TW201111379A - Novel thiazole-and oxazole-hepcidine-antagonists - Google Patents

Abstract

The present invention relates to novel hepcidin antagonists of general structural formula, pharmaceutical compositions containing them and the use thereof as drugs, in particular for the treatment of iron metabolism disorders such as, in particular, iron deficiency diseases and anaemia, in particular anaemia associated with chronic inflammatory disease (ACD: anaemia of chronic disease and AI: anaemia of inflammation).

Description

201111379 VI. Description of the Invention: [Technology of the Invention] The present invention relates to a novel hepcathine antagonist of the general formula (I), which comprises the pharmaceutical composition and the same for the treatment of iron Metabolic abnormalities, especially anemia associated with chronic inflammatory diseases (anemia of chronic diseases (ACD) and inflammatory anemia (AI)) or iron deficiency abnormalities and ischemic anemia. [Prior Art; J Background Iron is an important trace element in almost all organisms and is particularly important for growth and blood formation systems. The balance of iron metabolism is mainly determined by the blood redness of the aging red blood cells and the adjustment of the duodenum to the iron of the food. The released iron is absorbed through the intestines, especially by the special sputum transmission system. The filling (DMT-Buyun Iron|, Yunshen, and the self-blowing, transporting in the bloodstream, and transmitting to the corresponding _ And in the organs. Iron 2 in the human body for oxygen transport, oxygen uptake 'cell function (making human body electron transport), and finally important for energy metabolism system. Xin and muscle have an average of 4 to 5 grams of iron, The enzyme is in the enzyme, blood red: and the iron (about 2 grams) stored or preserved in the form of iron storage protein and protein is used to "fine hemoglobin iron. Because of this red two (75 days), new life The need to continue to form, there are limited d spheres in more than 2 million per second. Old sellers are removed (new red blood, 10,000 rate formation). This high regenerative capacity was achieved by 201111379 by macrophages, during which The macrophage cell phagocytose absorbs and cleaves the aging red blood cells' and circulates the iron contained in it for iron metabolism. Most of the iron needed for red blood cell production is about 25 mg per day, which is provided in this way. The daily iron demand for adults is between 0.5 and 1.5 mg per day, and for children and pregnant women. It takes 2 to 5 mg of iron. Daily iron loss (for example, due to skin and epidermal cell stripping) is relatively mild, but increased iron loss occurs, for example, during menstrual bleeding. In general, fluid loss A large reduction in iron metabolism, because about 2 milligrams of iron loss per 2 milliliters of blood. About 1 milligram of normal daily iron loss in healthy adults is usually replaced by daily food intake. Iron metabolism is regulated by resorption, exists The resorption rate of iron in food is between 6 and 12%, and in the case of iron deficiency, the maximum is up to 25%. » The resorption rate is regulated by the organ's iron demand and iron reserve specifications. The organ uses bivalent and trivalent iron ions. If the pH is sufficiently acidic, the iron (III) compound is traditionally dissolved in the stomach and thus resorbable. The resorption of iron occurs in the upper small intestine by mucosal cells. In this procedure, the second mussel non-heme iron is preceded by the membrane of the intestinal cells, for example, by ferric reductase (the membrane-bound duodenal cytochrome b) to be reduced to Fe2+, so that it can be transported later. egg Quality!)!^^(The divalent metal transporter is transported to the intestinal cells. On the other hand, the heme iron enters the intestinal cells unchanged through the cell membrane. In the intestinal cells, the iron is stored in the storage iron by storage iron. The protein is released into the blood by transporting the protein transferrin and binds to transferrin. Haipaxietine plays an important role in this procedure because it is an important regulator of iron uptake. Transported to blood by transferrin The bis-valent iron is converted to ferric iron by oxygen 4 201111379 (blue cytosolic, ferrous oxidase), and then transported by transferrin (see, for example, "balance: Molecular Control of Mammalian Iron Metabolism, Mw Hentze, Ceii 117, 2004, 285-297). The regulation of iron-containing S is controlled or regulated by hepcidin. Hapaxi; Ding is a peptide hormone produced in the liver. The general active type ' ^ : , the key regulator of iron metabolism and the media of inflammatory anemia — 』 — ^ '783-8) 'Even in the short-term K Miscellaneous; Ding η and Hai Pa Shi-20 , has been discovered. The sage is absorbed by the intestines and through the iron of the placenta and releases iron from the reticuloendothelial system. In vivo, hepaticin is synthesized from the so-called Qianhaipa (10), which is encoded by the so-called HAMP gene. If "sufficient iron and oxygen are supplied, more hepatidine is formed. The mucosal cells in the small intestine and the hepatocytes in the small intestine, the sea-capitacin iron and iron surface, whereby the m-series is transported from the fine M to the blood. Transporting the protein transporter system - transporting proteins from a membrane composed of amino acids, which are formed in the liver, spleen, kidney, heart, intestine and placenta and localized. It is the basal side membrane of the intestinal epithelial cells. In this way, the combined spleen < ferrocyanin thus produces iron output into the blood. In this case, the iron money can be used to transport iron. If Hapaasi (10) transports ferritin combined, the transport of the "transportation ___ scale solution, therefore, the iron from the fine mosquitoes are completely blocked. If the ferritin is purified by the hepatic iron in the mucosal cells, the iron can not be transported, and the iron 201111379 is lost by natural exfoliation of the cells via the feces. Therefore, iron absorption in the intestine is reduced by hepcidin. On the other hand, if the iron content in the serum is lowered, the production of hepcidin in the liver cells of the liver is lowered, and therefore, less of the hepcidin is released, so that less ferritin is passivated, so that A larger amount of iron is transported into the serum. In addition, transferrin is significantly localized in the reticuloendothelial system (RES), which is also a macrophage. Hepcidin plays an important role when iron metabolism is impaired by chronic inflammation, especially since interleukin-6 is increased in this inflammatory condition, resulting in an increase in the amount of hepcidin. As a result, more sea pacacetin binds to the transport of ferroblasts from giant scorpion cells, so the release of iron is blocked, which ultimately leads to inflammatory anemia (ACD or AI). Because mammalian organs cannot actively excrete iron, iron metabolism is basically controlled by the release of iron from cells by giant hepatocytes, hepatocytes, and intestinal cells. Hepcidin thus plays an important role in functional anemia. In this case, even if the iron is saved, the demand for iron for the generation of red blood cells is not fully satisfied. For this reason, it is assumed that the increased concentration of hepcidin 'specially limits the transport of iron from macrophages by blocking the transfer of ferritin', thus greatly reducing the release of iron that is circulated by phagocytosis. . Therefore, the abnormality of the hepaticin-regulating mechanism has a direct effect on the iron metabolism of organs. For example, if the performance of hepcidin, for example, is prevented by genetic defects, this directly leads to overloading of iron, which is called iron storage disease hemochromatosis. On the other hand, 'over-expressed by Haipaxi Kenting', for example, due to inflammation over 201111379 Wang 'for example, 'called ' inflammation, direct production of low blood (four) content. In: situation, this material results in reduced hemoglobin content, Reduced redness, and thus lead to anemia. Table ~ κ 猓 her use will be less due to the existence of anemia 'because the reduction of red blood cells caused by the use of chemotherapeutic agents can be due to the existence of anemia (four) - step strengthening. ~ Another symptom of state anemia includes fatigue, paleness and loss of concentration. The clinical syndrome of poor j contains low serum iron content (low blood sputum), low blood sulphur content, low blood cell capacity and reduced red (four) number, reduced net Red blood cells and increased soluble transferrin receptor values. Iron deficiency or iron anemia is traditionally treated by supplying iron. Iron replacement occurs by oral route or by intravenous administration of iron. And other substances that stimulate the production of red blood cells can also be used to treat the poor gold to promote the formation of red blood cells. Because of chronic diseases, 'diligent, chronic inflammatory diseases, the anaemia of anemia is only traditional treatment The method is inappropriately treated. In particular, cytokines (especially, such as 'inflammatory inflammatory axis') play a role in the anemia of the chronic inflammatory process (4). Hapaxi, the over-expressive system is particularly Chronic inflammatory diseases are s 'and are known to reduce the availability of iron to form red blood cells. Therefore, there is a need for an anemia that treats hepaticin, especially anemia that cannot be treated with conventional iron replacement, such as chronic inflammatory diseases. Anemia caused by anemia (ACD and AI). Anemia is caused by the aforementioned chronic inflammatory diseases, and malnutrition and low-iron diet or unbalanced low-iron diet. Anemia is also due to reduced or poor iron intake 2〇Πΐΐ379 Occasionally, such as 'due to gastrectomy or diseases such as gram-suppressed disease. Iron deficiency can also occur due to a large amount of blood loss, for example, due to injury, severe menstrual bleeding or blood donation. Increased iron demand is also known to occur For adolescents and children growing up and pregnant women. Because iron deficiency not only causes a decrease in red blood cell formation, it also leads to poor supply of oxygen to organs, which leads to the above Syndrome: For example, tiredness, paleness, and poor concentration, and in adolescents, and even long-term damage to cognitive development, in addition to the known (four) n-system effective treatment is also of particular interest for this salt. /t3 and Haipa Westing or transferrin binds and thus inhibits the combination of Hapaxi; Ding and Yunxin and avoids transfer of the compound which is inactivated by lysine or even if hepcidin is combined with transferrin to avoid hepaticin - Transferrin ^ ^ Departmentalization and because of (4) Free transport of ferritin by the sea (four) cardiac passivation ^ can be described as a hepaticin antagonist. Use this = Passi > antagonists _ can also, For example, by suppressing the white time, the table shouts #纽料巾...has the interaction of Yunsaki, and the adjustment mechanism of 嶋西汀, the method by which the ferrocidin enters the iron transport path in the serum. == is a chronic inflammatory disease, preparation: she, an equivalent substance can be used to treat the substance (4). The circulating heme iron releases the iron released from the intestine by the release of the two nucleus cells. This substance, 2° increased self-agent or hippocampus antagonist, so ... performance and / / alpha iron metabolism abnormalities, 4 4 201111379 iron deficiency, stomach blood, and diseases associated with anemia. In particular, this also includes anemia caused by sexual or chronic inflammatory diseases such as 'bone and joint diseases, such as rheumatoid arthritis, or diseases associated with inflammatory diseases. This substance is therefore particularly relevant to cancer, especially colorectal cancer, multiple myeloma, nest and endometrial cancer and prostate cancer, CKD 3 5 (chronic kidney disease) CHF (fi heart failure), Ra (rheumatoid arthritis), slE (systemic lupus erythematosus), and IBD (inflammatory bowel disease) are particularly beneficial. Conventional Techniques Seas that have an inhibitory or supporting effect on the biochemical regulatory pathway of iron metabolism are generally known from the art. For example, 'WO 2008/036933 describes an inhibitory effect on the expression of the human HAMp gene in cells at an early stage of the iron metabolic signaling pathway and thus inhibits the double-stranded a, which is formed by the AMP gene encoded by the AMP gene. Therefore, the formation of less Happa, therefore, Hapaxi, can not be used to inhibit transfer of iron, and iron can be transported into the blood by untransparent transfer of cells from the cells. Another compound which is intended to reduce the performance of hepcidin is known from 005/020487, which discloses a compound which is stabilized and thus results in a decrease in the performance of hepcidin. US 2007/0〇4618 is related to siRNA, which has a direct inhibitory effect on the expression of hepcathine-mRNA. Thus, all such compounds or methods begin with the formation of the iron metabolism pathway prior to the formation of Hepaxi (IV) and decrease its formation in the early stages. However, in addition, it is combined with Hapaxi (4) which has been formed in the body (10) and thus inhibits its binding to the membrane transport protein transfer iron, thereby making it impossible to use Hapaxi (10) to transport ferritin 201111379. It is known and disclosed in the prior art. Such compounds are therefore referred to as hepcidin antagonists, and members of this group based on hepcathine antibodies are specifically known. Various mechanisms for revealing the effects on the performance of hepcidin, for example, by anti-intentional RNA or DNA molecules, ribozymes, and anti-Hapaxitin antibodies, are also known in the art. These are disclosed, for example, in EP 1 392 345. WO09/058797 further discloses the use of anti-Hapaxistatin antibodies and their use for specific binding to human sea-pacicin-25, and thus their use in the treatment of low iron levels, particularly anemia. Further compounds which are formed as a hepatic antagonist and which are formed from the hippocamtin antibody population are known from EP 1 578 254, W008/097461, US 2006/019339, WO 09/044284 or "WO 09/027752. In addition, it is known to bind to transferrin-1 and thus activate transferrin to promote iron from such transfer factor], for example, from US 2007/218055. Compounds that are described as a hepatic anti-inflammatory agent or that inhibit the expression of hepcidin are higher molecular weight compounds, and those that are primarily obtainable by genetic engineering methods. Compounds that act on iron metabolism are also known. Or a low molecule that promotes action. Thus, the 'W008/109840 system reveals that it is particularly useful to treat iron metabolism abnormalities such as transfer iron abnormalities by regulating the inhibition or activation of DMT-1. Such compounds are specifically described as D Μ T-1 inhibitors. W008/109840. This means that preferably 10 201111379 can be used for diseases involving increased iron accumulation or iron storage diseases, such as hemochromatosis, Happening. Low molecular weight compounds which modulate the DMT-1 mechanism are also known from WO 08/121861. This document is particularly concerned with the treatment of specific pyrazole and pyrrole compounds, for example, the treatment of iron overload abnormalities in which the transferrin is abnormally dominant. In addition, 'US 2008/234384 is related to specific diaryl and diheteroaryl compounds for the treatment of abnormalities in iron metabolism, such as transfer iron abnormalities, which are also particularly useful for treatment by acting as DMT-1 inhibitors. Due to the abnormal accumulation of elevated iron. However, it is possible to use it in the case of iron deficiency syndrome. The DMT-1 regulatory mechanism is also referred to in this document in abbreviated form. The same applies to WO 08/151288, which discloses specific aromatic and heteroaromatic compounds that act on DMT-1 regulation and are therefore useful in the treatment of iron metabolism abnormalities. Therefore, the low molecular weight compound disclosed in the prior art for iron metabolism is based on the DMT] regulatory mechanism, and specifically discloses a drug for treating iron accumulation abnormality or iron overload syndrome such as hemochromatosis. Take "sevovain or." The chemical compounds based on the structure of sinister has not been disclosed to date for the treatment of abnormalities in iron metabolism. In addition, low molecular weight chemical structures that are useful as hepatic antagonists and are therefore suitable for the treatment of iron metabolism abnormalities have not been disclosed. The present invention is also directed to a novel thiazolylamine or oxazolamide compound having the structural formula (1) according to the present invention. 201111379 WO 20〇7/〇56l55 is a cool aminase inhibitor. The compound disclosed in the above is described in m VII (4) 155 A1, which discloses a special heterocyclic compound and its inhibitor. The basic structural formulae (1) to (6). From the compound group of the formula (5): The system is different from the combination of the invention having the structural formula (1)

Sulfhydryl, which has a corresponding to 4, although WO 2007/056155 Α1, a mono-tecroplex is disclosed, and its towel, the substituent χΒ6, represents a substitution. Therefore, it corresponds to the structure of the general formula (1) of the present invention. Because of 56155 Α1, a compound of the following structural formula

The individual compounds falling within the chemical formula (I) of the present invention are formally disclosed, and the specific action of such specific structural elements is not suggested in this document, nor is the specific effect of such special compounds in the treatment of abnormal iron metabolism. According to the English name and abstract, WO 2008/Μ6774 Α1 is related to the use of tetrahydroisoquinolinone derivatives for the treatment of intestinal cramps. Basic Structures The compounds disclosed between the general formulae (A), (Β) and (C) are substantially different from the compounds of the present invention having the structural formula (I). This document, in a specific embodiment (Compound No. 23 8), discloses a compound in which a substituent has a structure corresponding to the formula (I) of the present invention. Therefore, although WO 2008/146774 Α1, a compound having the following structural formula 12 201111379

HjC-S=0 HN

Formal disclosure of individual compounds within the chemical formula (10) of the present invention does not suggest the specific role of such specific structural elements, nor the potential role of such specific compounds in the treatment of abnormalities in iron metabolism. A guanamine derivative, a process for its preparation, and its use in the treatment of diabetes and obesity are from the preparation of a ruthenium derivative containing an azole moiety as an SGLT inhibitor "; Fukatsu, Kohji et al., Database Caplus Chemical Abstracts Service, STN, 2006. In particular, the following specific compounds are disclosed herein: 2-[2-[([1, Γ-biphenyl]-4-ylcarbonyl)amino]ethyl] -N-[2-(diphenylamino)ethyl]-4-oxazole carboxamide:

2-[2-[([1,Γ-Biphenyl]-4-ylcarbonyl)amino]ethyl]-N-[2-(4-morpholinyl)-3-phenoxypropyl]- 4-oxazole carboxamide:

2-[2-[([1,Γ-Biphenyl]-4-ylcarbonyl)amino]ethyl]-N-[2-(4-morpholinyl)-3- 13 201111379 Phenoxypropyl ]-4-thiazole carboxamide:

PhO 2-[2-[([1,Γ-biphenyl]-4-ylcarbonyl)amino]ethyl]-N-[2-(diphenylamino)ethyl]-4-thiazolecarboxylate amine:

2-(2-Aminoethyl)-4-thiazolecarboxylic acid-ethyl ester:

2-[2-[[(1,1-Didecylethoxy)carbonyl]amino]ethyl]-4-oxazolecarboxylic acid-曱 base:

MeO 2-[2-[([1,1'-Biphenyl]-4-ylcarbonyl)amino]ethyl]-4-thiazolecarboxylic acid-ethyl ester:

EtO

Ph 2-(2-Aminoethyl)-4-oxazolecarboxylic acid-methyl ester:

14 201111379 2-[2-[([U'-Lian]]yl)amino]ethyl]-4··»oxazolecarboxylic acid decyl ester:

The individual compounds corresponding to the specific compounds of the formula (1) of the present invention represent a mercapto group (or an alkoxy group), or the R2 and R3 groups are represented by a hydrogen group. A compound in which the substituent of the R2 and R3 positions of the formula (I) according to the present invention represents a selectively substituted alkyl group is not disclosed herein. This disclosure does not suggest the possible role of the disclosed structural elements or compounds in the treatment of iron metabolism abnormalities. W〇 2009/154739 A2 discloses a novel heterocyclic human and its role as a Sm0 receptor, and its use in the treatment of cancer and wound healing and tissue regeneration. This document also discloses a particular compound (VI):

Wherein the substituent R, according to the general formula (I) of the present invention, represents a substituted aryl (aromatic). Thus, although 'w〇2007/056155 A1', this particular compound is also officially disclosed in the chemical formula of the present invention (individual compounds within 10), this document does not suggest the specific role of such specific structural elements, nor such special The potential role of compounds in the treatment of abnormalities in iron metabolism. "Synthesis of DMA-based DMA standard light molecules 15 201111379 specific for guanoin" (Kobayashi Susumu et al., Synlett (1), 1992) reveals the production of thiazole derivatives Methods and their use in DNA binding. This document specifically discloses the following compounds: Compound 2a:

Ph-^ 〇

OEt Compound 5a: Ο

ΝΗ ν , S′ , Me Compound 6a: Ο

Compounds la: , S', Me and Ο

Ch Η I Me wherein the substituent of the formula (I) according to the invention at the positions R2 and R3 represents 16 201111379 fluorenyl (or alkoxycarbonyl). A compound in which a substituent of the formula (I) according to the present invention at the positions of R2 and R3 represents a selectively substituted alkyl group is not disclosed herein. This disclosure also does not suggest the possible role of the compounds disclosed herein in the treatment of iron metabolism abnormalities. "Individual porphyrin thiazole in terms of oxygen activation and DNA cleavage" (Hamamishi Norimitsu et al, Journal of the American Chemical Society, 114 (16), 1992) discloses novel brothmycin, and its production method Its role in DNA synthesis and DNA degradation. This document specifically discloses the following compounds falling within the general formula (I) of the present invention:

Wherein R = Boc (Boc protecting group) or hydrazine,

Wherein R = NPS (nitrophenylsulfonyl protecting group) or hydrazine,

Wherein R = Boc (Boc protecting group) or Η 17 201111379 and therefore a compound in which a substituent according to the invention represents a fluorenyl group (or B 〇 c = group). One of the substituents is based on the selection of 5 "months of general formula (I) at the R2 and R3 positions = alkoxycarbonyl group) or sulfonyl group (NPS == sulfonate), according to the The compounds of the general formula (1) at the R2 and R3 positions are representative of the tactile "The compounds are not disclosed here. This document also does not suggest the possible effects of the compounds disclosed herein in the treatment of abnormal iron metabolism." Analogs, synthesis of thiazolylamine associated with bromomycin octa 2(1) and i-NMR spectroscopy distribution (Ri〇rdan et al., Database

Caplus Chemical Abstracts Service, STN, 1982) discloses certain special thiazolylamine derivatives, and methods for their production. According to an excerpt from the STN database, the following compounds officially falling within the general formula (I) of the present invention are specifically disclosed herein: [3-[[[2-[2-(Ethylamino)ethyl]] -4-thiazolyl]carbonyl]amino]propyl]dimercapto-indenyl:

2-[2-(Ethylamino)ethyl]-4-thiazolecarboxylic acid-ethyl vinegar:

2-[2-(Ethylamino)ethyl]-N-[3-(methylthio)propyl]-4-thiazolecarboxylamine: 18 201111379

As the specific compound, the individual substituent of the formula (1) according to the present invention at the positions of R2 and R3 represents an indenyl group (ethinyl group). A compound in which one of the substituents of the formula (I) to the R2 and R3 positions according to the present invention represents a selectively substituted alkyl group is not disclosed herein. This document does not suggest the medical use of the structural elements or compounds disclosed herein or even the possible effects of treating iron metabolism abnormalities. One of the phytomycins, the biosynthesis synthesis of the sputum, and the "McGowan" (the Journal of the American Chemical Society, 1977), reveals some of the special dithiazole units of pebbins and methods for their production. This document also mentions the anticancer effect of bromomycin. In particular, the following compounds which formally fall within the general formula of the present invention are specifically disclosed in this document: Compound 4:

Wherein R compound 5: ’ R = C3 or phenyl, and

Wherein R = CH3 or phenyl and R, = (C6H5)3C or H. 19 201111379 In these compounds, the individual substituents of the formula (I) according to the invention at the R2 and R3 positions represent a fluorenyl (optionally substituted) fluorenyl group (ethinyl or benzylidene). Among the substituents of the formula (I) according to the invention at the R2 and R3 positions, which represent a selectively substituted alkyl group, are not disclosed herein. This disclosure does not suggest that the compound may be useful in the treatment of abnormalities in iron metabolism. "2'-(2-Aminoethyl)-2,4'-two-salt salicylic acid, one component of the anti-tumor antibiotic, bosin, and its synthesis" (Zee-Cheng et al. Database Caplus

Chemical Abstracts Service, STN, 1971) discloses the synthesis of 2,2-(2-aminoethyl)-2,4'-dioxet-4-deoxy acid. The following compounds which are formally present in the general formula (I) of the present invention are also specifically disclosed in the excerpt from the STN database: 2-[2-(phenylhydrazino)ethyl]-4-thiazolecarboxylate Acid-ethyl@:

And 2-[2-(benzhydrylamino)ethyl]_4_thiazole carboxamide:

With respect to these compounds, the individual substituents of the formula (1) according to the present invention at the positions of R2 and R3 represent an indenyl group (benzoyl group). Among the substituents of the formula (I) according to the invention at the R2 and R3 positions, which represent a selectively substituted alkane 20 201111379 group, are not disclosed herein. This disclosure does not suggest the possible role of r in the medical use or even in the treatment of iron metabolism. [Examination of the test] The purpose of the present invention is to provide a special use of ACD and AI for the deficiency of iron, and for the role of thief, especially for riding, blood, and thus antagonizing and thus regulating the metabolism of iron.昀' Ding compounds that antagonize interactions. In particular, the present invention is aimed at improving the population of molecular summer compounds and generally by using antagonists such as RNA, DNA or antibodies which can be obtained by a method or by a method. Or a compound which is simpler in synthetic route preparation by inhibiting the compound of the compound. Since the West's invention

The inventors have discovered a special compound antagonist of the S& amine group. T The present invention relates to a compound of the formula (I) R1 "

, Ν (.) wherein X is selected from: 5 or 〇; R1 is selected from the group consisting of: - hydrogen, - a selectively substituted amine group, - a selectively substituted alkyl group, 21 201111379 - Optionally substituted alkoxy, - optionally substituted alkenyl, - optionally substituted alkynyl, - optionally substituted aryl, or - optionally substituted heterocyclic; R2 and R3 Is the same or different, the group * and the mother ~ is selected from the following - selective substituted bases - selective substituted thiol, aryl or hetero-indolyl, -selective Substituted alkoxycarbonyl-selectively substituted alkyl, -substituted substituted alkenyl, -substituted substituted alkynyl, -substituted substituted aryl, or optionally substituted a ring group; or a salt that is acceptable for learning. Throughout the invention, the above substituted groups are defined as follows: The selective peak of the filament preferably comprises: in the embodiment of the invention, optionally substituted with a straight bond or a knives A labile group may be substituted which has a heterogeneous group of nitrogen, oxygen or sulfur in which the preferred one is from 1 to 3 carbon atoms. This specifically means that, for example, one of the aforementioned alkyl residues or a plurality of fluorene groups 22 201111379 can be replaced by NH, 0 or S. The optionally substituted alkyl group further comprises a cycloalkyl group preferably having from 3 to 8, more preferably 5 or 6, more preferably 6 carbon atoms. The substituent of the optionally substituted alkyl group as defined above preferably contains 1 to 3 substituents selected from, for example, the same or different groups of the following groups: a cycloal optionally substituted as defined below a base group, a hydroxyl group, an ifi group, a cyano group, an alkoxy group as defined below, a optionally substituted aryloxy group as defined below, a optionally substituted heterocyclic oxy group as defined below, a carboxyl group, a selectivity as defined below Substituted thiol, optionally substituted aryl as defined below, optionally substituted heterocyclyl as defined below, optionally substituted amino, thiol, as defined below, substituted Alkyl, aryl or heterocyclylsulfonyl (r-so2-). Examples of the alkyl residue having 1 to 8 carbon atoms include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a second butyl group, a third butyl group, a n-pentyl group, an isopentyl group, a second pentyl group, a third pentyl group, a 2-mercaptobutyl group, a positive Base group, 1-fluorenylpentyl group, 2-decylpentyl group, 3-methylpentyl group, 4-decylpentyl group, 1-ethylbutyl group, 2 -ethylbutyl group, 3-ethylbutyl group, 1,1-dimethylbutyl group, 2,2-dimercaptobutyl group, 3,3-dimethylbutyl group a group, a 1-ethyl-1-mercaptopropyl group, a n-heptyl group, a 1-methylhexyl group, a 2-decylhexyl group, a 3-decylhexyl group, a 4-fluorene group Hexyl group, 5-decylhexyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, 4-ethylpentyl group, U - dimethylpentyl group, 2,2-didecylpentyl group, 3,3-di 23 201111379 decylpentyl group, 4,4-didecylpentyl group, 1-propene Butyl group, n-octyl group, 1- a heptyl group, a 2-methylheptyl group, a 3-mercaptoheptyl group, a 4-mercaptoheptyl group, a 5-fluorenylheptyl group, a 6-fluorenylheptyl group, a 6-fluorenylheptyl group , 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, 5-ethylhexyl group, 1,1-dimethylhexyl group Group, 2,2-dimethylhexyl fluorene, 3,3-dimethylhexyl group, 4,4-dimethylhexyl group, 5,5-dimercaptohexyl group, 1-propyl group A pentyl group, a 2-propylpentyl group, and the like. Those having 1 to 6 carbon atoms, particularly methyl, ethyl, n-propyl and isopropyl and butyl are preferred. (^ to (: 4 alkyl, especially fluorenyl, ethyl and isopropyl, is most preferred. By one or more hetero-like groups such as -0-, -S- or -NH- An example of an alkyl group obtained by substitution is preferably one in which one or more thiol groups are replaced by -0 to form an ether group, such as methoxymethyl, ethoxymethyl , 2-methoxyethyl, etc. According to the invention, polyether hydrazines, such as poly(ethyleneoxy) groups, are included within the definition of alkyl groups. Naphthenes containing from 3 to 8 carbon atoms The base residue preferably comprises: a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. A cyclopropyl group, a ring The butyl group, the cyclopentyl group, and the cyclohexyl group are preferred. The cyclopentyl group is particularly preferred. Within the meaning of the present invention, the ii includes fluorine, chlorine, and moth, preferably II or chlorine. Examples of linear or branched alkyl residues substituted with halogen and having 1 to 8 carbon atoms include: fluoromethyl group, difluoroantimonyl group, trifluoromethyl group, chloranil Base group, 24 201111379 dichloro a group, a tris-steryl group, a bromomethyl group, a dibromofluorenyl group, a tribromomethyl group, a 1-fluoroethyl group, a 1-haloethyl group, a 1-bromo group Ethyl group, 2-fluoroethyl group, 2-gas ethyl group, 2-bromoethyl group, 1,2-difluoroethyl group, 1,2-dichloroethyl group 1,2-dibromoethyl group, 2,2,2-trifluoroethyl group, heptafluoroethyl group, 1-fluoropropyl group, 1-apropyl group, 1- Bromopropyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 3-fluoropropyl group, 3-chloropropyl group, 3-bromopropyl group a group, a 1,2-difluoropropyl group, a 1,2-di-propyl group, a 1,2-dibromopropyl group, a 2,3-difluoropropyl group, 2, a 3-di-propyl group, a 2,3-dibromopropyl group, a 3,3,3-trifluoropropyl group, a 2,2,3,3,3-pentafluoropropyl group, a 2-fluorobutyl group, a 2-cyclobutyl group, a 2-bromobutyl group, a 4-fluorobutyl group, a 4-cyclobutyl group, a 4-bromobutyl group, 4, 4,4-trifluorobutyl group, 2,2,3,3,4,4,4-heptafluorobutyl group, perfluorobutyl group, 2-fluoropentyl group, 2-gas Pentyl group, 2-bromopentyl group 5-fluoropentyl group, 5-airpentyl group, 5-bromopentyl group, perfluoropentyl group, 2-fluorohexyl group, 2-ahexyl group, 2-bromohexyl group Group, 6-fluorohexyl group, 6-ahexyl group, 6-bromohexyl group, perfluorohexyl group, 2-fluoroheptyl group, 2-heptyl group, 2-bromoheptyl group a group, a 7-fluoroheptyl group, a 7-chloroheptyl group, a 7-bromoheptyl group, a perfluoroheptyl hydrazine, etc. a cycloalkyl group substituted with a halogen and having 3 to 8 carbon atoms Examples of the residue include a 2-fluorocyclopentyl group, a 2-chlorocyclopentyl group, a 2-bromocyclopentyl group, a 3-fluorocyclopentyl group, a 3-cyclopentyl group. a 3-bromocyclopentyl group, a 2-fluorocyclohexyl group, a 2-chlorocyclohexyl group, a 2-bromocyclohexyl group, a 3-fluorocyclohexyl group, a 3-chlorocyclohexyl group, 3-bromocyclohexyl group, 4-fluorocyclohexyl group 25 201111379 group, 4-cyclohexyl group, 4-bromocyclohexyl group, difluorocyclopentyl group, dicyclopentyl group, Dibromocyclopentyl group, difluorocyclohexyl group, dichlorocyclohexyl group, dibromocyclohexyl group, trifluorocyclohexyl group, trichlorocyclohexyl group a group, a tribromocyclohexyl group, and the like. Examples of the alkyl residue substituted with a hydroxy group include the above alkyl residue having 1 to 3 hydroxy residues, such as hydroxyindenyl group, 2-hydroxyethyl group, 3-hydroxypropyl group and the like. Examples of the alkyl residue substituted with an alkoxy group include the above alkyl residue having 1 to 3 alkoxy residues as defined below, such as methoxyindenyl, ethoxymethyl, 2-indole An oxyethyl group, a 2-ethoxyethyl group, a 2-methoxypropyl group, a 3-methoxypropyl group or the like, a 2-methoxyethylene group or the like. 2-methoxyethyl is preferred. Examples of the alkyl residue substituted with an aryloxy group include the above alkyl residue having 1 to 3 aryloxy residues as defined below, such as phenoxymethyl, 2-phenoxyethyl, and 2- or 3-phenoxypropyl group and the like. The 2-phenoxyethyl group is preferred. Examples of the alkyl residue substituted with a heterocyclic oxy group include the above-mentioned alkyl residue containing 1 to 3 heterocyclic oxy residues as defined below, such as pyridin-2-yl thiol, -ethyl or -propyl, σ ratio β-decyloxymethyl, -ethyl or -propyl, thiophen-2-yloxymethyl, -ethyl or -propyl, thiophen-3-yloxymethyl, Ethyl or propyl, π-fusin-2-yloxycarbonyl, -ethyl or -propyl, π-pentan-3-yloxymethyl, -ethyl or -propyl. Examples of the alkyl residue substituted with a mercapto group include the above alkyl residue having 1 to 3 sulfhydryl residues as defined below. Examples of the alkyl group substituted with a cycloalkyl group include the above alkyl residue having 1 to 3, preferably 26 201111379, one (optionally substituted) cycloalkyl group, such as a cyclohexyldecyl group. , 2-cyclohexylethyl, 2- or 3-cyclohexylpropyl, and the like. Examples of the alkyl group substituted with an aryl group include the above alkyl residue having 1 to 3, preferably 1 (optionally substituted) aryl group as defined below, such as a phenyl fluorenyl group. Phenylmethyl (phenyl fluorenyl), 2-phenylethyl, 2- or 3-phenylpropyl, and the like are preferred. Further, a substituted aryl group as defined below, particularly a halogen-substituted aryl group, is preferably substituted with an alkyl group as defined above, such as, in particular, 3-methoxy-4-fluorophenyl group base:

Examples of the alkyl group substituted with a heterocyclic group include the above alkyl residue having 1 to 3, preferably 1 (optionally substituted) heterocyclic group as defined below, such as '2-σ σ -2- -2-yl-ethyl, 2-0 than β -3-yl-ethyl, 0 ratio. Ding-2-yl-methyl, yl-methyl, 2-π-pentan-2-yl-ethyl, 2-d-furan-3-yl-ethyl, π-furan-2-yl-fluorenyl , π-furan-3-yl-methyl, 2-. Desphen-2-yl-ethyl, 2-thien-3-yl-ethyl, thiophen-2-yl-indenyl, thiophen-3-yl-indenyl, 2-yl-l-ethylethyl such as ' 2-O-Lin-4-yl-ethyl*- phenanthrenyl, such as morpholin-4-yl-methyl, 1Η-imidazol-2-ylindenyl, each of which may optionally contain a condensation a benzene ring, such as 1 Η-benzimidazol-2-ylmethyl:

Particularly preferred is: 1 Η-benzimidazol-2-yl fluorenyl: 27 201111379

Binding position) and 1H-imidazol-2-ylmethyl: Μ

Examples of the alkyl residue substituted with an amine group include the above alkyl residue having 1 to 3, preferably 1 (optionally substituted) of an amine group as defined below, such as a mercaptoamine group. Methyl, mercaptoaminoethyl, mercaptoaminopropyl, 2-ethylaminoindenyl, 3-ethylaminoindenyl, 2-ethylaminoethyl, 3-ethylamino Ethyl and the like. The optionally substituted alkoxy group comprises a selectively substituted alkyl-0- group, wherein reference may be made to the definition of the previous alkyl group. Preferred alkoxy groups are linear or branched alkoxy groups having up to 6 carbon atoms, such as a decyloxy group, an ethoxy group, a n-propoxy group, isopropoxy a group, a n-butoxy group, an isobutoxy group, a second butoxy group, a third butoxy group, a n-pentyloxy group, an isopentyloxy group, a second a pentyloxy group, a third pentyloxy group, a 2-decylbutoxy group, a n-hexyloxy group, an isohexyloxy group, a third hexyloxy group, a second hexyloxy group a group, a 2-methylpentyloxy group, a 3-methylpentyloxy group, a 1-ethylbutoxy group, a 2-ethylbutoxy group, a 1,1-didecyl group An oxy group, a 2,2-dimercaptobutoxy group, a 3,3-dimercaptobutoxy group, a 1-ethyl-1- 28 201111379 and an alkoxy group, such as a ring Pentyloxy τ ; & propoxy group g V, TS2 3 ^ ^ ^ six... 咏 丞 丞 或 或 或 或 或 或 或 或 或 或 或 或 或 或 或 或 或Alkoxy group® Gil group, n-propenyl group, isopropoxy group, n-butoxy group from _s 〃 ^ , 1 base group, isobutoxy group, second butoxy group The group and the third butoxy group are preferred from the subtractive group. The methoxy group is particularly preferably 0. The selectively substituted alkenyl group throughout the invention preferably comprises: a linear or branched chain containing 2f 8 carbon atoms and an alkenyl group having 3 to 8 carbon atoms. 'It may be optionally substituted with 1 to 3 identical or different substituents such as a base, a gram or a silk group. Examples include ethylidene, 1-methylvinyl, allyl, u-dilute, isopropenyl, cyclopropyl, cyclobutenyl, cyclic Langyl, and cyclohexane. Ethyl or allyl is preferred throughout the invention. The selectively substituted alkynyl group preferably comprises: a linear or branched filament having 2 to _ carbon atoms and a ring fast radical having a carbon atom It may be optionally substituted with preferably 13 identical or different substituents. (d) In the domain of the substituted filaments, reference is made to the definition of a selectively substituted alkyl group having more than one carbon atom as defined above, wherein the optionally substituted alkyne comprises at least one CsC triple bond. Examples include: ethynyl, propynyl, butynyl, pentynyl, and alternative substitutions thereof as defined above. The ethynyl group and the selectively substituted ethynyl group are preferred. Throughout the invention, the selectively substituted aryl group preferably comprises: an aromatic hydrocarbon residue having from 6 to 14 carbon atoms excluding carbon atoms of a possible substituent, which may be mono- or bicyclic and which may be 1 to 3 identical or phase 29 201111379 Different from light base, as defined above! a cyano group, a cyano group, a selectively substituted amino group as defined above, a thiol group, a selectively substituted alkyl group as defined above, a selectively substituted aryl group as defined above, and a selective substitution as defined above An alkoxy group, a selectively substituted aryloxy group, as defined above, optionally substituted heterocyclic oxy, a selectively substituted aryl group, as defined above, a selectively substituted heterocyclic ring as defined below Substituent substitution. The aromatic olefin having 6 to 14 carbon atoms contains, for example, a phenyl group, a phenyl group, a phenanthryl group and a fluorenyl group, which may be optionally substituted one or more times with the same or different residues. The phenyl group and the optionally substituted phenyl group are particularly preferably a phenyl group substituted by a single or multiple substituents. Examples of the silk group substituted with an alkyl group include an aryl group as defined above which is substituted with a linear or branched alkyl group having 1 to 8, preferably 1 to 4 carbon atoms as described above. The tolyl group is preferably an alkylaryl group. Examples of the aryl group substituted with a halogen preferably include an aryl group as described above which is substituted with a halogen as described above. Examples of aryl residues substituted with dentate and having 3 to 8, preferably 6 carbon atoms in the aromatic ring system include: 2-fluorophenyl group, 2-qiphenyl group, 2-bromo group Phenyl group, 3-fluorophenyl group, 3-hydroxyphenyl group, 3-bromophenyl group, 4-fluorophenyl group, 4-chlorophenyl group, 4-bromo-styl group a group, a 24-difluorophenyl group, a 2'4-monofluorophenyl group, a 2,4-dimethylene group, a 3 Å difluorophenyl group, a 3,5-diphenyl group , 3,5-dibromophenyl group, etc., 2,4,6-trifluorophenyl group, 2,4,6-trisylphenyl group, 2,4,6-tribromophenylmethane group , 2chloro-3-fluorophenyl group, L-chloro-4-ylfluorophenyl group, 2-fluoro-3-3 chlorophenyl group, 3-fluoro-4-oxophenyl group, 2,3- Dichloro-4-tansyl group, 30 201111379 2,4-dichloro-3-fluorophenyl group, 2_fluoro-3,4_diphenyl group, 2,3-difluoro- a 4-phenylphenyl group, a 2,4-difluoro_3_chlorophenyl group, a 2-chloro-3-3,4•di-phenyl group, a 2-fluorophenyl group, a 2-chlorophenyl group , 3_phenyl, 1 chlorophenyl, phenyl and 4-phenylphenyl, and 2_chloro-3-ylphenyl, 3 gas·4·fluorophenyl, -3-chlorophenyl and 3 _Fluor·4·gas phenyl Better. It is particularly difficult to be a 3-gas phenyl group, a 4-fluorophenyl group, and especially a 3-gas _4-fluorophenyl group. Examples of the aryl group substituted with a benzyl group preferably include an aryl group as described above substituted with 1 to 3 radical residues, such as 2 minus phenyl, 3 phenylphenyl, 4- secret benzene Base, 2,4-di-diphenyl, 2,5-diphenyl, 2 6-dihydroxyphenyl, 3,5-dihydroxyphenyl, 3 6-dihydroxyphenyl, 2 4,6 trihydroxy Phenyl and the like. Two silk bases, a phenyl group and a 2 4_diphenyl group are preferred. Examples of the aryl group substituted with an alkoxy group preferably include: an aryl group as described above substituted with 1 to 3 alkoxy residues as described above, and a group such as '2'-f-decylphenyl group 3, methoxyphenyl, 4, methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 24-dimethoxyphenyl, and the like. Throughout the invention, the optionally substituted heterocyclic group preferably comprises: 1 to 3, preferably 1 to 2, heteroatoms selected from N, oxime or 3 and optionally substituted by 1 to 3 A cyclically substituted 5 to 8 member cyclic residue of a saturated or unsaturated heterocyclic ring of the aliphatic group, wherein, with respect to possible substituents, reference may be made to the definition of a possible alkyl substituent. A saturated or unsaturated, optionally substituted heterocyclic residue of 5 or 6 members is preferred, such as tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydro 31 201111379 °cephen-2-yl , tetrahydrobenz-3-yl, B, σ, -1-yl, π, B, pyridyl-2-yl, Dtb, pyro-3-yl, 吓, quot; 2-base, 吓 · -3- 、, ° ° 林-4_ base,. The base is -1-yl, ^^-2-yl, 11 sigma-3-yl, 11 ept-4-yl, α chen. Well-1-base,. Chen. Well-2-yl, tetrahydron-pyran-2-yl, tetrahydro D-pyran-3-yl, tetrahydropyran-4-yl, which is selectively condensed with an aromatic ring or the like. Throughout the invention, a selectively substituted heterocyclic group also includes a heteroaromatic hydrocarbon residue having from 4 to 9 ring carbon atoms, which additionally preferably contains from 1 to 3 identical or different selected from the ring. The heteroatoms of the S, Ο, N series, and thus preferably form a heteroaromatic residue of 5 to 12 members, which may preferably be monocyclic, but may also be bicyclic. Preferred aromatic heterocyclic residues include, for example, a ° ratio, such as, for example, n to D-but-2-yl, n to β--3-yl and a group, and D to pyridyl-indole-oxide , pyrimidinyl, morphine, 11 to speak. The thiophene group, the furyl group, the ° ratio, the base ratio, and the ratio. Sitting on the base, σ meters. Sitting on the base, ° plug. Sitting on the base. Oxanyl, or isoxazolyl, anthracenyl, fluorenyl, benzo[b]thienyl, benzo[b]furanyl, oxazolyl, benzimidazolyl, benzoxazolyl , benzothiazolyl, quinalhenyl, isoindolyl, naphthalene. a mono- or bicyclic aromatic heterocycle having 5 or 6 members, such as pyridyl, pyrimidinyl, morphine, 0 to D, imidazolyl, fluorenyl, and °Septenyl, and fluorene D, benzimidazolyl, benzo[b]thienyl, benzothiazolyl or benzo[b]furanyl. Particularly preferred is a 1H-imidazolyl group such as, for example, 1H-imidazole-2 group:

1H-imidazol-4-yl, or 3H-imidazol-4-yl and 1H-benzimidazol-2-yl: 32 201111379

(* in the combined position of each case). The heterocyclic residue according to the invention may preferably be one to three identical or different selected from the group consisting of, for example, a thiol group, a halogen group as defined above, a cyano group, an amine group as defined above, a fluorenyl group, an alkane as defined above. A thiol group, as defined above, and an alkoxy group as defined above, an aryloxy group as defined above, a heterocyclic oxy group as defined above, an aryl group as defined above, a substituent of a heterocyclic group as defined above. The heterocyclic group preferably includes: tetrahydrofuranyl group, '» ratio of each alkyl group, morphine group, ° base group or tetrahydro n-butan group, π ratio bite group, bite base N-oxide, . Dimethyl group, 哒π well base, α-pyramyl group'. Tertiary, thiol, β-l- yl, oxime, carbazolyl, thiazolyl, oxazolyl or isoxazolyl, indolyl, fluorenyl, benzo[b]nonyl , stupid [b]pyranyl, carbazolyl, benzimidazolyl, stupid and oxazolyl, benzothiazolyl, quinolyl, isoquinolinyl, naphthyridinyl, oxime, base ° evil Lin Ke. a 5- or 6-membered mono- or bicyclic aromatic heterocyclic ring such as piperidinyl, pyrimidinyl, fluorenyl, pyridinyl, imidazolyl, π-folyl and fluorenyl, and fluorenyl, Benzo-indolyl, benzo[b]nonyl,

The benzothiazolyl or benzo[b]furanyl group is preferred, and the imidazolyl and benzimidazolyl groups are particularly preferred. Examples of the A-heart-cyclinyl group preferably include a heterocyclic group 1 group-based group as described above, which is substituted with a linear or branched yarn of (1), preferably (1) carbon atoms as described above. A benzyl group, a methyl group and a (tetra) group, and an ethylidene group, preferably a pyridyl group. (4) a heterocyclic group substituted by a residue such as, for example, (d)yl, phenyl, 33 201111379 3-hydroxybenzimidazolyl, 4-hydroxy cold! and imidazolyl, 3,4-dihydroxyimidazolyl, 3, 5-monobenzopyranyl, 3,6-di-dibenzopyranyl and the like. Examples of the heterocyclic group substituted with an alkoxy group preferably include: a heterocyclic group as described above substituted with 1 to 3 alkoxy residues as described above, preferably such as 3-alkoxy A cylimidazolyl group, a 3-alkoxybenzimidazolyl group, a 4-alkoxybenzimidazolyl group, a 3,4-dialkoxyimidazolyl group, a 3,5-dialkoxybenzimidazole. Sodium, 3,6-dialkoxybenzimidazolyl, and the like. The optionally substituted thiol group here and thereafter comprises: a selectively substituted aliphatic fluorenyl group (alkyl fluorenyl group = alkyl _c 〇, wherein, regarding the alkyl group, reference may be made to the previous selective a substituted alkyl group), an optionally substituted aromatic fluorenyl group (aryl aryl group = aryl group _c 〇 _, wherein the aryl group may be referred to the definition of the previously selected substituted aryl group Or, a heterocyclic fluorenyl group (heterocyclic fluorenyl group = heterocyclic group _C0_, wherein the heterocyclic group may be referred to the definition of the previously optionally substituted heterocyclic group). A heterocyclic fluorenyl group (heterocyclic group -CO-) is preferred. The optionally substituted aliphatic fluorenyl group preferably comprises: a heart to a decyl group, such as a methyl group, an ethyl group, a propyl group, a butyl group, an butyl group, an isobutyl group, a pentyl group, an isoprene group醯基, 新戊醢基, 醯基基, etc.

Examples of substituted aliphatic thiol groups include, for example, the selective substitution of the tc2j_C6 ship group with an aromatic or heterocyclic group, wherein reference may be made to the previous aryl diheteroyl group and (32 to (: 6 ship base definition) , for example, phenylethenyl, D-septyl-ethenyl, thiophene-3-ylethenyl, furan-2-ylethylidene, furazan-3-yl-ethenyl, 2- or 3- -Phenylpropanyl, 2- or 3-thiophene-2, territorial, 2- or 3-porphin-3-yl-propenyl, 2 or 3-pyran-2-yl, I 34 201111379 or 3-furan-3-yl-propenyl. The optionally substituted aromatic fluorenyl (aryl fluorenyl) specifically comprises: c6 to Ci aryl aryl 'such as 'benzoinyl, fluorenyl hydrazine Selective substituted heterocyclic fluorenyl (heterocyclic fluorenyl) specifically includes: hydrazine to hydrazine (7) heterocyclic fluorenyl, such as furanyl, pyridinium, pyrrolidinium Base, piperidinyl, tetrahydrofuranyl, such as tetrahydrofuran-2-indole, etc. Throughout the invention, the selectively substituted amine group preferably comprises: an amine group, a mono or didecylamino group, a single or a Arylamino group, (N-alkyl) (N-aryl) amine group, Mono or diheterocyclylamino, (N-alkyl)(N-heterocyclyl)amino, (N-aryl)(N-heterocyclyl)amino, mono or didecylamino, and the like. With respect to the alkyl group, the aryl group, the heterocyclic group and the fluorenyl group, reference may be made to the corresponding selectively substituted top group, the selectively substituted aryl group, the selectively substituted heterocyclic group, and the selectivity. Definition of substituted fluorenyl group. The early or monoalkylamino group specifically comprises: 1 to 8, preferably 1 to 6 saturated or unsaturated, each of the alkyl group having a selectivity as described above. a straight or branched mono- or dialkylamino group of a carbon atom, and a mono- or dicyclodecylamino group or an (N-alkyl)(N-cycloalkyl)amine group. In this case, The (N-alkyl)(N-cycloalkyl)amine group is specifically described in each case as a substituted amine group in which the nitrogen atom is substituted with a calcined residue and substituted with a cycloalkyl residue. Examples of the dialkylamino group include a methylamino group, a dimethylamino group, an ethylamino group, a cyclohexylamino group or a (N-methyl)(N-cyclohexyl)amino group, wherein the stilbene group Each of the groups may be preferably substituted with a substituent. Alkylamino and (N-alkyl)(N-cycloalkyl)amine groups. Particularly preferred are substituted groups of (optionally substituted) aryl substituted alkyl groups, especially benzylmethyl groups. An amine group, and an amine group which is substituted with an alkyl group substituted with a halogen substituted aryl group of 35 201111379, such as a 3-chloro-4-cyclophenylguanidino group. Particularly preferred is a benzylamino group:

(* = binding position), or a substituted benzylamino group, such as a self-substituted methylamino group, such as:

F 11* (*=binding position), and a dialkylamino group such as a '(cycloalkyl)(alkyl)amine group, such as

(*=bind position). , a mono- or diaryl silk system comprising: a mono-, di-aryl-amino-tert-(tetra)phenylamine m-based wire having a aryl residue which is optionally substituted as described above by a member, The aryl group may be substituted with one or two substituents. The N-group is described in each case on the gas atom by a calcination residue f and an aryl residue f substituted by an amine 36 201111379 group, especially such as (N-A ()-(N-phenyl)amine group. The mono- or diheterocyclylamino group specifically includes a mono- or heterocyclic amino group having 3 to 8, preferably 5 to 6 members, of the optionally substituted heterocyclic residue as described above. The (N-alkyl)(N-heterocyclyl)amine group is particularly described in the case where the nitrogen atom is a substituted alkyl group and a substituted amine group substituted with a __heterocyclic residue. The (N-alkyl)(N-heterocyclyl)amine group is particularly described in the case where the nitrogen atom is substituted with an "aryl residue" and a substituted heterocyclic group. The early or dinonylamino group specifically comprises a substituted amine group substituted with a mono or dihydrazino residue. k choose! The substituted alkyl-, aryl or heterocyclylsulfonyl group (RS〇2·' wherein R is a selectively substituted alkyl, aryl or heterocyclic group as defined above) is preferably further preferred The ground represents a sulfhydryl group, an ethyl aryl group, a phenyl sulfonyl group or a fluorenyl sulfonyl group. The 1 + substituted alkoxy # group (RQ(Q=)C_) is selected to contain a selectively substituted alkoxy group as described above for the definition of a methoxy group. C Embodiment 3 Preferred Embodiments: Preferred Embodiments The compounds of the formula (1) have the following substituent definitions: x is selected from: s or hydrazine; r1 is selected from the group consisting of: 37 201111379 - Hydrogen, - a selectively substituted amino group, - a selectively substituted alkyl group, - a selectively substituted alkoxy group, - a selectively substituted alkenyl group, - a selectively substituted alkynyl group, - a choice a substituted aryl group, or a -substituted substituted heterocyclic group; R2 and R3 are the same or different, and each is selected from the group consisting of: - hydrogen, - a selective substituted alkane - or heterocyclylsulfonyl, - optionally substituted alkyl, - optionally substituted alkenyl, - optionally substituted alkynyl, - optionally substituted aryl, or selective Substituted heterocyclic group; however, when R1 is selected from a selectively substituted amino group or a selectively substituted alkoxy group and R2 and R2 are the same, R2 and R3 do not represent hydrogen. In a preferred embodiment, the compound of formula (I) has the following definitions of substituents: X is selected from: S or 0; R1 is selected from the group consisting of: - hydrogen 38 201111379 - Selectively substituted Amino, - optionally substituted alkyl, - optionally substituted alkoxy, - optionally substituted aryl, or -optically substituted heterocyclic; R2 and R3 are the same or different And each selected from the group consisting of: - hydrogen, - a selectively substituted indenyl group, - a selectively substituted alkoxycarbonyl group, - a selectively substituted alkyl group, - a selective a substituted aryl group, or a -substituted substituted heterocyclic group. In a more preferred embodiment, the compound of formula (1) has the definition of a substituent: X represents S or 0; R 1 is selected from the group consisting of: - hydrogen-selective substituted amine, - selectivity Substituted alkyl group, and R2 and R3 are the same or different, and each is selected from the group consisting of: - hydrogen, - a selectively substituted alkyl group, 39 201111379 - Selective substituted aromatic a base, or a -substituted substituted heterocyclic group. In a more preferred embodiment, the compound of formula (I) has the following definitions of substituents: X represents S; R1 is selected from a selectively substituted amine group; and R2 is selected from a selectively substituted alkyl group; R3 represents hydrogen. The particularly preferred embodiment of one of the formula (1)'s individual substituents has the following individual definitions: 1. X represents s or Ο' wherein X preferably represents S. 2. R1 represents hydrogen, a selectively substituted alkyl group, or a selectively substituted amine group, wherein 'R1 preferably represents a selectively substituted amine group, especially a selectively substituted alkane as defined above A substituted amino group. Particularly preferably, if R1 represents a selectively substituted amine group selected from the group consisting of a monoalkylamino group and an (N-alkyl)(N-cycloalkyl)amine group, such as an (optionally substituted) aryl group a substituted alkyl-substituted amine group, particularly a benzylmethylamino group, and an amine group carrying a substituent substituted with a self-substituted aryl group as a substituent, such as 3 gas-4 fluorophenyl group Amino group. 3. R2 represents hydrogen, a selectively substituted alkyl group, a selectively substituted aryl group, or a selectively substituted hetero-counter, which is preferably a representative of the substituted alkyl group. a heterocyclic group optionally substituted, particularly a mono- or bicyclic aromatic heterocyclic ring selected from 5- to 1 (H-members, such as, preferably, a substituted (optionally substituted) oxime or (optionally)峰代) benzyl (tetra) 40 201111379, substituted. 4. R3 represents hydrogen, a selectively substituted alkyl, a selectively substituted aryl, or a selectively substituted heterocyclic group, wherein R3 is more Preferably, it represents hydrogen. Particularly preferred compounds of the formula (1) are shown in the following table: 41 201111379

42 201111379

k 人 〇 <〇 QC X <N ca 2v ZX X Qi c5 X to compound 1 1 u zyzx c Example C

(ΒΗ^Φ垅J 43 201111379 and pharmaceutically acceptable salts thereof. In particular, the present invention also relates to a novel compound of the formula (I) having the meaning of a substituent as described above, one of the following compounds Or more were excluded: 201111379

Χ4Γ2 = 13 4i4= qfeΧΫ-ί-Ή·妹=;-ng4al-= UPM) (^d = Ϊ3) 45 201111379

S1HS)S IshMl Dad=1 46 201111379 • κ*—"<ΝΚϋϊ1ωιβΗ. x^ISto=uv4B-=3w) o X w I"{nh0'-"—121 u. MKUIN-y I ΗΝϋν t^ Fsto=3v4®-=3M)

XHuKwurra wi4AHo=H)ys

-<Kel«swl«ao\v/.a\y/olo^u

o AHQ&) 47 201111379

_(fi4=qtl410je Γο — aa I ^ a υ I"Η

48 201111379 In principle, in the case of the present invention, the preferred, better or particularly preferred meanings of the individual substituents R1 and R3 can be combined with each other. In other words, wherein, for example, the substituent R1 has a preferred or better meaning and the substituents R2 and R3 have the general meaning or the substituent R1 has a general meaning and the substituents R2 and R3 have a preferred or better meaning ( Compounds of I) are encompassed by the present invention. Depending on its structure, the presence of asymmetric carbon atoms, the compounds according to the invention may exist as stereoisomers (mirroromers, non-image isomers). Accordingly, the invention encompasses the use of mirror image or non-image isomers and individual mixtures thereof. The pure mirror image isomer form can be optionally obtained by conventional optical resolution methods, such as by fractional crystallization of the non-image isomers by reaction with the optically active compound. Since the compounds according to the invention can occur in tautomeric forms, the invention encompasses the use of all tautomeric forms. The compounds provided in accordance with the invention may be present in a mixture of various possible isomeric forms, particularly stereoisomers, such as E&Z, syn&anU, and optical isomers. E-isomers and ethylene isomers and optical isomers' and any mixtures of such specific isomers are claimed. The compound according to the present invention having the structural formula (I) can be obtained basically by the method as described below. (4) A compound of the formula (la): R1 plant Nh2 (, a) wherein 'R' and X are as defined above, and react with a compound of the following formula: 49 201111379 A-R2 wherein R2 is as defined above, and A is - It is possible to substitute a leaving group, such as a leaving group selected from the group of _ prime, preferably such as chlorine, to produce a compound of formula (lb)

R2 N', (lb) Η where R1, R2 and X are as defined above. The following reactions are also possible: (b) Compounds of formula (lb):

R2 N /—N (10) ^~/ nh

Wherein R1, R2 and X are as defined above, and react with a compound of the formula: A-R3 wherein R3 is as defined above, and A is a leaving group which may be substituted by R3, such as, for example, A leaving group selected from dentate, preferably such as a gas, produces a compound of formula (I). The following reactions are also possible: (c) Compounds of formula (Ic):

R2 / (Ic)

V 50

X 201111379 wherein R 2 , R 3 and X are as defined above, and R 4 is an alkyl group of (6) which is reacted with a compound of the following formula wherein R 5 and R 6 are the same or different and are selected from the following a group consisting of: - hydrogen, - a selectively substituted alkyl group, - a selectively substituted aryl group, and - a selectively substituted heterocyclic group, or wherein R5 and R6 are bonded to a nitrogen group thereof The atoms together form a saturated or unsaturated, optionally substituted 3- to 6-membered ring which optionally contains additional heteroatoms to give a compound of formula (Id):

Wherein R, R3, R5 and R6 and X are as defined above, and the compound corresponds to the general formula (I) wherein R1 represents a selectively substituted amino group as defined above. In particular, the compound according to the invention of the formula (Id)

51

X 201111379 wherein X, R 2 , R 3 , R 5 and R 6 are as defined above and can be obtained by the following method: Synthesis route 1: wherein X = S and wherein R 1 is selected from the group of selectively substituted amino compounds The starting point for the synthesis of the unpurchasable material of the formula (1) is the commercial N (t-butoxycarbonyl)-b-alanine of the formula (II). This is converted to the active ester starting from 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) under standard conditions, which is then in situ with an ammonium salt, preferably a system. Ammonium bicarbonate, reacts to form guanamine (III). The indoleamine of this formula (III) can then be converted to the desired thioguanamine (IV) using Lawesson's reagent under standard conditions [see, for example, O. Josse, Synthesis, 3, 1999, 404-406].

EEDQ

NH.HC0. CHCI,

Thioamine (IV) is then cyclized with commercial ethyl bromopyruvate (V) to form thiazole (VI) under standard conditions known to those skilled in the art [see, for example, KY Zee-Cheng, Journal 〇f Heterocyclic Chemistry, 7, 1970, 1439-1440; H. Sasaki, Heterocycles, 75, 2008, 52 201111379 1061-1074].

Thereafter, the ester group of thiazole (VI) is reacted with an amine of the formula (VII) to form a corresponding decylamine. In principle, there are two additional synthetic routes available for this purpose. Synthetic route la): The reaction of the ester group of thiazole (VI) with the amine of formula (VII) is carried out according to the following procedure under standard conditions to form the corresponding decylamine of formula (VIII) [see, for example: RC Larock, Comprehensive organic transformations, Wiley, NY, 1999, p. 1973-1976: Comments on the conversion of guanamine to guanamine]:

Synthetic route lb): In addition, compound (VI) can also be hydrolyzed to the corresponding slow acid (Via) by ester [see, for example, RC Larock, Comprehensive organic transformations, Wiley, NY, 1999, 1959-1968: 酉A review of hydrolysis, and then conversion with the corresponding amine (VII) under traditional standard conditions [see, for example, RC Larock, Comprehensive organic transformations,

Wiley, NY, 1999, 1941-1949: Comments on the formation of indoleamine] and converted to the desired indoleamine (VIII): 53 201111379

(Via) p/tll) Then, the guanamine (VIII) which can be obtained in this manner can be further reacted to form the compound of the formula (I), wherein R1 represents a selectively substituted amine group, and is in the above The formula (Id) indicates that, for this purpose, a person known as a BOC protecting group (t-butoxycarbonyl fluorene) is removed under acidic reaction conditions. The free amine of the formula (IX) which can be obtained in this way can then be alkylated under standard conditions [see, for example, MB Smith, J. March, March's advanced organic chemistry, 5th edition, Wiley, NY, 2001. 499-501: Comments on alkylation of amine groups] or thiolation [see, for example, MB Smith, J. March,

March's advanced organic chemistry, 5th edition, Wiley, NY, 2001. 506-512: Review of amino group thiolation] and reacts to form the target compound of formula (I) (Id) 'where R1 represents selectivity Substituted amine group. In this case, A represents a suitable leaving group which may be substituted by R2 or by R3, such as a leaving group selected from the group of Nans, preferably such as chlorine, and (Id)* Represents (Id) where X = S. 54 201111379

In order to obtain a compound of the formula (I) or (Id) in which one of the substituents R2 or R3 represents hydrogen, the reaction of the compound (IX) with the corresponding compound A-R2 or A-R3 is thus not required . In particular, preferred compounds according to Examples 1, 2 and 3 can be obtained by using the synthetic route 1 by the production method thus described. Another synthetic route 2 can also be used to produce a compound of the formula (1) wherein X represents hydrazine and wherein R1 is selected from the group of selectively substituted amine compounds, and thus can be represented by the formula (Id) described below. Synthetic Route 2 · The starting point for the synthesis of a substance of the formula (1) wherein χ = ο and wherein R 1 represents a selectively substituted amine group is a commercially available decylamine (x) which can be used under basic standard conditions. Commercially, ethyl bromopyruvate (v) is cyclized to form stagnation (XI) [see, for example, _ p. Ahmed, Synthetic Communications, 33, 2003, 2685-2694] 〇55 201111379

Then, the oxazole of the formula (XI) can be converted into the corresponding nitro compound (XII) by an addition reaction with hydrogen bromide and subsequent substitution with sodium nitrite [see 'for example, F. Ahmed, Synthetic Communications, 33, 2003, 2685-2694] 〇

The resulting nitrooxazole (XII) can then be reduced to form the amine compound (XIII) under standard conditions known to those skilled in the art. Preferred reaction systems for this are a) Pt/H2 or b) FeCl3/C/H2. The amine (XIII) obtainable in this way can be aminated (see, for example, MB, Smith, J. March, March's advanced organic chemistry, 5th edition, Wiley, NY, 2001. 499-501: Amine groups Comments on alkylation] or by thiolation [see, for example, MB Smith, J. March, Marches advanced organic chemistry, 5th ed., Wiley, NY, 2001. 506-512: Amino group thiolation Comments] Conversion to a compound of the formula (Xllla) or (Xlllb). In this case, A represents a suitable leaving group which makes η a substitution with R2 or R3, such as a leaving group selected from a halogen group, preferably such as chlorine, and R7 is selected from the following Groups of constituents: - hydrogen, - a selectively substituted alkyl group, 56 201111379 - a selectively substituted aryl group, and a - optionally substituted heterocyclic group. 〇

(XII) or a) Pt; K bjFeq^C/Ho dioxane II 'alkane no2 0

(Kill) A-R*

(Xllla) (Xlllb) Compounds of the formula (Xllla) or (Xlllb) can be further derivatized by methods known to those skilled in the art. Synthetic route 2a) The ester of one of the preferred derivatives (Xllla) and (X11lb) is converted to the corresponding guanamine of the formula (Id) or (XIV). In this case, the ester group can be reacted with an amine of the formula (VII) under standard conditions to form a corresponding compound [see, for example, rC Larock, Comprehensive organic transformations, Wiley, NY, 1999, 1973-1976: Review of ester conversion to guanamine]. 57 201111379

Ο

(Xlllb)

ΗΝ

(Id)** .R5, R6

(XIV) Synthetic Route 2b) In addition, the above synthetic route can be carried out via a free carboxylic acid (Xllla') or (Xlllb') similar to the synthetic route lb), and the active ester produced in situ also causes a phase when reacted with an amine. Corresponding to the amines of the formulae (Id) and (XIV). 〇

(id)**

Η (XIV) In this case, (Id)** corresponds to the compound (Id) at X=0, which corresponds to the group in which R1 is selected from the group of selectively substituted amine groups according to 58 201111379. A compound according to the invention of formula (I). The compound (XIV) wherein R7 has the meaning as defined above corresponds to the compound of the formula (I) wherein X = 0 and wherein R2 is selected from the group of selectively substituted indenyl groups. In particular, the method according to the synthesis route 3) is described in detail below, wherein the meanings of the substituents R1 to R3 and R5 and R6 correspond to the previous definition, and wherein R8 represents a selectively substituted heteromix as defined above. The cyclo group is particularly preferably a (optionally substituted) imidazolyl group or a (optionally substituted) benzimidazolyl group, and wherein the abbreviations used have the meanings defined in the following production examples: 59 201111379 Η,Ν

NH8oc Ο

OEt Ε (ΟΗ Processing Step 1 Ο

call

EtO

0oc2〇· TEA processing step 2

NHBOC

NHj EtO

Li〇HtTHF/MeOH Ο

Processing step 3 NHBoc

HO

NHR砰 Processing Step 4

Processing step 5

NHj

M2 ο

R®CHO TMOP.NaCNBHa Process Step e The reaction path shown here represents a reaction pattern that is known per se and can be carried out in a manner known per se. Corresponding salts are obtained by reaction with a pharmaceutically acceptable test or acid. The reaction between the various reactants can be carried out in various solvents, and there is no particular limitation with respect to this. Thus, examples of suitable solvents include water, decyl alcohol, ethanol, acetone, di-ethane, di-methane, tri-methane, dimethoxyethane, dimethoxy-diethyl ether, acetonitrile, butyronitrile, THF ( Tetrahydrofuran), 60 201111379 DMF (monomethylcarbamide), dioxane, ethyl acetate, butyl acetate, dimethyl acetamide, toluene, benzene, and trimethyl orthoformate (tm〇) f). Ethyl alcohol, mono- sulphur, THF, DMF, dichloromethane, and chloroform, and especially the solvent used in the preferred method of the above-mentioned synthesis route 3) are preferred. If the organic bath is miscible with water, the reaction can also be carried out in a substantially homogeneous mixture of water and solvent. The reaction system according to the present invention between the reactants, for example, is carried out at a temperature of the circumference. However, the temperature at ambient temperature, for example, up to 8 〇 or 9 〇〇 c, or up to 100 or up to 130 V, and temperatures below ambient temperature, such as 'as low as -20 ° C or more Less, can also be used. The p oxime which is carried out in accordance with the reaction of the present invention between the reactants is appropriately adjusted. The pH adjustment 'especially in the synthesis route 丨) is alkaline reaction to guanamine, preferably by adding a base. Suitable bases include inorganic and organic bases. Preferably, an inorganic base such as LiOH, NaOH, KOH, Ca(OH)2, Ba(OH)2, Li2C03, K2C03, Na2CO3, NaHC03, NH4HC03, or an organic base such as 'amine (such as 'preferred three Ethylamine (TEA), diethylisopropylamine), Βι^ΝΟΗ, piperidine, morpholine, alkylpyridine were used. Inorganic bases are particularly preferably used, and LiOH, NaOH, KOH, and NH4HC03 are optimally used with TEA. The pH can be selectively adjusted using an acid, especially during the synthesis of the path 1) removal of the BOC protecting group. Suitable acids include organic and inorganic acids ◎ inorganic acids, such as HQ, HBr, HF, H2S04, H3P〇4, or organic acids such as CF3COOH, acetamidine (CH3COOH, AcOH), p-benzoic acid, and 61 thereof 201111379 It is particularly preferable to use an acid such as an inorganic substance such as HCI. ^ The preferred method of the above method based on the synthetic route 3) will be better. Those skilled in the art will be able to select the most suitable solvent and optimum reaction conditions for the corresponding synthetic route and corresponding steps, particularly with regard to temperature, pH, catalyst and solvent. Accordingly, the present invention is also directed to novel intervening products obtainable by the manufacturing method according to the present invention, particularly intermediate products (1) which are specifically described in the production examples and which can be obtained by the treatment step (1). The inventors have surprisingly discovered that the compounds which form the subject of the present invention and which correspond to the structural formulae (1) and (10), (10) and (10) act as Hapapar antagonists and are therefore suitable as diseases for the treatment of hippocytosis and accompanying Or the secret of the relevant syndrome. Specially-based, according to this issue, the compound is suitable for the treatment of iron metabolism abnormalities, especially for the treatment of K deficiency/anemia, especially ACD and AI. The drug containing the compound of the formula (I) is suitable for use in human and animal medicines. Accordingly, the present invention also relates to a compound according to the present invention which is a structural formula (1) containing a substituent having a previously defined meaning as a drug. Particularly, the compound according to the present invention having the structural formula (1) having a substituent of the prior meaning is preferably used as a drug, and - or more of the following compounds are excluded: 62 201111379

Md, ο ?Λ-ν' II c JX: Μα.

o 2. Gas VT o

Ns

-N-d 丨 N-d

TftolH4[=M) Η C

Io n ΟA. σ

Oud o

N O 0\^Γ ο 12 ~(硪卜 W 躲=i-nCQ4®-= 3JAI) rxo

0 0\^. N Π & oxzv o

OMd - «〆,§

N O Χ 313) 63 201111379 4 £0 0

S / 夕 N· N ο

Article®-卩 UH} xh磘(砩婶赞砩机械wssdN=a N° 9^v-, 012N,

Hiw ο Γ y r s#r ννΛΣ ο ni ΟΛ^ 0Φ2

518-= i 23⁄4 64 201111379 tw«Jto=ov4fe-=3s) t^fgtonov diarrhea®-=3e

ΧΗυ^Ηυ) = Mechanical %3=^ a:s

(0fl8o=ov4o=-(-*H)

X^i4"Ku=H) s 65 201111379

f Containing έ 66 201111379 Therefore, the compounds according to the invention are also suitable for the manufacture of a syndrome for the treatment of iron deficiency anemia, such as: fatigue, lack of momentum, poor concentration, low cognitive efficiency, finding correct word difficulties, forgetfulness Unnatural paleness, irritability, accelerated heart rate (tachycardia), ulcer or tongue hypertrophy, splenomegaly, pregnancy cravings (pica), headache, loss of appetite, increased susceptibility, depression, or suffering from ACD or The drug of AL patients. Thus, the compounds according to the invention are also suitable for the manufacture of a medicament for the treatment of a patient suffering from a syndrome of iron deficiency anemia. The administration takes place over a period of months, until the iron content is improved (by, for example, the patient's jk redness, transferrin saturation, and ferritin values) or as a result of iron deficiency anemia or A deliberate improvement in the state of health caused by ACD or AI. The preparations according to the invention may be administered to children, adolescents and adults. The compounds of the present invention may additionally be administered concomitantly with other active compounds or drugs known to treat abnormalities in iron metabolism and/or for the treatment of diseases associated with abnormalities in iron metabolism, particularly iron deficiency and/or anemia. The active ingredient or drug is used in combination. Examples of such agents which can be used in combination for the treatment of abnormalities in iron metabolism and other diseases associated with iron deficiency and/or anemia may include, for example, iron-containing compounds such as iron salts and iron-carbohydrates. Compounds such as iron-maltose or iron-dextrin miscible compounds, vitamin D and/or derivatives thereof. The compound to be used in combination with the compound of the present invention can be administered orally or parenterally, or the compound according to the present invention and the compound for use in combination can be administered by combining the administration methods. 67 201111379 A compound according to the invention and a combination of the aforementioned compounds according to the invention and another active ingredient or medicament can be used for the treatment of abnormalities in iron metabolism, in particular such as iron deficiency and/or anemia, in particular anemia of cancer, Chemotherapy-induced anemia, inflammatory-induced anemia (AI), anemia of congestive heart failure (CHF), chronic kidney disease 3-5 (CKD 3-5) anemia, chronic inflammation-induced anemia (ACD), Anemia of rheumatoid arthritis (RA), anemia of systemic lupus erythematosus (SLE), and anemia of inflammatory bowel disease (IBD), or the manufacture of drugs for the treatment of such diseases. The compounds according to the invention and combinations of the aforementioned compounds according to the invention with further active ingredients or medicaments are particularly useful in the manufacture of iron deficiency anemia, for example, iron deficiency anemia in pregnant women, children and adolescents Potential iron deficiency anemia, iron deficiency anemia caused by abnormal gastrointestinal tract, due to blood loss, for example, due to gastrointestinal bleeding (eg, due to ulcers, cancer, pruritus, inflammatory abnormalities, ingestion of acetylsalicylic acid), menstrual period , injured, iron deficiency anemia, iron deficiency anemia due to oral inflammatory diarrhea (spme), iron deficiency anemia due to reduced iron absorption from the diet (especially for children and adolescents with partial eclipse) A weak immune system caused by anemia, impaired brain performance caused by iron deficiency anemia, and restless leg syndrome. The use according to the invention results in an improvement in the values of iron, heme, ferritin and transferrin, especially in adolescents and children, but also in adults, accompanied by short-term memory testing (STM), long-term memory testing (LTM) ), Raven's progressive matrix test, Wei's Adult Intelligence Scale (WAIS) and / or mood coefficient (BaronEQ-i'YV test; youth version) improvement, or neutrophil blood volume, antibody volume and / Or an improvement in lymphocyte function. 68 201111379 The present invention further relates to one or more additional pharmaceutically active compounds and one or more of one or more of the compounds according to the invention and one or more of the compounds of formula (I) A pharmaceutically acceptable carrier and/or a pharmaceutical composition of an adjuvant and/or a solvent. These are traditional pharmaceutical carriers, adjuvants or solvents. The pharmaceutical composition is suitable, for example, intravenous, intraperitoneal, intramuscular, intravaginal, intraorbital, transdermal, subcutaneous, mucocutaneous, oral, rectal, transdermal, topical, intradermal, intragastric or dermal Internally applied, and is, for example, a pill, a lozenge, a gastric-resistant lozenge, a film lozenge, a layered lozenge, a formulation for sustained release for oral, subcutaneous or dermal administration (especially a patch) , extended release products, sugar coated tablets, small suppositories, gels, ointments, syrups, granules, suppositories, emulsions, dispersions, microcapsules, micro-formulations, nano-formulations, micro-fats Formulations, capsules, gastric juice resistant capsules, powders, inhaled powders, microcrystalline formulations, inhalation sprays, powders, drip, nasal drops'. Nasal sprays, aerosols, ampoules, solutions, juices , in the form of suspensions, infusion solutions or injection solutions. The compounds according to the invention and the pharmaceutical compositions containing such compounds are preferably administered orally and/or parenterally, especially intravenously. For this purpose, the compounds according to the invention are preferably present in the form of pills, lozenges, gastric-resistant lozenges, film lozenges, layered lozenges, sustained release formulations for oral administration, extended release Formulations, sugar coated tablets, granules, emulsions, dispersions, microcapsules, micro-formulations, nano-formulations, micro-lipid formulations, capsules, gastric-resistant capsules, powders, micro-crystals Drug, powder, drip, ampoule, solution, suspension, infusion 69 201111379 A pharmaceutical composition of the type of solution or injection solution. The compounds according to the invention may comprise a wide variety of different organic or inorganic carrier materials and/or adjuvants, conventionally for pharmaceutical purposes, and are used in solid pharmaceutical formulations, such as excipients (such as, Sucrose, solute, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate), binding agents (such as cellulose, methylcellulose, hydroxypropylcellulose, polypropylpyrrolidone) , gelatin, gum arabic, polyethylene glycol, sucrose, starch), disintegrant (such as starch, hydrolyzed starch, carboxymethyl cellulose, calcium salt of carboxymethyl cellulose, hydroxypropyl starch, glycol starch Sodium, sodium bicarbonate, calcium phosphate, calcium citrate), lubricants and lubricating agents (such as magnesium stearate, talc, sodium lauryl sulfate), flavors (such as citric acid, menthol, glycerin, orange Powder), preservatives (such as sodium benzoate, sodium bisulfite, decyl p-hydroxybenzoate, propyl p-hydroxybenzoate), stabilizers (such as 'citric acid, sodium citrate, acetic acid) and Titriplex a polycarboxylic acid, such as, for example, diethylenetriaminepentaacetic acid (DTPA), a suspending agent (such as decyl cellulose, polyvinylpyrrolidone, aluminum stearate), a dispersing agent, an excipient (such as water) , organic solvent), beeswax, cocoa butter, polyethylene white petrol, etc., the pharmaceutical composition is administered. Liquid pharmaceutical formulations, such as solutions, suspensions and gels, conventionally contain a liquid carrier such as water and/or a pharmaceutically acceptable organic solvent. In addition, the liquid formulation of this type may also contain pH_adjusting agents, emulsifiers or dispersing agents, buffering agents, preservatives, wetting agents, gelling agents (for example, methylcellulose), colorants and/or fragrances. substance. The composition according to the present invention may be isotonic, in other words, it may have the same osmotic pressure as blood. 70 201111379 The iso-permeability of this composition can be adjusted using sodium chloride or other pharmaceutically acceptable agents such as dextrose, maltose, boric acid, sodium tartrate, propylene glycol or other inorganic or organic soluble materials. The viscosity of the liquid composition can be adjusted using a pharmaceutically acceptable thickening agent such as decyl cellulose. Other suitable thickeners include, for example, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose, carbomer, and the like. The preferred concentration of thickener will depend on the reagent selected. A pharmaceutically acceptable preservative can be used to increase the stability of the liquid composition. Benzoyl alcohol may be suitable even if a large amount of a preservative (including, for example, paraben, thimerosal, chlorobutanol or gasified benzodiazepine) may be used. The active ingredient may, for example, be administered in a unit dose of from 0.001 mg/kg to 500 mg/kg body weight, for example, up to 1 to 4 times per day. However, the dosage may be increased or decreased depending on the age, weight and condition of the patient, the severity of the disease, or the nature of the administration. A preferred embodiment relates to a compound according to the invention and a composition according to the invention comprising a compound according to the invention and a combination preparation according to the invention comprising a compound according to the invention and a composition for use in the preparation of a composition Use of a drug for oral or parenteral administration. The invention is illustrated in more detail by the following examples. These examples are given by way of example only, and those skilled in the art can extend these particular embodiments to other claimed compounds. EXAMPLES Pharmacological studies: The following materials were used: 71 201111379 Reagent lot number annotation MDCK-FPN-Halo Tag strain 7 Haipaxitin 100 μΜ in water raw solution Lot# 571007 Peptides International HaloTag®TMR Ligand Lot# 257780 Promega, cat# G8251 Opera common coke imaging system PerkinElmer Perkin Elmer 384 Cell carrier plate cat# 6007430 to formaldehyde Lot# 080416 Electron Microscopy Sciences cat# 15710-S Draq5 Biostatus, cat no: DR51000 The ethylenediamine compound of the invention The seabaxietine-antagonist effect is determined by "transfer internalization analysis" as described below. Pharmacological analysis: The following materials were used: 72 201111379 Reagent batch number annotation MDCK-FPN-Halo Tag strain 7 Haipaxiding 100 •571007 Peptides μΜ in water raw material solution International HaloTag®TMR with 257780 Promega, Cat# Position G8251 Opera Common coke plate imaging system PerkinElmer Perkin Elmer 384 Cell carrier plate Cat# 6007430 to formaldehyde batch No. 080416 Electron Microscopy Sciences Cat# 15710-S Draq5 Biostatus, Cat no: DR51000 The indoleamine compound of the present invention is resistant to hepcidin The nodule effect is determined by the transfer internalization analysis as described below. The principle of transfer iron internalization analysis resists the biological effects of seabuckles (4) on the biological action of its receptor (iron-powder ferritin (Fpn)), which inhibits Fpn in living cells. It is identified based on the ability of the internalization of the West's temptation. For this purpose, a stable cell strain (Martin dabies kidney epithelial cell line, MDCK) was produced by Ί 'expressed in its c-terminus and a fluorescent receptor protein 73 201111379 (HaloTag®, promega c〇rp_) recombination Fused human transferrin. Neem internalization is monitored by labeling such cells with a fluorescent ligand (HaloTag®-TMR, tetradecylrhodamine) which is covalently bound to the HaloTag receptor gene fused to Fpn. Images produced by conjugated focal fluorescence microscopy showed cell surface locations in Fpn lacking hepcidin and lacked Fpn surface patches in the presence of hepcidin. An optimized image analysis algorithm was used to detect cell surface and quantify the corresponding membrane glory bound to the Fpn-HaloTag fused protein. This analysis energizes image-based analysis to quickly assess compounds that block the endocytosis induced by seawater in Fpn. This assay is a direct in-tube equivalent of the proposed in vivo mechanism for drug candidates and is therefore suitable as a high throughput for identifying compounds that counteract the effects of hepcidin on its receptor transporter. Start the analysis. Details of the analysis procedure • 7500 cells per well (MDCK-FPN-HaloTag) were inoculated into a well of 3 84 wells (384 cell carrier plates, Perkin Elmer, Cat. No. 6007430) 50 μM per well DMEM medium (Dulbeccos Modified Eagle Medium with 10% fetal bovine serum (FBS) containing 1% penicillin, 1% streptomycin, and 450 pg/ml of G-418), followed by 37 °C /5 % C02 culture overnight. • The volume of the medium was reduced to 10 μΐ, and 10 μΜ of 5 μΜ HaloTag-TMR ligand (Promega, Cat. No. G 8251) was added to the DMEM medium to stain the Fpn-HaloTag fused protein. • Incubate for 15 minutes at 37 ° C / 5 % C02. • The HaloTag-TMR ligand was removed and the cells were washed in a new DMEM culture and the volume was reduced to 20 μM in DMEM medium. • A solution of 3 μΐ of test compound (dissolved in DMSO) per well was added (10 μΐ final volume). • 7 μΐ of 43 μΜhaipaxetine (Peptides International, Cat. No. PLP-4392-s, diluted in water in DMEM medium 1 () 0 μΜ raw material solution) added to each well at 100 ηΜ Haipacidine concentration. • Cells were incubated overnight at 37 ° C / 5 % C02. • The cells were fixed by directly adding a pair of awake (PFA, Electron Microscopy Sciences, Cat. No. 15710-S) to the cells to give a final concentration of 4%, followed by incubation at room temperature for 15-20 minutes. • The PFA solution was removed and the cells were washed with PBS (phosphate buffered saline solution). In each case, 30 μM was left in the plate. • 2〇01〇^95 (6丨〇81&〇18,€&[.\〇.〇1151〇〇〇) is added to produce a final concentration of 2.5 μΜ to stain the nuclei, and these plates are foiled Plate sealant seal. • These panels were analyzed with the Opera plate imaging system (〇pera conjugate focal plane imaging system, Perkin Elmer) for 7 images per hole; each image was 440 ms exposure time, 1 μΜ focus height. Data Analysis • The optimization algorithm was used for image analysis to confirm and quantify fluorescence bound to the cell surface as a measure of the cell surface location of the Fpn-HaloTag. • The final display is the percentage of cells that correspond to the fluorescence of the display membrane: the lowest value was obtained for the wells treated with 1〇〇ηΜhaipaxitin (negative control group showed 〇% of Fpn internalization inhibition), and not sea The cells treated with paroxine produced a maximum percentage of cells with membrane fluorescence of 75 201111379 (positive control group showed 100% Fpn internalization inhibition). • On each plate, the median of 6 positive and 6 negative control values is used to calculate the percent inhibition of the test compound according to the following equation: R-R compound I = 100 X ------- -----------------

Rii — Ri where: R positive control group display value (middle)

Rs negative control group display value (middle) R compound Displayed value of compound I Percent inhibition of individual compound • Diluted series of compounds (11 concentrations, 1:2 dilution step) were tested in dose analysis (concentration range 0.04 to 40 μΜ), and the standard signal values of the repeated tests (average of 6 titrations on a separate plate) were used for robustness criteria with four parameters (lower asymptote, upper asymptote, IC50, gradient) The curve adaptation of the dose action model. The following results were obtained: 76 201111379 Example compound transfer factor IC50 [μΜ] I 丨: %] (intermediate inhibition of 10 μΜ substance concentration [%]) 1 9 / /~CO <50 >50 2 η/ 0乂厂9 ">50>50 3 ar ° If") η >50 <50 Manufacturing Example: I. Purification by preparative HPLC and column chromatography The following manufacturing examples are according to the manufacturing method of the present invention. Execution, selectivity followed by preparative HPLC and/or purification by column chromatography under the following conditions: II Preparation HPLC (neutral conditions):

Method: Gilson semi-preparative HPLC with 119 UV detector and 5.11 Unipoint control software 77 201111379 Static phase/column: Waters SunFire Prep C18 OBD (5 μιη 19 χ 100 mm), ambient temperature moving phase: A: Water B: acetonitrile Flow rate: 20 ml / min

Injection volume: 1000 μΐ Detection: UV eluent:

Time (minutes) Solvent Ο.ό to 2.0 5 % Β + 95 % A 2.0 to 2.5 Fixed gradient to 10 %B+ 90 % A 2.5 to 14.5 Fixed gradient to 100 % Β 14.5 to 16.5 100 % Β 16.5 to 16.7 Fixed gradient to 5 % Β + 95 % A 16.7 to 17_2 5 % Β + 95 % A Ι.ΙΙPreparation HPLC (acidic conditions): Method: Gilson 215 autosampler and fractional collector stationary phase / column: Waters SunFire Prep Cl8 OBD (5 Μιη 19 χ 100 mm), ambient temperature moving phase: A: 0·1 % TFA/water enthalpy: 0.1 % TFA/acetonitrile flow rate. 26 ml/min injection volume: 1000 μΐ Detection: Waters Micromass Platform LCZ single quadrupole Spectrometer 78 201111379

Waters 600 Solvent Delivery Module Waters 515 Auxiliary Pump Waters 2487 UV-Detector Eluent

Time (minutes) Solvent 0.0 to 1.0 90 % A + 10 % B 1.0 to 7.5 Fixed gradient from 90 % A + 10 % B to 100 % B 7.5 to 9.0 100 % B 9·0 to 9.1 Fixed gradient from 100 % B to 90 % A + 10 % B 9.1 to 1〇.〇90 % A + 10 % B Ι·ΙΙΙ Column chromatography Rapid vermiculite gel chromatography using 230 to 400 mesh of vermiculite gel or Pre-filled on the stone column.

II. Analysis The identification and purity of HPLC-MS compounds was determined by HPLC MS (high performance liquid chromatography with mass spectrometry) and by HPLC with UV detection (PD A, photodiode array). Method: MS19_7MIN_HIRES-POS/High Resolution Method MS Detection: TIC (Total Ion Count) HPLC-MS System: Shimadzu LCMS 2010EV System Quality Range: 100-1000 m/z Scanning Speed: 2000 amu/sec In detail, the following methods are special used:

ΪΙ·ΙMethod A Static phase/column: Waters Atlantis dC18 (2.1 X 100 mm, 3 μπι tube 79 201111379 column);

40 °C Flow rate: 0.6 ml/min Mobile phase: A: 0.1% formic acid/water B: 0.1% citric acid/acetonitrile Flow rate: 0.6 ml/min Injection volume: 3 μΐ Detection: UV, wavelength; 215 nm Eluent gradient Time Organic Content (minutes) (%) 0.00 5 5.00 100 5.40 100 5.42 5

Time (minutes) Solvent 0 to 5 Fixed gradient from 95 % A + 5 % Β to 100 % B 5.0 to 5.4 100 % B 5.4 to 5.42 Fixed gradient from 100 % B to 95 % A + 5 % B 5.42 to 7.0 95 % A + 5 % B

II.II Method B Stationary phase/column: Waters Atlantis dC18 (2·1 X 50 mm, 3 μηι) 80 201111379 Mobile phase: A: 0.1% formic acid/water B: 0.1% citric acid/acetonitrile flow rate: 1 ml/ Minute injection volume: 3 μΐ Detection: UV; wavelength 215 nm eluting agent

Time (minutes) Solvent 0·0 to 2.5 Fixed gradient from 95 % A + 5 % B to 100 % B 2.5 to 2.7 100 % B 2.71 to 3.0 95 % A + 5 % B

II.III Method C Stationary phase/column: Waters Atlantis dC18 (2.1 X 30 mm, 3 μηη column), Flow rate: 1 ml/min Mobile phase: Α: 0.1% formic acid/water: 0.1% citric acid/acetonitrile Injection volume: 3 μΐ Detection: UV; wavelength 215 nm eluting agent

Time (minutes) Solvent 0.0 to 1.5 Fixed gradient from 95 % A + 5 % B to 100 % B 1.5 to 1.6 100 % B 1.60 to 1.61 Fixed gradient from 100 % B to 95 % A + 5 % B 1.61 to 2.00 95 % A + 5 % B

MS detection: WatersLCT or LCTPremier or ZQ or ZMD 81 201111379

UV detection: Waters 2996 photodiode array or Waters 2787 UV or Waters 2788 UV III. Description of the compounds Some of the compounds described below are isolated by TFA or HCl salts, which are not replicated under the chemical names shown. In the context of the present invention, the chemical names indicated refer to the corresponding compounds of the neutral form and their TFA salts or other salts, if appropriate, especially pharmaceutically acceptable salts. IV. Abbreviations

Boc20 di-tert-butyl dicarbonate d day DCM di-methane methane DIPEA N,N-diisopropylethylamine DMF N,N-didecylguanamine

EtOAc ethyl acetate

EtOH ethanol h hour HATU 1-[bis(didecylamino) fluorene]-1H-1,2,3-triazole [4,5-b]-pyridine 3-oxide hexafluorophosphate HPLC high Performance liquid chromatography

MeCN acetonitrile min min MW molecular weight TEA triethylamine TFA trifluoroacetic acid 82 201111379 TMOF tridecyl ortho phthalate V. by intermediate of synthesis route 3) VI by synthesis route 3) intermediate product intermediate: 2 -(2-Amino-ethyl-thiazole-4-carboxylic acid ethyl ester (treatment step 1) ethyl bromopyruvate (0.77 ml '5.0 mmol) was added to one in EtOH (10 mL) A solution of tributylsulfonium-(3-amino-3-thiopropoxy)-aminodecanoate (1.02 g, < 5.0 mmol), and the mixture was heated under reflux for one hour. The product of diethyl ether and chloroform was triturated to give intermediate 1 (1.16 g, 1%) which was used without purification or characterization. Intermediate 2: 2-(2-Third Oxytoxylamino-ethyl)_嗔η sit·4_oleic acid ethyl ester (treatment step 2) ΤΕΑ (6.4 ml, 46.0 mmol) and di-dicarbonate second _ (3. gram , 13.8 mmoles, added to MeCN (150 mL) and DMF (40 mL) 2-(2-Amino-ethyl)-喔η sit-4-reo-ethyl ester (intermediate 1) (3.03 grams, 11.5 millimoles) The mixture was stirred at ambient temperature for 18 hours. The solvent was evaporated in vacuo and the product was crystallisjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjh The organic phase was washed with saturated EtOAc (3 mL) eluted eluted eluted elut elut elut elut elut elut elut elut ]: 323 (M+Na) 83 201111379 Intermediate 3: 2-(2-Tertoxycarbonylamino-ethyl)-thiazole_4_carboxylic acid (Processing Step 3) Aqueous lithium hydride (2 Μ, 14 ml, 28.4 mmoles, added to 2-(2_t-butoxycarbonylamino-ethyl)-thiazole-4-carboxylic acid-ethyl ester in THF/MeOH (60 mL / 40 mL) A solution of the intermediate 2) (1 71 g, 5 annus) was stirred and the mixture was stirred at ambient temperature for 2 hours. The mixture was concentrated in vacuo and the product was partitioned between diethyl ether and water. The mixture was acidified to pH = 4 and EtOAc (EtOAc (EtOAc) (EtOAc) m/z]: 294 (M +Na) Intermediate 4: {2-[4·(cyclohexylmethyl-carbamoyl).carbazole-2-yl]-ethyl}carbamic acid·t-butyl-ester (Process 4) 2-(2-Tertioxycarbonylamino-ethyl)-thiazole-4-carboxylic acid (intermediate product 3) (0.41 g, 1-5 mm) in DMF (10 mL), HATU ( A solution of 67.67 g '1.8 mmoles) and N-methylcyclohexylamine (intermediate product 2) (0.24 ml, 1.8 mmol) was cooled to hydrazine. D Add DIPEA (0.78 ml, 4.5 mmol) and mix in 〇. (: stirring for 10 minutes and stirring at ambient temperature) hr. The mixture was diluted with EtOAc (50 mL) and washed with 1 M EtOAc (X2), and NaHC03 and sol. The organic phase was dried (MgS04) and vacuumed. The crude product was purified by column chromatography using MeOH/DCM (0-10) eluting to give intermediate 4 (0.57 g, 100%). MW: 367.51 84 201111379 HPLC-MS (Method B): [m /z]: 390 (M+Na), 368 Intermediate 5: {2-[4-(3-Gas-4-fluoro-phenylmethylcarbamoyl)-thiazol-2-yl]-ethyl} - Carbamate-t-butyl-acetic acid production is similar to intermediate product 4 by the treatment step using: 2-(2-Tertiaryoxyamino-ethyl)_&lt;• _4_ oxic acid (middle product 3) (0.41 g, 1.5 mmol), HATU (0.68 g, 1.8 mmol), 〇ΙΡΕΑ (0·78 ml, 4.5 mmol) and 3-chloro- 4-Fluorobenzylamine (0.29 g '1.8 mmol) was purified by column chromatography using MeOH/DCM (0 - 0.5%) eluting to give intermediate 5 (0.41 g, 66 %). MW: 413.90 HPLC-MS (Method B): [m/Z]: 436 (M+Na) Intermediate 6: [2-(4-phenylphenylamino) The decyl- stilbazole-2-yl)-ethyl]-carbamic acid tert-butyl-ester is produced analogously to the intermediate product 4 by the treatment step 4 using the following: 2-(2-third butyl Oxycarbonylamino-ethyl)-thiazole_4_carboxylic acid (intermediate product 3) (0.62 g, 2.26 mmol), HATU (0.90 g, 2.38 mmol), DIPEA (0.88 ml, 6-79 mmol) The ear) and phenylhydrazineamine (0.26 mL, 2.38 mmol) were purified by column chromatography using heptane / EtOAc (2: 1) eluting to afford intermediate 6 (0.60 g, 73 %) MW: 361.47 HPLC-MS (Method B): [m/z]: 384 (M+Na) Intermediate 7: 2·(2-Amino-ethyl)------- Hexyl-methyl &lt; decylamine 85 201111379 (Processing Step 5) TFA (20% solution in DCM '2 mL) was added to <2-[4-(cyclohexyl-methyl-) in DCM (8 mL) A solution of carbachol-2-yl]-ethyl}-carbamic acid-tert-butyl-ester (intermediate product 4) (0.56 g, 1.5 mmol) was stirred at ambient temperature for a few hours. The solvent was removed in vacuo and the product was dissolved in EtOAc (30 mL). The mixture was washed with saturated NaHC03 (x3) and sol. The crude product was purified by stirring the decylamine-containing amine solution with a carbonate resin for 30 min, filtered and concentrated to give intermediate 7 (0.12 g, 30%). MW: 267.40 HPLC-MS (Method B): [m/z]: 268 Intermediate 8: 2-(2·Amino-ethyl)------ The benzylamine amine production system is similar to the intermediate product 7 which is carried out by the treatment step 5 using the following: {2-[4-(3-chloro-4-1-benzylaminocarbamimidyl)-thiazide -2-yl]-ethyl-carbamic acid-t-butyl-ester (intermediate product 5) (0.40 g '〇·96 mmol) and TFA (20% solution in DCM, 2 ml), not Further purification gave intermediate 8 (207 mg, 69%). MW: 313.78 HPLC-MS (method B): [m/z]: 314 Intermediate 9: 2-(2-Amino-ethyl-thiazole·4-carboxylic acid benzylamine amine production system similar to intermediate product 7 is carried out by the treatment step 5 using the following: 86 201111379 [2-(4-Benzylaminoguanidino)-oxime]-i-yl-2-yl]-ethyl]-aminodecanoic acid_third butyl-S (intermediate 6) (0.59 g, 1.64 mmol) and tfa (20% in DCM-solution, </ </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; MW: 261.35 HPLC-MS (Method B): [m/z]: 262 V. II Example Compounds by Synthetic Path 3) Example Compound 3: 2-{2-[(1Η-benzimidazole- 2-ylindenyl)-amino]-hexyl}-thiazole-4-carboxylic acid-cyclohexyldecyl-decylamine (treatment step 6) 1H-benzimidazole-2-carbaldehyde (67 mg, 0.46 mmol) Add 2-(2-amino-ethyl)-° plug to MeOH (2 liter). A solution of -4-decanoic acid-cyclohexyl-mercapto-guanamine (intermediate product 7) (0.12 g, 0.46 mmol) was obtained, and the mixture was stirred at ambient temperature for 18 hours. To increase the imine formation, trimethyl orthoacetic acid vinegar (0.5 ml) was added and stirred for an additional 2 hours. Sodium cyanohydride (34 mg, 0. 55 mmol) was added and the mixture was stirred for an additional 18 hours. The mixture was concentrated in vacuo and purified by preparative HPLC (neut.). ΕΟΑΙ3328876 VIT-1077 MW: 397.54 HPLC-MS (Method A): [m/z]: 398 The results are shown in Figure 3. Example Compound 2: 2-{2-[(1Η-imidazol-2-ylmethyl)-amino]ethylthiazole-4-carboxylic acid_3_gas-4_fluoro-benzylamine amide 87 201111379 The manufacturing system is similar to the example compound 3 which is carried out by the treatment step 6 using the following: 2-(2-Amino-ethyl)-°Sapy-4-deoxy-3-chloro-4-fluoro- Benzyl decylamine (intermediate product 8) (0.20 g, 0.65 mmol), TM0F (1 ml), 1H-imidazole-2-carboxylic acid (68.3 mg '0.71 mmol) and cyano-dehydrogenation ( 44.7 mg, 〇71 mmol, after purification by preparative HPLC (neutral conditions) gave Example Compound 2 (11.3 mg, 4%). EOAI3330064 VIT-1086 HP-AU001016-H10 (Manufacturer: TRIPOS) HPLC-MS (Method A): [m/z]: 394 The results are shown in Figures 2a and 2b. Example Compound 1 : 2-{2-[(1Η-Benzimidazol-2-ylmethyl) -Amino]-ethyl}-thiazole-4-carboxylic acid-benzylamine preparation is carried out analogously to Example Compound 3 by treatment step 6 using the following: 2-(2-Amino-B - Thiazole-4-carboxylic acid-phenylhydrazinamide (intermediate product 9) (〇·15 mg, 0.59 mmol), TMOF (1 ml), 1H-benzimidazole 2-furfural (95 mg, 0.65 mmol) and sodium cyanoborohydride (41.0 mg, 〇·65 mmol) were purified by preparative HPLC (acidic conditions) to give the title compound. TFA salt type (43.7 mg, 12%). EOAI3330486 VIT-1089 HP-AU001013-HD01 (manufacturer: TRIPOS) MW: 391.5 or 391.49 HPLC-MS (method A): [m/z]: 392 88 201111379 In the first and fifth figures, the following is a brief description of the drawings: Panels 1 and 2b: HPLC-MS of Example Compound 2: Figure 3: Example Compound 3 HPLC-MS [Key component symbol description] (none) 89

Claims (1)

201111379 VII. Patent application scope 1. A compound of the formula (I), Wherein X is selected from the group consisting of: S or 0; R1 is selected from the group consisting of: - hydrogen, - a selectively substituted amine group, - a selectively substituted alkyl group, - a selectively substituted alkoxy group a group, a selectively substituted alkenyl group, a -substituted substituted alkynyl group, a -substituted substituted aryl group, or a -selective substituted heterocyclic group; R2 and R3 are the same or different, and Each is selected from the group consisting of: - hydrogen, - a selectively substituted alkyl-, aryl- or heterocyclylsulfonyl group, - a selectively substituted indenyl group, - a selective substitution Alkenyloxycarbonyl, - optionally substituted alkyl, - optionally substituted alkenyl, 90 201111379 - selectively substituted alkynyl, - optionally substituted aryl, or optionally substituted a heterocyclic group; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein X is selected from the group consisting of: S or hydrazine; R1 is selected from the group consisting of: - hydrogen, - a selectively substituted amine group, - a selective substitution Alkyl, - optionally substituted alkoxy, - optionally substituted alkenyl, - optionally substituted alkynyl, - optionally substituted aryl, or - optionally substituted heterocyclic R2 and R3 are the same or different, and each is selected from the group consisting of: - gas, - a selectively substituted alkyl- or heterocyclylsulfonyl group, - a selectively substituted Refining group, - a selectively substituted alkenyl group, - a selectively substituted alkynyl group, - a selectively substituted aryl group, or a selectively substituted heterocyclic group; 91 201111379 Conditionally if R1 is selected from A selectively substituted amino group or a selectively substituted alkoxy group and R2 and R3 are the same, and R2 and R3 do not represent hydrogen, or a pharmaceutically acceptable salt thereof. 3. The compound according to claim 1 or 2, wherein X is selected from the group consisting of: S or hydrazine; and R1 is selected from the group consisting of: - hydrogen-selective substituted amine group, - selective Substituted alkyl, - optionally substituted alkoxy, - optionally substituted aryl, or -optically substituted heterocyclic; R2 and R3 are the same or different and each is selected a group consisting of: - hydrogen, - a selectively substituted indenyl group, - a selectively substituted alkoxycarbonyl group, - a selectively substituted alkyl group, - a selectively substituted aryl group, or - a selectively substituted heterocyclic group; or a pharmaceutically acceptable salt thereof. 4. A compound according to any one of claims 1 to 3 wherein X represents S or hydrazine; R1 is selected from the group consisting of: 92 201111379 - Hydrogen-selective substituted amine group, - a selectively substituted alkyl group, R2 and R3 are the same or different, and each is selected from the group consisting of: - hydrogen, - a selectively substituted alkyl group, - a selectively substituted aryl group Or a selectively substituted heterocyclic group; or a pharmaceutically acceptable salt thereof. 5. The compound of any one of claims 1 to 4 wherein X represents S; R1 is selected from a selectively substituted amine group; and R2 is selected from a selectively substituted alkyl group; And R3 represents hydrogen; or a pharmaceutically acceptable salt thereof. 6. The compound of any one of claims 1 to 4, wherein X has the meaning of S, or a pharmaceutically acceptable salt thereof. 7. The compound of any one of claims 1 to 6, wherein R1 is selected from the group consisting of a selectively substituted amine group, or a pharmaceutically acceptable salt thereof. 8. The compound of any one of claims 1 to 7 wherein R2 is selected from the group consisting of a selectively substituted alkyl group, or a pharmaceutically acceptable salt thereof. The compound of any one of claims 1 to 8, wherein R3 is hydrogen, or a pharmaceutically acceptable salt thereof. 93 201111379 10. A compound according to any one of claims 1 to 9 which is selected from the group consisting of: F Or a pharmaceutically acceptable salt thereof. A method for producing a compound of the formula (I) according to claim 1 of the patent application, comprising: (a) a compound of the formula (la): R1 Ο (la) wherein R1 and X are as defined above, 94 201111379 reacts with a compound of the formula: A-R2 wherein R2 is as defined above, and A is one which allows substitution of R2 for a suitable leaving group, Producing a compound of formula (lb) Wherein R1, R2 and X are as defined above, or (b) a compound of formula (lb): R2 (lb) / N \ Η X wherein R1, R2 and X are as defined above, and a compound of the formula wherein R3 is as defined above, and A is one which allows substitution of the leaving group which may be substituted by R3. And obtaining a compound of formula (1), or (c) a compound of formula (Ic): Wherein R2, R3 and X are as defined above, and R4 is in particular (^ to the alkyl group of 6 and reacts with a compound of the following formula: 95 201111379 hn, R6 To obtain the compound of formula (Id) N 〇^γΝ. wherein R, R and X are as defined above, and r5&amp;r6 are the same or different and are selected from the group consisting of: -hydrogen, -selectivity Substituted alkyl, - optionally substituted aryl, and - optionally substituted heterocyclic group, or wherein R5 and V are combined with a nitrogen atom to which they are combined - saturated or unsaturated ^ The selective sputum replaces 3 to 6 of the stomach ring, which may optionally contain additional heteroatoms. 12. A compound such as any of the patent applications is a drug. 13. If you apply for a patent scope! Compounds of any of the items in the 1G category are used for (7) treatment of iron (4), especially for the treatment of iron deficiency and/or anemia, especially for cancer anemia, chemotherapy-induced poverty, and inflammation-induced anemia ( AI), anemia of congestive heart failure (CHF), anemia of chronic kidney disease 夂$ (CKD3-5), anemia caused by chronic inflammation (ACD), anemia of rheumatoid arthritis (RA), systemic Lean lupus (SLg) is poor 96 201111379 Blood, and anemia of inflammatory bowel disease (IBD). A composition comprising one or more of the compounds of any one of claims 1 to 10, and one or more of the pharmaceutical carriers and/or auxiliary substances and/or solvents. 15. A combined preparation comprising one or more of the compounds of any one of claims 1 to 10, and at least one additional pharmaceutically active compound, particularly for treating abnormal iron metabolism And a compound accompanying the syndrome, preferably a compound containing iron. 16. The use of a compound according to any one of claims 1 to 10, a composition according to claim 14 and a combined preparation according to claim 15 of the patent application, for use in To manufacture a disease and associated syndrome for the treatment of hepaticin, especially for the treatment of iron metabolism abnormalities, particularly iron deficiency diseases and/or anemia, particularly ACD and AI, and accompanying syndromes. 17. The use of a compound according to any one of claims 1 to 10, a composition according to claim 14 and a combined preparation according to claim 15 of the patent application, for use in the preparation A drug for oral or parenteral administration. 97