell proliferation is the sign of cancer, it depends on the cdk activity that raises in these cells.By the cdk activity that raises in the cdc2/ cell periodic protein B kinase inhibitor anticancer, can suppress propagation, and can recover the normal control that the cell cycle carries out.
So needing the effective little compound of identification, these compounds conduct and cell proliferation and suppress signal specially by regulating and control acceptor and non-receptor tyrosine and serine/threonine kinase to regulate and to adjust unusual or unsuitable cell proliferation, differentiation or metabolism.Especially, recognition methods and the special compound that suppresses the Tyrosylprotein kinase function are useful, thereby described Tyrosylprotein kinase is for angiogenesis or the too high formation of vascular permeability causes oedema, ascites, seepage, exudate and macromole to blend apposition outward and relative disease is essential.
Summary of the invention
The present invention relates to following formula: compound and physiologically acceptable salt thereof
Figure A0081368200971
Wherein R replaces or unsubstituted aliphatic series, aromatics, heterocycle or aralkyl, and R 2Be hydrogen, low alkyl group or aryl.R 1Be hydrogen or-A-Z, wherein A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-; And Z is H, low alkyl group, aralkyl, trihalomethyl group, R 3CO-, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, thiophene, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole, benzothiazole, tetrahydrofuran (THF), triazine and applicable N-oxide compound thereof, these ring systems can be randomly by one or more halogens, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5Replace.The R that every place occurs 3Be independently selected from replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl.The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; R 4And R 5Can be randomly and the nitrogen that links to each other with it combine expression morpholino, pyrrolidino (pyrrolidino), piperidino-(1-position only), imidazoles-1-base, Piperazino (piperazino), parathiazan generation, azepines subbase (azepino) or perhydro--carotene 1,4-diazacyclo heptantriene (diazepin)-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Numeric suffix n is the integer of 0-3.
For R, suitable substituents comprises halogen, low alkyl group, R 3O-, hydroxyl, HOC (O)-, R 3OC (O)-, R 3OC (O) R 6-, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl, nitro ,-C (O) NR 4R 5,-NR 4R 5, R 3CO-,-(CH 2) n-R 7,-C (O) (CH 2) n-R 7,-C (O)-(CH 2) n-C (O)-R 7,-O (CH 2) nR 7,-C (O) NR 4(CH 2) nR 7, C (O) O (CH 2) nR 7,-OC (O) (CH 2) nR 7,-NR 4C (O) (CH 2) nR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N[R 6-R 7] 2,-R 6C (O) NR 4(CH 2) nR 7,-R 6C (O) O (CH 2) nR 7,-R 6OC (O) (CH 2) nR 7, R 6NR 4C (O) (CH 2) nR 7,-R 6CH[C (O) OR 4] [NR 5C (O) R 4] or the aryl or aralkyl that replaces, wherein substituting group be selected from halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-CONR 4R 5, low alkyl group, R 3O-, C (O) OR 4Or-OC (O) R 3R 6Be low alkyl group or aryl.R 7Be alkoxyl group, haloalkyl, low alkyl group piperazine, hydroxyl, R 3O-, R 3C (O)-or-NR 4R 5
For R 3, R 4And R 5, suitable substituents comprises one or more following groups that are selected from: halogen, low alkyl group, hydroxyl, lower alkoxy, carboxyl, lower alkyl esters, the preferred trifluoromethyl of trihalomethyl group, 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) NH (alkyl) and-C (O) N (alkyl) 2
Aliphatic group comprises straight or branched C 1-C 18Hydrocarbon or ring C 3-C 18Hydrocarbon, they are fully saturated, perhaps contain one or more unsaturated units.Low alkyl group is complete saturated straight or branched C 1-C 6Hydrocarbon or C 3-C 6Cyclic hydrocarbon.
Aromatic group one speech used herein comprises carbocyclic ring system (for example benzyl and cinnamylidene) and fused polycycle aromatic ring system (for example naphthyl).In addition, aromatic group comprises hetero-aromatic ring system (for example pyridine, thiophene, furans, pyrroles, imidazoles, oxazole, thiazole, pyrazoles, triazole, pyrimidine and pyrazine) and heteroaryl ring system, and wherein carbocyclic ring aromatic ring, carbocyclic ring non-aromatic ring or hetero-aromatic ring and one or more other hetero-aromatic ring (for example benzoglyoxaline, benzothiazole, indoles, tetrahydro indole, azaindole, indazole, isoxazole, isothiazole, imidazoles and quinoline) condense.Aryl one speech used herein is meant the aromatic group with 5 or 6 atoms.Aralkyl is the aromatic substituent that links to each other with compound by the aliphatic group with 1-6 carbon atom.That heterocyclic radical one speech used herein is meant is single-, two-or three-ring heterocyclic radical, they be not aromatics or have certain degree of unsaturation, this is unsaturated not to constitute aromatic group.
The mixture of tautomer, steric isomer, enantiomorph and these compounds comprises in the present invention.The pharmaceutically acceptable additive salt of these compounds is also included among the present invention.
In one embodiment, R 2Be hydrogen, and R is preferably indoles or the replacement or the unsubstituted imidazoles, 1,2 of replacement, 3-triazole, 1,2,4-triazole, benzoglyoxaline, pyrroles, pyrazoles, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene or piperazine.
In a preferred embodiment, R 2Be hydrogen, n is 0, and Z is cyclopropyl, 3-pyridyl or pyrazinyl.In another preferred embodiment, R 2Be hydrogen, A is-O-that n is 0, and Z is ethyl, propyl group or sec.-propyl.In still another preferred embodiment, R 2Be hydrogen, A is CH 2, n is 2, and Z be randomly by halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-C (O) NR 4R 5, low alkyl group, R 3O-,-C (O) OR 4Or-OC (O) R 3The benzene that replaces.
In a preferred embodiment, the present invention relates to compound and the physiologically acceptable salt that following formula is represented:
Figure A0081368200991
Wherein:
R is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrroles, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is when R is unsubstituted indol-3-yl, R 1Be not-NH 2In another preferred embodiment, the present invention relates to compound and the physiologically acceptable salt thereof that following structural is represented:
Figure A0081368201001
Wherein:
R is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrroles, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-, (CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is:
When R is unsubstituted indol-3-yl, R 1Be not-NH 2With
When R replaces or unsubstituted benzene or unsubstituted imidazoles, 1,2,3-triazoles, 1,2, when 4-triazole, pyridine, pyrimidine, pyrazine, pyrroles, pyrazoles, oxazole or thiazole, R 1Not low alkyl group, (C 3-C 6) cycloalkyl, benzene or-C (O) NR 4R 5, R wherein 4And R 5Be H, low alkyl group or isocyclic aryl independently of one another.
In another preferred embodiment, the present invention relates to compound and the physiologically acceptable salt thereof that following structural is represented:
Figure A0081368201021
Wherein:
R is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrroles, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-, (CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is: a) R is not pyrroles-3-base or pyrroles-3-base of being replaced by alkyl or isocyclic aryl; B) R is not indol-3-yl or the indol-3-yl that replaced by alkyl or isocyclic aryl; And c) R is not azaindole or the azaindole that replaced by alkyl or isocyclic aryl in the 2-position.
In another preferred embodiment, the present invention relates to compound and the physiologically acceptable salt thereof that following structural is represented:
Figure A0081368201031
Wherein:
R is the pyrroles who replaces or is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-, (CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is: a) when R was the pyrroles who replaces, this pyrroles was by R 3OC (O) R 6, R 3OR 6-, trihalomethyl group,
The trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,-C (O) N (R 4) (CH 2) pR 7,
-C(O)O(CH 2) pR 7、-OC(O)(CH 2) pR 7、-N(R 4)C(O)(CH 2) pR 7、
-R 6NR 4R 5、-R 6N(R 4)-R 6-R 7、-R 6N(R 6-R 7) 2、R 6C(O)N(R 4)(CH 2) pR 7、
-R 6C(O)O(CH 2) pR 7、-R 6OC(O)(CH 2) pR 7、-R 6N(R 4)C(O)(CH 2) pR 7、
-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), the aryl or aralkyl that replaces replaces, wherein
The R that every place occurs 6Be low alkyl group or aryl independently;
The R that every place occurs 7Be independently alkoxyl group, haloalkyl, low alkyl group piperazine, hydroxyl,
R 3O-, R 3C (O)-or NR 4R 5With
P is the integer of 1-3; B) when R is indol-3-yl, this indol-3-yl is replaced by following groups: R 3OC (O) R 6, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,-C (O) N (R 4) (CH 2) pR 7,-C (O) O (CH 2) pR 7,-OC (O) (CH 2) pR 7,-N (R 4) C (O) (CH 2) pR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2, R 6C (O) N (R 4) (CH 2) pR 7,-R 6C (O) O (CH 2) pR 7,-R 6OC (O) (CH 2) pR 7,-R 6N (R 4) C (O) (CH 2) pR 7,-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), the aryl or aralkyl that replaces, and c) when R was pyrazole-3-yl, this pyrazole-3-yl was replaced by following groups: R 3OC (O) R 6,
R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,
-C(O)N(R 4)(CH 2) pR 7、-C(O)O(CH 2) pR 7、-OC(O)(CH 2) pR 7、
-N(R 4)C(O)(CH 2) pR 7、-R 6NR 4R 5、-R 6N(R 4)-R 6-R 7、-R 6N(R 6-R 7) 2、
R 6C(O)N(R 4)(CH 2) pR 7、-R 6C(O)O(CH 2) pR 7、-R 6OC(O)(CH 2) pR 7、
-R 6N (R 4) C (O) (CH 2) pR 7,-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), replace
Aryl or aralkyl.
In another preferred embodiment, the present invention relates to compound and the physiologically acceptable salt thereof that following structural is represented:
Figure A0081368201051
Wherein:
R is the pyrroles who replaces or is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is: a) when R is unsubstituted indol-3-yl, and R 1Be not-NH 2B) replace or unsubstituted benzene or unsubstituted imidazoles, 1,2,3-triazoles, 1,2 as R, when 4-triazole, pyridine, pyrimidine, pyrazine, pyrroles, pyrazoles, oxazole or thiazole; R 1Not low alkyl group, (C 3-C 6) cycloalkyl, benzene or-C (O) NR 4R 5, R wherein 4And R 5Be H, low alkyl group or isocyclic aryl independently of one another; C) R is not pyrroles-3-base or pyrroles-3-base of being replaced by alkyl or isocyclic aryl; D) R is not indol-3-yl or the indol-3-yl that replaced by alkyl or isocyclic aryl; E) R is not azaindole or the azaindole that replaced by alkyl or isocyclic aryl in the 2-position; F) when R was the pyrroles who replaces, this pyrroles was replaced by following groups: R 3OC (O) R 6, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,-C (O) N (R 4) (CH 2) pR 7,-C (O) O (CH 2) pR 7,-OC (O) (CH 2) pR 7,-N (R 4) C (O) (CH 2) pR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2, R 6C (O) N (R 4) (CH 2) pR 7,-R 6C (O) O (CH 2) pR 7,-R 6OC (O) (CH 2) pR 7,-R 6N (R 4) C (O) (CH 2) pR 7,-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), the aryl or aralkyl that replaces, the R that wherein every place occurs 6Be low alkyl group or aryl independently; The R that every place occurs 7Be alkoxyl group, haloalkyl, low alkyl group piperazine, hydroxyl, R independently 3O-, R 3C (O)-or NR 4R 5With
P is the integer of 1-3; G) when R is indol-3-yl, this indol-3-yl is replaced by following groups: R 3OC (O) R 6, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,-C (O) N (R 4) (CH 2) pR 7,-C (O) O (CH 2) pR 7,-OC (O) (CH 2) pR 7,-N (R 4) C (O) (CH 2) pR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2, R 6C (O) N (R 4) (CH 2) pR 7,-R 6C (O) O (CH 2) pR 7,-R 6OC (O) (CH 2) pR 7,-R 6N (R 4) C (O) (CH 2) pR 7,-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), the aryl or aralkyl that replaces, and h) when R was pyrazole-3-yl, this pyrazole-3-yl was replaced by following groups: R 3OC (O) R 6, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl ,-(CH 2) p-R 7,-O (CH 2) pR 7,-C (O) N (R 4) (CH 2) pR 7,-C (O) O (CH 2) pR 7,-OC (O) (CH 2) pR 7,-N (R 4) C (O) (CH 2) pR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2, R 6C (O) N (R 4) (CH 2) pR 7,-R 6C (O) O (CH 2) pR 7,-R 6OC (O) (CH 2) pR 7,-R 6N (R 4) C (O) (CH 2) pR 7,-R 6CH (C (O) OR 4) (N (R 4) C (O) R 4), the aryl or aralkyl that replaces.In a more preferred embodiment, the present invention relates to any above-claimed cpd, wherein A be-NH-,-O-,-S-,-S (O)-or-S (O) 2-; And Z is cyclopropyl, 3-pyridyl or pyrazinyl.
In another preferred embodiment, the present invention relates to any above-claimed cpd, wherein A is-O-; And Z is ethyl, n-propyl or sec.-propyl.
In another preferred embodiment, the present invention relates to any above-claimed cpd, wherein A is-CH 2-; And Z is a phenyl, and wherein said phenyl randomly is selected from following group and replaces by one or more: halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-CONR 4R 5, low alkyl group, R 3O-,-C (O) OR 4With-OC (O) R 4
In another preferred embodiment, the present invention relates to any above-claimed cpd, wherein R is selected from following group and replaces by one or more independently of one another: halogen, low alkyl group, R 3O-, hydroxyl, HOC (O)-, R 3OC (O)-, R 3OC (O) R 6-, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl, nitro ,-C (O) NR 4R 5,-NR 4R 5, R 3CO-,-(CH 2) n-R 7,-C (O) (CH 2) n-R 7,-C (O)-(CH 2) n-C (O)-R 7,-O (CH 2) nR 7,-C (O) NR 4(CH 2) nR 7, C (O) O (CH 2) nR 7,-OC (O) (CH 2) nR 7,-NR 4C (O) (CH 2) nR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2,-R 6C (O) NR 4(CH 2) nR 7,-R 6C (O) O (CH 2) nR 7,-R 6OC (O) (CH 2) nR 7, R 6NR 4C (O) (CH 2) nR 7,-R 6CH (C (O) OR 4) (NR 5C (O) R 4) and optional aryl that replaces and the optional aralkyl that replaces.Optional aryl that replaces and the optional aralkyl that replaces randomly are selected from following substituting group and replace by one or more: halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-CONR 4R 5, low alkyl group, R 3O-, C (O) OR 4Or-OC (O) R 3R 6Be low alkyl group or aryl.R 7Be alkoxyl group, haloalkyl, low alkyl group piperazine, hydroxyl, R 3O-, R 3C (O)-or-NR 4R 5In aspect of this embodiment, R is pyrryl, indyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydro indole base or quinolyl.This embodiment on the other hand in, R is pyrroles-2-base, pyrroles-3-base, indoles-2-base, indol-3-yl, azaindole-3-base, pyrazoles-4-base, imidazoles-2-base, imidazol-4 yl, thiophene-2-base or quinoline-5-base.
In another embodiment preferred, the present invention relates to any above-claimed cpd, wherein R 1Be trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl group, sec.-propyl, cyclopropyl, 2-methyl cyclopropyl, 2,2,3,3-tetramethyl-ring propyl group, 2-phenycyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl ,-(CH 2) p-O-phenyl ,-(CH 2) p-O-(4-methoxyphenyl) ,-(CH 2) p-O-(4-chloro-phenyl-) ,-(CH 2) p-O-(4-aminomethyl phenyl) ,-(CH 2) p-O-(3-aminomethyl phenyl) ,-(CH 2) p-O-(4-phenyl) ,-(CH 2) p-O-(4-hydroxyphenyl) ,-(CH 2) p-O-(4-nitrophenyl) ,-(CH 2) p-O-(4-aminophenyl) ,-(CH 2) p-O-(4-formamyl phenyl) ,-(CH 2) p-O-(4-methoxycarbonyl phenyl) ,-the NH-phenyl ,-NH-(4-methoxyphenyl) ,-NH-(4-chloro-phenyl-) ,-NH-(4-fluorophenyl) ,-NH-(4-isopropyl phenyl), isopropoxy, oxyethyl group, cyclopentyloxy ,-(CH 2) p-indyl ,-(CH 2) p-pyridyl ,-(CH 2) p-benzothiazolyl ,-(CH 2) p-pyrryl ,-(CH 2) p-tetrahydrofuran base ,-(CH 2) p-pyrazinyl ,-(CH 2) p-furyl ,-(CH 2) p-thienyl ,-(CH 2) p-phenyl ,-(CH 2) p-isoxazolyls ,-(CH 2) p-(5-methyl-isoxazole base) ,-(CH 2) p-pyrimidyl ,-(CH 2) p-pyridazinyl ,-(CH 2) n-C (O)-OMe ,-(CH 2) n-C (O)-OEt or the benzyl that is randomly replaced by one or more Cl, F, OMe, methyl or amino.P is the integer of 1-3.In aspect of this embodiment, R randomly is selected from following group and replaces by one or more: Br, Cl, F, amino methyl, N, N-dimethylamino methyl, carboxyl, carboxymethyl, propyloic, carbonyl methyl, carbonyl ethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4-morpholino methyl ,-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 3And be selected from following optional substituted part: methyl, ethyl, propyl group, sec.-propyl, butyl and phenyl, wherein said optional substituted part is randomly replaced by one or more Br, Cl, F, hydroxyl, nitro, amino or low alkyl group.
On the other hand, the invention provides pharmaceutical composition, wherein contain one or more The compounds of this invention and pharmaceutically acceptable carrier or thinners as herein defined.
On the other hand, the invention provides the method that suppresses one or more protein kinase activities, this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites:
Figure A0081368201091
Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
Preferable methods is an arrestin kinases in the curer of needs wherein in the aforesaid method.
Preferable methods is that compound wherein is the mixture of steric isomer in any aforesaid method.
Preferable methods is that steric isomer wherein is an enantiomorph in any aforesaid method.
Preferable methods is that steric isomer wherein is E and Z isomer in any aforesaid method.
Preferable methods is that compound wherein is the mixture of constitutional isomer in any aforesaid method.
Preferable methods is that constitutional isomer wherein is a tautomer in any aforesaid method.
Preferable methods is that wherein said protein kinase is receptor tyrosine kinase or nonreceptor tyrosine kinase in any aforesaid method.
Preferable methods is that wherein said Tyrosylprotein kinase is selected from KDR, Flt-1, TIE-2, FGFR, PDGFR, IGF-1-R, c-Met, Lck, Src, fyn, Lyn, Blk and yes in any aforesaid method.
On the other hand, the present invention relates to treat or fundamentally suppressing needs curer's the hyperproliferation disease or the method for inflammatory diseases, and this method comprises uses any The compounds of this invention as defined herein to described curer.
On the other hand, the present invention relates to treat or need to suppress the method for curer's vasculogenesis, this method comprises uses any The compounds of this invention as defined herein to described curer.
On the other hand, the present invention relates to induce the method that needs curer's blood vessel formation against function, this method comprises uses any The compounds of this invention as defined herein to described curer.
On the other hand, the present invention relates to treat or suppress the method that needs curer's disease or illness to carry out, this method comprises uses any The compounds of this invention as defined herein to described curer, and wherein said disease or illness are selected from cancer, sacroiliitis, atherosclerosis, restenosis, psoriasis, vascular tumor, angiogenesis of cardiac muscle, crown and brain pleurapophysis, the ischemic limb vessel generates, keratopathy, flush, neovascular glaucoma, macular degeneration, wound healing, peptide ulceration, with the helicobacter diseases associated, the vasculogenesis disease that virus causes, fracture, diabetic retinopathy, Crohn disease, inflammatory bowel disease, the fever that cat scratcs causes, retinopathy or precocity, ulcer, the Tiroidina hyperplasia, burn, wound, acute lung injury, chronic lung disease, apoplexy, polyp, tumour, synovitis, chronic and alterative inflammation, ovarian hyperstimulation syndrome, lung and cerebral edema, keloid, fibrosis, liver cirrhosis, carpal tunnel syndrome, Sepsis, adult respiratory distress syndrome, many organ dysfunction syndrome, ascites and seepage hydrops and the oedema relevant with tumour.
On the other hand, the present invention relates to influence needs the method that curer's vascular permeability is too high or oedema produces, and this method comprises uses any The compounds of this invention as defined herein to described curer.Preferable methods is in this method, wherein act as Ivy extract to what oedema produced.
Preferred method in above-mentioned any method is that wherein protein kinase is a serine kinase.
Preferred method in above-mentioned any method is that wherein protein kinase is a threonine kinase.
The particularly preferred compound of the present invention is:
3-cyclopropyl-4-{[(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-(3,5-two bromo-4-hydroxyl benzylidenes)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[(3,5-dimethyl-4-[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
3-(3-pyridyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl-2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(imidazoles-2-yl))-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(1-methyl cyclopropyl))-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethyllaminoethyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-(2-furyl))-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(morpholino methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl) methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(1-pyrrolidyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-oxo-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
3-(2-thienyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-encircles propoxy--4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(the 5-pyrimidinylethyl]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
3-(2-styroyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
3-(2-styroyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl v2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-bromine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
3-(4-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl) pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-diethylin methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
3-(5-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
3-(2-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
3-(3-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole--2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles 2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-(4-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-4,5-hydrogen-1H-5-pyrazolone,
3-cyclopropyl-4-(1-4-[(1,1-Dimethyl Ammonium) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-4,5-dihydro-1H-5-pyrazolone maleate,
4-[1-(4-[[2-(dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1H-2-pyrryl) methylene radical]-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-4-[2-(diethylin) ethyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-1-[4-(3-chlorine propionyl)-3,5-dimethyl-1H-2-pyrryl] methylene radical-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-4-[(dimethylamino) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(5-methyl-3-isoxazolyl)-4,5-dihydro-1H-5-pyrazolone,
3-cyclopropyl-4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxyl group phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-phenoxymethyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-benzyl-4-{[3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(4-methylenedioxy phenoxy ylmethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
2-amino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-styroyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-phenylamino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-xylyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methylbenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-anisole amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-benzyl chloride base)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(indol-3-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3, the 4-dimethoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-anisole ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-phenyl phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-(4-methylbenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-oxyethyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-oil of mirbane ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopentyloxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-tertiary butyl urea groups-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-methylpyrrole-2-yl) methylene radical] the 2-pyrazolin-5-one,
3-(4-formamyl styroyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-methoxycarbonyl styroyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,
3-(ethoxycarbonylmethyl group)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(the amino carbonyl methyl of 4-anisole)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{ (3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-3-sec.-propyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclobutyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[[1-(3, the 5-dichlorophenyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopentyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-methyl cyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-(benzothiazole-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-4-(3-pyridyl)]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(pyrroles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-propyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-methyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-isopropyl benzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-phenylamino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical]-the 2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-chlorobenzene amino carbonyl methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-methoxycarbonyl ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ethoxycarbonyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-sec.-propyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(anti--the 2-phenycyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclohexyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropylamino-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4[(4-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,
4-{[3,5-dimethyl-4-(2-morpholino B aminocarbonyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-diethanolamino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(3,4-two (ethoxycarbonyl) pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-pyridyl ethyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl-2-styroyl)-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-chloro-3-methoxycarbonyl-4-methoxycarbonyl methylpyrrole-2-yl) methylene radical-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3-(2-carboxy ethyl)-4-methylpyrrole-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(3-aminophenyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[2-(4-morpholino ethyl) aminocarboxyl pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(4-methyl isophthalic acid-piperazinyl methyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(5-methyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylamino-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-2-pyrazolin-5-one maleate,
4-{[4-(3-chlorine propionyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-hydroxy piperidine subbase methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,
4-{[4-(4-benzyl piepridine subbase) methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(3-diethylin propyl group)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(3-hydroxypropyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one hydrochloride,
4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-cyclopropyl-4-{[(2-diethyllaminoethyl)-3,5-dimethyl-4-pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(4-diethylin butyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl-N-oxide compound)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl ethanoyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[3-(1-pyrrolidyl propyl group)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-oxyethyl group oxalyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-benzyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-phenoxymethyl-2-pyrazolin-5-one,
3-(4-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylenedioxy phenoxy ylmethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene amino)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-anisole amino)-2-pyrazolin-5-one,
3-(4-benzyl chloride base)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
3-(4-chlorobenzene amino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-methoxy-benzyl)-2-pyrazolin-5-one,
3-(3, the 4-dimethoxy-benzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-hydroxybenzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(indol-3-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-anisole ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-phenyl phenoxymethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-phenyl propyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-phenyl propyl)-2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene ethyl)-2-pyrazolin-5-one,
3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-styroyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-oil of mirbane ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-propoxy--2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(2-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(7-skatole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxycarbonyl styroyl)-2-pyrazolin-5-one,
3-isopropoxy-4-[(1-isopropyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-sec.-propyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene amino carbonyl methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ethoxycarbonylmethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(the amino carbonyl methyl of 4-anisole)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-(2-aminocarboxyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclobutyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-dimethylamino carbonyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-pyridyl)-2-pyrazolin-5-one,
3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-methyl cyclopropyl)-2-pyrazolin-5-one,
3-cyclohexyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-pyridyl)-2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
3-dimethylamino-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(pyrroles-2-yl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(6-methoxyl group benzo thiazol-2-yl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-antazoline-5-ketone,
The 4-[(indol-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-antazoline-5-ketone,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(tertiary butyl)-2-pyrazolin-5-one,
3-ethoxycarbonyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-methoxycarbonyl ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(anti--2-phenyl-1-cyclopropyl)-2-pyrazolin-5-one,
3-cyclobutyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(1,7-dimethyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
3-cyclopropyl amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(1,7-dimethyl indole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-trifluoroacetamido-2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-the 3-tertiary butyl-2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{1-methyl-6-[2-(4-morpholino) ethyl] the aminocarboxyl indol-3-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxycarbonyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-formamyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-nitroindoline-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-sec.-propyl amino-2-pyrazolin-5-one,
3-(4-carboxyl styrene base)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
3-isopropoxy-4-[(3-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(2-methoxycarbonyl-2-kharophen ethyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-benzyl-2-pyrazolin-5-one,
3-benzyl-4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-amino-4-[(7-azaindole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(4-leptodactyline)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-sec.-propyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-cyclobutyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-fluoroanilino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-antazoline-5-ketone,
4-[(7-azaindole-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(tertiary butyl)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-isopropyl benzene amino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(3-methylbenzene amino)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(3-methylbenzene amino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-benzyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(4-dimethylamino phenyl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
The 4-[(4-dimethylamino phenyl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(imidazoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopropyl-4-[(imidazoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(imidazol-4 yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopropyl-4-[(thiophene-2-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-sec.-propyl-1-antazoline-5-ketone,
3-isopropoxy-4-[(pyrroles-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(8-hydroxyquinoline-5-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-4-(1-pyrrolidyl methyl)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-H3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-2-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
3-(4-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
3-(5-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
3-(2-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
3-(3-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-(4-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-methylene }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical)-3-pyrazinyl-2-pyrazolin-5-one,
4-{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-ethyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-diethyllaminoethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{4-[2-(1-imidazolyl) methyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-ethyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(the 1-imidazolyl } methyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-cyclopropyl amino methyl-3,5-two cyclopropyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-dimethylamino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one and
4-{[3-methylol-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one.
Formula I compound can exist with the salt form with pharmaceutically acceptable acid.The present invention includes this salt.The example of this salt comprise hydrochloride, hydrobromate, vitriol, mesylate, nitrate, maleate, acetate, Citrate trianion, fumarate, tartrate [for example (+)-tartrate, (-)-tartrate or its mixture comprise racemic mixture], succinate, benzoate and with the salt of amino acid such as L-glutamic acid.These salt can be according to the known method preparation of this area professional.
Some has acid substituent formula I compound and can exist with the salt form of itself and pharmaceutically acceptable alkali.The present invention includes these salt.The example of this salt comprises sodium salt, sylvite, lysine salt and arginic acid salt.These salt can be according to the known method preparation of this area professional.
Some formula I compound and salt thereof can be existing more than a kind of crystalline form, and the present invention includes every kind of crystalline form and composition thereof.
Some formula I compound and salt thereof can also exist with the form of solvate, for example hydrate, and the present invention includes every kind of solvate and composition thereof.
Some formula I compound can contain one or more chiral centres, and exists with different optically active forms.When formula I compound contained a chiral centre, this compound existed with the form of two kinds of enantiomorphs, and the present invention includes this two kinds of enantiomorphs and their mixture.These two kinds of enantiomorphs can split by the known method of this area professional, for example can isolating diastereoisomeric salt by formation, as pass through crystallization process; Formation can isolating diastereoisomeric derivative or title complex, for example by crystallization process, gas liquid chromatography or liquid chromatography; The single-minded reagent of a kind of enantiomorph and enantiomorph carries out selective reaction, for example enzymatic esterification; Or in chiral environment, carry out solution-air or liquid chromatography, for example on chiral support, as be combined with the silica gel of chiral ligand, perhaps in the presence of chiral solvent.Obviously, if required enantiomorph is converted into another kind of chemical entities by above-mentioned a kind of separation method, then following step must be to discharge required enantiomeric form.Perhaps, can carry out asymmetric synthesis, perhaps a kind of enantiomorph is converted into another kind of enantiomorph, synthetic specific enantiomorph by asymmetric conversion by using optically active reagent, substrate, catalyzer or solvent.
When formula I compound contained more than a chiral centre, it can exist with the diastereo-isomerism form.This diastereo-isomerism be to can separating according to the known method of this area professional, for example chromatogram or crystallization, and the single enantiomorph of each centering can separate as mentioned above.The present invention includes each diastereomer of formula I compound and composition thereof.
Some formula I compound can exist with different tautomeric forms or different rotamerism forms, and the present invention includes every kind of tautomer of formula I compound and/or geometrical isomer and composition thereof.
Some formula I compound can exist with different separable stable conformation forms.Reversing asymmetric is owing to restricted rotation around the asymmetric singly-bound, for example because due to steric hindrance or the ring strain, it makes can separate different conformers.The present invention includes every kind of conformer of formula I compound and composition thereof.
Some formula I compound can exist with zwitterionic form, and the present invention includes every kind of zwitterionic form of formula I compound and composition thereof.
The compounds of this invention is suitable for use as serine/threonine and tyrosine kinase inhibitor.Specifically, The compounds of this invention is suitable for use as tyrosine kinase inhibitor, and Tyrosylprotein kinase is important in hyperproliferation disease, the particularly process at vasculogenesis.For example, the some of them compound is the inhibitor of receptor kinase such as KDR, Flt-1, FGFR, PDGFR, c-Met or IGF-1-R.Because these compounds are anti--vasculogenesis medicines, they are that the PD of important composition is an important substance for suppressing vasculogenesis wherein.Some compound of the present invention is effective serine/threonine kinase such as erk, map kinase, cdks, Plk-1 or Raf-1 inhibitor.These compounds are applicable to treatment cancer and hyperproliferation disease.In addition, some compound is effective non-receptor kinase such as src, lyn, lck, fyn, blk, hck inhibitor.These compounds are applicable to treatment cancer, hyperproliferation disease and Immunological diseases.
The invention provides the method that suppresses Tyrosylprotein kinase and activity of serine/threonine kinases, this method comprises and suppresses the formula I compound administration of described kinase activity concentration to described kinases with being enough to.
The present invention also comprises the application of these compounds in the pharmaceutical composition of the above-claimed cpd that contains pharmacy effective dose and pharmaceutically acceptable carrier or vehicle.These pharmaceutical compositions can perhaps be treated the too high diseases associated of oedema, seepage, transudate or ascites and other and vascular permeability to individual administration with the angiogenesis in the disease of slowing down or stopping vasculogenesis and help.The some drugs composition can be to individual administration, to treat cancer and hyperproliferation diseases by suppressing serine/threonine kinase such as cdk, Plk-1, erk etc.Detailed Description Of The Invention
The compounds of this invention has angiogenesis inhibitor character.These angiogenesis inhibitor character are to produce owing to suppress the essential protein tyrosine kinase of angiogenesis to small part.Therefore, these compounds can be as the active medicine of these diseases of antagonism, and described disease is a sacroiliitis for example, atherosclerosis, psoriasis, vascular tumor, angiogenesis of cardiac muscle, crown and brain pleurapophysis, the ischemic limb vessel generates, wound healing, peptide ulceration, with the helicobacter diseases associated, the vasculogenesis disease that virus causes, fracture, Crow-Fukase syndrome (POEMS), preeclampsia, menorrhagia, the fever that cat scratcs causes, flush, neovascular glaucoma and retinopathy as with diabetic retinopathy, retinopathy of prematurity or the macula lutea degenerative change diseases associated relevant with the age.In addition, the some of them compound can be used as the active medicine of solid tumor resisting, malignant ascite, hematopoiesis cancer (hematopoietic cancers) and hyperproliferation disease such as Tiroidina hyperplasia (particularly Graves disease) and tumour (as the polycystic ovary syndrome (Si-Le syndrome) of stroma of ovary feature), because these diseases need the propagation of vascular cell for its growth and/or transfer.
Moreover some compound can be as the active medicine of the following disease of treatment: the brain that burn, chronic lung disease, apoplexy, polyp, allergy, chronic and alterative inflammation, delayed-type hypersensitivity, ovarian hyperstimulation syndrome, cerebral edema, high-altitude, wound or the hypoxgia relevant with cerebral tumor causes or pulmonary edema, eye and macular edema, ascites and other are wherein too high with vascular permeability, seepage, transudate, protein exosmoses or oedema is the disease that disease shows.These compounds also are applicable to treats the disease that causes scleroproein and extrtacellular matrix deposition, promotion matrix propagation (for example keloid, fibrosis, liver cirrhosis and gastral cavity pipe syndrome) of exosmosing of protein wherein.VEGF produces to increase and causes inflammatory process to strengthen for example monocyte recruitement and activation.The compounds of this invention also is applicable to treatment inflammatory diseases such as inflammatory bowel disease (IBD) and Crohn disease.
VEGF is unique, and they are the angiogenesis growth factors of only knowing at present that vascular permeability is too high and oedema forms that cause.In fact, the appearance of the too high and oedema of the vascular permeability relevant with administration with the expression of many other somatomedins produces mediation by VEGF.Inflammatory cytokine stimulates VEGF to produce.Hypoxgia causes the obvious rise of VEGF in multiple tissue, therefore reduces the reaction that relevant situation causes the VEGF/VPF mediation usually with infraction, obturation, local asphyxia, anaemia or circulation.Vascular permeability is too high, the associating oedema, the saturating endothelium exchange of change and macromole exosmose (wherein often being attended by hemocyte oozes out) can cause the matrix over-deposit, unusual between matter propagation, fibrosis etc.Therefore, the perviousness of VEGF mediation is too high has important contribution to the illness with these nosetiology features.
Should see that the disease of listing is above mediated to important degree by the protein hydroxyphenylaminopropionic acid kinase activity that relates to KDR/VEGFR-2 and/or Flt-1/VEGFR-1 Tyrosylprotein kinase.By suppressing the activity of these Tyrosylprotein kinases, being suppressed of above-mentioned disease is because the too high composition of the vasculogenesis of disease condition or vascular permeability is reduced by strictness.The effect of some The compounds of this invention by its selectivity to specific Tyrosylprotein kinase, makes to use and hangs down the side effect minimization that the selectivity tyrosine kinase inhibitor occurs.Some The compounds of this invention still is effective FGFR, PDGFR, c-Met and IGF-1-R inhibitor.Vasculogenesis and hyper-proliferative that these receptor kinases can directly or indirectly be strengthened in the various diseases are replied, thereby its restraining effect can stop disease to be carried out.
The compounds of this invention has the activity of inhibition to protein kinase.That is, these compounds are by the conduction of protein kinase adjustment signal.The compounds of this invention suppresses the protein kinase of serine/threonine and tyrosine-kinase enzyme.Especially, these compound selective ground suppress the KDR/FLK-1/VEGFR-2 tyrosine kinase activity.Some The compounds of this invention also suppresses the activity of the kinases of other Tyrosylprotein kinases such as Flt-1/VEGFR-1, FGFR, PDGFR, IGF-1R, c-Met, Src-subtribe such as Lck, Src, fyn, yes etc.In addition, some The compounds of this invention significantly is suppressed at serine/threonine kinase such as PKC, map kinase, erk, CDKs, Plk-1 or the Raf-1 that cell proliferation and cell cycle play an important role in carrying out.General formula compound of the present invention can (be R by changing substituting group at kinase whose effect of specific protein and specificity usually 1, R 2, R 3, R 4, R 5, R 6And R 7) character, quantity and arrangement and conformation restriction and change or optimizing.In addition, it is active that the metabolite of some compound also has significant protein kinase inhibition.
When the individuality of needs was used The compounds of this invention, The compounds of this invention suppressed the too high and oedema formation of these individual vascular permeabilities.It is believed that these compounds have an effect with the too high KDR tyrosine kinase activity relevant with the oedema forming process of vascular permeability by suppressing.The KDR Tyrosylprotein kinase is known as FLK-1 Tyrosylprotein kinase, NYK Tyrosylprotein kinase or VEGFR-2 Tyrosylprotein kinase again.When combining with the lip-deep kdr tyrosine kinase receptor of vascular endothelial cell, the KDR Tyrosylprotein kinase is activated when vascular endothelial growth factor (VEGF) or another kind of activatory part (for example VEGF-C, VEGF-D, VEGF-E or HIV Tat albumen).Behind this KDR tyrosine-kinase enzyme activation, the too high generation of vascular permeability, liquid menses tube wall from blood enters a matter chamber, thereby forms the oedema zone.Hemocyte oozes out also often with this reaction.Similarly, excessively vascular permeability is too high can break the normal molecular exchange of passing through endothelium in crisis tissue and the organ (for example lung and kidney), thereby causes that macromole blends deposition outward.After acute the replying (it is believed that this has promoted angiogenesis subsequently) that KDR is stimulated, the KDR Tyrosylprotein kinase of prolongation stimulates propagation and chemotaxis and the neovascularization that causes vascular endothelial cell.By suppressing the KDR tyrosine kinase activity, perhaps activate the generation of part by blocking-up, combine with kdr tyrosine kinase receptor by blocking-up activation part, by stoping receptor dimerization and transphosphorylation, by the mechanism (D.Mukhopedhyay etc. that suppress KDR tyrosine kinase activity (the phosphorylation function of inhibitory enzyme) or other block its downstream signal conduction by some, CancerRes.58:1278-1284 (1998), the document is combined in herein as a reference), what perviousness was too high with relevant exosmoses, oedema formation subsequently and apposition and vasculogenesis reaction can be suppressed or minimize.
One group of preferred The compounds of this invention has the KDR tyrosine kinase activity of inhibition and does not significantly suppress Flt-1 tyrosine kinase activity (the Flt-1 Tyrosylprotein kinase is also referred to as the VEGFR-1 Tyrosylprotein kinase).KDR Tyrosylprotein kinase and Flt-1 Tyrosylprotein kinase are activated with kdr tyrosine kinase receptor with Flt-1 tyrosine kinase receptor bonded VEGF respectively.Because the Flt-1 tyrosine kinase activity can mediate important result in endothelium maintenance and vascular function, so the inhibition of this enzymic activity can cause toxicity or disadvantageous effect.At least vasculogenesis is replied, the induction of vascular perviousness is too high and oedema formation is unnecessary for blocking in this inhibition, is uneconomical and nugatory for individuality therefore.Some preferred The compounds of this invention is unique, because they suppress by activation part activatory VEGF-receptor tyrosine kinase (KDR) activity, and does not suppress other also by some activation part activated receptors Tyrosylprotein kinase, for example Flt-1.Therefore, preferred The compounds of this invention has selectivity on its tyrosine-kinase enzyme inhibition activity.
The compounds of this invention also is applicable to treatment ulcer-bacterium, fungi, Mooren's ulcer and ulcerative colitis.
The compounds of this invention is applicable to that also undesirable vasculogenesis wherein appears in treatment in virus infection, oedema or the sedimentary disease of a matter, for example herpes simplex, zoster, AIDS, parapoxvirus, psoriasis, Kaposi, protozoal infections and toxoplasmosis, endometriosis, ovarian hyperstimulation syndrome, preeclampsia, menorrhagia, systemic lupus erythematosus, sarcoidosis, synovitis, inflammatory bowel disease, Crohn disease, the reaping hook cell anemia, Lyme disease, pemphigoid, osteitis deformans, HSV, the Osler-Weber-Rendu disease, chronic inflammatory diseases, chronic closed tuberculosis, asthma, rheumatoid arthritis and osteoarthritis, and burn, wound, oedema after radiation or the apoplexy.
Except retinopathy and macular degeneration, The compounds of this invention also is applicable to treatment illness in eye for example eye and macular edema, eye neovascularity disease, scleritis, radial keratotomy, uveitis, hyalitis, myopia, recessed, the chronic detachment of retina of eye, laser operation infectious-related complication, conjunctivitis, fundus flavimaculatus Stargardt disease and eales's disease.
The compounds of this invention also is applicable to treatment cardiovascular disorder for example atherosclerosis, restenosis, vessel sealing and carotid artery obstruction disease.
The compounds of this invention is applicable to that also for example solid tumor, sarcoma (particularly Ewing's sarcoma and osteosarcoma), retinoblastoma, rhabdosarcoma, neuroblastoma, hematopoiesis malignant tumour comprise pleura or pericardial effusion and the malignant ascite that leukemia and lymphoma, tumour cause with Cancer-Related indication in treatment.
The compounds of this invention also is applicable to treatment Crow-Fukase (POEMS) syndrome and diabetic disease such as glaucoma, diabetic retinopathy and microangiopathy.
Should see that the disease of listing is above mediated to important degree by the protein hydroxyphenylaminopropionic acid kinase activity that relates to vegf receptor (for example KDR and Flt-1).By suppressing the activity of these receptor tyrosine kinases, being suppressed of above-mentioned disease is because the vasculogenesis composition of disease condition is reduced by strictness.The effect of The compounds of this invention by its selectivity to specific Tyrosylprotein kinase, makes to use and hangs down the side effect minimization that the selectivity tyrosine kinase inhibitor occurs.
On the other hand, the invention provides formula I compound (comprising collateral condition) as medicine, when beginning definition above protein kinase activity, for example tyrosine kinase activity, serine kinase enzymic activity and threonine kinase activity inhibitor.The formula I compound (comprising collateral condition) of definition is used for the application of the medicine of arrestin kinase activity when beginning above the invention provides again on the one hand, in preparation.
In the present invention, use following definition:
" physiologically acceptable salt " is meant biopotency and the character that those have kept free alkali, and the salt by obtaining with reactions such as mineral acid example hydrochloric acid, Hydrogen bromide, sulfuric acid, nitric acid, phosphoric acid or organic acid such as sulfonic acid, carboxylic acid, organic phosphoric acid, methylsulfonic acid, ethyl sulfonic acid, tosic acid, Whitfield's ointment, lactic acid and tartrate.
" alkyl " is meant saturated aliphatic hydrocarbon, comprises straight chain and branched group with 1-6 carbon atom or the cyclic hydrocarbon with 3-6 carbon atom.
" alkoxyl group " is meant " O-alkyl ", and wherein " alkyl " as defined above.Pharmaceutical preparation
The compounds of this invention can with itself or in pharmaceutical composition to the human patients administration, in pharmaceutical composition this compound and suitable carriers or vehicle with treatment or improve that vascular permeability is too high, the dosage of oedema and diseases related mixes.Can also with the mixture of these compounds with simple mixture or suitable in the pharmaceutical composition of preparation to patient's administration.The treatment effective dose further be meant be enough to prevent or weaken that unsuitable neovascularization, hyperproliferation disease are carried out, perviousness that oedema, VEGF are relevant is too high and/or the amount of the hypotensive compound that VEGF is relevant.The technology of preparing and use the application's compound is found in " Remington ' s Pharmaceutical Sciences, " Mack Publishing Co., Easton, PA, nearest version.Route of administration
Suitable route of administration can for example comprise per os, eye drip, rectum, through mucous membrane, part or through enteral administration; Parenterai administration comprises in intramuscular, subcutaneous, intramedullary injection and the sheath, in the ventricle in direct injection, intravenously, intraperitoneal, the nose or intraocular injection.
Perhaps, can the part but not this compound of systemic administration for example is injected directly into compound the oedema position, normally with the form administration of prolonged action preparation or extended release preparation.
Moreover, can for example use the liposome of endothelial cell specific antibodies dressing with medicine with the administration of targeted drug release system.Composition/preparation
Pharmaceutical composition of the present invention can prepare according to known mode itself, for example by routine mixing, dissolving, granulation, system drageeing, levigate, emulsification, incapsulate, wrap and carry or freeze drying process.
Therefore, being used for pharmaceutical composition of the present invention can use one or more physiologically acceptable carriers to prepare in a conventional manner, and carrier comprises that vehicle and auxiliary agent are beneficial to active compound is processed into pharmaceutically useful preparation.Appropriate formulations depends on selected route of administration.
For injection, medicine of the present invention can be at aqueous solution, preferably prepare in the compatible buffer reagent of physiology such as Hanks ' solution, Ringer's solution or physiological saline buffer.For mucosal, in preparation, use the permeate agent suitable to permeability barrier.This permeate agent is normally known in the art.
For oral administration, can easily, prepare active compound this compound by being mixed with pharmaceutically acceptable carrier well known in the art.For being ingested by patient's per os of receiving treatment, this carrier makes The compounds of this invention can be mixed with tablet, pill, drageeing, capsule, liquid, gel, syrup, slurries and suspension etc.Oral drug preparation can obtain by following method: active compound is mixed with solid excipient, randomly grind the gained mixture, and add as required after the proper auxiliary agent this mixture pelleting, obtain tablet or drageeing core.Suitable vehicle especially filler for example steamed bun stuffed with sugar draw together lactose, sucrose, N.F,USP MANNITOL or Sorbitol Powder; Cellulose preparation is W-Gum, wheat starch, Starch rice, potato starch, gelatin, tragacanth gum, methylcellulose gum, Vltra tears, Xylo-Mucine and/and polyvinylpyrrolidone (PVP) for example.If desired, can add disintegrating agent, cross-linked polyvinylpyrrolidone for example, agar or alginic acid or its salt such as sodiun alginate.
The drageeing core is with suitable coatings dressing.For this reason, concentrated sugar solution be can use, gum arabic, talcum, polyvinylpyrrolidone, carbopol (carbopol) glue, polyoxyethylene glycol and/or titanium dioxide, lacquer solution and suitable organic solvent or solvent mixture wherein can be randomly contained.Can in tablet or drageeing dressing, add dyestuff or pigment feature with identification or differentiation various combination active compound doses.
Pharmaceutical preparation that can the oral administration administration comprises by the pushing away of gelatin preparation-box-like (push-fit) capsule and by gelatin and the softening agent soft seal capsule of glycerine or sorbyl alcohol preparation for example.Push away-box-like capsule can contain with filler such as lactose, tackiness agent such as starch and/or lubricant such as talcum or Magnesium Stearate and randomly with stablizer blended activeconstituents.In soft capsule, active compound can be dissolved or suspended in suitable liquid for example in fatty oil, whiteruss or the liquid macrogol.Can add stablizer in addition.All oral preparations all should be the dosage that is suitable for this form of medication.
For the cheek administration, said composition can be tablet or the lozenge of preparing in a usual manner.
For passing through inhalation, be used for compound of the present invention usually with the form of aerosol spray by pressurized package or atomizer administration, wherein use suitable propellent for example Refrigerant 12, trichlorofluoromethane, dichloro tetrafluoro ethane, carbonic acid gas or other suitable gas.For pressurized aerosol, dose unit can be by installing valve to determine to discharge metering.The for example gelatine capsule and the cartridge case that are used for sucker or insufflator can be mixed with the form that contains this compound powder mixture and suitable powder matrix such as lactose or starch.This compound can be mixed with the injection form that is used for parenterai administration, for example concentrated medicine mass (bolus) injection or continuous infusion liquid.Injection formulations can be a unit dosage, and for example ampoule or multi-dose container wherein contain sanitas.Said composition can be suspension, solution or the emulsion in oil or water carrier, and can contain preparation with reagent for example suspension agent, stablizer and/or dispersion agent.
The pharmaceutical preparation of parenterai administration comprises the active compounds in water-soluble form aqueous solution.In addition, the suspension of active compound can be prepared into suitable oil-containing injectable suspensions.Suitable lipophilic solvent or carrier comprise fatty oil such as sesame oil or Acrawax such as ethyl oleate or triglyceride level or liposome.Moisture injectable suspensions can contain the material that increases suspension viscosity, for example Xylo-Mucine, sorbyl alcohol or dextran.Randomly, this suspension can also contain suitable stabilizers or increase the reagent of the stability of compound with permission preparation height concentrated solution.
Perhaps, activeconstituents can be before use with for example aseptic apirogen water powder formulated of suitable carriers form.
This compound can also be mixed with composition for rectal administration for example suppository or enema,retention, for example contains conventional suppository bases such as theobroma oil or other glyceryl ester.
Except above-mentioned preparation, this compound can also be mixed with prolonged action preparation.This prolonged action preparation can pass through implantation administration (for example subcutaneous or intramuscular implant or by the intramuscularly administration).Therefore, for example, this compound can be prepared (for example in the emulsion that can accept in the oil) with suitable polymerization or hydrophobic material or ion exchange resin, perhaps is mixed with to be difficult for molten derivative and for example to be difficult for molten salt.
The example that is used for pharmaceutically acceptable carrier of hydrophobic compound of the present invention is the solubility promoter system, comprises benzylalcohol, non-polar surfactant, organic polymer and water that can be miscible with water.This solubility promoter system can be a VPD solubility promoter system.VPD is that 3%w/v benzylalcohol, 8%w/v non-polar surfactant tween 80 and 65%w/v Liquid Macrogol are mixed with volume required solution in dehydrated alcohol.(the VPD: 5W) form of this VPD solubility promoter system by the VPD that carries out dilution in 1: 1 with 5% D/W.The compound of this complete solubilizing hydrophobic of solubility promoter system, and the toxicity that itself produces through being administered systemically is very low.Certainly, only otherwise destroy its solvability and toxicity characteristic, the ratio of solubility promoter system can have very big change.In addition, the characteristic of co-solvent component can change: for example can use other low toxicities, non-polar surfactant to replace tween 80; The umber size of polyoxyethylene glycol can change; Can replace polyoxyethylene glycol, for example polyvinylpyrrolidone with the other biological compatible polymer; And can replace glucose with other sugar or polysaccharide.
Perhaps, can use other drug delivery systems of using for the dewatering medicament compound.Liposome and emulsion are known dewatering medicament administration vehicle and carrier.Also can use for example dimethyl sulfoxide (DMSO) of some organic solvent, although its toxicity cost is bigger usually.In addition, this compound can use the sustained release system administration, for example contains the semi-transparent matrix of the solid hydrophobic polymkeric substance of therapeutical agent.Various lasting releasable material are to determine, and are that this area professional is known.According to its chemical property, continue release capsule and discharge compound several weeks to reaching 100 days.According to the chemical property and the biologically stable of therapeutical agent, can use other strategies of stabilizing protein.
Pharmaceutical composition can also contain suitable solid or gel phase carrier or vehicle.The example of described carrier or vehicle is including, but not limited to lime carbonate, calcium phosphate, various sugar, starch, derivatived cellulose, gelatin and polymkeric substance such as polyoxyethylene glycol.
Many organic molecular compounds of the present invention can use with the salt form of itself and drug compatibility counter ion.Can form drug compatibility salt with many acid, described acid includes but not limited to hydrochloric acid, sulfuric acid, acetate, lactic acid, tartrate, oxysuccinic acid, succsinic acid etc.Compare more soluble in water or other protonic solvents of salt with corresponding free alkali.Effective dose
Being applicable to that pharmaceutical composition of the present invention comprises wherein contains the composition that reaches its expection order effective amount of actives.Especially, the treatment significant quantity means the existing symptom development of effective prevention or alleviates the amount that curer has symptom now.Significant quantity fixes in this area professional's the limit of power really.
For chemical compound lot used in the inventive method, can at first estimate the treatment significant quantity by cell analysis.For example, can in cell and animal model, work out dosage to reach the circulation composition scope, to be included in the IC that measures in the cell analysis 50Value (promptly reach and specify the maximum test compound concentration that suppresses of protein kinase activity half).In some cases, in the presence of the 3-5% serum albumin, measure IC 50Value is suitable, because should measure near the keying action of plasma proteins to compound.This information can be used for determining more accurately people's effective dose.In addition, in blood plasma, can reach the most preferably whole body of security level to the drug compound signal conduction of arrestin kinases in intact cell effectively.
The treatment effective dose is meant the amount of the compound that causes patient's doing well,improving.The toxicity of this compound and therapeutic efficiency can be measured in cell culture or experimental animal by standard pharmaceutical procedures, for example measure maximum tolerated dose (MTD) and ED 50Value (effective dose of 50% maximum reaction).Dosage ratio between toxicity and the result of treatment is a therapeutic index, and it can be expressed as MTD and ED 50The ratio.The compound that the preferred therapeutic index is high.The data that obtained by these cell culture analyses and zooscopy can be used for preparing the human dosage range.These dosage of this compound preferably fall into the circulation composition scope, comprise little or avirulent ED 50Value.According to formulation and the route of administration used, this dosage can change in this scope.Accurate preparation, administration volume and dosage can be selected according to patient's situation by the doctor.(referring to for example Fingl etc., 1975, " The Pharmacological Basis of Therapeutics ", Ch.1 pl).In the crisis treatment, may use MTD to realize rapid reaction with acute concentrated medicine mass form or by the infusion approach.
Can regulate one by one the dosage and the timed interval, so that the blood plasma level of active substance is enough to keep kinase regulatory effect or minimum effective concentration (MEC).The MEC difference of each compound, but can estimate by vitro data; For example use analysis mentioned above to estimate to reach the 50-90% protein kinase and suppress required concentration.Reach the required dosage of MEC and depend on personal feature and route of administration.Yet, can use HPLC analysis or biological assay to determine plasma concentration.
Dosing interval also can use the MEC value to determine.Should adopt and keep that blood plasma level is higher than the time of MEC 10-90%, preferred 30-90%, most preferably time of 50-90% is until the dosage regimen administered compound that reaches required doing well,improving.If topical or selectivity picked-up, then the local effective concentration of medicine can be not relevant with plasma concentration.
Certainly, the dosage of composition depends on severity, administering mode and prescriber's the judgement of the object of receiving treatment, patient's body weight, sufferer.Packing
If desired, said composition can provide to contain one or more packing or dispenser device forms that contain the unit dosage of activeconstituents.This packing can for example comprise metal or plastic foil, for example Blister Package.This packing or dispenser device can attach medication instruction.Also can prepare and contain the composition that is formulated in the The compounds of this invention in consistency pharmaceutically acceptable carrier, be placed in the proper container, and stick the label of disease shown in the treatment.
In some preparation, it is favourable that The compounds of this invention is used with very little particle form, for example can grind by liquid and obtain this small-particle.
By the application of following description explanation The compounds of this invention in pharmaceutical compositions.In this was described, term " active compound " was meant any The compounds of this invention, but referred in particular to the final product compound of any embodiment the preceding.A) capsule
In the capsule preparation, the active compound of 10 weight parts can be separated coalescence with the lactose of 240 weight parts and mix.This mixture is filled in the hard gel capsule, and every capsules contains unitary dose or part unit dose of active compound.B) tablet
Can prepare tablet by following ingredients.
Weight part
Active compound 10
Lactose 190
W-Gum 22
Polyvinylpyrrolidone 10
Magnesium Stearate 3
With active compound, lactose and some starch depolymerization, mixing, and with the ethanolic soln of polyvinylpyrrolidone with the gained mixture pelleting.Dry granules is mixed with Magnesium Stearate and remaining starch.In tabletting machine that this mixture compacting is in blocks then, every contains unitary dose or part unit dose of active compound.C) enteric coated tablet
Can prepare tablet according to the method for above-mentioned (b).Can use 20% sour O-phthalic acid cellulose and 3% diethyl phthalate at ethanol: the solution in the methylene dichloride (1: 1), according to ordinary method that tablet is enteric coated.D) suppository
In preparation suppository, the active compound of 100 weight parts can be mixed in the triglyceride level suppository base of 1300 weight parts, and make this mixture form suppository, every suppository contains the treatment effective amount of actives.
If desired, in composition of the present invention, the pharmacological component associating that active compound can be compatible with other.For example, The compounds of this invention can with one or more additional pharmaceutical actives combination medicine-feedings, described pharmaceutically active substance suppresses or prevention VEGF produce, weaken in the cell to VEGF reply, block signal conduction in the cell, suppress vascular permeability too high, reduce inflammation or inhibition or prevention oedema and form or neovascularization.The compounds of this invention can be before additional pharmaceutical actives, afterwards or administration simultaneously, any administration process all is suitable.Additional pharmaceutical actives is including, but not limited to Ivy extract steroid, NSAIDS, ras inhibitor, anti-TNF agent, anti-IL-1 agent, antihistaminic, PAF-antagonist, COX-1 inhibitor, cox 2 inhibitor, NO synthase inhibitor, pkc inhibitor and PI3 kinase inhibitor.The compounds of this invention and additional pharmaceutical actives add up or collaborative having an effect.Therefore, compare, will suppress vasculogenesis, vascular permeability is too high and/or suppresses that the combinations of substances administration that oedema forms can alleviate hyperproliferation disease, vasculogenesis greatly, vascular permeability is too high or the deleterious effect of oedema with using every kind of material separately.In the treatment of malignant disease, expection can be made up with antiproliferative or cytotoxin chemotherapy.
The present invention also comprises the purposes of formula I compound as medicine.
Src and Syk family kinases play keying action in regulating immunologic function.Src family comprises Fyn at present, Lck, Fgr, Fes, Lyn, Src, Yes, Hck and Blk.Should be appreciated that at present Syk family includes only Zap and Syk.Janus family kinases relates to the conduction by many acceptors of somatomedin and former inflammatory cytokine signal.Although it is well known that kinase whose member BTK of Tec family and ITK play a part less, the treatment benefit is arranged with the adjusted but proof of inhibitor in immunobiology.Kinases RIP, IRAK-1, IRAK-2, NIK, TPL-2/COT, IKK-1 and IKK-2 relate to crucial former inflammatory cytokine TNF and IL-1 signal conducting path.Because formula I compound can suppress in these kinases one or more, so they can be with acting on the immunomodulator that keeps homotransplant and treatment autoimmune disease.By its ability of regulating the T cytoactive or strengthening inflammatory process, these compounds can be used for treating this autoimmune disease.Because rejection, or the host is to the repulsion to the host of the transplant rejection of solid organ or bone marrow graft, and graft is the effectively toxic restriction of immunosuppressor at present, and will have benefited from the improved active drug of therapeutic index.The gene target test has proved that Src plays an important role in the biology to the responsible osteoclast of bone resorption.Regulate the ability of Src by it, formula I compound can also be used for the treatment of hypercalcemia and the treatment metastatic tumor of bone that osteoporosis, osteopetrosis, osteitis deformans, tumour cause.
Verified many protein kinases are proto-oncogenes.Rhexis (at the ltk of karyomit(e) 5 kinases breakpoint), transposition for example have BCR Abl gene (Philadelphia karyomit(e)), for example block c-Kit or EGFR or sudden change (for example Met) and cause albumen out of control to produce, it is converted into the oncogene product by proto-oncogene.In other tumours, advance tumorigenesis by autocrine or paracrine part/growth factor receptors interaction.Many src-family kinases is relevant with the downstream signal conduction usually, thereby has strengthened tumorigenesis, and itself is by undue expression or suddenly change and can become oncogene.By suppressing these proteic protein kinase activities, lysis is interrupted.Vascular restenosis may relate to FGF and/or promoted unstriated muscle of PDGF and endothelial cell proliferation.Ligand stimulation is former vasculogenesis in the body of FGFR, PDGFR, IGF1-R and c-Met, and has strengthened angiogenesis-dependent disease.Suppressing FGFr, PDGFr, c-Met or IGF1-R kinase activity can be to suppress these phenomenon efficient strategy.Therefore, suppressing normal or unusual c-kit, c-met, c-fms, the member of src-family, EGFr, erbB2, erbB4, BCR-Ab1, PDGFr, FGFr, IGF1-R and other acceptors or cytoplasmic tyrosine kinase is valuable in treating optimum and true tumor hyperplasia.
Under many pathologic conditions (for example entity primary tumor and metastatic tumor, Kaposi, rheumatoid arthritis, because unsuitable eye neovascularity generates blindness, psoriasis and the atherosclerosis that causes), in case continue vascularization, disease be accidental.Usually polypeptide growth factor that is produced by diseased tissue or relevant inflammatory cell and corresponding endothelial cell specific receptor tyrosine kinase (for example KDR/VEGFR-2, Flt1/VEGFR-1, Tie-2/Tek and Tie) thereof are important for the new function vascular system of stimulating endothelial cell growth, migration, machineization, differentiation and foundation necessity.It is believed that VEGF " the vascular permeability factor " is too high at the mediation vascular permeability, activity during the kinase whose VEGF of VEGFR stimulates plays an important role in following illness: tumour ascites forms, brain and pulmonary edema, pleura and PE hydrops, delayed-type hypersensitivity, post-traumatic tissue edema and organ dysfunction, burn, local asphyxia, diabetic complication, endometriosis, adult respiratory distress syndrome (ARDS), ypotension and perviousness relevant after the cardiopulmonary bridging are too high, and the glaucoma that causes of edema oculi or because unsuitable neovascularity generates the blindness that causes.Except VEGF, the VEGF-E of the VEGF-C of identification and VEGF-D and encoding viral or HIV-Tat albumen can also cause the too high reaction of vascular permeability by stimulating the VEGFR kinases recently.Tie-2 also expresses in selecting the hemopoietic stem cell of population, wherein Tie-2 play an important role in it is raised, adheres, regulates and breaks up (Blood, 4317-4326 (1997)); This expression population Tie-2 can be used as systemic vascular and generates endothelium for generations.Therefore, some the formula I medicine that can block the kinase whose kinase activity of endothelial cell specific disease that can suppress to relate to these situations is carried out.
Formula I compound or its salt or the pharmaceutical composition that contains treatment significant quantity this compound or its salt can be used for treating optimum and true tumor hyperplasia and disease of immune system.Described disease comprises autoimmune disease for example rheumatoid arthritis, thyroiditis, type i diabetes, multiple purulence sclerosis, sarcoidosis, inflammatory bowel disease, Crohn disease, myasthenia gravis and systemic lupus erythematosus; Psoriasis, organ graft repels (for example kidney repulsion, graft versus host disease repels), optimum and true tumor hyperplasia, human cancer is lung for example, mammary gland, stomach, bladder, colon, pancreas, ovary, the prostate gland and the rectum cancer and hematopoiesis malignant tumour (leukemia and lymphoma), and relate to for example diabetic retinopathy of inappropriate angiopoietic disease, retinopathy of prematurity, because the choroid neovascularization that the macular degeneration relevant with the age causes, infantile hemangioma with the people.In addition, this inhibitor can be used for treating oedema diseases associated, ascites, seepage and the exudate that mediates with VEGF, comprises for example macular edema, cerebral edema, acute lung injury and adult respiratory distress syndrome (ARDS).
The compounds of this invention also is applicable to the above-mentioned disease of prevention.
The present invention provides on the other hand that formula I compound or its salt is too high at preparation treatment Mammals, particularly people's vascular permeability, the application in the medicine of angiogenesis-dependent disease, hyperplasia and/or disease of immune system.
The present invention also provides the method for too high, the unsuitable neovascularization of treatment vascular permeability, hyperplasia and/or disease of immune system, and this method comprises the formula I compound of Mammals, particularly people's administering therapeutic significant quantity to needs.
Compound suppresses the external usefulness of these protein kinases and can measure by following method.
By test compound with respect to inhibition exogenesis substrate (for example synthetic peptide) amount of phosphorylation of contrast can measure compound usefulness (Z.Songyang etc., Nature.373:536-539).
Use rhabdovirus system to produce the KDR Tyrosylprotein kinase:
Use produces people's KDR intracellular region domain encoding sequence (aa789-1354) by the cDNAs of HUVEC cellular segregation by PCR.Also in the many-His6 sequence of the terminal introducing of this proteic N-.With Xba 1 and Not 1 site of this fragment cloning to transfection carrier pVL1393.Use BaculoGold transfection reagent (PharMingen), produce recombinant baculovirus (BV) by cotransfection.The BV plaque purification of will recombinating, and analyze by Western and to test.For purifying protein, 2 * 106/ml SF-9 cell is grown in the SF-900-II substratum, and infect with 0.5 plaque forming unit/cell (MOI).At back 48 hours harvested cells of infection.Purifying KDR
By in the cell precipitation thing of 1L cell culture, add the molten born of the same parents' buffer reagent of 50 ml Triton X-100 (20mM Tris, pH 8.0,137mM NaCl, 10% glycerine, 1%Triton X-100,1mM PMSF, 10 μ g/ml Trypsin inhibitor,Trasylols, the bright Trypsin inhibitor,Trasylol of 1 μ g/ml), make expression (His) 6The SF-9 cytolysis of KDR (aa789-1354).Lysate with the rotating speed of 19,000 rpm, revolve in the tube at Sorval SS-34, centrifugal 30 minutes at 4 ℃.Cell lysates is adorned 5 ml NiCl 2The chelating agarose column, with 50 mM HEPES, pH7.5,0.3 M NaCl balance.With the identical buffer reagent wash-out KDR that contains the 0.25M imidazoles.Elisa assay (hereinafter) coupled columns cut with SDS-PAGE and measurement kinase activity is analyzed.The KDR of purifying is at 25mM HEPES, exchange and-80 ℃ of storages in pH7.5,25mM NaCl, the 5 mM DTT buffer reagents.Kinase whose generation of people Tie-2 and purifying
Use produces people's Tie-2 intracellular region domain encoding sequence (aa775-1124) by the mazolytic cDNAs template of people by PCR.At the many-His of the terminal introducing of N- 6Sequence, and this assembling is cloned into Xba 1 and Not 1 site of transfection carrier pVL1939.Use BaculoGold transfection reagent (PharMingen), produce reorganization BV by cotransfection.The BV plaque purification of will recombinating, and analyze by Western and to test.For purifying protein, 2 * 106/ml SF-9 cell is grown in the SF-900-II substratum, and infect with 0.5 MOI.According to the described similar method of KDR, the kinases of the His-mark that uses in the purifying screening.The generation and the purifying of people Flt-1 Tyrosylprotein kinase
Use rhabdovirus expression vector pVL1393 (Phar Mingen, Los Angeles, CA).The nucleotide sequence of the many-His6 of coding is placed the 5 ' end in the Nucleotide district in kinases district in coding whole people Flt-1 (amino acid 786-1338) cell.Use produces the nucleotide sequence in coding kinases district by the cDNA library of HUVEC cellular segregation by PCR.Histidine residues makes this albumen according to carry out protein affinity purification feasible with KDR and the similar method of ZAP70.The SF-9 insect cell is with 0.5 MOI, and in back 48 hours results of infection.EGFR tyrosine-kinase enzyme source
EGFR is available from Sigma (Cat # E-3641; 500 units/50 μ l), and the EGF part derive from Oncogene Research Products/Calbiochem (Cat # PF011-100).The expression of ZAP70
Used rhabdovirus expression vector be pVL1393 (Pharmingen, Los Angeles, Ca.).With coded amino acid M (H) 6 LVPR 9The nucleotide sequence of S places the 5 ' end in the district of the whole ZAP70 of coding (amino acid/11-619).Use produces the nucleotide sequence of coding ZAP70 coding region by the cDNA library of Jurkat immortalization T-cellular segregation by PCR.Histidine residues makes this proteic protein affinity purification feasible (vide infra) that carries out.LVPR 9The S bridge has constituted the recognition sequence by the zymoplasm proteolytic cleavage, makes that to remove affinity labeling from enzyme feasible.The SF-9 insect cell is with 0.5 MOI, and in back 48 hours results of infection.The extraction and purification of ZAP70
In the buffer reagent of forming by 20mM Tris pH8.0,137mM NaCl, 10% glycerine, 1% TritonX-100,1mM PMSF, the bright Trypsin inhibitor,Trasylol of 1 μ g/ml, 10 μ g/ml Trypsin inhibitor,Trasylols and 1mM sodium orthovanadate, with SF-9 cytolysis.With the solubility lysate chelating agarose HiTrap post (Pharmacia) of packing into, with 50mM HEPES pH7.5,0.3M NaCl balance.Fusion rotein 250mM imidazoles wash-out.This enzyme is preserved in the buffer reagent that contains 50mM HEPES pH7.5,50mM NaCl and 5mM DTT.The Lck source
The Lck of Lck or clipped form can buy (for example available from UpstateBiotechnology Inc. (Saranac Lake, N.Y) and Santa Cruz BiotechnologyInc. (Santa Cruz, Ca.)) or adopt ordinary method to obtain by known natural or recombinant sources purifying.The enzyme-linked immunosorbent assay of PTKs (ELISA)
Adopt enzyme-linked immunosorbent assay (ELISA) to measure and measure the existence of tyrosine kinase activity.This ELISA carries out according to known solutions, these schemes are described in for example Voller etc., 1980, ＂ enzyme-linked immunosorbent assay ＂: Manual of Clinical Immunology, the 2nd edition, edited by Rose and Friedman, pp 359-371 Am.Soc.of Microbiology, Washington, D.C..
Adopt the scheme of the disclosure to measure specific PTK activity.For example, provide the scheme of preferably carrying out the ELISA experiment below.Adopting these schemes mensuration compounds is that this area professional is in power to the activity of other acceptors PTK member of family and nonreceptor tyrosine kinase.In order to measure selection of inhibitors, in analysis, concentration is about the general PTK substrate (for example poly-(Glu of apparent Km twice 4Tyr) randomcopolymer, 20,000-50 000MW) uses with ATP (being generally 5 μ M).
Use the following step to analyze the restraining effect of The compounds of this invention to KDR, Flt-1, Flt-4/VEGFR-3, Tie-2, EGFR, FGFR, PDGFR, IGF-1-R, c-Met and ZAP70 tyrosine kinase activity: buffer reagent and solution: PGT is poly-, and (Glu, Tyr) 4: 1 at-20 ℃ of storage powder.Powder dissolution in the salt solution (PBS) of phosphate buffered, is made the solution of 50mg/ml.-20 ℃ of storage 1ml aliquots containigs.When the preparation plate, it is diluted to 250 μ g/ml in GibcoPBS.Reaction buffer: 100mM Hepes, 20mM MgCl 2, 4mM MnCl 2, 5mM DTT, 0.02% BSA, 200 μ M NaVO 4, pH7.10.ATP: in the aliquots containig of-20 ℃ of storage 100mM.In water, be diluted to 20 μ M washing buffers: the buffer reagent that contains the PBS antibody dilution of 0.1% Tween 20: 0.1% bovine serum albumin (BSA) tmb substrate in PBS: tmb substrate is mixed by 9: 1 with peroxide solutions or use the K-Blue substrate that derives from Neogen facing with preceding.Stop bath: 1M phosphoric acid step 1. making sheet:
PGT liquid storage (50mg/ml, refrigerated) is diluted to 250 μ g/ml in PBS.In every hole of the flat height affinity elisa plate (Corning #25805-96) of Corning modification, add 125 μ l.Add 125 μ l PBS to blank well.Cover with seal strip, and 37 ℃ of overnight incubation.With 250 μ l washing buffers washing 1 time, and in 37 ℃ of dry thermostat containers dry about 2 hours.With the plate sealed in sealing bag in 4 ℃ of storages until use.2. tyrosine-kinase enzyme reaction: the inhibitor solution in the 20% DMSO aqueous solution of-preparation 4 * concentration.-preparation feedback buffer reagent-preparation enzyme solution makes that required unit is 50 μ l, for example for KDR, makes 1ng/ μ l, amounts to 50ng in every hole in reaction.In storage on ice.-by 100mM liquid storage preparation 4 * ATP aqueous solution.In storage on ice.-in every hole, add 50 μ l enzyme solution (, being generally 5-50ng enzyme/hole)-addings 25 μ l 4 * inhibitor-adding 25 μ l 4x ATP and be used for inhibitor analysis-with termination reaction-wash plate in incubated at room temperature 10 minutes-to every hole adding 50 μ l 0.05N HCl according to kinase whose given activity *The final concentration of reaction: 5 μ M ATP, 5% DMSO3. antibodies-by two steps dilution (100x, 200x then), the aliquots containig of 1mg/ml PY20-HRP (Pierce) antibody (phosphotyrosine antibody) is diluted to 50ng/ml-in the PBS of 0.1% BSA solution and in every hole, adds 100 μ l Ab.Incubated at room temperature 1 hour.Cultivated 1 hour at 4 ℃.-washing 4x plate 4. color reactions-preparation tmb substrate also adds 100 μ l-in 650nm monitoring OD value in every hole, until reaching 0.6-1M phosphoric acid termination reaction.Jolting on plate reader.-read the OD value at 450nm immediately
Best incubation time is slightly different with zymin with the enzyme reaction condition, and mostly by the experience decision.For Lck, used reaction buffer is 100mM MOPSO, pH6.5,4mMMnCl 2, 20mM MgCl 2, 5mM DTT, 0.2% BSA, 200mM NaVO 4, under similar analysis condition.
Formula I compound can be used for treating with suppressed by formula I compound determine, comprise the undetermined protein tyrosine kinase diseases associated of top NM Buddhist monk.The compound that all this paper enumerate significantly suppresses the KDR kinases under 50 micromoles or lower concentration.Some The compounds of this invention also significantly suppresses other PTKs such as lck under 50 micromoles or lower concentration.The Cdc2 source
People's recombinase and analyze buffer reagent can buy (New England Biolabs, Beverly, MA.USA) or adopt ordinary method to obtain from known natural or recombinant sources purifying.Cdc2 measures
Used scheme is to use the reagent of purchase and carries out less change.Briefly, being supplemented with fresh 300 μ M ATP (31 μ Ci/ml) and final concentration 30 μ g/ml histone IIIss, by 50mM Tris pH7.5,100mM NaCl, 1mM EGTA, 2mM DTT, 0.01% Brij, 5% DMSO and 10mM MgCl 2Carry out this reaction in the buffer reagent of forming (commodity buffer reagent).Have or the unrestraint agent in the presence of, make the 80 μ L volumes that contain unit of enzyme 25 ℃ of reactions of carrying out 20 minutes.Make this reaction terminating by adding 120 μ L, 10% acetate.By mixing object point on phosphorylated cotton paper, use the 75mM phosphoric acid washing then 3 times, washed 5 minutes at every turn, substrate is separated with unconjugated mark.In the presence of liquid scintillator, use the β rolling counters forward.
Some The compounds of this invention significantly suppresses cdc2 in the concentration that is lower than 50uM.PKC kinases source
The PKC of catalytic subunit can buy (Calbiochem).The PKC kinase assays
Use radioactivity kinase assay (Yasuda, I., Kirshimoto according to disclosed method, A., Tanaka, S., Tominaga, M., Sakurai, A., Nishizuka, Y.Biochemicaland Biophysical Research Communication 3:166,1220-1227 (1990)).Briefly, respond all by 50mM Tris HCl pH7.5,10mM MgCl 2, 2mMDTT, 1mM EGTA, 100 μ M ATP, 8 μ M peptides, 5% DMSO and 33Carry out in the kinase buffer agent that P ATP (8Ci/mM) forms.Compound and enzyme are mixed in reaction vessel, and make the reaction beginning by adding ATP and substrate mixture.After adding 10 μ L termination buffer reagent (the 5mM ATP in 75mM phosphoric acid) termination reaction, a part should be mixed object point on phosphorylated cotton filter paper.The sample of trace washed 5-15 minute in room temperature 75mM phosphoric acid washing 3 times at every turn.Quantitative in conjunction with carrying out by liquid scintillation counting to radio-labeled.The Erk2 enzyme source
Reorganization mouse enzyme and analyze buffer reagent can buy (New England Biolabs, BeverlyMA.USA) or can adopt ordinary method to obtain from known natural or recombinant sources purifying.The Erk2 enzymatic determination
Briefly, under the condition of supplier suggestion, being supplemented with fresh 100 μ M ATP (31 μ Ci/ml) and 30 μ M myelin basic protein, by 50mM Tris pH7.5,1mMEGTA, 2mM DTT, 0.01% Brij, 5% DMSO and 10mM MgCl 2Carry out this reaction in the buffer reagent of forming (commodity buffer reagent).Reaction volume and as above PKC is measured described (referring to above) in conjunction with the measuring method of radioactivity.The external model of T-cell activation
In case, support it to breed the somatomedin of phase subsequently with one kind of secretion IL-2-the introducing of T-cell by mitogen or antigen activation.Thus, can measure the generation of IL-2 or initial stage T-cell or suitably the cell proliferation of T-clone as T-cell activation surrogate.All these are measured all and describe to some extent in the literature, and (in CurrentProtocols in Immunology, Vol 2,7.10.1-7.11.2) to have quoted its parameter fully as proof.
Briefly, by together cultivating with allotype stimulator cell, can make the T-cell activation, this is the method that is known as unidirectional mixed lymphocyte reacion.According to the guidance of manufacturers, by Ficoll-Hypaque gradient (Pharmacia), purifying effector and stimulator peripheral blood vessel monocyte.Make the deactivation of stimulator cell mitogen by handling with ametycin (Sigma) or gamma-radiation method.Having or not having in the presence of the test compound, effector and stimulator cell are together cultivated in 2: 1 ratio.Usually in droplet plate at the bottom of the U-shaped (Costar Scientific) with 10 5Effector and 5 * 10 4Stimulator mixes and coated plate (200 μ l volume).This cell mixes people AB serum, 5 * 10 being supplemented with heat-killed foetal calf serum (Hyclone Laboratories) or deriving from male sex blood donor -5Cultivate among the RPMI 1640 of M 2 mercapto ethanol and 0.5% DMSO.This culture is being gathered in the crops the day before yesterday (normally the 3rd day) with 0.5 μ Ci's 3H-thymidine (Amersham) carries out pulse.The results culture (Betaplate harvester, Wallac), and by liquid flashing (Betaplate, Wallac) absorption of appraisal isotropic substance.
Can use same culture systems, estimate the T-cell activation by the generation of measuring IL-2.At the 18-24 that begins to cultivate hour, remove supernatant liquor, and, measure IL-2 concentration by ELISA (R and d system) according to the guidance of manufacturers.The body inner model of T-cell activation
Effect can directly measured the T-cell activation or prove that it is to test in the inhibition animal model of T-cytological effect device in the body of compound.T-cell receptors and mono-clonal anti-CD 3 antibodies (Ab) complexing by constant ratio can make the T-cell activate in vivo.In this model, in bloodletting preceding 2 hours, give BALB/c mouse peritoneal injection 10 μ g anti--CD3 Ab.Injection anti--CD3 Ab before 1 hour, make animals received single dose compound medicine in advance.Measure the serum level of former inflammatory cytokine interferon-(IFN-γ) and tumor necrosis factor-alpha (TNF-α) by ELISA, these factors are T-cell activation indicator.Use similar model, use specific antigen such as keyhole worm relative hemocyanin (KLH) to cause the T-cell in vivo, exhaust lymph-node cell with same antigen then and carry out external exciting.As mentioned above, measure the state of activation of cytokine production with the assessment culturing cell.Briefly, at the 0th day, be used in the subcutaneous immune C57BL/6 mouse of emulsive 100 μ g KLH in the complete Freund's adjuvant (CFA).With compound animal is handled in advance the day before yesterday in immunity, and after immunity, with compound animal was handled in the 1st, 2 and 3 day.Gathered in the crops the lymphoglandula that exhausts at the 4th day, and (be supplemented with heat inactivation foetal calf serum (Hyclone Laboratories), 5 * 10 at tissue culture medium (TCM) -5The RPMI 1640 of M 2 mercapto ethanol and 0.5% DMSO) in 6 * 10 6The concentration of/ml is carried out 24-28 hour cultivation to its cell.Then by ELISA, to culture supernatants carry out autocrine T-cell growth factor interleukin-2 (IL-2) and/or IFN-γ level assessment.
Also exemplary compounds is carried out the human body diseases animal model test.For example experimental from immune encephalomyelitis (EAE) and collagen-induced sacroiliitis (CIA).The EAE model of anthropomorphic dummy's multiple sclerosis all has description (to summarize FASEB J.5:2560-2566,1991 in rat and mouse; Murine model:Lab.Invest.4 (3): 278,1981; Rodent model:J.Immunol146 (4): 1163-8,1991).Briefly, use emulsion immune mouse or the rat of myelin basic protein (MBP) or its neuropeptide derivative and CFA.By add bacteriotoxin for example bordetella pertussis can cause acute illness.Go up adoptive transfer by the T-cell from the animal of MBP/ peptide immunity, cause recurrence/disease alleviated.
By with the immunity of II Collagen Type VI, can on the DBA/1 mouse, cause CIA (J.Immunol:142 (7): 2237-2243).The sacroiliitis sign promptly appears in 10 days mouse behind antigen stimulation, and can reach 90 days mark after immunity.In EAE and CIA model, administered compound prophylactically or when disease begins.Effectively medicine should reduce severity of disease and/or incidence.
Suppress one or more vasculogenesis acceptor PTK and/or protein kinase as the The compounds of this invention of the lck of mediation Inflammatory response can be in these animal models the severity and the incidence of ameliorate osteoarthritis.
Can also be in mouse homotransplantation object model or skin (summary, Ann.Rev.Immunol., 10:333-58,1992; Transplantation:57 (12): 1701-17D6,1994) or in heart (Am.J.Anat.:113:273, the 1963) transplantation model compound is tested.Briefly, the skin graft of full depth is transplanted on the BALB/c mouse from the C57BL/6 mouse.Since the 6th day, check the sign of transplant rejection every day.In the newborn heart transplantation model of mouse, on the auricle of heart with new life from the heterotopic transplantation of C57BL/6 mouse to the CBA/J mouse that grows up.4-7 days hearts begin to beat after transplanting, use dissecting microscope and check to beat and stop to estimate the repulsion situation with naked eyes.Cell receptor PTK analyzes
Following cell analysis is used to measure activity and the exposure level of different The compounds of this invention to KDR/VEGFR2.Can adopt technology well known in the art, according to the scheme same with other Tyrosylprotein kinases, design uses the similar acceptor PTK of ligands specific stimulator to analyze.
Measure the KDR phosphorylation of VEGF-inductive in Human umbilical vein endothelial cells (HUVEC) by the Western blotting:
1. (San Diego CA), and cultivates according to the guidance of manufacturers HUVEC cell (from mixing the blood donor) available from Clonetics.Only use early stage going down to posterity (3-8 generation) to carry out this analysis.Use complete EBM substratum (Clonetics), with cell at the 100mm culture dish (Falcon that tissue culture is used; Becton Dickinson; Plymouth, England) the middle cultivation.
2. for the inhibition activity of assessing compound, with trypsin acting in cell, and with cell with 0.5-1.0 * 10 5The amount of cells/well is seeded in 6 holes bunch plate (Costar; Cambridge is in each hole MA).
3. inoculation is after 3-4 days, and this plate reaches 90-100% and merges.Shift out substratum from institute porose, with 5-10ml PBS drip washing cell, and with the 5ml EBM base culture base of no additive (being serum-free) 18-24 hour.
4. the inhibitor that in 1ml EBM substratum (25 μ M, 5 μ M or 1 μ M final concentration of cells), adds serial dilution, and 37 ℃ of cultivations 1 hour.Then to be added in the 2mlEBM substratum in porose, people that final concentration is 50ng/ml recombinates VEGF 165(R ﹠amp; DSystems), and at 37 ℃ cultivated 10 minutes.The control cells that is untreated or only handles with VEGF is used to the phosphorylation estimating the background phosphorous acidification and caused by VEGF.Porose with the cold PBS drip washing institute of the 5-10ml that contains 1mM sodium orthovanadate (Sigma) then, make cytolysis, and containing proteinase inhibitor (PMSF 1mM, Trypsin inhibitor,Trasylol 1 μ g/ml, pepstatin 1 μ g/ml, bright Trypsin inhibitor,Trasylol 1 μ g/ml, vanadic acid sodium 1mM, Sodium Fluoride 1mM) and the 200 μ l RIPA buffer reagents (50mM Tris-HCl pH7,150mM NaCl, 1%NP-40,0.25% Sodium desoxycholate, 1mM EDTA) of 1 μ g/mlDnase in smash that (all chemical all derive from Sigma Chemical Company to pieces, St Louis, MO).Lysate is with 14, and the rotation of the rotating speed of 000rpm is to remove stoning.
By adding cold (20 ℃) ethanol (2 times of volumes) minimum 1 hour or spending the night at most, make the albumen precipitation of equivalent then.Throw out is containing the Laemli sample buffer reagent (BioRad of 5% mercaptoethanol; Hercules, CA) in preparation again, and boiled 5 minutes.By polyacrylamide gel electrophoresis (6%, 1.5mm Novex, San Deigo CA) resolves albumen, and uses the Novex system that it is transferred on the nitrocellulose filter.With after bovine serum albumin (3%) sealing, this albumen at 4 ℃ with anti--KDR polyclonal antibody (C20, Santa Cruz Biotechnology; SantaCruz, CA) or with anti-Tyrosine O-phosphate monoclonal antibody (Lake Placid NY) surveys and to spend the night for 4G10, UpstateBiotechnology.Washing and with HRP-conjugated F (ab) 2Goat is anti--and rabbit or goat-anti--mouse IgG cultivate after 1 hour, uses emission chemoluminescence (ECL) system (Amersham Life Sciences, Arlington Height, IL) visualize bands of a spectrum.Some example of the present invention has significantly suppressed cell VEGE inductive KDR Tyrosylprotein kinase phosphorylation in the concentration less than 50 μ M.Uterus edema model in the body
This analysis to measure compound in mouse, suppress the ability of the acute increase of uterus weight, the acute increase of mouse uterine weight occurs in in post-stimulatory several leading hour of the oestrogenic hormon.It is because the oedema that uterus vascular system perviousness increase causes causes that the uterus weight of this early stage generation increases known.(Endocrinology (1993) 133:829-837) has proved that VEGF mRNA in uterus oedema that oestrogenic hormon stimulates and the uterus expresses the intimate temporary transient relation of increase for Cullinan-Bove and Koss.These results are confirmed by the monoclonal antibody of using neutralize VEGF, and the monoclonal antibody of neutralize VEGF has obviously reduced the acute increase (WO 97/42187) of oestrogenic hormon stimulation back uterus weight.Therefore, this system can as inhibition VEGF signal transmission in the body and the perviousness of being correlated be too high and the model of oedema.
Material: all hormones all with the form of lyophilized powder available from Sigma (St.Louis, MO) or Cal Biochem (La Jolla is CA) and according to supplier's explanation preparation.
Carrier component (DMSO, Cremaphor EL) available from Sigma (St.Louis, MO).
Mouse (Balb/c; age in 8-12 week) available from Taconic (Germantown; NY), and according to the common protection of animal it is raised in bioclean animal breeding plant with using council's guide (Animal Care and Use CommitteeGuidlines).Method:
The 1st day: the serogan (PMSG) of giving the conceived mare of (i.p.) injection 12.5 units in the Balb/c mouse peritoneum.
The 3rd day: the gonad-stimulating hormone (hCG) of accepting the human chorionic of 15 units in the mouse peritoneum.
The 4th day: mouse is divided into only one group of 5-10 at random.According to solubleness and carrier, use the test compound of 1-100mg/kg by intraperitoneal or intravenously or oral route.The vehicle Control group is only accepted carrier, and has two groups not process.
After 30 minutes, to experimental group, vehicle group and 1 untreated fish group animal peritoneal injection 17-estradiol (500 μ g/kg).After 2-3 hour, by sucking CO 2Put to death animal.Along midline incision, separate every uterus, and under uterine cervix, excise with uterus and oviducal joint.Remove fat and reticular tissue, weigh then (weight in wet base) with carefully and not destroying the uterus integrity.By the uterus is squeezed with 1 liter of vial filling water, blot the liquid in uterus between two filter paper.After blotting again to uterus weigh (blot back weight).Weight in wet base is the content liquid in uterus with the difference that blots back weight.The average content liquid of treatment group and untreated fish group or vehicle treated group are compared.Measure significance by student's test (Student ' s test).The stimulated control group is not used to monitor the estradiol reaction.
The result shows that when being administered systemically by all means, some The compounds of this invention suppresses oedema and forms.
Some The compounds of this invention as the vasculogenesis receptor tyrosine kinase inhibitors also demonstrates activity in the Matrigel of neovascularization implant model.This Matrigel neovascularization model relates in the clarification ＂ of subcutaneous implantation marble ＂ extracellular matrix and forms neovascularity, this be existence by the former angiogenesis factor that produces tumour cell cause (for example referring to Passaniti, A., Deng, Lab.Investig. (1992), 67 (4), 519-528; Anat.Rec. (1997), 249 (1), 63-73; Int.J.Cancer (1995), 63 (5), 694-701; Vasc.Biol. (1995), 15 (11), 1857-6).This model preferably moves 3-4 days, and terminal point comprise relative with the animal of not handling with inhibitor, after the excision implant naked eyes of neovascularization visible/microvessel density of image scoring, microscopically measures and quantitative hemoglobin analysis (Drabkinmethod).This model can also be used bFGF or HGF as stimulator.
The xenograft tumour that some The compounds of this invention that suppresses one or more oncogenes, proto-oncogene or propagation deopendent protein kinase or vasculogenesis acceptor PTK also suppresses former mouse, rat or people in mouse growth or suppress its transfer in mouse model.
Example
By the base catalysis aldol condensation, eliminate the core texture of the synthetic The compounds of this invention of reaction then.Reaction scheme I is the general expression of this reaction.According to the proper raw material II of the synthetic general formula I V compound of the present invention of general reaction scheme I and III be can buy and/or can prepare according to method preparation well known in the art and/or according to methods described herein.
Figure A0081368202111
Reaction scheme I:4-[(replaces) methylene radical]-the general synthetic method of 2-pyrazolin-5-one.1.4-[(pyrroles-2-yl) methylene radical]-2-pyrazolin-5-one (V). Embodiment 1:3-cyclopropyl-4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one.
With 3-cyclopropyl-2-pyrazolin-5-one (790mg, 6.3mmol), 4,5-dimethyl pyrrole-2-formaldehyde (800mg, 6.5mmol) and the reaction mixture of 100mg piperidines in 50mL ethanol stirred 3.5 hours at 90 ℃.Removal of solvent under reduced pressure.Solid residue is through the flash column chromatography purifying, and use (3: 7) ethyl acetate: hexane is made moving phase, is further purified by recrystallization from toluene then.Embodiment 40:3-tertiary butyl urea groups-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one.
With 3-amino-4-[(pyrroles-2-yl) methylene radical]-2-pyrazolin-5-one (1.7mmol) and the reaction mixture of tert-butyl isocyanate (1mL) in the 5mL ethyl acetate stirred 2 hours at 80 ℃.Filter and collect product and recrystallization from ethanol.Embodiment 88:4-{[4-(2-dimethylamino ethoxycarbonyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one.
With 4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3 isopropoxies-2-pyrazolin-5-one (200mg, 0.68mmol) handle with oxalyl chloride (0.2ml) by the mixture in methylene dichloride (20ml) and 1 DMF.Continue to stir 24 hours, and add dimethylaminoethanol (0.6g, 6.7mmol) solution in methylene dichloride (5ml).Continue to stir 24 hours.Evaporating solvent is to doing solid residue NaHCO 3(5%) handles and uses dichloromethane extraction.Remove the solid recrystallization from normal heptane that obtains after desolvating.Embodiment 194:4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one N-oxide compound
With embodiment 176 (0.2g, 0.54mmol) and metachloroperbenzoic acid (0.2g, 1.1mmol) mixture in chloroform (50ml) was stirring at room 48 hours.Remove and desolvate to doing, resistates is through flash chromatography purifying (methylene dichloride/ethanol 9: 1).Productive rate 30%, 192 ℃ of fusing points (ethanol).
Table 1: other synthetic compounds with structural formula V
Embodiment Substituting group on the ring A R 1 Recrystallization solvent Productive rate % Method
???1 4, the 5-dimethyl Cyclopropyl Toluene ????30 See embodiment 1
???2 Do not have Benzyl Toluene: heptane ????64 See embodiment 1
???3 Do not have 4-methoxyl group phenoxymethyl Methyl alcohol ????36 See embodiment 1
???4 Do not have Phenoxymethyl ????NA ????33 See embodiment 1
???5 Do not have 4-chlorophenoxy methyl Ethanol ????33 See embodiment 1
???6 Do not have The 4-methoxy-benzyl Ethanol ????21 See embodiment 1
???7 4-(2-propyloic)-3-methyl Benzyl ????NA See embodiment 1
???8 3-(2-propyloic)-4-methyl Benzyl Virahol See embodiment 1
???9 Do not have 4-methylenedioxy phenoxy ylmethyl Methyl alcohol ????42 See embodiment 1
???10 Do not have Amino Virahol ????90 See embodiment 1
???11 Do not have Isopropoxy Virahol ????52 See embodiment 1
???12 Do not have Styroyl ????NA ????86 See embodiment 1
???13 Do not have Phenylamino Virahol ????86 See embodiment 1
???14 Do not have The 4-methyl-benzyl Methyl alcohol ????60 See embodiment 1
???15 Do not have 4-methylbenzene amino Methyl alcohol ????86 See embodiment 1
???16 Do not have 4-anisole amino DMF: water ????92 See embodiment 1
???17 Do not have 4-benzyl chloride base Ethanol ????56 See embodiment 1
???18 Do not have 4-chlorobenzene amino Ethanol ????90 See embodiment 1
???19 Do not have 3-chlorophenoxy methyl ????NA ????50 See embodiment 1
???20 Do not have Indol-3-yl Ethanol ????90 See embodiment 1
???21 Do not have The 3-methoxy-benzyl Methyl alcohol ????21 See embodiment 1
???22 Do not have 3, the 4-dimethoxy-benzyl Ethanol ????83 See embodiment 1
???23 Do not have 4-phenetole ethyl Ethanol ????91 See embodiment 1
???24 Do not have 4-phenyl phenoxymethyl Methyl alcohol ????72 See embodiment 1
???25 Do not have The 2-phenyl propyl Heptane ????10 See embodiment 1
????26 Do not have The 3-phenyl propyl Toluene: heptane ????60 See embodiment 1
????27 Do not have The 4-leptodactyline Methyl alcohol ????76 See embodiment 1
????28 3, the 5-dimethyl Styroyl Methyl alcohol ????51 See embodiment 1
????29 Do not have 4-methylbenzene ethyl Ethanol ????53 See embodiment 1
????30 3, the 5-dimethyl Isopropoxy Heptane ????55 See embodiment 1
????31 Do not have Oxyethyl group Ethanol ????76 See embodiment 1
????32 Do not have 4-oil of mirbane ethyl Toluene ????48 See embodiment 1
????33 Do not have The 4-fluoroanilino Virahol ????66 See embodiment 1
????34 Do not have The 4-chlorobenzene ethyl Ethanol ????60 See embodiment 1
????35 4, the 5-dimethyl Isopropoxy Methyl alcohol ????55 See embodiment 1
????36 3,5-dimethyl-4-ethyl Isopropoxy Toluene ????47 See embodiment 1
????37 3,5-dimethyl-4-ethyl Styroyl Heptane ????49 See embodiment 1
????38 1-(4-hydroxybutyl) Isopropoxy ????NA ????80 See embodiment 1
????39 Do not have Cyclopentyloxy Methyl alcohol ????75 See embodiment 1
????40 Do not have Tertiary butyl urea groups Ethanol ????87 See embodiment 40
????41 The 4-methyl Isopropoxy Toluene ????34 See embodiment 1
????42 The 4-methyl 4-amino-benzene ethyl ????NA ????27 See embodiment 1
????43 The 1-methyl Isopropoxy Toluene ????55 See embodiment 1
????44 The 5-methyl Isopropoxy Methyl alcohol: water ????30 See embodiment 1
????45 3,5-dimethyl-4-ethyl 4-amino-benzene ethyl Toluene ????50 See embodiment 1
????46 The 5-methyl Oxyethyl group Methyl alcohol ????58 See embodiment 1
????47 3,5-dimethyl-4-ethyl 4-formamyl styroyl DMF: water ????82 See embodiment 1
????48 3,5-dimethyl-4-ethyl 4-methoxycarbonyl styroyl Methyl alcohol ????70 See embodiment 1
????49 3,5-dimethyl-4-ethoxycarbonyl Isopropoxy Ethanol ????81 See embodiment 1
????50 3,5-dimethyl-4-ethoxycarbonyl 4-amino-benzene ethyl Ethanol ????62 See embodiment 1
????51 The 5-ethyl Isopropoxy Heptane ????48 See embodiment 1
????52 3,5-dimethyl-4-ethyl The 4-leptodactyline Virahol ????35 See embodiment 1
????53 Do not have Ethoxycarbonylmethyl group Ethanol ????35 See embodiment 1
????54 Do not have The amino carbonyl methyl of 4-anisole Methyl alcohol ????46 See embodiment 1
????55 3-(2-carboxy ethyl)-4-methyl Sec.-propyl Ethanol ????32 See embodiment 1
????56 Do not have Cyclopropyl Ethanol ????50 See embodiment 1
????57 Do not have Cyclobutyl Ethanol ????65 See embodiment 1
????58 Do not have The 3-pyridyl Ethanol ????50 See embodiment 1
????59 1-(3, the 5-dichlorophenyl) Cyclopropyl Ethanol ????30 See embodiment 1
????60 Do not have 2,2,3,3-tetramethyl-ring propyl group Toluene ????55 See embodiment 1
????61 3, the 5-dimethyl Cyclopropyl Toluene ????33 See embodiment 1
????62 Do not have Cyclopentyl Toluene ????66 See embodiment 1
????63 Do not have 2-methyl cyclopropyl Hexane ????44 See embodiment 1
????64 Do not have Benzothiazole-2-base DMF: water ????60 See embodiment 1
????65 4, the 5-dimethyl The 3-pyridyl Ethanol ????35 See embodiment 1
????66 3,5-dimethyl-4-ethyl Cyclopropyl Ethanol ????50 See embodiment 1
????67 Do not have Pyrroles-2-base Methyl alcohol ????88 See embodiment 1
????68 The 4-methyl Cyclopropyl Ethanol ????35 See embodiment 1
????69 The 4-methyl Benzothiazole-2-base Ethanol ????48 See embodiment 1
????70 3, the 5-dimethyl The 3-pyridyl Ethanol ????24 See embodiment 1
????71 3,5-dimethyl-4-ethyl The 3-pyridyl Ethanol ????51 See embodiment 1
????72 The 5-methyl Cyclopropyl Ethanol ????50 See embodiment 1
????73 The 5-methyl The 3-pyridyl Ethanol ????47 See embodiment 1
????74 The 5-ethyl Cyclopropyl Ethanol: water ????21 See embodiment 1
????75 3,5-dimethyl-4-ethoxycarbonyl Cyclopropyl Ethanol ????83 See embodiment 1
????76 The 5-phenyl Isopropoxy Methyl alcohol ????66 See embodiment 1
????77 Do not have Propyl group ????NA ????49 See embodiment 1
????78 Do not have Methyl ????NA ????6 See embodiment 1
????79 Do not have 4-isopropyl benzene amino ????NA ????50 See embodiment 1
????80 Do not have The 3-phenylamino ????NA ????80 See embodiment 1
????81 1-(4-hydroxybutyl) Cyclopropyl Ethanol ????34 See embodiment 1
????82 4-(2-propyloic)-3-methyl Isopropoxy Ethanol ????46 See embodiment 1
????83 4-carboxyl-3, the 5-dimethyl Isopropoxy ????NA ????41 See embodiment 1
????84 4, the 5-tetramethylene Isopropoxy Ethanol ????77 See embodiment 1
????85 3,4-dimethyl-4-morpholino methyl Isopropoxy ????NA ????30 See embodiment 1
????86 3,5-dimethyl-4-dimethylamino methyl Isopropoxy Heptane ????30 See embodiment 1
????87 4-ethanoyl-3, the 5-dimethyl Isopropoxy Ethanol ????62 See embodiment 1
????88 3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) Isopropoxy Heptane ????40 See embodiment 88
????89 3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) Isopropoxy Toluene: heptane ????41 See embodiment 88
????90 The 5-ethoxycarbonyl Isopropoxy Methyl alcohol ????79 See embodiment 1
????91 The 5-carboxyl Isopropoxy Toluene ????83 See embodiment 1
????92 Do not have 4-chlorobenzene amino carbonyl methyl DMF/ water ????50 See embodiment 1
????93 The 5-phenyl Cyclopropyl Ethanol ????72 See embodiment 1
????94 3,5-dimethyl-4-ethyl Tetrahydrofuran (THF)-3-base Toluene ????44 See embodiment 1
????95 4-carboxyl-3, the 5-dimethyl Cyclopropyl Ethanol ????69 See embodiment 1
????96 3,5-dimethyl-4-ethoxycarbonyl The 3-pyridyl Ethanol ????86 See embodiment 1
????97 3,5-dimethyl-4-morpholino methyl Cyclopropyl ????NA ????34 See embodiment 1
????98 3, the 4-dimethyl Pyrazinyl Methyl alcohol ????60 See embodiment 1
????99 4-(2-carboxy ethyl)-3-methyl Cyclopropyl Methyl alcohol ????51 See embodiment 1
????100 3,5-dimethyl-4-dimethylamino methyl Cyclopropyl ????NA ????67 See embodiment 1
????101 The 5-ethoxycarbonyl Cyclopropyl Ethanol ????91 See embodiment 1
????102 4, the 5-tetramethylene Cyclopropyl Ethanol ????84 See embodiment 1
????103 Do not have 2-methoxycarbonyl ethyl Ethanol ????56 See embodiment 1
????104 Do not have Ethoxycarbonyl ????NA ????40 See embodiment 1
????105 Do not have Sec.-propyl ????NA ????44 See embodiment 1
????106 Do not have Instead-the 2-phenycyclopropyl Toluene ????46 See embodiment 1
????107 Do not have Cyclohexyl Toluene ????32 See embodiment 1
????108 4, the 5-tetramethylene Cyclopropyl amino Ethanol ????50 See embodiment 1
????109 5-morpholino methyl Cyclopropyl Ethyl acetate ????72 See embodiment 1
????110 The 5-carboxyl Cyclopropyl Ethanol ????50 See embodiment 1
????111 4-chlorine Oxyethyl group Ethanol ????88 See embodiment 1
????112 The 4-bromine Oxyethyl group Ethanol ????70 See embodiment 1
????113 5-chlorine Oxyethyl group ????NA ????37 See embodiment 1
????114 4-chlorine Cyclopropyl Ethanol ????42 See embodiment 1
????115 The 4-bromine Cyclopropyl Ethanol ????50 See embodiment 1
????116 4, the 5-tetramethylene Pyrazinyl Ethanol ????85 See embodiment 1
????117 4, the 5-tetramethylene The 3-pyridyl Ethanol ????84 See embodiment 1
????118 4-carboxyl-3, the 5-dimethyl Pyrazinyl ????DMF ????66 See embodiment 1
????119 3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) Cyclopropyl ????NA ????71 See embodiment 88
????120 3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) Pyrazinyl ????NA ????20 See embodiment 88
????121 3,5-dimethyl-4-dimethylamino methyl Pyrazinyl Toluene ????76 See embodiment 1
????122 3,5-dimethyl-4-dimethylamino methyl maleate Pyrazinyl Ethanol ????98 The maleate (seeing footnote) that forms by the free alkali of embodiment 121
????123 3,5-dimethyl-4-(2-morpholino B aminocarbonyl) Pyrazinyl Toluene ????20 See embodiment 1
????124 3, the 5-dimethyl The 2-pyridyl Ethanol ????36 See embodiment 1
????125 3,5-dimethyl-4-ethyl The 2-pyridyl Ethanol ????50 See embodiment 1
????126 4, the 5-tetramethylene The 2-pyridyl Ethanol ????58 See embodiment 1
????127 3, the 5-dimethyl The 2-furyl Ethanol ????51 See embodiment 1
??128 3,5-dimethyl-4-morpholino methyl Pyrazinyl ????NA ????28 See embodiment 1
??129 3, the 5-dimethyl The 2-thienyl Ethanol ????25 See embodiment 1
??130 The 4-ethoxycarbonyl Cyclopropyl Ethanol ????68 See embodiment 1
??131 3,5-dimethyl-4-trifluoroacetamido methyl Cyclopropyl Ethanol ????70 See embodiment 1
??132 4-amino methyl-3, the 5-dimethyl Cyclopropyl Ethanol ????30 See embodiment 1
??133 3, the 5-dimethyl Benzothiazole-2-base Ethanol ????40 See embodiment 1
??134 3,5-dimethyl-4-morpholino methyl Benzothiazole-2-base Ethanol ????40 See embodiment 1
??135 3,5-dimethyl-4-ethyl Pyrazinyl Ethanol ????74 See embodiment 1
??136 The 4-ethoxycarbonyl Pyrazinyl Toluene ????26 See embodiment 1
??137 The 4-carboxyl Pyrazinyl Methyl alcohol ????70 See embodiment 1
??138 3,5-dimethyl-4-diethanolamine ylmethyl Pyrazinyl Ethanol ????50 See embodiment 1
??139 3,5-dimethyl-4-trifluoroacetamido methyl Pyrazinyl ????NA ????78 See embodiment 1
??140 4-ethoxycarbonyl-3-phenyl Cyclopropyl Ethanol ????68 See embodiment 1
??141 3,5-dimethyl-4-(1-pyrrolidyl methyl) Pyrazinyl Toluene ????23 See embodiment 1
??142 3,5-dimethyl-4-dimethylamino methyl The 2-furyl Toluene ????20 See embodiment 1
??143 3,5-dimethyl-4-dimethylamino methyl The 2-thienyl Toluene ????48 See embodiment 1
??144 3,5-dimethyl-4-dimethylamino methyl The 3-pyridyl Toluene ????51 See embodiment 1
??145 3,5-dimethyl-4-ethoxycarbonyl Phenyl Ethanol ????89 See embodiment 1
??146 3,5-dimethyl-4-ethyl Phenyl Methyl alcohol ????34 See embodiment 1
??147 3,4-two (ethoxycarbonyl) Oxyethyl group Ethanol ????54 See embodiment 1
??148 The 4-ethoxycarbonyl Oxyethyl group Methyl alcohol ????30 See embodiment 1
??149 3,5-dimethyl-4-ethoxycarbonyl 2-(3-pyridyl) ethyl Ethanol ????81 See embodiment 1
??150 3,5-dimethyl-4-ethoxycarbonyl 1-methyl-2-styroyl Ethanol ????52 See embodiment 1
??151 4-carboxyl-3, the 5-dimethyl Oxyethyl group DMF: water ????81 See embodiment 1
??152 The 5-nitro Oxyethyl group Ethanol ????64 See embodiment 1
??153 The 4-nitro Oxyethyl group Toluene ????95 See embodiment 1
??154 The 4-carboxyl Oxyethyl group ??NA ????40 See embodiment 1
??155 3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) Oxyethyl group Heptane ????86 See embodiment 88
??156 5-chloro-3-methoxycarbonyl-4-methoxycarbonyl methyl Oxyethyl group Ethanol ????46 See embodiment 1
??157 3-(2-carboxy ethyl)-4-methyl Oxyethyl group ??NA ????54 See embodiment 1
??158 3,5-dimethyl-4-ethoxycarbonyl Oxyethyl group Ethanol ????82 See embodiment 1
??159 4, the 5-tetramethylene Oxyethyl group Heptane ????80 See embodiment 1
??160 3,5-dimethyl-4-ethoxycarbonyl Trifluoromethyl Ethanol ????45 See embodiment 1
??161 3,5-dimethyl-4-ethoxycarbonyl The 5-isoxazolyl DMF: water ????74 See embodiment 1
??162 3,5-dimethyl-4-ethoxycarbonyl The 3-aminophenyl Ethanol ????76 See embodiment 1
??163 4-morpholino B aminocarbonyl Oxyethyl group ??NA ????30 See embodiment 88
??164 4-ethoxycarbonyl-3-phenyl Pyrazinyl Toluene ????70 See embodiment 1
??165 4-(4-methyl isophthalic acid-piperazinyl methyl)-3, the 5-dimethyl Pyrazinyl ??DMF ????58 See embodiment 1
??166 4-diethylin methyl-3, the 5-dimethyl Pyrazinyl ??NA ????20 See embodiment 1
??167 3,5-dimethyl-4-piperidine subbase methyl Pyrazinyl Toluene ????25 See embodiment 1
??168 3,5-dimethyl-4-piperidine subbase methyl The 5-isoxazolyl ????NA ????35 See embodiment 1
??169 3,5-dimethyl-4-dimethylamino methyl The 5-isoxazolyl ????NA ????30 See embodiment 1
??170 5-methyl-4-dimethylamino methyl Pyrazinyl Toluene-heptane ????75 See embodiment 1
??171 3,5-dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylamino-methyl] Pyrazinyl Methyl alcohol ????40 See embodiment 1
??172 3-dimethylamino methyl-4, the 5-tetramethylene Cyclopropyl ????NA ????30 See embodiment 1
??173 3-dimethylamino methyl-4, the 5-tetramethylene Pyrazinyl ????NA ????30 See embodiment 1
??174 3,5-dimethyl-4-dimethylamino methyl maleate Cyclopropyl Ethanol ????90 The maleate (seeing footnote) that forms by the free alkali of embodiment 100
??175 4-(3-chlorine propionyl)-3, the 5-dimethyl Pyrazinyl Toluene ????88 See embodiment 1
??176 4-(2-diethyllaminoethyl)-3, the 5-dimethyl Pyrazinyl Ethanol ????95 See embodiment 1
??177 3,5-dimethyl-4-(dimethylamino methyl) 5-methyl-3-isoxazolyl Toluene/heptane ????40 See embodiment 1
??178 3,5-dimethyl-4-(4-hydroxy piperidine subbase methyl) Pyrazinyl Methyl alcohol ????40 See embodiment 1
??179 4-amino methyl-3,5-dimethyl maleic acid salt Pyrazinyl Methyl alcohol ????76 See embodiment 1
??180 4-(4-benzyl piepridine subbase methyl)-3, the 5-dimethyl Pyrazinyl Toluene ????80 See embodiment 1
??181 3,5-dimethyl-4-(2-hydroxyethyl) Pyrazinyl ????NA ????80 See embodiment 1
???182 3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] Pyrazinyl Toluene ????67 See embodiment 1
???183 3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] Cyclopropyl Toluene ????20 See embodiment 1
???184 3,5-dimethyl-4-(2-hydroxyethyl) Cyclopropyl ????NA ????23 See embodiment 1
???185 3,5-dimethyl-4-(2-ethylamino ethyl) Pyrazinyl ????NA ????35 See embodiment 1
???186 4-(3-diethylin propyl group)-3, the 5-dimethyl Pyrazinyl Ethanol ????52 See embodiment 1
???187 3,5-dimethyl-4-(3-hydroxypropyl) Pyrazinyl Ethanol ????82 See embodiment 1
???188 3,5-dimethyl-4-dimethylamino ethanoyl hydrochloride Pyrazinyl Ethanol/ether ????51 See embodiment 1
???189 3,5-dimethyl-4-dimethylamino ethanoyl Oxyethyl group Ethanol/ether ????44 See embodiment 1
???190 4-(2-diethyllaminoethyl)-3, the 5-dimethyl Cyclopropyl Heptane ????54 See embodiment 1
???191 3,5-dimethyl-4-(2-dimethylaminoethyl) Pyrazinyl Toluene ????48 See embodiment 1
???192 3,5-dimethyl-4-(4-hydroxybutyl) Pyrazinyl Methyl alcohol ????58 See embodiment 1
???193 4-(4-diethylin butyl)-3, the 5-dimethyl Pyrazinyl Toluene ????60 See embodiment 1
???194 4-(2-diethyllaminoethyl-N-oxide compound)-3, the 5-dimethyl Pyrazinyl Ethanol ????30 See embodiment 194
???195 3,5-dimethyl-4-(1-pyrrolidyl ethanoyl) Pyrazinyl ????NA ????57 See embodiment 1
???196 4-diethylin ethanoyl-3, the 5-dimethyl Pyrazinyl ????NA ????52 See embodiment 1
??197 3-sec.-propyl-5-methyl Pyrazinyl Ethanol ????44 See embodiment 1
??198 3,5-dimethyl-4-[3-(1-pyrrolidyl propyl group)] Pyrazinyl Ethanol ????30 See embodiment 1
??199 4-dimethylamino methyl-3-sec.-propyl-5-methyl Pyrazinyl Toluene ????40 See embodiment 1
??200 4-dimethylamino methyl-3-sec.-propyl-5-methyl Cyclopropyl Toluene ????40 See embodiment 1
??201 3,5-dimethyl-4-(2-oxyethyl group oxalyl group) Pyrazinyl Ethanol ????40 See embodiment 1
??202 3,5-dimethyl-4-(2-ethylamino ethyl) Cyclopropyl ????NA ????60 See embodiment 1
??203 3,5-dimethyl-4-(2-cyclopropylamino ethyl) Pyrazinyl Toluene ????40 See embodiment 1
??204 3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] Pyrazinyl ????NA ????40 See embodiment 1
??205 3,5-dimethyl-4-(2-cyclopropyl amino-ethyl) Cyclopropyl Toluene ????36 See embodiment 1
??206 3,5-dimethyl-4-(2-diethyl hydrogen base ethyl) The 2-pyrimidyl Toluene ????35 See embodiment 1
??207 3,5-dimethyl-4-(2-diethyllaminoethyl) The 2-pyridazinyl Toluene ????40 See embodiment 1
??208 3,5-dimethyl-4-(2-diethyllaminoethyl) The 2-pyrimidyl Toluene ????50 See embodiment 1
??209 3,5-dimethyl-4-(2-diethyllaminoethyl) The 2-pyridazinyl Toluene ????30 See embodiment 1
Table 1A: physical data with synthetic compound of structural formula V.
Embodiment ????Mp.(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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 ????68.55 ????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 ???(0.3?H 2O) * ????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?H 2O) * ???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 ????14.30
????24 ????(0.25?H 2O) * ???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?H 2O) * ???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?H 2O) * ??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 ????6.08 ????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 ?? 13C and 1H NMR and analysis LC/MS data are consistent with specified 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 ??184-186 ????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 2O) * ????255-57 ????61.68 ????61.48 ????6.47 ????6.45 ????21.58 ????21.68
????179 ???(0.5?H 2O) ????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?H 2O) ????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 HRMN is consistent with specified structure with the EM data
????186 ???(3?H 2O) ????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 ???(ClH.2 ????H 2O) ????＞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?H 2O) ????220 ????61.94 ????61.66 ????5.93 ????5.72 ????21.68 ????21.54
????196 ???(0.5?H 2O) ????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?H 2O) ????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?H 2O) ????203-205 ????65.23 ????65.05 ????5.82 ????5.84 ????24.20 ????23.77
????205 ???(0.4?H 2O) ????158-160 ????67.64 ????67.93 ????7.81 ????7.74 ????17.53 ????17.40
????206 ???(0.2?H 2O) ????144-146 ????64.91 ????64.87 ????7.19 ????7.30 ????22.71 ????22.53
????207 ???(0.2?H 2O) ????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
*For ultimate analysis, the solvent of amount shown in the molecular weight that is calculated comprises.
Footnote: at room temperature, form maleate, cooling, and the product of filtering for crystallizing then by in ethanol, in free alkali, adding the ethanolic soln of toxilic acid.The II.4-[(indol-3-yl) methylene radical]-2-pyrazolin-5-one (VI).
Figure A0081368202281
Embodiment 210:3-benzyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one.
With 3-benzyl-2-pyrazolin-5-one (905mg, 5.2mmol), the 3-indolecarboxaldehyde (800mg, 5.6mmol) and the reaction mixture of piperidines (100mg) in ethanol (50mL) stirred 3 hours at 90 ℃.After the cool overnight, filter and collect product, recrystallization carries out purifying from ethanol then.
Table 2: other have the synthetic compound of structural formula VI.
Embodiment Substituting group on the indoles R 1 Recrystallization solvent Productive rate % Method
????210 Do not have Benzyl Ethanol ????76 See embodiment 210
????211 1-(4-hydroxybutyl) Benzyl Methyl alcohol ????51 See embodiment 210
????212 Do not have 4-methoxyl group phenoxymethyl Virahol ????67 See embodiment 210
????213 Do not have Phenoxymethyl Virahol ????94 See embodiment 210
????214 Do not have 4-chlorophenoxy methyl Ethanol ????65 See embodiment 210
????215 Do not have The 4-methoxy-benzyl Ethanol ????90 See embodiment 210
????216 Do not have 4-methylenedioxy phenoxy ylmethyl Ethanol ????93 See embodiment 210
????217 Do not have Styroyl Ethanol ????84 See embodiment 210
????218 Do not have Sec.-propyl Methyl alcohol ????81 See embodiment 210
????219 Do not have The 4-methyl-benzyl Ethanol ????95 See embodiment 210
????220 Do not have Phenylamino Virahol ????52 See embodiment 210
????221 Do not have 4-methylbenzene amino Methyl alcohol ????60 See embodiment 210
????222 Do not have 4-anisole amino Ethanol ????96 See embodiment 210
????223 Do not have 4-benzyl chloride base Ethanol ????77 See embodiment 210
????224 1-(4-hydroxybutyl) The 4-methoxy-benzyl DMF: water ????89 See embodiment 210
????225 Do not have 4-chlorobenzene amino DMF: water ????86 See embodiment 210
????226 Do not have The 3-methoxy-benzyl DMF: water ????99 See embodiment 210
????227 Do not have 3, the 4-dimethoxy-benzyl DMF: water ????88 See embodiment 210
????228 Do not have The 4-hydroxybenzyl DMF: water ????56 See embodiment 210
????229 Do not have 3-chlorophenoxy methyl Virahol ????89 See embodiment 210
????230 Do not have Indol-3-yl Methyl alcohol ????58 See embodiment 210
????231 Do not have 4-anisole ethyl Virahol ????88 See embodiment 210
????232 Do not have 4-phenyl phenoxymethyl ????NA ????91 See embodiment 210
????233 Do not have The 2-phenyl propyl Methyl alcohol ????60 See embodiment 210
????234 Do not have The 3-phenyl propyl Ethanol ????76 See embodiment 210
????235 Do not have The 4-leptodactyline Methyl alcohol ????51 See embodiment 210
????236 Do not have 4-methylbenzene ethyl Ethanol ????86 See embodiment 210
????237 Do not have Oxyethyl group Ethanol ????90 See embodiment 210
????238 1-(4-hydroxybutyl) Isopropoxy Toluene: heptane ????43 See embodiment 210
????239 1-(4-hydroxybutyl) Styroyl Methyl alcohol ????80 See embodiment 210
????240 Do not have 4-oil of mirbane ethyl Virahol ????83 See embodiment 210
????241 Do not have Propoxy- DMF: water ????43 See embodiment 210
????242 Do not have The 4-fluoroanilino Ethyl acetate ????65 See embodiment 210
????243 Do not have 4-amino-benzene ethyl Methyl alcohol: water ????74 See embodiment 210
????244 The 2-methyl Isopropoxy Methyl alcohol ????40 See embodiment 210
????245 The 7-methyl Isopropoxy Ethanol ????98 See embodiment 210
????246 The 7-methyl Styroyl DMF: water ????97 See embodiment 210
????247 Do not have Cyclopentyl Ethanol ????56 See embodiment 210
????248 The 1-methyl Isopropoxy Ethanol ????81 See embodiment 210
??249 Do not have 4-methoxycarbonyl styroyl Ethanol ????77 See embodiment 210
??250 The 1-sec.-propyl Isopropoxy Toluene: heptane ????71 See embodiment 210
??251 The 1-methyl The 4-leptodactyline Ethanol ????50 See embodiment 210
??252 Do not have Sec.-propyl Ethanol ????76 See embodiment 210
??253 Do not have 4-chlorobenzene amino carbonyl methyl DMF: water ????40 See embodiment 210
??254 Do not have Ethoxycarbonylmethyl group Methyl alcohol ????40 See embodiment 210
??255 Do not have The amino carbonyl methyl of 4-anisole DMF: water ????40 See embodiment 210
??256 Do not have Cyclopropyl DMF: water ????50 See embodiment 210
??257 Do not have The 3-pyridyl Ethanol ????50 See embodiment 210
??258 Do not have 2-aminocarboxyl ethyl Methyl alcohol ????55 See embodiment 210
??259 Do not have Cyclobutyl Ethanol ????79 See embodiment 210
??260 Do not have 2-(dimethylamino carbonyl) ethyl Ethanol ????97 See embodiment 210
??261 1-(4-hydroxybutyl) Cyclopropyl Ethanol ????80 See embodiment 210
??262 Do not have The 4-pyridyl Ethanol ????91 See embodiment 210
??263 Do not have Cyclopentyl Ethanol ????75 See embodiment 210
??264 Do not have 2,2,3,3-tetramethyl-ring propyl group Ethanol ????32 See embodiment 210
??265 Do not have 2-methyl cyclopropyl Ethanol ????34 See embodiment 210
??266 1-(4-hydroxybutyl) Cyclohexyl Toluene ????41 See embodiment 210
??267 1-(4-hydroxybutyl) The 4-pyridyl Ethanol ????50 See embodiment 210
??268 Do not have Benzothiazole-2-base Ethanol ????50 See embodiment 210
??269 Do not have The 2-pyridyl ????67 See embodiment 210
??270 Do not have Dimethylamino Ethanol ????77 See embodiment 210
??271 Do not have Pyrroles-2-base Ethanol ????83 See embodiment 210
??272 Do not have 6-methoxyl group benzo thiazol-2-yl Ethanol ????60 See embodiment 210
??273 The 1-methyl Cyclopropyl Ethanol ????76 See embodiment 210
??274 The 7-methyl Cyclopropyl Ethanol ????60 See embodiment 210
??275 The 1-methyl The 3-pyridyl Ethanol ????64 See embodiment 210
??276 Do not have Propyl group ???NA ????63 See embodiment 210
??277 Do not have Methyl ???NA ????68 See embodiment 210
??278 Do not have Trifluoromethyl ???NA ????14 See embodiment 210
??279 1-(4-hydroxybutyl) Hydrogen ???NA ????62 See embodiment 210
??280 1-(4-hydroxybutyl) Methyl ???NA ????36 See embodiment 210
??281 1-(4-hydroxybutyl) Trifluoromethyl ???NA ????7 See embodiment 210
??282 1-(4-hydroxybutyl) The tertiary butyl ???NA ????50 See embodiment 210
??283 Do not have Ethoxycarbonyl Ethanol ????74 See embodiment 210
??284 Do not have 2-methoxycarbonyl ethyl Ethanol ????79 See embodiment 210
??285 Do not have Instead-2-phenyl-1-cyclopropyl Ethanol ????92 See embodiment 210
??286 1-(4-hydroxybutyl) Cyclobutyl Ethanol ????26 See embodiment 210
??287 6-carboxyl-1-methyl Cyclopropyl Ethanol ????26 See embodiment 210
??288 5-methoxyl group-1-methyl Cyclopropyl Ethanol ????75 See embodiment 210
??289 The 1-methyl Pyrazinyl Ethanol ????82 See embodiment 210
??290 1, the 7-dimethyl Cyclopropyl Ethanol ????97 See embodiment 210
??291 The 1-methyl Tetrahydrofuran (THF)-3-base Ethanol ????78 See embodiment 210
??292 The 1-methyl Cyclopropyl amino Ethanol ????54 See embodiment 210
??293 6-carboxyl-1-methyl Isopropoxy DMF: water ????45 See embodiment 210
??294 1, the 7-dimethyl Isopropoxy Methyl alcohol ????53 See embodiment 210
??295 5-methoxyl group-1-methyl Isopropoxy Ethanol ????72 See embodiment 210
??296 The 1-methyl The 4-fluoroanilino Methyl alcohol ????80 See embodiment 210
??297 The 1-methyl Trifluoroacetamido Methyl alcohol ????70 See embodiment 210
??298 The 1-methyl 4-amino-benzene ethyl Toluene ????64 See embodiment 210
??299 The 1-methyl Amino Ethanol ????80 See embodiment 210
??300 Do not have The 4-chlorobenzene ethyl Ethanol ????85 See embodiment 210
??301 The 1-methyl Oxyethyl group Ethanol ????80 See embodiment 210
??302 The 1-methyl The 5-isoxazolyl DMF: water ????83 See embodiment 210
??303 The 1-methyl The tertiary butyl Ethanol ????92 See embodiment 210
??304 6-carboxyl-1-methyl Pyrazinyl ??DMF ????98 See embodiment 210
??305 1-methyl-6-[2-(4-morpholino) ethyl] aminocarboxyl Pyrazinyl ??NA ????20 See embodiment 210
Table 2A: physical data with synthetic compound of structural formula VI.
Embodiment ??Mp.(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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?H 2O) * ??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 ????72.49 ????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?.6 ????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 3OH) * ??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?H 2O) * ??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 3OH) * ??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 ????12.30 ????12.21
????239 ??205-207 ????74.39 ????74.32 ????6.50 ????6.58 ????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 3OH) * ??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 ????12.17 ????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?H 2O) * ???＞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?H 2O) * ???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 ????5.54 ????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?H 2O) * ???230-232 ????69.44 ????69.89 ????4.85 ????4.84 ????17.99 ????18.10
????276-282 ??? 13C and 1H NMR and analysis LC/MS data are consistent with specified 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 ???160-164(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 ????19.00
????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 ????5.59 ????5.67 ????20.92 ????20.91
*For ultimate analysis, the solvent of amount shown in the molecular weight that is calculated comprises.
Footnote: at room temperature, form maleate, cooling, and the product of filtering for crystallizing then by in ethanol, in free alkali, adding the ethanolic soln of toxilic acid.III.4-[(indoles-2-yl) methylene radical]-2-pyrazolin-5-one (VII).
Figure A0081368202351
Table 3: synthetic compound with structural formula VII.
Embodiment Substituting group on the indoles ??R 1 Recrystallization solvent Productive rate % Method
??306 Do not have Isopropoxy Ethanol ????81 See embodiment 210
??307 Do not have The 4-leptodactyline Ethanol ????45 See embodiment 210
??308 Do not have 4-amino-benzene ethyl ??NA ????20 See embodiment 210
??309 Do not have 4-methoxycarbonyl styroyl Toluene ????75 See embodiment 210
??310 Do not have 4-formamyl styroyl DMF: water ????90 See embodiment 210
??311 Do not have Cyclopropyl Ethanol ????35 See embodiment 210
??312 The 3-dimethylamino methyl Cyclopropyl ??NA ????20 See embodiment 210
??313 Do not have The 3-pyridyl Ethanol ????62 See embodiment 210
??314 The 5-methoxyl group Isopropoxy Methyl alcohol ????78 See embodiment 210
??315 The 1-methyl Isopropoxy DMF: water ????89 See embodiment 210
??316 Do not have Tetrahydrofuran (THF)-3-base Ethyl acetate ????30 See embodiment 210
??317 The 5-methoxyl group Cyclopropyl Ethanol ????33 See embodiment 210
??318 The 5-nitro Cyclopropyl ????DMF ????84 See embodiment 210
??319 Do not have Isopropylamino Methyl alcohol ????80 See embodiment 210
??320 Do not have 4-carboxyl styrene base DMF: water ????65 See embodiment 210
??321 Do not have Phenyl Ethanol ????55 See embodiment 210
??322 The 3-methyl Isopropoxy Methyl alcohol ????76 See embodiment 210
??323 3-(2-methoxycarbonyl-2-kharophen ethyl) Isopropoxy Toluene: heptane ????40 See embodiment 210
??324 Do not have Oxyethyl group Ethanol ????55 See embodiment 210
??325 3-(4-morpholino methyl) Oxyethyl group Ethanol ????65 See embodiment 210
??326 3-(4-morpholino methyl) Cyclopropyl Ethyl acetate ????46 See embodiment 210
??327 The 5-methoxyl group Pyrazinyl ????NA ????91 See embodiment 210
??328 The 5-methoxyl group The 2-pyridyl ????NA ????90 See embodiment 210
??329 4-chloro-6, the 7-dihydro Oxyethyl group Ethanol ????54 See embodiment 210
??330 4-chloro-6, the 7-dihydro Pyrazinyl Toluene ????83 See embodiment 210
??331 4-oxo-1,5,6, the 7-tetrahydrochysene Pyrazinyl Toluene ????40 See embodiment 210
??332 The 3-dimethylamino methyl Oxyethyl group Toluene-heptane ????41 See embodiment 210
Table 3A: physical data with synthetic compound of structural formula VII.
Embodiment ??Mp.(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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?H 2O) * ??263-265 ????69.44 ????69.51 ????5.09 ????5.05 ????15.43 ????15.21
????311 ????(0.75?H 2O) * ??238-240 ????68.04 ????67.68 ????5.55 ????5.11 ????15.87 ????15.75
????312 ????(0.25?H 2O) * ??202(d) ????69.10 ????69.13 ????6.60 ????6.46 ????17.91 ????17.56
????313 ????(0.5?H 2O) * ??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 ????4.47 ????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
*For ultimate analysis, the solvent of amount shown in the molecular weight that is calculated comprises.IV.4-[(7-azaindole-3-yl) methylene radical]-2-pyrazolin-5-one (VIII).
Figure A0081368202381
Table 4: synthetic compound with structural formula VIII.
Embodiment Substituting group on the azaindole R 1 Recrystallization solvent Productive rate % Method
????333 Do not have Benzyl DMF: water ????71 See embodiment 210
????334 1-(4-hydroxybutyl) Benzyl Ethyl acetate ????30 See embodiment 210
????335 Do not have 4-methoxyl group phenoxymethyl DMF: water ????80 See embodiment 210
????336 Do not have Isopropoxy Methyl alcohol ????61 See embodiment 210
????337 Do not have Amino DMF: water ????92 See embodiment 210
????338 Do not have The 4-methoxy-benzyl DMF: water ????96 See embodiment 210
????339 Do not have Phenylamino DMF: water ????77 See embodiment 210
????340 Do not have The 4-methyl-benzyl Ethanol ????95 See embodiment 210
????341 Do not have The 4-leptodactyline Ethanol ????84 See embodiment 210
????342 1-(4-hydroxybutyl) The 4-leptodactyline Methyl alcohol ????80 See embodiment 210
????343 Do not have Sec.-propyl Ethanol ????30 See embodiment 210
????344 Do not have Cyclopropyl Ethanol ????50 See embodiment 210
????345 Do not have Cyclobutyl Ethanol ????74 See embodiment 210
????346 Do not have The 3-pyridyl Ethanol ????40 See embodiment 210
????347 Do not have Phenyl ??NA ????56 See embodiment 210
????348 Do not have The 4-fluoroanilino ??NA ????14 See embodiment 210
????349 Do not have Propyl group ??NA ????24 See embodiment 210
????350 Do not have Methyl ???NA ????77 See embodiment 210
????351 Do not have Trifluoromethyl ???NA ????17 See embodiment 210
????352 Do not have The tertiary butyl ???NA ????80 See embodiment 210
????353 1-(4-hydroxybutyl) Trifluoromethyl ???NA ????6 See embodiment 210
????354 Do not have 4-isopropyl benzene amino ???NA ????30 See embodiment 210
????355 Do not have 3-methylbenzene amino ???NA ????70 See embodiment 210
????356 1-(4-hydroxybutyl) 3-methylbenzene amino ???NA ????30 See embodiment 210
????357 Do not have Styroyl DMF: water ????63 See embodiment 210
Table 4A: physical data with synthetic compound of structural formula VIII.
Embodiment ??Mp.(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
???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 ???(1?H 2O) * ??＞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 2O) * ??249-252 ????63.54 ????63.45 ????4.70 ????4.75 ????21.79 ????21.68
???340 ???(0.5?H 2O) * ??＞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 ???(0.2?5H 2O) * ??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 13C and 1H NMR and analysis LC/MS data are consistent with specified structure
????357 ??317-319 ????72.13 ????71.69 ????5.09 ????5.04 ????17.70 ????17.65
*For ultimate analysis, the solvent of amount shown in the molecular weight that is calculated comprises.
Footnote: at room temperature, form maleate, cooling, and the product of filtering for crystallizing then by in ethanol, in free alkali, adding the ethanolic soln of toxilic acid.V.4-(phenylmethylene)-2-pyrazolin-5-one (IX).
Figure A0081368202401
Table 5: synthetic compound with structural formula IX.
Embodiment Substituting group on the ring A ??R 1 Recrystallization solvent Productive rate % Method
????358 The 4-dimethylamino Benzyl Ethanol ????32 See embodiment 210
????359 The 4-dimethylamino Isopropoxy Toluene: heptane ????51 See embodiment 210
????360 The 4-dimethylamino Styroyl ??NA ????45 See embodiment 210
????361 The 4-dimethylamino Cyclopropyl Ethanol ????77 See embodiment 210
Table 5A: physical data with synthetic compound of structural formula IX.
Embodiment ?Mp.(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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-[(pyrazoles-4-yl) methylene radical]-2-pyrazolin-5-one (X).
Table 6: synthetic compound with structural formula X.
Embodiment Substituting group on the ring A ??R 1 Recrystallization solvent Productive rate % Method
????362 The 3-methyl Isopropoxy Ethyl acetate ??80 See embodiment 210
????363 The 3-methyl Cyclopropyl Toluene ??51 See embodiment 210
Table 6A: physical data with synthetic compound of structural formula X.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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
VII.4-[(imidazoles-2-yl) methylene radical]-2-pyrazolin-5-one (XI).
Figure A0081368202411
Table 7: synthetic compound with structural formula XI.
Embodiment Substituting group on the ring A ??R 1 Recrystallization solvent Productive rate % Method
????364 Do not have Isopropoxy Toluene ????45 See embodiment 210
????365 Do not have Cyclopropyl Ethanol ????42 See embodiment 210
Table 7A: physical data with synthetic compound of structural formula XI.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????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
The VIII.4-[(imidazol-4 yl) methylene radical]-2-pyrazolin-5-one (XII).
Figure A0081368202421
Table 8: synthetic compound with structural formula XII.
Embodiment Substituting group on the ring A R 1 Recrystallization solvent Productive rate % Method
??366 Do not have Isopropoxy Ethanol ????81 See embodiment 210
Table 8A: physical data with synthetic compound of structural formula XII.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
??366 ??259-260 ??54.53 ???54.84 ??5.49 ??5.68 ????25.43 ???25.37
IX.4-[(thiophene-2-yl) methylene radical]-2-pyrazolin-5-one (XIII).
Table 9: synthetic compound with structural formula XIII.
Embodiment Substituting group on the ring A ??R 1 Recrystallization solvent Productive rate % Method
????367 Do not have Cyclopropyl Ethanol ????20 See embodiment 210
Table 9A: physical data with synthetic compound of structural formula XIII.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????367 ?275-277 ??60.53 ??60.68 ??4.61 ??4.74 ??12.83 ??12.50
X.4-[(methylene radical indol-3-yl)]-1-antazoline-5-ketone (XIV).
Figure A0081368202431
Table 10: synthetic compound with structural formula XIV.
Embodiment Substituting group on the indoles ??R 1 Recrystallization solvent Productive rate % Method
??368 Do not have Sec.-propyl Ethanol ????54 See embodiment 210
Table 10A: physical data with synthetic compound of structural formula XIV.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????368 ?241-242 ??71.88 ??71.73 ??6.41 ??6.47 ??15.72 ??15.71
XI.4-[(pyrroles-3-yl) methylene radical]-2-pyrazolin-5-one (XV).
Figure A0081368202441
Table 11: synthetic compound with structural formula XV.
Embodiment Substituting group on the pyrroles ????R 1 Recrystallization solvent Productive rate % Method
??369 Do not have Isopropoxy Methyl alcohol ????70 See embodiment 210
Table 11A: physical data with synthetic compound of structural formula XV.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
????369 ?252-255 ??60.26 ??60.35 ?5.98 5.82 ??19.17 ??19.13
XII.4-[(quinoline-5-yl) methylene radical]-2-pyrazolin-5-one (XVI).
Figure A0081368202442
Table 12: synthetic compound with structural formula XVI.
Embodiment Substituting group on the quinoline ???R 1 Recrystallization solvent Productive rate % Method
??370 The 8-hydroxyl Isopropoxy Methyl alcohol ??40 See embodiment 210
Table 12A: physical data with synthetic compound of structural formula XVI.
Embodiment ??M.p. ??(℃) Ultimate analysis
Carbon Hydrogen Nitrogen
Calculated value Measured value Calculated value Measured value Calculated value Measured value
?370 ??＞300 ??64.64 ??64.43 ??5.09 ??5.01 ??14.13 ??13.98
X. raw material is synthetic.
A. synthetic 3-keto esters (XIX).
The synthetic 3-keto esters of employing general method has been shown in the scheme II. Scheme II: synthetic 3-keto esters embodiment 371:3-(2,2,3,3-tetramethyl-ring propyl group)-3-oxo ethyl propionate.
Under nitrogen atmosphere, to ice-cooled 2,2-dimethyl-1,3-diox-4, the 7-diketone (4.7g, (5g is 0.063mol) with 2,2 0.032mol) to add pyridine in the solution in anhydrous methylene chloride (37mL), 3, and 3-tetramethyl-cyclopropyl carbonyl chlorine (5g, 0.031mol).Kept 1 hour at 0 ℃, make it rise to ambient temperature overnight then.Change this mixture over to separating funnel then,, and wash with water twice with 3% hydrochloric acid washed twice.The organic layer dried over mgso is filtered and concentrating under reduced pressure then, obtains 5g scarlet oil.This oil refluxed 3 hours in dehydrated alcohol (60mL).Evaporating solvent, product is through distillation purifying.Embodiment 377:3-(6-methoxyl group benzo thiazol-2-yl)-3-oxo ethyl propionate.
(0.032mol) (7.2g 0.082mol), keeps temperature to be lower than 25 ℃ to middle adding ethyl acetate for 1.5g, 50% oily dispersion liquid to sodium hydride.Adding 2-ethoxycarbonyl-2-(6-methoxyl group) benzothiazole (5.25g, 0.022mol).Warm this mixture is to refluxing gently, then in stirred overnight at room temperature.With frozen water (50mL) termination reaction, and be adjusted to pH7.7 with concentrated hydrochloric acid.The product precipitation is filtered and collected, and washes with water, and is dry then.Embodiment 378:4-(4-phenyl phenoxy group)-ethyl 3-oxobutanoate.
At 0 ℃, with 2 hours, in 75mL dimethyl formamide (being called ＂ DMF ＂ hereinafter), add sodium hydride (5.0g, 0.114mol) and the 4-phenylphenol (15.3g, 0.09mol).Be added in 4-chloroacetyl acetacetic ester among the DMF (75mL) (5.0g, 0.03mol).This mixture stirred 1 hour at 0 ℃, and stirring at room 12 hours, neutralized with 50% phosphoric acid then, and use dichloromethane extraction.This product is through the silica gel chromatography purifying, and with (8: 2) toluene: ethanol is made moving phase.
Table 13: synthetic compound with structural formula XIX.
Embodiment ??R 1 Productive rate % ??b.p.(℃) ??m.p.(℃) Method
??371 2,2,3,3-tetramethyl-ring propyl group ????67 ??68(0.2mmHg) ????NA See embodiment 371
??372 2-methyl cyclopropyl ????50 ??62-4(0.2mmHg) ????NA See embodiment 371
??373 Instead-the 2-phenycyclopropyl ????64 ??138-40(0.2mmHg) ????NA See embodiment 371
??374 Tetrahydrofuran (THF)-3-base ????60 ??82-6(0.2mmHg) ????NA See embodiment 371
??375 The 3-mehtoxybenzyl ????62 ??132(0.2mmHg) ????NA See embodiment 371
??376 Styroyl ????55 ??110(0.2mmHg) ????NA See embodiment 371
??377 6-methoxyl group benzo thiazol-2-yl ????65 ??NA ????160 See embodiment 377
??378 4-phenyl phenoxymethyl ????33 ??NA ????83 See embodiment 378
??379 3-chlorophenoxy methyl ????32 ??147(8mmHg) ????NA See embodiment 378
??380 Pyrazinyl ????71 ??NA ????82 See embodiment 377
B. synthetic cyclopentyloxy thiocarbonyl ethyl acetate.
Figure A0081368202471
Scheme II I: synthetic alkoxyl group or aryloxy imines are for carbonylic acetic acid carbethoxy hydrochloride (R 9Be to replace or unsubstituted aliphatic series or aromatic group).Embodiment 381: synthetic cyclopentyloxy imines is for carbonylic acetic acid carbethoxy hydrochloride (XXII).
With anhydrous ethyl cyanacetate (14g, 0.12mol) and anhydrous cyclopentanol (12g, the mixture of 0.15mol 0 ℃ with hydrogen chloride gas saturated 3 hours, spend the night 0 ℃ of maintenance, dilute with ether then.The product precipitation is filtered and is collected and wash with ether.
Output 22.4g, (77%), fusing point 110-112 ℃
Figure A0081368202472
Reaction scheme IV: synthetic alkoxyl group sulfo-or aryloxy thiocarbonyl ethyl acetate.Embodiment 382: cyclopentyloxy thiocarbonyl ethyl acetate (XXIV)
The cyclopentyloxy imines is used hydrogen sulfide treatment 8 hours for the mixture of carbonylic acetic acid carbethoxy hydrochloride (22g 0.09mol) in anhydrous pyridine (150ml), kept 48 hours in room temperature.The concentrated hydrochloric acid acidifying of this reaction mixture, and use extracted with diethyl ether.Ether washes with water mutually, and is dry and through distillation purifying.
Output 15g, (75%), fusing point 140-142 ℃ (15mm Hg).C. Synthetic 2-pyrazolin-5-one is by following four kinds of method Synthetic 2-pyrazolin-5-ones.
Figure A0081368202481
Reaction scheme V: the method 1 of Synthetic 2-pyrazolin-5-one.
Figure A0081368202482
Reaction scheme VI: the method 2 of Synthetic 2-pyrazolin-5-one. Reaction scheme VII: the method 3 of Synthetic 2-pyrazolin-5-one. Reaction scheme VIII: the method 4 of Synthetic 2-pyrazolin-5-one.Embodiment 383:3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one.
To 3-(2,2,3,3-tetramethyl-ring propyl group-3-oxo ethyl propionate (4.41g, 0.020mol) add in the solution in dehydrated alcohol (60ml) hydrazine hydrate (1.1g, 0.024mol).Made reaction mixture refluxed 3 hours.After the cooling, evaporating solvent, resistates is developed with hexane, obtains white solid.Embodiment 411:3-(4-hydroxybenzyl)-2-pyrazolin-5-one
3-(4-the methoxy-benzyl)-suspension of 2-pyrazolin-5-one (2.5mmol) in the 100ml methylene dichloride of stirring-78 ℃ of coolings, is handled with 7.5ml boron tribromide (1M dichloromethane solution).-78 ℃ keep 1 hour after, stirring at room reaction mixture 12 hours.Make this mixture termination reaction with 50ml water.Water phase separated alkalizes with 5% sodium hydrogen carbonate solution.Filter the precipitation that forms, and crystallization from methyl alcohol.Embodiment 413:3-(4-formamyl styroyl)-2-pyrazolin-5-one
With 3-(4-methoxycarbonyl the styroyl)-mixture of 2-pyrazolin-5-one (7.7mmol) in 25% ammonium hydroxide (30ml) stirring at room 12 hours.The vacuum concentration solvent filters the solid product and the drying that form.Embodiment 414:3-(2-aminocarboxyl ethyl)-2-pyrazolin-5-one
With 3-(ethoxycarbonylmethyl group)-2-pyrazolin-5-one (1g, 5.8mmol) and NaCN (28mg, 0.58mmol) mixture in the methanol solution of 30ml 9M ammonia in sealed tube in 45 ℃ the heating 3 days.After the cooling, evaporating solvent is suspended in resistates in the water.Filter the solid of collecting precipitation.Embodiment 416:3-(4-anisole amino)-2-pyrazolin-5-one
3-amino-2-pyrazolin-5-one (20mmol), 4-anisidine (25mol) mixture in 50ml acetate was refluxed 4 hours.Evaporating solvent is suspended in resistates in the water.Cross filter solid and crystallization from methyl alcohol.
Table 14: synthetic compound with structural formula XXVI.
Embodiment ?R 1 Productive rate % ??M.p.(℃) Recrystallization solvent Method
??383 2,2,3,3-tetramethyl-ring propyl group ????44 ????195-7 ??NA See embodiment 383
??384 Ethoxycarbonylmethyl group ????44 ????115-6 Toluene See embodiment 383
??385 Pyrroles-2-base ????30 ????205-8 ??NA See embodiment 383
??386 Indol-3-yl ????69 ????250-3 ??NA See embodiment 383
??387 6-methoxyl group benzo thiazol-2-yl ????40 ????269-70 ??NA See embodiment 383
??388 2-methyl cyclopropyl ????70 ????196-7 Water See embodiment 383
??389 Instead-the 2-phenycyclopropyl ????65 ????194-5 Ethanol See embodiment 383
??390 Tetrahydrofuran (THF)-3-base ????36 ????204-5 Ethanol See embodiment 383
??391 The 4-methoxy-benzyl ????73 ????192-5 ??NA See embodiment 383
??392 The 4-methyl-benzyl ????80 ????212-4 Ethanol: water See embodiment 383
??393 4-benzyl chloride base ????67 ????206-8 Ethanol See embodiment 383
??394 The 4-methoxy-benzyl ????72 ????163-5 ??NA See embodiment 383
??395 3, the 4-dimethoxy-benzyl ????69 ????193-5 ??NA See embodiment 383
??396 Styroyl ????72 ????204-7 ??NA See embodiment 383
??397 The 2-phenyl propyl ????72 ????215 ??NA See embodiment 383
??398 The 2-phenyl propyl ????76 ????200-1 Ethanol See embodiment 383
??399 4-anisole ethyl ????85 ????230 Ethanol See embodiment 383
??400 4-methylbenzene ethyl ????90 ????251-2 ??NA See embodiment 383
??401 The 4-chlorobenzene ethyl ????63 ????243 ??NA See embodiment 383
??402 4-oil of mirbane ethyl ????69 ????247 DMF: water See embodiment 383
??403 4-amino-benzene ethyl ????61 ????220-2 ??NA See embodiment 383
??404 4-methoxycarbonyl styroyl ????77 ????259-60 Ethanol See embodiment 383
??405 4-phenyl phenoxymethyl ????50 ????250 Ethanol See embodiment 383
??406 4-methoxyl group phenoxymethyl ????70 ????216-8 Ethanol See embodiment 383
??407 4-chlorophenoxy methyl ????38 ????224-6 Ethanol See embodiment 383
????408 3-chlorophenoxy methyl ????40 ????232-4 Ethanol See embodiment 383
????409 4-methylenedioxy phenoxy ylmethyl ????77 ????207-10 Methyl alcohol See embodiment 383
????410 Cyclopentyloxy ????75 ????180-1 Toluene See embodiment 383
????411 The 4-hydroxybenzyl ????75 ????233 Methyl alcohol See embodiment 411
????412 The 4-leptodactyline ????70 ????205-6 Water See embodiment 411
????413 4-formamyl styroyl ????90 ????＞270 DMF: water See embodiment 413
????414 2-aminocarboxyl ethyl ????66 ????193-6 ???NA See embodiment 414
????415 2-dimethylamino carbonyl ethyl ????38 ????203-9 ???NA See embodiment 414
????416 4-anisole amino ????30 ????232-4 Methyl alcohol See embodiment 416
????417 4-chlorobenzene amino ????28 ????262-4 Ethanol See embodiment 416
????418 The 4-fluoroanilino ????35 ????259-60 ???NA See embodiment 416
????419 Cyclopropylamino ????82 ????155-158 ???NA See embodiment 383
????420 Pyrazinyl ????86 ????193(d) Ethanol See embodiment 383
????421 Isopropylamino ????20 ????123-25 Ethanol See embodiment 383
????422 The 2-pyrimidyl ????55 ????278-80 Ethanol See embodiment 383
????423 The 3-pyridazinyl ????83 ????294-95 Ethanol See embodiment 383
????424 The 4-pyrimidyl ????72 ????290-300 Ethanol See embodiment 383
????425 The 4-pyrimidyl ????60 ????288-291 Ethanol See embodiment 383
D. synthetic aldehyde embodiment 426:1-(4-acetoxyl group butyl)-azaindole-3-formaldehyde
Maintain the temperature at 5-10 ℃, under nitrogen atmosphere, (1.2g 30mmol) drips 7-azaindole-3-formaldehyde (4.19g in the suspension in dry DMF (65ml) to 60% sodium hydride that is stirring (oily dispersion liquid), 28mmol) at anhydrous N, the solution in the dinethylformamide (50ml).After interpolation is finished, continue to stir 30 minutes under same temperature, (6.16g, 31mmol) at anhydrous N, the solution in the dinethylformamide (15ml) makes this mixture be warmed to room temperature to drip acetate 4-bromine butyl ester then.Stirring at room reaction mixture 137 hours, add entry (100ml) then, and (2 * 100ml) extract this mixture with methylene dichloride.(anhydrous magnesium sulfate drying is used in 3 * 100ml) washings to the organic phase water, filters and removal of solvent under reduced pressure, obtains oil (6.8g, 93%), and this oil need not to be further purified and can use.Embodiment 427:1-(4-hydroxybutyl)-7-azaindole-3-formaldehyde
(2.3g 8.8mmol) adds sodium hydroxide (0.2g, 17.5mmol) solution in water (35ml) in the solution in methyl alcohol (40ml) to 1-(4-acetoxyl group butyl)-7-azaindole-3-formaldehyde.This mixture was 60 ℃ of heating 0.5 hour, and evaporating solvent is to doing then.Resistates is dissolved in the mixture (50ml: 50ml), separate water layer of ethyl acetate and water.Organic phase washes with water, uses dried over mgso, filters and be evaporated to dried.Resistates need not to be further purified and can use.Productive rate 78%.90 ℃ of fusing points.Embodiment 428:1-(4-hydroxybutyl) pyrrole-2-aldehyde
Method according to embodiment 51 obtains product, and different is to replace 7-azaindole-3-formaldehyde with pyrrole-2-aldehyde.This product is used (5: 5) ethyl acetate: the hexane wash-out through the silica gel chromatography purifying.Productive rate 67%.Embodiment 429:3-sec.-propyl-5-methylpyrrole-2-formaldehyde
Under 0 ℃ and nitrogen atmosphere, (2.1ml 27mmol) drips POCl in the solution in anhydrous ethylene dichloride (50ml) to dry DMF 3(2.1ml, 23mmol).This solution was warmed to room temperature 1 hour.Then, this suspension is cooled to 0 ℃, and with dripping 3-sec.-propyl-5-methylpyrrole (2g, 16mmol) solution in ethylene dichloride (20ml) in 20 minutes.After 24 hours, add entry in stirring at room, add NaOH to pH:8 then.The extraction organic layer, dry also removing desolvated to drying.Resistates is through the flash chromatography purifying.Productive rate 67%, fusing point 90-93 ℃.Embodiment 430:3,5-dimethyl-4-morpholino methylpyrrole-2-formaldehyde
To morpholine (0.35g, 4mmol), 37% formaldehyde (0.32g 4mmol) and in the solution of acetate (2ml) adds 3,5-dimethyl pyrrole-2-formaldehyde (0.5g, 4mmol).This mixture stirs under room temperature and nitrogen atmosphere and spends the night, and uses NaHCO then 3The diluting reaction thing is to pH8.Aqueous solution ethyl acetate extraction, the organic layer dried over mgso.The vacuum-evaporation ethyl acetate obtains the pure solid of 0.4g.
According to synthesizing following compounds with embodiment 430 described similar methods:
3,5-dimethyl-4-dimethylamino methyl pyrrole-2-aldehyde,
3-(4-morpholino) methyl-indoles-2-formaldehyde,
3,5-dimethyl-4-diethylin methylpyrrole-2-formaldehyde,
3,5-dimethyl-4-piperidine subbase methylpyrrole-2-formaldehyde,
3,5-dimethyl-4-[(4-methyl isophthalic acid-piperazinyl) methyl] pyrrole-2-aldehyde,
3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrrole-2-aldehyde,
5-methyl-4-dimethylamino methyl pyrrole-2-aldehyde,
3,5-dimethyl-4-[N-methyl-N-(2-dimethylaminoethyl) amino methyl] pyrrole-2-aldehyde,
3,5-dimethyl-4-diethanolamino methylpyrrole-2-formaldehyde,
4-(4-benzyl piepridine subbase methyl)-3,5-dimethyl pyrrole-2-formaldehyde,
4-dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-formaldehyde,
3,5-dimethyl-4-(4-hydroxy piperidine subbase methyl) pyrrole-2-aldehyde and
3-dimethylamino methyl-4,5-tetramethylene pyrrole-2-aldehyde.Embodiment 431:3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-formaldehyde
Keep temperature to be lower than 10 ℃, with 3,5-dimethyl pyrrole-2-formaldehyde (2.6g, 0.02mol) and N-(methylol) trifluoroacetamide (3g, mixture 0.02mol) add in the sulfuric acid (15ml) in batches.Make reaction mixture be warmed to room temperature 4 hours, reactant is poured in the frozen water (100ml), the solid of filtering-depositing also washes with water.Gained white solid (productive rate 78%) need not to be further purified and can use.M.p.200℃。Embodiment 432:4-amino methyl-3,5-dimethyl pyrrole-2-formaldehyde
With 3, and 5-dimethyl-4-trifluoroacetamido methylpyrrole-2-formaldehyde (3.9g, 15.7mmol), the mixture heating up of NaOH 10% (19ml) and methyl alcohol (100ml) refluxed 1 hour.This solution of concentrating under reduced pressure is to half volume.Add entry, the solid of filtering-depositing.Productive rate 72%, m.p.210-20 ℃ (d).Embodiment 433: acetate 3-ethanoyl-4-oxo amyl group ester
Under mechanical stirring, with pentane-2, the 4-diketone (60g, 0.6mol), acetate 2-bromine ethyl ester (100g, 0.6mol), Anhydrous potassium carbonate (83g, 0.6mol), IK (99.6g, 0.6mol) and the mixture heating up of anhydrous propanone (500ml) refluxed 24 hours.This mixture of concentrating under reduced pressure, and be poured into hydrochloric acid (1.7M, 400ml) in.With ether, ethyl acetate and dichloromethane extraction, separate this product by continuous.The organic extracting solution salt water washing that merges removes and desolvates to dried, and distillation residue, obtains the 38g acetate, b.p.75-80 ℃ (0.1mm Hg).
According to embodiment 433 described similar methods, preparation acetate 4-ethanoyl-5-oxo-hexyl ester [productive rate 60%, b.p.110 ℃ (0.2mm Hg)] and acetate 5-ethanoyl-6-oxo-hexyl ester [productive rate 77%, b.p.102 ℃ (0.2mm Hg)].Embodiment 434:4-(2-acetoxyl group ethyl)-3,5-dimethyl pyrrole-2-t-butyl formate
Under being lower than 20 ℃ of temperature and stirring, by (26g, (11.3g, 0.165mol) solution in water (17ml) is handled it, and places and spend the night 0.165mol) to drip Sodium Nitrite in the solution in acetate (48ml) to tert-butyl acetoacetate.With acetate 3-ethanoyl-4-oxo amyl group ester (30g; 0.161mol) solution in acetate (56ml) is heated to 80 ℃; add zinc powder (26.2g this moment in batches; 0.40mol) and sodium acetate (26.3g; 0.32mol) mixture; drip simultaneously above-mentioned oxyimino derivative (97ml, 0.165mol).Vigorous stirring reaction mixture during adding makes zinc always excessive, and maintains the temperature at 90-100 ℃.Add when finishing, this mixture is boiled 15 minutes gently, and in stirred overnight at room temperature.Reaction mixture is poured in the frozen water, placed 2hr.Cross filter solid and recrystallization from aqueous ethanolic solution.Productive rate 78%, 92 ℃ of fusing points.
According to embodiment 434 described similar methods, preparation 4-(3-acetoxyl group propyl group)-3,5-dimethyl pyrrole-2-t-butyl formate [produces 60%, m.p.73 ℃ (hexane)] and 4-(4-acetoxyl group butyl)-3,5-dimethyl pyrrole-2-t-butyl formate [productive rate 52%, m.p.62 ℃ (hexane)].Embodiment 435:3,5-dimethyl-4-(2-hydroxyethyl) pyrrole-2-aldehyde.
With 4-(2-acetoxyl group ethyl)-3, (15g 53mmol) is dissolved among the TFA (40ml) 5-dimethyl pyrrole-2-t-butyl formate, and stirs this solution 10 minutes under 40 ℃ and nitrogen atmosphere.Reaction mixture is cooled to 0 ℃ then, and the dropping triethyl orthoformate (9.6ml, 58mmol).Make this mixture be warmed to 20 ℃, and stirred 1 hour, pour in the frozen water then.Use dichloromethane extraction, use this extracting solution of 10% ammoniacal liquor and water washing successively, and use dried over mgso.4-(2-acetoxyl group ethyl)-3,5-dimethyl pyrrole-2-formaldehyde use (7: 3) ethyl acetate: the hexane wash-out through the silica gel chromatography purifying.Productive rate 45%, m.p.125-27 ℃ (water).
(5g 23mmol) adds NaOH10% (10ml) in the solution in ethanol (20ml) to above-claimed cpd.In this mixture of stirring at room 30 minutes, concentrate final solution, dilute with water, and use dichloromethane extraction.Dry organic extracting solution, and remove and desolvate to doing.Productive rate 98%, m.p.100 ℃ (ethyl acetate).
According to embodiment 435 described similar methods, preparation 3,5-dimethyl-4-(3-hydroxypropyl) pyrrole-2-aldehyde [productive rate 60%, m.p.85 ℃ (ethyl acetate/hexane)] and 3,5-dimethyl-4-(4-hydroxybutyl) pyrrole-2-aldehyde [productive rate 38%, m.p.99 ℃ (hexane)].Embodiment 436:4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-formaldehyde.
At 0-5 ℃, to stirring 3,5-dimethyl-4-(2-hydroxyethyl) pyrrole-2-aldehyde (4.3g, 25.7mmol) and triethylamine (5.2g, 51mmol) be added in methylsulfonyl chloride (4ml among the anhydrous THF (4ml) in the solution in anhydrous THF (60ml), 51mmol), and in this mixture of stirring at room 1 hour.In this mixture, add entry then, the solid of filtering-depositing.Productive rate 89%, m.p.142-44 ℃.
With above-mentioned methanesulfonates (23mmol), K 2CO 3(23mmol), the mixture heating up to 100 of diethylamine (90mmol) and 2-propyl alcohol (70ml) ℃, kept 0.5 hour.Remove and desolvate to dried, the resistates water treatment, and use dichloromethane extraction.Dry organic extracting solution, and evaporating solvent is to doing.Productive rate 70%, m.p.70 ℃ (normal heptane).
According to embodiment 436 described similar methods, with the isolated in form of oil and prepare 3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrrole-2-aldehyde, 3,5-dimethyl-4-(2-ethylamino ethyl) pyrrole-2-aldehyde, 4-(3-diethylin propyl group)-3,5-dimethyl pyrrole-2-formaldehyde, 4-(4-diethylin butyl)-3,5-dimethyl pyrrole-2-formaldehyde, 3,5-dimethyl-4-[3-(1-pyrrolidyl propyl group)] pyrrole-2-aldehyde.Embodiment 437:4-(2-chloracetyl)-3,5-dimethyl pyrrole-2-formaldehyde
Under room temperature and nitrogen atmosphere, with 30 minutes, to 3,5-dimethyl pyrrole-2-formaldehyde (5g, 40mmol) 1, add in the solution in the 2-ethylene dichloride (50ml) in batches Aluminum chloride anhydrous (42g, 315mmol).Stir after 15 minutes, with dripped in 1 hour chloroacetyl chloride (17g, 150mmol).Add finish after, in this mixture of stirring at room 16 hours.This mixture is poured in the trash ice, separated organic layer, use anhydrous magnesium sulfate drying, and removal of solvent under reduced pressure.Productive rate 57%, m.p.205-09 ℃ (toluene).Embodiment 438:3,5-dimethyl-4-(2-diethylin ethanoyl) pyrrole-2-aldehyde
To 4-(2-chloracetyl)-3, (1g 5mmol) adds diethylamine (5ml) in the solution in THF (20ml) to 5-dimethyl pyrrole-2-formaldehyde.In this mixture of stirring at room 24 hours.Removal of solvent under reduced pressure, resistates water, NaHCO 3(5%) handles, and use dichloromethane extraction.After the dry also filtration, remove and desolvate, resistates need not to be further purified and can use.
According to embodiment 438 described similar methods, synthetic 3,5-dimethyl-4-(2-dimethylamino ethanoyl) pyrrole-2-aldehyde and 3,5-dimethyl-4-[2-(1-pyrrolidyl) ethanoyl] pyrrole-2-aldehyde.Embodiment 439:3,5-dimethyl-4-oxyethyl group oxalyl group pyrrole-2-aldehyde
Under room temperature and nitrogen atmosphere, with 30 minutes, to 3,5-dimethyl pyrrole-2-formaldehyde (7.6g, 62mmol) 1, add in the solution in the 2-ethylene dichloride (140ml) in batches Aluminum chloride anhydrous (37g, 277mmol).Stir after 30 minutes, and the adding Nitromethane 99Min. (11.2ml, 179mmol).This mixture is 0 ℃ of cooling, and with dripped in 1 hour glyoxylate ethyl chloride (12.8g, 94mmol).Add finish after, in this mixture of stirring at room 4 hours.This mixture is poured in the trash ice, separated organic layer, dry and evaporation obtains white solid.Productive rate 45%, m.p.125-127 ℃ (toluene).
The NMR of all compounds spectrum data are all consistent with corresponding chemical structure among the embodiment of front.
Although described the present invention in detail with reference to its embodiment preferred, this area the professional should be appreciated that, under the condition that does not deviate from the defined spirit and scope of the invention of claims, can carry out many changes to its form and details.

Claims (45)

1. the method that suppresses one or more protein kinase activities comprises and uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites: Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
2. the process of claim 1 wherein that it is to carry out that described protein kinase suppresses in the need curer.
3. the method for claim 2, compound wherein is the mixture of steric isomer.
4. the method for claim 3, steric isomer wherein is an enantiomorph.
5. the method for claim 3, steric isomer wherein is E and Z isomer.
6. the method for claim 2, compound wherein is the mixture of constitutional isomer.
7. the method for claim 6, constitutional isomer wherein is a tautomer.
8. the method for claim 2, wherein said protein kinase is receptor tyrosine kinase or nonreceptor tyrosine kinase.
9. the method for claim 8, wherein said Tyrosylprotein kinase is selected from KDR, Flt-1, TIE-2, FGFR, PDGFR, IGF-1-R, c-Met, Lck, Src, fyn, Lyn, Blk and yes.
10. treating or fundamentally suppressing needs curer's the hyperproliferation disease or the method for inflammatory diseases, and this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites to described curer:
Figure A0081368200031
Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
R 3Be selected from replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
11. treatment or inhibition need the method for curer's vasculogenesis, this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites to described curer:
Figure A0081368200051
Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
12. induce the method that needs curer's blood vessel formation against function, this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites to described curer:
Figure A0081368200061
Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
13. the method that treatment or inhibition need curer's disease or illness to carry out, this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites to described curer:
Figure A0081368200071
Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3,
Wherein said disease or illness are selected from cancer, sacroiliitis, atherosclerosis, restenosis, psoriasis, vascular tumor, angiogenesis of cardiac muscle, crown and brain pleurapophysis, the ischemic limb vessel generates, keratopathy, flush, neovascular glaucoma, macular degeneration, wound healing, peptide ulceration, with the helicobacter diseases associated, the vasculogenesis disease that virus causes, fracture, diabetic retinopathy, Crohn disease, the fever that inflammatory bowel disease, cat scratcs cause, retinopathy or precocity, ulcer, the Tiroidina hyperplasia is burnt, wound, acute lung injury, chronic lung disease, apoplexy, polyp, tumour, synovitis, chronic and alterative inflammation, ovarian hyperstimulation syndrome, lung and cerebral edema, keloid, fibrosis, liver cirrhosis, carpal tunnel syndrome, Sepsis, adult respiratory distress syndrome, many organ dysfunction syndrome, ascites and seepage hydrops and the oedema relevant with tumour.
14. influence needs the method that curer's vascular permeability is too high or oedema produces, this method comprises uses the compound shown in the following formula and physiologically acceptable salt and bioactive metabolites to described curer: Wherein:
R is selected from replacement or unsubstituted: aliphatic group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
R 1Be hydrogen or-A-Z;
R 2Be that hydrogen or be selected from replaces or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3CO-, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3O-or be selected from following one group ring system: (C 3-C 6) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replaces by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR 4R 5With-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3.
15. the method for claim 14 wherein act as Ivy extract to what oedema produced.
16. the method for claim 2, wherein said protein kinase is a serine kinase.
17. the method for claim 2, wherein said protein kinase is a threonine kinase.
18. the salt compound that following structural is represented and physiologically acceptable:
Figure A0081368200101
Wherein:
R is selected from replacement or unsubstituted: indoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, benzoglyoxaline, 4,5,6,7-tetrahydro indole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrroles, pyrazoles, oxazole and thiazole;
R 1Be hydrogen or-A-Z;
A is-(CH 2) n-,-(CH 2) nNH-,-(CH 2) nO-,-(CH 2) nS-,-(CH 2) nS (O)-or-(CH 2) nS (O) 2-;
Z is-H, low alkyl group, aralkyl, trihalomethyl group, trihalomethyl group carbonyl, R 3OC (O)-,-NR 4R 5,-C (O) NR 4R 5, R 3CO-, R 3O-or be selected from following one group ring system: C 3-C 6Naphthenic hydrocarbon, isoxazole, isothiazole, imidazoles, benzene, pyrroles, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, imidazoles, furans, triazine, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system can be randomly be selected from following one group group and replace by one or more: halogen, low alkyl group, R 3O-, HO-, HOC (O)-, R 3OC (O)-, trihalomethyl group, nitro, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl, heterocyclic radical-alkyl ,-CN ,-C (O) NR 4R 5Or-NR 4R 5
The R that every place occurs 3Be independently from each other replacement or unsubstituted: low alkyl group, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
The R that every place occurs 4And R 5Independently of one another for hydrogen or be selected from and replace or unsubstituted: low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl;
Randomly, R 4And R 5With the nitrogen that links to each other with it combine expression morpholino, pyrrolidino, piperidino-(1-position only), imidazoles-1-base, Piperazino, parathiazan generation, azepines subbase or perhydro--carotene 1,4-diazacyclo heptantriene-1-base, wherein each group randomly is selected from following one group group and replaces by one or more: low alkyl group, hydroxyl, lower alkoxy low alkyl group, aromatic group, (C 3-C 6) cycloalkyl, heterocyclic radical, aralkyl, (C 3-C 6) cycloalkyl-alkyl and heterocyclic radical-alkyl; And
N is the integer of 0-3;
Condition is when R is unsubstituted indol-3-yl, R 1Be not-NH 2
19. the compound of claim 18, wherein:
A is-NH-,-O-,-S-,-S (O)-or-S (O) 2-; And
Z is cyclopropyl, 3-pyridyl or pyrazinyl.
20. the compound of claim 18, wherein:
A is-O-; And
Z is ethyl, n-propyl or sec.-propyl.
21. the compound of claim 18, wherein:
A is-CH 2-; And
Z is a phenyl, and wherein said phenyl randomly is selected from following one group group and replaces by one or more: halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-CONR 4R 5, low alkyl group, R 3O-,-C (O) OR 4With-OC (O) R 4
22. be selected from following one group compound:
3-cyclopropyl-4-{[(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-(3,5-two bromo-4-hydroxyl benzylidenes)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[(3,5-dimethyl-4-[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
3-(3-pyridyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl-2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(imidazoles-2-yl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(imidazoles-2-yl))-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
3-(1-methyl cyclopropyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(1-methyl cyclopropyl))-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethyllaminoethyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-furyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-(2-furyl))-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(morpholino methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl) methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(1-pyrrolidyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-oxo-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
3-(2-thienyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ring propoxy--4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-encircles propoxy--4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-encircles propoxy--4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,
3-encircles propoxy--4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
3-[2-(5-pyrimidinylethyl)]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
3-(2-styroyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
3-(2-styroyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-hydroxyphenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-bromine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,
4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-[2-(4-aminophenyl) ethyl]-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
3-(4-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl) pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-diethylin methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
3-(5-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical v3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
3-(2-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
3-(3-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-(4-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-(5-methyl-3-isoxazolyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-4,5-dihydro-1H-5-pyrazolone,
3-cyclopropyl-4-(1-4-[(1,1-Dimethyl Ammonium) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-4,5-dihydro-1H-5-pyrazolone maleate,
4-[1-(4-[[2-(dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1H-2-pyrryl) methylene radical]-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-4-[2-(diethylin) ethyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-1-[4-(3-chlorine propionyl)-3,5-dimethyl-1H-2-pyrryl] methylene radical-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,
4-(1-4-[(dimethylamino) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(5-methyl-3-isoxazolyl)-4,5-dihydro-1H-5-pyrazolone,
3-cyclopropyl-4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxyl group phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-phenoxymethyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-benzyl-4-{[3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(4-methylenedioxy phenoxy ylmethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
2-amino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-styroyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-phenylamino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-xylyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methylbenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-anisole amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-benzyl chloride base)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(indol-3-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3, the 4-dimethoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-anisole ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-phenyl phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-(4-methylbenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-oxyethyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-oil of mirbane ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopentyloxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-tertiary butyl urea groups-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-methylpyrrole-2-yl) methylene radical] the 2-pyrazolin-5-one,
3-(4-formamyl styroyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-methoxycarbonyl styroyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,
3-(ethoxycarbonylmethyl group)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(the amino carbonyl methyl of 4-anisole)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{ (3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-3-sec.-propyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclobutyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[[1-(3, the 5-dichlorophenyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(pyrroles-2-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopentyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-methyl cyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-(benzothiazole-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-4-(3-pyridyl)]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(pyrroles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-propyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-methyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-isopropyl benzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-phenylamino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical]-the 2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(4-ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-chlorobenzene amino carbonyl methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,4-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-methoxycarbonyl ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ethoxycarbonyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-sec.-propyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(anti--the 2-phenycyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclohexyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropylamino-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4 [(4-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-ones,
4-[(4-bromine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-pyrazinyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-pyridyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,
4-{[3,5-dimethyl-4-(2-morpholino B aminocarbonyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-diethanolamino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(3,4-two (ethoxycarbonyl) pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-pyridyl ethyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl-2-styroyl)-2-pyrazolin-5-one,
4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(5-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(4-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(5-chloro-3-methoxycarbonyl-4-methoxycarbonyl methylpyrrole-2-yl) methylene radical-3-oxyethyl group-2-pyrazolin-5-one,
4-{[3-(2-carboxy ethyl)-4-methylpyrrole-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-oxyethyl group-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
3-(3-aminophenyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[2-(4-morpholino ethyl) aminocarboxyl pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(4-methyl isophthalic acid-piperazinyl methyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,
4-[(5-methyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylamino-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-2-pyrazolin-5-one maleate,
4-{[4-(3-chlorine propionyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-hydroxy piperidine subbase methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,
4-{[4-(4-benzyl piepridine subbase) methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(3-diethylin propyl group)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(3-hydroxypropyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one hydrochloride,
4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
3-cyclopropyl-4-{[(2-diethyllaminoethyl)-3,5-dimethyl-4-pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-dimethylaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(4-diethylin butyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl-N-oxide compound)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(1-pyrrolidyl ethanoyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-[3-(1-pyrrolidyl propyl group)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-oxyethyl group oxalyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-benzyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-benzyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-phenoxymethyl-2-pyrazolin-5-one,
3-(4-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylenedioxy phenoxy ylmethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene amino)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-anisole amino)-2-pyrazolin-5-one,
3-(4-benzyl chloride base)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
3-(4-chlorobenzene amino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-methoxy-benzyl)-2-pyrazolin-5-one,
3-(3, the 4-dimethoxy-benzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-hydroxybenzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(3-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(indol-3-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-anisole ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-phenyl phenoxymethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-phenyl propyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-phenyl propyl)-2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene ethyl)-2-pyrazolin-5-one,
3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-styroyl-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-oil of mirbane ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-propoxy--2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(2-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(7-skatole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-methoxycarbonyl styroyl)-2-pyrazolin-5-one,
3-isopropoxy-4-[(1-isopropyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-sec.-propyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene amino carbonyl methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-ethoxycarbonylmethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(the amino carbonyl methyl of 4-anisole)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-(2-aminocarboxyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclobutyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(2-dimethylamino carbonyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(4-pyridyl)-2-pyrazolin-5-one,
3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-methyl cyclopropyl)-2-pyrazolin-5-one,
3-cyclohexyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-pyridyl)-2-pyrazolin-5-one,
3-(benzothiazole-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
3-dimethylamino-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(pyrroles-2-yl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(6-methoxyl group benzo thiazol-2-yl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-antazoline-5-ketone,
The 4-[(indol-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-antazoline-5-ketone,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(tertiary butyl)-2-pyrazolin-5-one,
3-ethoxycarbonyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(2-methoxycarbonyl ethyl)-2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-(anti--2-phenyl-1-cyclopropyl)-2-pyrazolin-5-one,
3-cyclobutyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical [3-pyrazinyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(1,7-dimethyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
3-cyclopropyl amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-[(1,7-dimethyl indole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-fluoroanilino)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-3-trifluoroacetamido-2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-chlorobenzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(5-isoxazolyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(1-skatole-3-yl) methylene radical]-the 3-tertiary butyl-2-pyrazolin-5-one,
4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{1-methyl-6-[2-(4-morpholino) ethyl] the aminocarboxyl indol-3-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-(4-leptodactyline)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-amino-benzene ethyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-methoxycarbonyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-(4-formamyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
3-isopropoxy-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(1-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(5-nitroindoline-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-sec.-propyl amino-2-pyrazolin-5-one,
3-(4-carboxyl styrene base)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(indoles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
3-isopropoxy-4-[(3-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-{[3-(2-methoxycarbonyl-2-kharophen ethyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-oxyethyl group-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-oxyethyl group-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,
4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-oxo-1,5,6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-benzyl-2-pyrazolin-5-one,
3-benzyl-4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-the 2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-amino-4-[(7-azaindole-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(4-leptodactyline)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-sec.-propyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-cyclobutyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-fluoroanilino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-antazoline-5-ketone,
4-[(7-azaindole-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(tertiary butyl)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(4-isopropyl benzene amino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-(3-methylbenzene amino)-2-pyrazolin-5-one,
4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(3-methylbenzene amino)-2-pyrazolin-5-one,
4-[(7-azaindole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-benzyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(4-dimethylamino phenyl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
The 4-[(4-dimethylamino phenyl) methylene radical]-3-styroyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,
3-isopropoxy-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(imidazoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopropyl-4-[(imidazoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(imidazol-4 yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
3-cyclopropyl-4-[(thiophene-2-yl) methylene radical]-the 2-pyrazolin-5-one,
The 4-[(indol-3-yl) methylene radical]-3-sec.-propyl-1-antazoline-5-ketone,
3-isopropoxy-4-[(pyrroles-3-yl) methylene radical]-the 2-pyrazolin-5-one,
4-[(8-hydroxyquinoline-5-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,
3-cyclopropyl-4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-4-(1-pyrrolidyl methyl)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5 methylpyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
3-pyrazinyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-2-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
3-(2-furyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,
3-(2-furyl)-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
3-(4-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
3-(5-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
3-(2-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
3-(3-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
3-(4-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,
4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-methylene }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical)-3-pyrazinyl-2-pyrazolin-5-one,
4-{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-ethyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino-ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[4-(2-diethyllaminoethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) ethyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino-ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{4-[2-(1-imidazolyl) methyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-ethyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclobutyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopentyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclohexyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-amino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(the 1-imidazolyl } methyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-cyclopropyl amino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-diethylin methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-dimethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[4-(2-ethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{{4-[2-(1-imidazolyl) methyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-[(4-cyclopropyl amino methyl-3,5-two cyclopropyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,
4-{[3-dimethylamino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one and
4-{[3-methylol-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one.
23. the compound of claim 18, compound wherein are the mixture of steric isomer.
24. the compound of claim 23, steric isomer wherein is an enantiomorph.
25. the method for claim 24, steric isomer wherein are E and Z isomer.
26. the method for claim 18, compound wherein are the mixtures of constitutional isomer.
27. the method for claim 26, constitutional isomer wherein is a tautomer.
28. suppress the method for one or more protein kinase activities, comprise the compound of using claim 18.
29. the method for claim 28, wherein said compound is used the curer that needs suppress one or more protein kinases.
30. the compound of claim 29, compound wherein are the mixture of steric isomer.
31. the compound of claim 30, steric isomer wherein is an enantiomorph.
32. the method for claim 30, steric isomer wherein are E and Z isomer.
33. the method for claim 29, compound wherein are the mixtures of constitutional isomer.
34. the method for claim 29, constitutional isomer wherein is a tautomer.
35. the method for claim 29, wherein said protein kinase is a Tyrosylprotein kinase.
36. the method for claim 35, wherein said Tyrosylprotein kinase is selected from KDR, Flt-1, TIE-2, Lck, Src, fyn, Lyn, Blk and yes.
37. influence the method for curer hyperproliferation disease, this method comprises the compound of described curer being used claim 18.
38. influence the method for curer vasculogenesis, this method comprises the compound of described curer being used claim 18.
39. pharmaceutical composition wherein contains compound and the pharmaceutically acceptable carrier or the thinner of claim 18.
40. pharmaceutical composition wherein contains compound and the pharmaceutically acceptable carrier or the thinner of claim 22.
41. the compound of claim 18, wherein R is selected from following one group substituting group and replaces by one or more by independent of each other: halogen, low alkyl group, R 3O-, hydroxyl, HOC (O)-, R 3OC (O)-, R 3OC (O) R 6-, R 3OR 6-, trihalomethyl group, trihalomethyl group carbonyl, nitro ,-C (O) NR 4R 5,-NR 4R 5, R 3CO-,-(CH 2) n-R 7,-C (O) (CH 2) n-R 7,-C (O)-(CH 2) n-C (O)-R 7,-O (CH 2) nR 7,-C (O) NR 4(CH 2) nR 7, C (O) O (CH 2) nR 7,-OC (O) (CH 2) nR 7,-NR 4C (O) (CH 2) nR 7,-R 6NR 4R 5,-R 6N (R 4)-R 6-R 7,-R 6N (R 6-R 7) 2,-R 6C (O) NR 4(CH 2) nR 7,-R 6C (O) O (CH 2) nR 7,-R 6OC (O) (CH 2) nR 7, R 6NR 4C (O) (CH 2) nR 7,-R 6CH (C (O) OR 4) (NR 5C (O) R 4), the optional aryl that replaces and the optional aralkyl that replaces;
Wherein optional aryl that replaces and the optional aralkyl that replaces randomly are selected from following one group substituting group and replace by one or more: halogen, trihalomethyl group, hydroxyl ,-NR 4R 5, nitro ,-CONR 4R 5, low alkyl group, R 3O-, C (O) OR 4Or-OC (O) R 3
R 6Be low alkyl group or aryl;
R 7Be alkoxyl group, haloalkyl, low alkyl group piperazine, hydroxyl, R 3O-, R 3C (O)-or-NR 4R 5
42. the compound of claim 41, wherein R is pyrryl, indyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydro indole base or quinolyl.
43. the compound of claim 42, wherein R is pyrroles-2-base, pyrroles-3-base, indoles-2-base, indol-3-yl, azaindole-3-base, pyrazoles-4-base, imidazoles-2-base, imidazol-4 yl, thiophene-2-base or quinoline-5-base.
44. the compound of claim 18 or 43, wherein R 1Be trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl group, sec.-propyl, cyclopropyl, 2-methyl cyclopropyl, 2,2,3,3-tetramethyl-ring propyl group, 2-phenycyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl ,-(CH 2) p-O-phenyl ,-(CH 2) p-O-(4-methoxyphenyl) ,-(CH 2) p-O-(4-chloro-phenyl-) ,-(CH 2) p-O-(4-aminomethyl phenyl) ,-(CH 2) p-O-(3-aminomethyl phenyl) ,-(CH 2) p-O-(4-phenyl) ,-(CH 2) p-O-(4-hydroxyphenyl) ,-(CH 2) p-O-(4-nitrophenyl) ,-(CH 2) p-O-(4-aminophenyl) ,-(CH 2) p-O-(4-formamyl phenyl) ,-(CH 2) p-O-(4-methoxycarbonyl phenyl) ,-the NH-phenyl ,-NH-(4-methoxyphenyl) ,-NH-(4-chloro-phenyl-) ,-NH-(4-fluorophenyl) ,-NH-(4-isopropyl phenyl), isopropoxy, oxyethyl group, cyclopentyloxy ,-(CH 2) p-indyl ,-(CH 2) p-pyridyl ,-(CH 2) p-benzothiazolyl ,-(CH 2) p-pyrryl ,-(CH 2) p-tetrahydrofuran base ,-(CH 2) p-pyrazinyl ,-(CH 2) p-furyl ,-(CH 2) p-thienyl ,-(CH 2) p-phenyl ,-(CH 2) p-isoxazolyls ,-(CH 2) p-(5-methyl-isoxazole base) ,-(CH 2) p-pyrimidyl ,-(CH 2) p-pyridazinyl ,-(CH 2) n-C (O)-OMe ,-(CH 2) n-C (O)-OEt and the benzyl that is randomly replaced by one or more Cl, F, OMe, methyl or amino,
Wherein p is the integer of 1-3.
45. the compound of claim 44, wherein R randomly is selected from following group and replaces by one or more: Br, Cl, F, amino methyl, N, N-dimethylamino methyl, carboxyl, carboxymethyl, propyloic, carbonyl methyl, carbonyl ethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4-morpholino methyl ,-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 3Randomly substitutedly be selected from following group: methyl, ethyl, propyl group, sec.-propyl, butyl and phenyl, wherein said optional substituted group is randomly replaced by one or more Br, Cl, F, hydroxyl, nitro, amino or low alkyl group.
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