Abstract:
A Maillard reaction inhibitor containing, as an active ingredient, an amidinoheterocyclic derivative or its pharmaceutically acceptable salt, which is useful for the prevention and/or cure of various complications of diabetes and maturity-onset disorders. The amidinoheterocyclic derivatives are also useful as Maillard reaction inhibitors for cosmetics, external endermic medicines, foods, drinks, luxury grocery items and functional foods.

Description:
FIELD OF THE INVENTION 
     The present invention relates to pyrazole derivatives and their salts, which have a Maillard reaction inhibiting activity and are useful for prevention and/or cure of various complications of diabetes and maturity-onset disorders. 
     Recently, denaturation of proteins by glucose has become greatly highlighted as one factor of causing complications of diabetes, which is considered to be caused by the Maillard reaction occurring in living bodies. 
     A Maillard reaction is considered to be a series of reactions, in which the amino groups of proteins are non-enzymatically saccharified (glycated) with glucose to form Amadori rearrangement products as primary glycation products and the proteins are cross-linked and denatured by the advanced glycation to give advanced glycation end products (AGE) which are brown and are hardly soluble and which are hardly decomposed by proteases. 
     The advancement of the non-enzymatical glycation or the formation of AGE proteins by the reaction is remarkable especially under hyperglycemic conditions or in the protein sites where the speed of metabolizing proteins is low or proteins are not metabolized. It is considered that the reaction causes denaturation, hypergasia or functional disorder of proteins in various protein sites in diabetics, for example, hemoglobin, serum albumin, collagen and elastin in connective tissues, myelin, lens crystallin of eyeballs, etc. in them, and is one factor of causing complications of diabetes, such as retinopathy, nephropathy, cardiovascular disorders, neuropathy, cataract, etc. In addition, the Maillard reaction in living bodies is considered to be one mechanism of aging and it is presumed that the reaction has a close relation to the maturity-onset disorders. 
     Therefore, it is considered extremely effective to inhibit the Maillard reaction to inhibit the advancement of the non-enzymatic glycation and the formation of AGE products for various disorders such as various complications of diabetes and various senile disorders. Heretofore, development and study of compounds having a Maillard reaction inhibiting activity has been attempted. 
     Various compounds having a Maillard reaction inhibiting activity have heretofore been reported. 
     For instance, mentioned are aminoguanidine, α-hydrazinohistidine, lysine and their mixtures described in Japanese Patent Laid-Open No. 62-142114, which were reported as Maillard reaction inhibitors. It is reported that the described compounds react with the carbonyl moiety in the Amadori rearrangement products of the primary glycation products to block the moiety to thereby inhibiting the secondary glycation, and finally, inhibiting the crosslinking of proteins and the resultant formation of AGE products. 
     SUMMARY OF THE INVENTION 
     We, the present inventors, have found that various pyrazole derivatives of the general formula I, which are quite different from conventional Maillard reaction inhibiting compounds in their chemical structures, have excellent effects as Maillard reaction inhibitors. On this basis, we have made the present invention. 
     Specifically, the present invention provides a method of inhibiting the formation of advanced glycation endproducts which comprises administration of a compound of the general formula I ##STR1## wherein 
     R 1  represents a hydrogen atom, a lower alkyl group, or a phenyl group; 
     R 2  represents a hydrogen atom, a lower alkyl group, a phenyl group, an amino group, a lower alkoxy group, a carboxyl group, or a lower alkoxycarbonyl group; X represents a nitrogen atom, or a group of a formula --CR 3  --; and 
     R 3  represents a hydrogen atom, a lower alkyl group, a phenyl group, a halogen atom, or a lower alkanoyl group; 
     the dotted line represents an optional double bond when X is CR 3  -- 
     R 4  represents a hydroxy group when the optional double bond is not present; 
     with the proviso that when X represents CR 3  -- and R 2  represents hydrogen and the optional double bond is present, then R 1  together with R 3  can be a --CH═CH--CH═CH-- group, optionally substituted by a hydrogen atom, a hydroxyl group, a nitro group, an amino group or a sulfamoyl group; 
     with the further proviso that when R 1  and R 2  both represent a lower alkyl group and X represents CR 3  -- and the dotted line represents a double bond then 
     R 3  represents: 
     (i) a fluorine atom, a nitro group, an unsubstituted lower alkyl group having 3 or more carbon substituted by a lower alkanoyl group; or 
     (ii) a lower alkyl group substituted by any of a halogen atom, a lower alkanoyl group, a lower alkoxy group, a lower alkoxycarbonyl group and a phenyl group of the formula: ##STR2##  in which R 5  and R 6  and R 7  are the same or different and each represents a hydrogen atom, and amino group, a nitro group, a hydroxyl group, a lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group or an aralkyloxy group, and R 6  and R 7  together may form a lower alkylenedioxy group; or 
     (iii) a carbonyl group substituted by any of a hydroxyl group, a lower alkyl group, an aralkyloxy group, an optionally lower alkyl-substituted amino group and an optionally lower alkoxy substituted lower alkoxy group; or 
     (iv) together with R 2  can form a lower alkylene group having 3 or more carbon atoms; 
     with the still further proviso that when X represents CR 3  --, R 3  represents hydrogen, the double bond is present and R 2  represents an amino group, then R 1  can represent a lower alkyl-substituted or unsubstituted thienyl or furyl group, a phenyl-substituted lower alkyl or lower alkenyl group, or a phenyl group of the formula in which R 8 , R 9  and R 10  are the same or different and each represents a hydrogen atom, a halogen atom, an amino group, a nitro group, or an optionally halogen-substituted lower alkyl or lower alkoxy group; 
     and with the still further proviso that when X represents CR 3  --, the optional bond is not present and R 4  is a hydroxy group, then R 1  and R2 are the same or different and each represents a halogen atom-substituted or unsubstituted lower alkyl group; R 3  represents a hydrogen atom; and R 2  and R 3  may together form a lower alkylene group; 
     and the pharmaceutically acceptable acid addition salts thereof. 
     Effect of the Invention: 
     The compounds of formula (I) and their pharmaceutically acceptable salts of the present invention have a Maillard reaction inhibiting activity as well as a low toxicity. Therefore, they are useful for prevention and/or cure of various complications of diabetes, for example, retinopathy, nephropathy, cardiovascular disorders such as coronary cardiopathy, peripheral cardiovascular disorders or cerebrovascular disorders, diabetic neuropathy, cataract, and arteriosclerosis and atherosclerosis which are considered to be caused by the Maillard reaction. 
     In addition, they are expected to be useful also as medicines for prevention and/or cure of atherosclerosis, senile cataract and cancer which are considered to be caused by aging of proteins. 
     Moreover, since they may prevent crosslinking of proteins such as collagen and elastin, they may also be used as cosmetics and external endermic medicines. 
     Further, it is well known that the Maillard reaction has relation to deterioration of proteins and amino acids not only in living bodies but also in foods, drinks and luxury grocery items, the compounds of the present invention may be used as the Maillard reaction inhibitor not only in the functional foods for the above-mentioned medicines and cosmetics but also in foods, drinks and luxury grocery items containing proteins and amino acids. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     More particularly, the present invention provides a method of inhibiting the formation of advanced glycation endproducts which comprises administration of a compound of the general formula I ##STR3## wherein 
     R 1  represents a hydrogen atom, a lower alkyl group, or a phenyl group; 
     R 2  represents a hydrogen atom, a lower alkyl group, a phenyl group, an amino group, a lower alkoxy group, a carboxyl group, or a lower alkoxycarbonyl group; X represents a nitrogen atom, or a group of a formula --CR 3-  ; and 
     R 3  represents a hydrogen atom, a lower alkyl group, a phenyl group, a halogen atom, or a lower alkanoyl group; 
     the dotted line represents an optional double bond when X is CR 3  -- 
     R 4  represents a hydroxy group when the optional double bond is not present; 
     with the proviso that when X represents CR 3  -- and R 2  represents hydrogen and the optional double bond is present, then R 1  together with R 3  can be a --CH═CH--CH═CH-- group, optionally substituted by a hydrogen atom, a hydroxyl group, a nitro group, an amino group or a sulfamoyl group; 
     with the further proviso that when R 1  and R 2  both represent a lower alkyl group and X represents CR 3  -- and the dotted line represents a double bond then 
     R 3  represents: 
     (i) a fluorine atom, a nitro group, an unsubstituted lower alkyl group having 3 or more carbon substituted by a lower alkanoyl group; or 
     (ii) a lower alkyl group substituted by any of a halogen atom, a lower alkanoyl group, a lower alkoxy group, a lower alkoxycarbonyl group and a phenyl group of the formula: ##STR4##  in which R 5  and R 6  and R 7  are the same or different and each represents a hydrogen atom, and amino group, a nitro group, a hydroxyl group, a lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group or an aralkyloxy group, and R 6  and R 7  together may form a lower alkylenedioxy group; or 
     (iii) a carbonyl group substituted by any of a hydroxyl group, a lower alkyl group, an aralkyloxy group, an optionally lower alkyl-substituted amino group and an optionally lower alkoxy substituted lower alkoxy group; or 
     (iv) together with R 2  can form a lower alkylene group having 3 or more carbon atoms; 
     with the still further proviso that when X represents CR 3  --, R 3  represents hydrogen, the double bond is present and R 2  represents an amino group, then R 1  can represent a lower alkyl-substituted or unsubstituted thienyl or furyl group, a phenyl-substituted lower alkyl or lower alkenyl group, or a phenyl group of the formula ##STR5## in which R 8 , R 9  and R 10  are the same or different and each represents a hydrogen atom, a halogen atom, an amino group, a nitro group, or an optionally halogen-substituted lower alkyl or lower alkoxy group; 
     and with the still further proviso that when X represents CR 3  --, the optional bond is not present and R 4  is a hydroxy group, then R 1  and R2 are the same or different and each represents a halogen atom-substituted or unsubstituted lower alkyl group; R 3  represents a hydrogen atom; and R 2  and R 3  may together form a lower alkylene group; 
     and the pharmaceutically acceptable acid addition salts thereof. 
     Unless otherwise specifically defined, the terminology &#34;lower&#34; as referred to herein for the definition of the general formula means a linear or branched carbon chain having from 1 to 6 carbon atoms. 
     The &#34;lower alkyl group&#34; includes, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, and isopentyl group, a neopentyl group, a tert-pentyl group, a 1-methylbutyl group, a 2-methylbutyl group, a 1,2-dimethylpropyl group, a hexyl group, an isohexyl group, etc. 
     The &#34;lower alkyl group having 3 or more carbon atoms&#34; is an alkyl group having from 3 to 6 carbon atoms of the above-mentioned lower alkyl groups, which includes, for example, a propyl group, a butyl group, an isobutyl group, a pentyl group and a hexyl group. 
     The &#34;lower alkanoyl group&#34; includes, for example, a formyl group, acetyl group, a propionyl group, a butyryl group, a isobutyryl group, a valeryl group, an isovaleryl group, a pivaloyl group, a hexanoyl group, etc. 
     The &#34;lower alkoxycarbonyl group&#34; includes, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, and isobutoxycarbonyl group, a sec-butoxycarbonyl group, a tert-butoxycarbonyl group, a pentyl(amyl)oxycarbonyl group, an isopentyl(amyl)oxycarbonyl group, a hexyloxycarbonyl group, an isohexyloxycarbonyl group, etc. 
     The &#34;lower alkoxy group&#34; includes, for example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy (amyloxy) group, an isopentyloxy group, a tert-pentyloxy group, a neopentyloxy group, a 2-methylpropoxy group, a 1,2-dimethylpropoxy group, a 1-ethylpropoxy group, a hexyloxy group, etc. 
     The &#34;aralkyloxy group&#34; is preferably a phenyl-lower alkoxy group, including, for example, a benzyloxy group, a phenethyloxy group, a phenylpropoxy group, a phenylbutoxy group, a phenylpentyloxy group, a phenylhexyloxy group, etc. Preferred is a benzyloxy group. 
     The &#34;lower alkylenedioxy group&#34; is a group having oxo groups at the both ends of a lower alkylene chain, which includes, for example, a methylenedioxy group (--OCH 2  O--), an ethylenedioxy group (--O(CH 2 ) 2  O--), a propylenedioxy group, etc. 
     The &#34;lower alkenyl group&#34; is an alkenyl group having from 2 to 6 carbon atoms, including, for example, a vinyl group, an allyl group, a 1-propenyl group, a butenyl group, a pentenyl group, a hexenyl group, etc. 
     The &#34;lower alkylene group&#34; includes, for example, a methylene group, an ethylene group, a propylene group, a butylene group, a pentamethylene group, a hexamethylene group, etc. 
     The &#34;lower alkylene group having 3 or more carbon atoms&#34; is preferably an alkylene group having from 3 to 6 carbon atoms, including, for example, a propylene group, a tetramethylene group, a 1-methyltrimethylene group, a 2-methyltrimethylene group, a 3-methyltrimethylene group, an ethylethylene group, a dimethylethylene group, a pentamethylene group, a methyltetramethylene group, a dimethyltrimethylene groups, a pentamethylene group, a hexamethylene group, etc. Preferred are a propylene group, a tetramethylene group and a pentamethylene group. 
     The &#34;halogen atom&#34; is preferably a fluorine atom, a chlorine atom, a bromine atom, etc. 
     The &#34;amino group optionally substituted by a lower alkanoyl group or a lower alkoxycarbonyl group&#34; means an unsubstituted amino group and an amino group substituted by one substituent of the above-mentioned lower alkanoyl group or lower alkoxycarbonyl group. The latter includes, for example, an acetylamino group, a propionylamino group, a butyrylamino group, a methoxycarbonylamino group, an ethoxycarbonylamino group, a propoxycarbonylamino group, etc. 
     The &#34;halogen atom&#34; is preferably a fluorine atom, a chlorine atom, a bromine atom, etc. 
     The &#34;lower alkyl group&#34; moiety of the substituted lower alkyl group is preferably a methyl group, an ethyl group or a propyl group. The substituent of the group is as mentioned above. Concretely, the substituent &#34;lower alkanoyl group&#34; is preferably an acetyl group or a propionyl group; the &#34;lower alkoxy group&#34; is preferably a methoxy group or an ethoxy group; and the &#34;lower alkoxycarbonyl group&#34; is preferably a methoxycarbonyl group or an ethoxycarbonyl group. 
     The &#34;lower alkyl group&#34; of R 5 , R 6  and R 7  in the phenyl group of a formula: ##STR6## is as mentioned above, and it is preferably a methyl group, an ethyl group or a tert-butyl group. 
     The &#34;optionally lower alkyl-substituted amino group&#34; of the substituent of the substituted carbonyl group means an unsubstituted amino group or an amino group substituted by one of the above-mentioned alkyl groups. The latter includes, for example, a methylamino group, an ethylamino group, a propylamino group, a butylamino group and a pentylamino group. 
     The &#34;optionally lower alkoxy-substituted lower alkoxy group&#34; means the above-mentioned lower alkoxy group or a lower alkoxy group substituted by an alkoxy group at any position thereof. The latter is preferably a methoxyethoxy group or an ethoxyethoxy group. 
     The &#34;lower alkyl-substituted thienyl or furyl group&#34; is a thienyl or furyl group substituted by one of the above-mentioned alkyl groups. It includes, for example, a 2-methylthienyl group, a 2-ethylthienyl group, a 2-propylthienyl group, a 2-methylfuryl group, a 2-ethylfuryl group, a 2-propylfuryl group, etc. 
     The &#34;halogen-substituted lower alkyl or lower alkoxy group&#34; is the above-mentioned lower alkyl or lower alkoxy group substituted by the above-mentioned halogen atom(s), including, for example, a monochloromethyl group, a monofluoromethyl group, a trifluoromethyl group, a trifluoroethyl group, a monochloromethoxy group, a monofluoromethoxy group, a trifluoromethoxy group, etc. 
     Equivalent to the compounds of formula (I) for the purposes of the present invention are the pharmaceutically acceptable salts formed with acids. These acid addition salts include, for example, the acid-addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; and the acid-addition salts with organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, citric acid, tartaric acid, carbonic acid, picric acid, methanesulfonic acid, ethanesulfonic acid, glutamic acid, etc. 
     A compound of formula (I) may contain an asymmetric carbon atom, depending upon the kind of the substituents. The present invention also includes medicines containing, as the active ingredient, an isolated optical isomer of a compound of formula (I) or a mixture of optical isomers thereof. 
     A compound of formula (I) may be isolated as its hydrate or solvate, for example, with ethanol or the like or as its polymorphic substance. The present invention also includes them. 
     Certain of the compounds of formula I which are active ingredients of the medicines to be provided by the present invention are disclosed in Chem. Abs., 69:59251k; J. Am. Chem. Soc., 74:4562 (1952); Chem. Abs., 79:29768c; Chem. Abs., 87:196219s; Helv. Chim. Acta, 58:761 (9175); J. Heterocyclic. Chem., 11:691 (1974); Japanese Patent Laid-Open No. 50-151872; Arch. Immunol. Ther. Exp., 24:871 (1976); Heterocycles, 22:2013 (1984); Zh. Obshch. Khim., 57:584 (1987); and J. Indian. Chem. Soc., 13:509 (1936); and almost all of them are known. 
     However, these publications do not disclose that these amidinoheterocyclic derivatives possess Maillard reaction inhibiting activity. 
     In one embodiment, the present invention comprises a Maillard reaction inhibitor containing, as an active ingredient, an amidinoheterocyclic derivative of the following general formula (Ia) or its pharmaceutically acceptable salt, and the object of the present invention is to provide the inhibitor of the formula: ##STR7## wherein 
     R 1  represents a hydrogen atom, a lower alkyl group, or phenyl group; 
     R 2  represents a hydrogen atom, a lower alkyl group, a phenyl group, an amino group, a lower alkoxy group, a carboxyl group, or a lower alkoxycarbonyl group; X represents a nitrogen atom, or a group of a formula --CR 3  ═; 
     and R 3  represents a hydrogen atom, a lower alkyl group, a phenyl group, a halogen atom, or a lower alkanoyl group. 
     Representative compounds of formula Ia include: 
     (1) 1-Amidino-1,2,4-triazole and its pharmaceutically acceptable salts; 
     (2) 1-Amidinopyrazole and its pharmaceutically acceptable salts; 
     (3) 1-Amidino-3,5-dimethylpyrazole and its pharmaceutically acceptable salts; 
     (4) 1-Amidino-4-chloro-3,5-dimethylpyrazole and its pharmaceutically acceptable salts; 
     (5) 1-Amidino-4-bromo-3,5-dimethylpyrazole and its pharmaceutically acceptable salts; 
     (6) 1-Amidino-3,5-dimethyl-4-phenylpyrazole and its pharmaceutically acceptable salts; 
     (7) 1-Amidino-5-aminopyrazole and its pharmaceutically acceptable salts; 
     (8) 1-Amidino-5-amino-3-methylpyrazole and its pharmaceutically acceptable salts; 
     (9) 1-Amidino-5-amino-3-phenylpyrazole and its pharmaceutically acceptable salts; 
     (10) 1-Amidino-5-methoxy-3-methylpyrazole and its pharmaceutically acceptable salts; 
     (11) 1-Amidino-5-ethoxy-3-methylpyrazole and its pharmaceutically acceptable salts; 
     (12) (1-Amidino-3-methylpyrazol-5-yl)carboxylic acid and its pharmaceutically acceptable salts; 
     (13) Ethyl (1-amidino-3-methylpyrazol-5-yl)carboxylate and its pharmaceutically acceptable salts; 
     (14) 4-Acetyl-l-amidino-5-methylpyrazole and its pharmaceutically acceptable salts; 
     (15) 1-Amidino-3,5-diphenylpyrazole and its pharmaceutically acceptable salts; 
     (16) 1-Amidino-3,4,5-trimethylpyrazole and its pharmaceutically acceptable salts; and 
     (17) 1-Amidino-3,5-dimethyl-4-ethylpyrazole and its pharmaceutically acceptable salts. 
     Of these, preferred compounds are Compounds (2), (3), (4), (5), (7), (8), (9), (13) and (14); and especially preferred is compound (3). 
     Preparation of the compounds of formula (Ia): 
     Most of the amidinoheterocyclic derivatives (Ia) and their salts of the present invention are produced in accordance with the methods described in the above-mentioned publications. Of the compounds of formula (Ia) which are the active ingredients of the present invention, those not specifically described in the above-mentioned publications may also be produced in accordance with the methods described in the above-mentioned publications or by their modifications. 
     In a second embodiment, the present invention comprises the novel amidinoindazole derivatives of formula Ib, and their preparation constitutes a further aspect of the present invention. 
     These novel amidinoindazole derivatives and their salts are those of the general formula Ib ##STR8## wherein R represents a hydrogen atom, a hydroxyl group, a nitro group, an amino group or a sulfamoyl group. 
     As mentioned above, R in the compounds of Formula (Ib) of the present invention represents a hydrogen atom, a hydroxyl group, a nitro group, an amino group or a sulfamoyl group. 
     R may be bonded to any carbon atom on the benzene ring of the indazole moiety of the compounds of the present invention. 
     The compounds of Formula (Ib) of the present invention form salts with acids. 
     The compounds of formula Ib of the present invention may be produced by various methods. Some typical methods for producing the compounds of formula Ib are mentioned below: ##STR9## wherein R is as above; and X represents a halogen atom. 
     The halogen atom of X includes, for example, a chlorine atom, a bromine atom, etc. 
     The compounds of formula Ib of the present invention may be produced by reacting an indazole compound of formula IIb and a halogenoformamidine of formula IIIb or its salt or the cyanamide of formula IVb for N-amidination. 
     The reaction is effected by warming or heating under reflux the indazole compound of formula IIb and a reaction-corresponding amount of the halogenoformamidine IIIb or its salt or the cyanamide of formula IVb in an inert solvent. 
     The inert solvent usable in the reaction includes, for example, benzene, tetrahydrofuran (THF), chloroform, ethyl acetate, toluene, 1,4-dioxane, etc. 
     Where a halogenoformamidine is used alone in the reaction, addition of an acid such as hydrochloric acid, hydrobromic acid or nitric acid to the reaction system is preferred. ##STR10## 
     Compounds (IVb) of the present invention may be produced by reducing the nitro compound of formula (Vb). 
     The reduction may be effected by an ordinary process, for example, in the presence of a noble metal catalyst such as palladium carbon, platinum oxide or the like for catalytic reduction, in a solvent which is generally used in catalytic reduction such as methanol, ethanol, ethyl acetate or the like, under normal pressure or elevated pressure. 
     In a third embodiment, the present invention comprises the novel pyrazole derivatives of formula Ic, and their preparation constitutes a further aspect of the present invention. 
     These novel pyrazole derivatives are those of the general formula (Ic) and their salts are those of the formula ##STR11## wherein 
     R 1  represents a lower alkyl group; 
     R 2  represents 
     (i) a fluorine atom, a nitro group, an unsubstituted low alkyl having 3 or more carbon atoms, or an amino group optionally substituted by a lower alkanoyl group or a lower alkoxycarbonyl group; or 
     (ii) a lower alkyl group substituted by any of a halogen atom, a lower alkanoyl group, a lower alkoxy group, a lower alkoxycarbonyl group and a phenyl group of a formula: ##STR12## in which 
     R 6 , R 7  and R 8  are same or different and each represents a hydrogen atom, an amino group, a nitro group, a hydroxyl group, a lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group or an aralkyloxy group, and R 6  and R 7  may together form a lower alkylenedioxy group; or 
     (iii) a carbonyl group substituted by any of a hydroxyl group, a lower alkyl group, an aralkyloxy group, an optionally lower alkyl-substituted amino group and an optionally lower alkoxy-substituted lower alkoxy group; and 
     R 2  and R 3  may together form a lower alkylene group having 3 or more carbon atoms. 
     Some typical methods for producing the compounds of formula Ic are mentioned below. ##STR13## where R 1 , R 2  and R 3  have the same definitions as mentioned above for formula Ic; and X represents a halogen atom. 
     The halogen atom of X includes, for example, a chlorine atom, a bromine atom, etc. 
     The compounds of formula Ic of the present invention may be produced by reacting a pyrazole compound of formula IIc and a halogenoformamidine salt of formula IIIc or cyanamide of formula IVc for N-amidination. 
     The reaction is effected by warming or heating under reflux the pyrazole compound of formula IIc and a reaction-corresponding amount of the halogenoformamidine salt (IIIc) or cyanamide (IVc) in a solvent. 
     The solvent usable in the reaction includes, for example, benzene, tetrahydrofuran (THF), chloroform, ethyl acetate, toluene, 1,4-dioxane, etc. 
     Where cyanamide is used in the reaction, the pyrazole compound (IIc) to be reacted therewith is preferably in the form of its acid-additional salt with hydrochloric acid, hydrobromic acid, nitric acid or the like. ##STR14## where R 1 , R 2  and R 3  have the same definitions as mentioned above for formula Ic. 
     The compounds of formula (Ic) of the present invention may be produced by reacting the diketone compounds of formula (Vc) and an aminoguanidine salt of formula (VIc) for cyclization. 
     The diketone compound (Vc) is reacted with a reaction-corresponding amount of the aminoguanidine salt (VIc) in a solvent at room temperature or under heat. 
     The solvent usable in the reaction includes, for example, water, methanol, ethanol, tetrahydrofuran (THF), 1,4-dioxane, etc. 
     The acid-addition salt of aminoguanidine includes its hydrochloride, hydrobromide and nitrate. 
     Third Method (nitration): 
     Of the compounds of formula (Ic) of the present invention, those where R 3  is a nitro group may be produced by ordinary nitration. 
     For instance, compound of formula (Ic) of the present invention where R 3  is a hydrogen atom and a reaction-corresponding amount or excess amount of a nitrating reagent are stirred in an inert solvent with cooling with ice or at room temperature to obtain the corresponding compound of formula (Ic) where R 3  is a nitro group. As the inert solvent, preferred are acetonitrile, acetic acid and the like. 
     Fourth Reaction (reduction): 
     Of the compounds of formula (Ic) of the present invention, those where R 3  is an amino group may be produced by reducing compound (Ic) where R 3  is a nitro group. 
     The reduction may be effected by an ordinary process. For instance, for catalytic reduction, compound (Ic) where R 3  is a nitro group is reduced in the presence of a noble metal catalyst such as palladium-carbon, platinum oxide or the like, in a solvent which is generally used in catalytic reduction, such as methanol, ethanol, ethyl acetate or the like, at normal pressure or elevated pressure. 
     Fifth Method: 
     Of the compounds of formula (Ic) of the present invention, those where R 3  is a carboxylic acid group may be produced by removing the benzyl group from the corresponding benzyl ester. 
     The removal of the benzyl group may be effected in accordance with the above-mentioned fourth method. For instance, the benzyl group may easily be removed by hydrogenation of the corresponding benzyl ester in the presence of a noble metal catalyst such as palladium-carbon, platinum oxide or the like, in methanol, ethanol, ethyl acetate or the like ordinary solvent. 
     In a fourth embodiment, the present invention comprises the novel 5-aminopyrazole derivatives of formula Id, and their preparation constitutes a further aspect of the present invention. 
     These novel 5-aminopyrazole derivatives and their salts are those of the general formula Id ##STR15## where R 1  represents a lower alkyl group having 3 or more carbon atoms, a lower alkyl-substituted or unsubstituted thienyl or furyl group, a phenyl-substituted lower alkyl or lower alkenyl group, or a phenyl group of a formula: ##STR16## in which R 8 , R 9  and R 10  are same or different and each represents a hydrogen atom, a halogen atom, an amino group, a nitro group, or an optionally halogen-substituted lower alkyl or lower alkoxy group; 
     provided that when R 8  is a hydrogen atom or a bromine atom, one of R 9  and R 10  is a group except hydrogen. 
     Methods of producing compounds of formula (Id): 
     The compounds of the present invention may be produced by various methods. Some typical methods for producing the compounds of formula (Id) are mentioned below. ##STR17## where R 1  has the same definition as mentioned above for formula Id. 
     Compounds (Id) of the present invention may be produced by reacting an acetonitrile compound of Formula (IId) and an aminoguanidine salt of Formula (IIId) for cyclization. 
     The cyclization is conducted by heating optionally under reflux the acetonitrile compound (IId) and a reaction-corresponding amount of the aminoguanidine salt (IIId) in a solvent. 
     The solvent usable in the reaction includes, for example, methanol, ethanol, THF, DMF, acetic acid, etc. 
     As acid-addition salts of aminoguanidine, mentioned are its hydrochloride, hydrobromide, nitrate, etc. 
     Second Method (reduction): 
     Of the compounds of formula (Id) of the present invention, those where R 1  is a phenyl-substituted lower alkyl group or any of R 8 , R 9  and R 10  is an amino group may be produced by reducing Compound (I) where R 1  is a phenyl-substituted lower alkenyl group or any of R 2 , R 3  and R 4  is a nitro group. 
     The reduction may be effected by an ordinary process. For instance, for obtaining the Compound of formula (If) where R 1  is a phenyl-substituted lower alkyl group by catalytic reduction, the Compound of Formula (If) where R 1  is a phenyl substituted lower alkenyl group is reduced in the presence of a noble metal catalyst such as palladium-carbon, platinum oxide or the like, in a solvent which is generally used in catalytic reduction, such as methanol, ethanol, ethyl acetate or the like, at normal pressure or elevated pressure. For obtaining Compound (Id) where any of R 8 , R 9  and R 10  is an amino group, Compound (Id) where any of R 8 , R 9  and R 10  is a nitro group is reduced with a metal such as iron, zinc, tin or the like in the presence of hydrochloric acid, acetic acid, ammonium chloride or the like in a solvent such as water, acetic acid or the like, at room temperature or under heat. 
     In a fifth embodiment, the present invention comprises the novel 5-hydroxypyrazoline derivatives of formula Ie, and their preparation constitutes a further aspect of the present invention. 
     These novel 5-hydroxypyrazoline derivatives and their salts are those of the general formula Ie ##STR18## where R 1  and R 2  are same or different and each represents a halogen atom-substituted or unsubstituted lower alkyl group, provided that when one of them is methyl group, the other is a group except it; 
     R 3  represents a hydrogen atom; and 
     R 2  and R 3  may together form a lower alkylene group. 
     Methods of producing the formula of Compounds (Ie): 
     The compounds of the present invention may be produced by various methods. One typical method for producing Compounds (Ie) is mentioned below. ##STR19## where R 1 , R 2  and R 3  have the same definitions as mentioned above for formula Ie. 
     compounds (Ie) of the present invention may be produced by reacting the diketone compound of Formula (IIe) and amidinoguanidine (IIIe) or its salt for cyclization. 
     The cyclization is effected by stirring the diketone compound (IIe) and a reaction-corresponding amount of amidinoguanidine (IIIe) or its salt in an inert solvent at room temperature or under heat. 
     The inert solvent usable in the reaction includes, for example, water, methanol, ethanol, THF, DMF, etc. 
     Pharmaceutical Effect of the Compounds of formula (I): 
     The Maillard reaction inhibiting activity of the compounds of the present invention has been verified by the following test method, and the compounds have an excellent effect. 
     Maillard reaction inhibiting activity test: 
     Test method: 
     Lysozyme and ribose were dissolved in 0.1M sodium phosphate buffer (pH 7.4) containing 3 mM of sodium azide to have a concentration of 6 mg/ml and 100 mM, respectively, and incubated for 7 days at 37° C. After the incubation, a certain amount of it was taken out and subjected to electrophoresis with SDS-PAGE. After the electrophoresis, this was stained with 0.04% Coomassie Brilliant Blue R-250 and the amounts of the dimer and trimer formed were determined with a densitometer. 
     The compound of the present invention to be tested was added prior to the incubation in a concentration of 1 mM, 3 mM, 10 mM or 30 mM. The inhibiting effect of the compound of each concentration to the dimer and trimer was measured, and the IC 50  value of the compound was obtained from the measured data. 
     The Maillard reaction inhibiting activity of compounds of formula (Ia) of the present invention as obtained by the above-mentioned test is shown in Table 1 below along with the substituents of them. 
     
                       TABLE 1______________________________________ ##STR20##                    (Ia)Test                                 Inhibiting ActivityNo.  R.sup.1       R.sup.2 X    R.sup.3                         Salt   (IC.sub.50, mM)______________________________________ 1   H      H       N    --   HCl    27.1 2   H      H       CR.sup.3                    H    HCl    8.8 3   Me     Me      CR.sup.3                    H    HCl    7.7 4   Me     Me      CR.sup.3                    Cl   HNO.sub.3                                10.4 5   Me     Me      CR.sup.3                    Br   HNO.sub.3                                9.3 6   Me     Me      CR.sup.3                    Ph   HCl    12.3 7   H      NH.sub.2               CR.sup.3                    H    HCl    4.3 8   Me     NH.sub.2               CR.sup.3                    H    HCl    4.7 9   Ph     NH.sub.2               CR.sup.3                    H    HCl    2.410   Me     OMe     CR.sup.3                    H    HCl    27.011   Me     OEt     CR.sup.3                    H    HCl    26.012   Me     CO.sub.2 H               CR.sup.3                    H    HCl    16.113   Me     CO.sub.2 Et               CR.sup.3                    H    HCl    6.614   H      Me      CR.sup.3                    Ac   HCl    7.315   Ph     Ph      CR.sup.3                    H    HCl    30.016   Me     Me      CR.sup.3                    Me   HCl    27.117   Me     Me      CR.sup.3                    Et   HCl    26.4______________________________________ 
    
     Formulation of Medicines: 
     A medicinal composition containing, as the active ingredient, one or more of the compounds of formula (I), their pharmaceutically acceptable salts, their pharmaceutically acceptable hydrates and the like is formed into tablets, powder, fine granules, granules, capsules, pills, oral liquid, injection, suppositories, ointment, plaster and the like, along with conventional pharmaceutical carriers, vehicles and other additives. They are administered perorally or parenterally. 
     The clinical dose of the compound of the present invention to patients is suitably determined in consideration of the condition, body weight, age and sex of the patient to which it is given. In general, its peroral dose for an adult is from 0.1 to 500 mg/day, preferably from 10 to 200 mg/day, which is administered all at a time or is divided into plural administrations. Since the dose may vary under various conditions, a smaller dose than the defined range may often be sufficient. 
     The solid composition of the present invention for peroral administration may be in the form of tablets, powder, granules, etc. In preparing the solid composition of the kind, one or more active substances are blended with at least one inactive diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, fine crystalline cellulose, starch, polyvinyl pyrrolidone, magnesium metasilicate aluminate, etc. The composition may contain, as usual, any other additives than the inert diluent, for example, a lubricant such as magnesium stearate, a disintegrator such as potassium cellulose glycolate, a stabilizer such as lactose, and a dissolution aid such as glutamic acid or aspartic acid. The tablets and pills may be coated, if desired, with a film of a gastric-soluble or enteric-soluble substance such as sucrose, gelatin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose phthalate or the like. 
     The peroral liquid composition of the present invention contains a pharmaceutically acceptable emulsifier, solution, suspension, syrup, elixir or the like and contains an ordinary inactive diluent such as pure water or ethanol. The composition may contain, in addition to the inactive diluent, other auxiliaries such as a solubilizer, a dissolution aid, a moisturizer or a suspension, as well as a sweetener, a flavoring, an aromatic and an antiseptic. 
     The injection for parenteral administration of the present invention contains a germ-free aqueous or non-aqueous solution, suspension or emulsion. The aqueous solution and suspension include, for example, a distilled water for injection and a physiological saline solution. The non-aqueous solution and suspension include, for example, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, Polysorbate 80 (trade name), etc. The composition may further contain other additives such as an isotonic agent, an antiseptic, a moisturizer, an emulsifier, a dispersing agent, a stabilizer (for example, lactose), a solubilizer and a dissolution aid. The additives are sterilized, for example, by filtration of them through a bacteria-retentive filter, or by adding a microbicide thereto or by irradiation to them. As the case may be, a germ-free solid composition for injection is prepared and this may be dissolved in a germ-free water or a germ-free solvent for injection before use. 
     When cosmetics or external endermic medicines containing the Maillard reaction inhibiting compound of the present invention are prepared, they may contain compound (I) or its salt of the present invention in an amount of from 0.05 to 10 parts by weight to the total weight. The cosmetics and external endermic medicines may be prepared by ordinary methods using general cosmetic bases and external medicinal bases. 
     Foods, drinks, luxury grocery items and functional foods containing the Maillard reaction inhibiting compound of the present invention may also be prepared by ordinary methods. 
     EXAMPLES 
     The present invention will be explained in more detail by means of the following examples, Needless to say, the present invention is not limited to only them. 
     The chemical structural formulae of the compounds of the present invention as obtained in the following examples are shown in the following tables. 
     Formulation Example 
     Peroral tablets (film-coated tablets): 
     
         ______________________________________Composition______________________________________Core TabletActive ingredient of formula (I)                     30     mgCalcium hydrogen phosphate anhydride                     68     mgCrystalline cellulose     20     mgLight silicic acid anhydride                     2      mgHydroxypropyl cellulose   5      mgCalcium Carboxymethyl cellulose                     4.2    mgMagnesium stearate        0.8    mgSub-total                 130    mgCoatingHydroxypropylmethyl cellulose 2910                     3.8    mgPolyethylene glycol 6000  0.5    mgTitanium oxide            2.0    mgIron sesquioxide          0.1    mgTalc                      0.1    mgSub-total                 6.5    mgTotal                     136.5  mg______________________________________ 
    
     130 mg-tablets containing the active ingredient of formula (I) or its pharmaceutically acceptable salt of the invention: 
     150 g of the active ingredient of formula (I) or its pharmaceutically acceptable salt of the invention, 340 g of calcium hydrogen phosphate anhydride, 100 g of crystalline cellulose and 10 g of light silicic acid anhydride were weighed and put in a fluidized-bed granulation coater (manufactured by Ohkawara Seisakusho KK) and uniformly blended therein. 250 g of 10% hydroxypropyl cellulose solution was sprayed thereover for granulation. After drying, the granules were passed through a 20-mesh sieve, to which added were 21 g of calcium carboxymethyl cellulose and 4 g of magnesium stearate. The resulting granules were tableted in a rotary tableting machine (manufactured by Hata Seisakusho KK), using a pounder of 7 mm×8.4 R, to form tablets of 130 mg/tablet. 
     The tablets were coated in a coating machine (Freund Industry Co.), where 325 g of a coating liquid comprising 19 g of hydroxypropylmethyl cellulose, 2.5 g of polyethylene glycol 6000, 10 g of titanium oxide, 0.5 g of iron sesquioxide and 0.5 g of talc were sprayed over the tablets. Thus, film-coated tablets each having a coating of 6.5 mg/tablet were obtained. 
     The preparation of the compounds of the present invention will be explained in more detail by means of the following examples. Needless to say, the present invention is not limited to only them. 
     The chemical structural formulae of the compounds of the present invention as obtained in the following examples are shown in the following tables. 
     Example 1 
     940 mg of indazole and 920 mg of chloroformamidine hydrochloride were heated under reflux in 30 ml of benzene of THF for 5 hours, and the crystals formed were removed by filtration. These were recrystallized from ethanol ether to obtain 826 mg of 2H-indazole-2-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 186° to 187° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.9 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 48.87   4.61      28.49 18.03Measured    48.59   4.65      28.57 18.24______________________________________ 
    
     Mass spectrum (m/z): 160 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 7.22 (1H, dd, J=8.5, 7.0 Hz), 7.48 (1H, dd, J=9.0, 7.0 Hz), 7.71 (1H, d, J=9 Hz), 7.84 (1H, d, J=8.5 Hz), 9.47 (1H,s), 10.04 (4H, brs) 
     In the same manner as in Example 1, compounds of the following Examples 2-7 were obtained. 
     Example 2 
     End product: 5-Nitro-2H-indazole-2-carboxamidine hydrochloride 
     Starting compound: 5-Nitroindazole 
     Physico-chemical properties: 
     Melting point: 193° to 196° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.8 N.sub.5 O.sub.2 Cl):     C (%) H (%)     N (%)   C %)______________________________________Theoretical 39.77   3.34      28.98 14.67Measured    39.45   3.32      29.25 14.86______________________________________ 
    
     Mass spectrum (m/z): 205 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 7.87-8.23 (2H, m), 9.06-9.09 (1H, s), 10.26 (4H, brs) 
     Example 3 
     End product: 6-Nitro-2H-indazole-2-carboxamidine hydrochloride 
     Starting Compound: 6-Nitroindazole 
     Physico-chemical properties: 
     Melting point: 173° to 175° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.8 N.sub.5 O.sub.2 Cl.0.3H.sub.2O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 38.90   3.51      28.35 14.35Measured    39.01   3.56      28.24 14.17______________________________________ 
    
     Mass spectrum (m/z): 205 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 7.90 (1H, d, J=9.5 Hz), 8.19 (1H, d, J=9.5 Hz), 8.67 (1H, s), 9.66 (1H, s), 10.30 (4H, brs) 
     Example 4 
     End product: 7-Nitro-2H-indazole-2-carboxamidine hydrochloride 
     Starting compound: 7-Nitroindazole 
     Physico-chemical properties: 
     Melting point: 230° to 233° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.8 N.sub.5 O.sub.2 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 39.77   3.34      28.98 14.67Measured    39.67   3.22      28.98 14.56______________________________________ 
    
     Mass spectrum (m/z): 205 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 7.35-7.54 (1H, m), 8.38-8.59 (2H, m), 9.76 (1, s), 10.21 (4H, brs) 
     Example 5 
     End product: 5-Hydroxy-2H-indazole-2-carboxamidine hydrochloride 
     Starting compound: 5-Hydroxyindazole 
     Physico-chemical properties: 
     Melting point: 188° to 191° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.9 N.sub.4 OCl.1H.sub.2 O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 41.34   4.86      24.10 15.25Measured    41.21   4.74      24.22 15.31______________________________________ 
    
     Mass spectrum (m/z): 176 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 6.87 (1H, d, J=2 Hz), 7.14 (1H, dd, J=2, 9.5 Hz), 7.59(1H, d, J=9.5 Hz), 9.08 (1H, d, J=1 Hz), 9.86 (5H, brs) 
     Example 6 
     End product: 6-Hydroxy-2H-indazole-2-carboxamidine hydrochloride 
     Starting compound: 6-Hydroxyindazole 
     Physico-chemical properties: 
     Melting point: 187° to 188° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.9 N.sub.4 OCl.3H.sub.2 O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 40.71   4.95      23.73 15.02Measured    40.57   4.65      23.98 14.61______________________________________ 
    
     Mass spectrum (m/z): 176 [(M-HCl) +  ] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 6.83 (1H, s), 6.90 (1H, d, J=9.1 Hz), 7.69 (1H, d, J=9.1 Hz), 9.32 (1H, s), 9.82 (4H, br), 10.43 (1H, br) 
     Example 7 
     End product: 7-Sulfamoyl-2H-indazole-2-carboxamidine hydrochloride 
     Starting compound: 7-Sulfamoylindazole 
     Physico-chemical properties: 
     Melting point: 208° to 209° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.10 N.sub.4 O.sub.2 SCl.2H.sub.2O):  C (%) H (%)     N (%)   S (%)   Cl (%)______________________________________Theoretical    34.40   3.75      25.07 11.48   12.69Measured 34.49   3.70      24.73 11.11   12.89______________________________________ 
    
     Mass spectrum (m/z): 240 [(MH-Cl)+] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 7.32 (1H, dd, J=8.6, 7.1 Hz), 7.55 (2H, brs), 7.90 (1H, dd, J=7.1, 0.9 Hz), 8.13 (1H, dd, J=8.6, 0.9 Hz), 9.65 (1 H,s), 10.20 (4H, br) 
     Example 8 
     One g of 10% palladium-carbon was added to a solution of 4.85 g of 5-nitro-2H-indazole-2-carboxamidine hydrochloride and 100 ml of methanol, with cooling with ice, and this was stirred in hydrogen atmosphere of normal pressure at the same temperature for 20 minutes. The reaction solution was filtered to remove the insoluble substances therefrom, and the solution was distilled under reduced pressure. 
     The residue was dissolved in methanol-ether, and 4N hydrogen chloride-1,4-dioxane solution was added thereto. The precipitated crystals were removed by filtration and recrystallized from methanol-ether to obtain 1.90 g of 5-amino-2H-indazole-2-carboxamidine dihydrochloride. 
     Physico-chemical properties: 
     Melting point: 177° to 178° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.11 N.sub.5 Cl.sub.2.0.7H.sub.2 O)    C (%)       H (%)   N (%)______________________________________Theoretical      36.85         4.79    26.86Measured   36.66         4.56    26.90______________________________________ 
    
     Mass spectrum (m/z): 176 [(M-2HCl)+] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 5.80 (H, br), 7.38(1H, d, J=9.5 Hz), 7.65 (1H, s), 7.80 (1H, d, J=9.5 Hz), 9.39 (1H, s), 10.00 (4H, br) 
     In the same manner as in Example 8, compounds of the following Examples 9 and 10 were obtained. 
     Example 9 
     End product: 6-Amino-2H-indazole-2-carboxamidine dihydrochloride 
     Starting compound: 6-Nitro-2H-indazole-2-carboxamidine hydrochloride 
     Physico-chemical properties: 
     Melting point: 189° to 191° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.11 N.sub.5 Cl.sub.2.0.3H.sub.2 O):    C (%)       H (%)   N (%)______________________________________Theoretical      37.90         4.61    27.62Measured   38.14         4.36    27.81______________________________________ 
    
     Mass spectrum (m/z): 176 [(M-2HCl)+] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 6.96 (1H, d, J=9.3 Hz), 7.08 (1H, s), 7.75 (1H, d, J=9.3 Hz), 7.95 (3H, brs), 9.34 (1H, s), 9.85 (4H, brs) 
     Example 10 
     End product: 7-Amino-2H-indazole-2-carboxamidine dihydrochloride 
     Starting compound: 7-Nitro-2H-indazole-2-carboxamidine hydrochloride 
     Physico-chemical properties: 
     Melting point: 195° to 198° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.11 N.sub.5 Cl.sub.2.0.4H.sub.2 O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 37.63   4.66      27.43 27.77Measured    37.71   4.83      27.42 27.62______________________________________ 
    
     Mass spectrum (m/z): 176 [(MH-2HCl)+] 
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 6.66-7.34 (3H, m), 7.68 (3H, brs), 9.34 (1H, s), 9.96 (4H, brs) 
     
         ______________________________________Example No.      Chemical Structural Formula______________________________________       ##STR21##2       ##STR22##3       ##STR23##4       ##STR24##5       ##STR25##6       ##STR26##7       ##STR27##8       ##STR28##9       ##STR29##10       ##STR30##______________________________________ 
    
     Example 11 
     A solution of 2.06 g of 3-propyl-2,4-pentanedione in 10 ml of methanol was added little by little to a solution of 1.56 g of aminoguanidine hydrochloride in 5 ml of water, 30 ml of methanol and 1 ml of concentrated hydrochloric acid, and stirred overnight at room temperature. The solvents were removed by distillation under reduced pressure, and the residue was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) and then recrystallized from ethanol-ether to obtain 1.70 g of 3,5-dimethyl-4-propyl-1H-pyrazole-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 204° to 206° C. 
     Mass: 180 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.17 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 49.88   7.91      25.85 16.36Measured    49.88   7.92      25.97 16.26______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.88 (3H, t, J=7 Hz), 1.25-1.65 (2 H, m), 2.20 (3H, s), 2.26-2.49 (2H, m), 2.45 (3H, s), 9.30 (4H, brs) 
     In the same manner as in Example 11, compounds of the following Examples 12 to 34 were obtained. 
     Example 12 
     End product: 4-Butyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-Butyl-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 193° to 197° C. 
     Mass: 194 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.19 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 52.05   8.30      24.28 15.36Measured    51.88   8.31      24.29 15.55______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.80-1.00 (3H, m), 1.17-1.60 (4H, m), 2.20 (3H, s), 2.28-2.49 (2H, m), 2.45 (3H, s), 9.31 (4H, brs) 
     Example 13 
     End product: 3,5-Dimethyl-4-(2-methylpropyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-Isobutyl-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 212° to 214° C. 
     Mass: 194 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.19 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 52.05   8.30      24.28 15.36Measured    51.91   8.24      24.30 15.21______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.87 (6H, d, J=6.6 Hz), 1.50-1.85 (1H, m), 2.19 (3H, s), 2.24 (2H, d, J=8.6 Hz), 2.43 (3H, s), 9.26 (4H, brs) 
     Example 14 
     End product: 3,5-Dimethyl-4-pentyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-Pentyl-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 184° to 186° C. 
     Mass: 208 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.21 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 53.98   8.65      22.89 14.48Measured    53.82   8.45      22.91 14.37______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.79-0.93 (3H, m), 1.15-1.60 (6H, m), 2.20 (3H, s), 2.28-2.48 (2H, m), 2.43 (3H, s), 9.26 (4H, brs) 
     Example 15 
     End product: 4-Benzyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-Benzyl-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 191° to 195° C. 
     Mass: 228 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.13 H.sub.17 N.sub.4 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 58.98   6.47      21.16 13.39Measured    58.84   6.44      21.21 13.48______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.11 (3H, s), 2.50 (3H, s), 3.79 (2H, s), 7.14-7.31 (5H, m), 9.31 (4H, brs) 
     Example 16 
     End product: 3,5-Dimethyl-4-(3-oxobutyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-Acetyl-2,6-heptanedione 
     Physico-chemical properties: 
     Melting point: 151° to 154° C. 
     Mass: 208 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.17 N.sub.4 OCl.0.4 = 3H.sub.2 O):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      48.02   7.09       22.40 14.17Measured   47.87   7.16       22.58 14.33______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.08 (3H, s), 2.21 (3H, s), 2.43 (3H, s), 2.43 (3H, s), 2.48-2.69 (4H, m), 9.23 (4H, brs) 
     Example 17 
     End product: Methyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-propionate hydrochloride 
     Starting compound: Methyl 4-acetyl-5-oxohexanoate 
     Physico-chemical properties: 
     Melting point: 145° to 147° C. 
     Mass: 224 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.17 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      46.07   6.57       21.49 13.60Measured   45.88   6.53       21.51 13.72______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.22 (3H, s), 2.43 (3H, s), 2.44-2.77 (4H, m), 3.59 (3H, s), 9.25 (4H, brs) 
     Example 18 
     End product: 3-Methyl-4,5,6,7-tetrahydro-1H-indazole-1-carboxamidine hydrochloride 
     Starting compound: 2-Acetylcyclohexanone 
     Physico-chemical properties: 
     Melting point: 226° to 228° C. 
     Mass: 178 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.15 N.sub.4 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      50.35   7.04       26.10 16.51Measured   50.27   7.14       26.06 16.29______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 1.67-1.74 (4H, m), 2.18 (3H, s), 2.37-2.42 (2H, m), 2.88-2.91 (2H, m), 9.16 (4H, brs) 
     Example 19 
     End product: Methyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylate hydrochloride 
     Starting compound: Methyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 193° to 196° C. 
     Mass: 196 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.13 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      41.30   5.63       24.08 15.24Measured   40.90   5.57       24.07 15.16______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.40 (3H, s), 2.72 (3H, s), 3.82 (3H, s), 9.77 (4H, brs) 
     Example 20 
     End product: Methyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-acetate hydrochloride 
     Starting compound: Methyl 3-acetyl-4-oxopentanoate 
     Physico-chemical properties: 
     Melting point: 185° to 187° C. 
     Mass: 210 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.15 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      43.82   6.13       22.71 14.37Measured   43.75   6.05       22.80 14.11______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.18 (3H, s), 2.44 (3H, s), 3.57 (2H, s), 3.63 (3H, s), 9.35 (4H, brs) 
     Example 21 
     End product: 3,5-Dimethyl-4-(4-nitrobenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(4-Nitrobenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 185° to 188° C. 
     Mass: 273 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.13 H.sub.16 N.sub.5 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      50.41   5.21       22.61 11.45Measured   50.07   4.86       22.70 11.45______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.12 (3H, s), 2.51 (3H, s), 3.98 (2H, s), 7.44 (2H, d, J=8.5 Hz), 8.18 (2H, d, J=8.5 Hz), 9.32 (4H, brs) 
     Example 22 
     End product: 3,5-Dimethyl-4-(4-methoxybenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(4-Methoxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 192° to 194° C. 
     Mass: 258 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.14 H.sub.19 N.sub.4 OCl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      57.04   6.50       19.01 12.03Measured   56.80   6.48       19.02 12.02______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.10 (3H, s), 2.48 (3H, s), 3.71 (5H, s), 6.78-7.12 (4H, m), 9.24 (4H, brs) 
     Example 23 
     End product: Ethyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylate hydrochloride 
     Starting compound: Ethyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 174° to 176° C. 
     Mass: 210 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.15 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      43.82   6.13       22.71 14.37Measured   43.79   6.06       22.87 14.50______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 1.31 (3H, t, J=7 Hz), 2.40 (3H, s), 2.72 (3H, s), 4.28 (2H, q, J=7 Hz), 9.74 (4H, brs) 
     Example 24 
     End product: Propyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylate hydrochloride 
     Starting Compound: Propyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 146° to 148° C. 
     Mass: 224 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.17 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      46.07   6.57       21.49 13.60Measured   45.83   6.85       21.59 13.55______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.97 (3H, t, J=7 Hz), 1.69-1.73 (2H, m), 2.40 (3H, s), 2.72 (3H, s), 4.20 (2H, t, J=6.5 Hz), 9.78 (4H, brs) 
     Example 25 
     End product: Butyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylate hydrochloride 
     Starting compound: Butyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 138° to 140° C. 
     Mass: 238 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.19 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      48.09   6.97       20.39 12.90Measured   47.91   6.95       20.41 12.92______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 0.93 (3H, t, J=7 Hz), 1.37-1.45 (2H, m), 1.65-1.70 (2H, m), 2.40 (3H, s), 2.70 (3H, s), 4.24 (2H, t, J=6.5 Hz), 9.69 (4H, brs) 
     Example 26 
     End product: Benzyl 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylate hydrochloride 
     Starting compound: Benzyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 160° to 162° C. 
     Mass: 272 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.14 H.sub.17 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      54.46   5.55       18.15 11.48Measured   54.30   5.45       18.28 11.43______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.39 (3H, s), 2.71 (3H,s), 5.32 (2H, s), 7.35-7.47 (5H, m), 9.76 (4H, brs) 
     Example 27 
     End product: 3,5-Dimethyl-4-(3,4-methylenedioxybenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(3,4-Methylenedioxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 181° to 183° C. 
     Mass: 272 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.14 H.sub.17 N.sub.4 O.sub.2 Cl.0.1H.sub.2O):    C (%)      H (%)   Cl (%)______________________________________Theoretical      54.14        5.58    18.04Measured   53.99        5.57    17.76______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.11 (3H, s), 2.46 (3H, s), 3.69 (2H, s), 5.96 (2H, s), 6.61-6.83 (3H, m), 9.11 (4H, brs) 
     Example 28 
     End product: 4-(4-Benzyloxybenzyl)-3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(4-benzyloxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 197° to 199° C. 
     Mass: 334 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard: δ: 2.10 (3H, s), 2.47 (3H, s), 3.71 (2H, s), 5.06 (2H, s), 6.93 (2H, d, J=8.5 Hz), 7.06 (H, d, J=8.5 Hz), 7.30-7.43 (5H, m), 9.17 (4H, brs) 
     Example 29 
     End product: 3,5-Dimethyl-4-(4-methoxycarbonylbenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(4-Methoxycarbonylbenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 183° to 185° C. 
     Mass: 286 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.15 H.sub.19 N.sub.4 O.sub.2 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      55.81   5.93       17.36 10.98Measured   55.71   5.86       17.44 11.00______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.10 (3H, s), 2.50 (3H, s), 3.83 (3H, s), 3.89 (2H, s), 7.31 (2H, d, J=8 Hz), 7.89 (2H, d, J=8 Hz), 9.32 (4H, brs) 
     Example 30 
     End product: 3,5-Dimethyl-4-(4-hydroxybenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(4-Hydroxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 191° to 193° C. 
     Mass: 244 (M-HCl) +   
     Elementary analysis (as C 13  H 17  N 4  OCl): 
     
         ______________________________________Elementary analysis (as C.sub.13 H.sub.17 N.sub.4 OCl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      55.61   6.10       19.96 12.63Measured   55.41   6.11       19.89 12.71______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.09 (3H, s), 2.47 (3H, s), 3.65 (2H,s), 6.68 (2H, d, J=8.3 Hz), 6.93 (2H, d, J=8.3 Hz), 9.25 (4H, brs), 9.29 (1H, s) 
     Example 31 
     End product: 3,5-Dimethyl-4-(3,5-dimethyl-4-hydroxybenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(3,5-Dimethyl-4-hydroxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 195° to 197° C. 
     Mass: 272 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.15 H.sub.21 N.sub.4 OCl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      58.34   6.85       18.14 11.48Measured   58.12   6.82       18.29 11.47______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.09 (3H, s), 2.10 (6H, s), 2.47 (3H, s), 3.59 (2h, S), 6.66 (2H, s), 8.04 (1H, s), 9.24 (4H, brs) 
     Example 32 
     End product: 4- (3,5-Di-tert-butyl-4-hydroxybenzyl) -3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2,4-pentanedione 
     Physico-chemical properties: 
     Melting point: 195° to 197° C. 
     Mass: 356 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.21 H.sub.33 N.sub.4 OCl.0.2H.sub.2 O):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      63.60   8.49       14.13 8.94Measured   63.32   8.38       14.12 9.16______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 1.34 (18H, s), 2.18 (3H, s), 2.49 (3H, s), 3.65 (2H, s), 6.80 (1H, s), 6.90 (2H, s), 9.19 (4H, brs) 
     Example 33 
     End product: 2-Methoxyethyl 1-amidino-3,5-dimethyl-1H-pyrazole-1-carboxylate hydrochloride 
     Starting compound: 2-Methoxyethyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 123° to 125° C. 
     Mass: 241 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.17 N.sub.4 O.sub.3 Cl):    C (%) H (%)      N (%)   Cl (%)______________________________________Theoretical      43.40   6.19       20.25 12.81Measured   43.11   6.06       20.23 13.02______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.40 (3H, s), 2.71 (3H, s), 3.30 (3H, s), 3.64 (2H, t, J=4.6 Hz), 9.71 (4H, brs) 
     Example 34 
     End product: 2-Ethoxyethyl 1-amidino-3,5-dimethyl-1H-pyrazole-1-carboxylate hydrochloride 
     Starting compound: 2-Ethoxyethyl 2-acetylacetoacetate 
     Physico-chemical properties: 
     Melting point: 120° to 122° C. 
     Mass: 255 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 1.12 (3H, t, J=7 Hz), 2.40 (3H, s), 2.72 (3H, s), 3.49 (2H, q, J=7 Hz), 3.67 (2H, t, J=4, 9 Hz), 4.34 (2H, t, J=4.9 Hz), 9.73 (4H, brs) 
     Example 35 
     (1) 1.86 g of aminoguanidine hydrochloride were added to a solution of 3.0 g of triacetylmethane and 30 ml of methanol with cooling at -10° C., and the reaction mixture was stirred for one day with cooling with ice. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) and then recrystallized from ether-chloroform to obtain 484 mg of 4-acetyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine. 
     Physico-chemical properties: 
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.38 (3H, s), 2.42 (3H, s), 2.76 (3H, s), 6.54 (3H, brs) 
     (2) 0.7 ml of 4N-hydrochloric acid-1,4-dioxane solution were dropwise added to a solution of 484 mg of 4-acetyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine in 1 ml of ethanol and 5 ml of ether. The crystals precipitated out were taken out by filtration to obtain 488 mg of 4-acetyl-3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 164° to 166° C. 
     Mass: 180 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.13 N.sub.4 Cl):    C (%)     H (%)   N (%)______________________________________Theoretical      44.35       6.05    25.86Measured   44.30       6.07    25.67______________________________________ 
    
     Example 36 
     2 g of nitronium tetrafluoroborate were added little by little to a suspension of 2.01 g of 3,5-dimethyl-1H-pyrazole-1-carboxamidine nitrate in 150 ml of absolute acetonitrile, with cooling with ice in argon atmosphere, and the reaction mixture was stirred for 30 minutes with cooling with ice. The solvent was removed by distillation under reduced pressure, and the residue was washed with chloroform to obtain 2.43 g of 3,5-dimethyl-4-nitro-1H-pyrazole-1-carboxamidine nitrate. 
     Physico-chemical properties: 
     Mass: 183 (M-HNO 3 ) 
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.51 (3H, s), 2.77 (3H, s), 9.83 (4H, brs) 
     Example 37 
     500 mg of 10% palladium-carbon were added to a solution of 984 mg of 3,5-dimethyl-4-nitro-1H-pyrazole-1-carboxamidine nitrate in 20 ml of methanol, and stirred for 45 minutes in hydrogen atmosphere of normal pressure with cooling with ice. The reaction solution was filtered to remove the insoluble solids therefrom, and the solvent was removed by distillation under reduced pressure. The resulting residue was dissolved in 5 ml of water, 160 mg of sodium hydroxide were added thereto, and the mixture was extracted with chloroform. 
     The organic layer was dried with anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was dissolved in 5 ml of ethanol and 2 ml of 4N-hydrochloric acid-1,4-dioxane solution, and the solvents were removed by distillation under reduced pressure. The resulting residue was recrystallized from ethanol-ether-chloroform to obtain 810 mg of 4-amino-3,5-dimethyl-1H-pyrazole-1-carboxamidine dihydrochloride. 
     Physico-chemical properties: 
     Melting point: 167° to 169° C. 
     Mass: 153 (M-2HCl)+ 
     
         ______________________________________Elementary analysis (as C.sub.6 H.sub.13 N.sub.5 Cl.sub.2.0.5H.sub.2 O):    C (%)     H (%)   N (%)______________________________________Theoretical      30.65       6.00    29.79Measured   30.74       5.97    30.10______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 2.34 (3H, s), 2.62 (3H,s), 9.58 (7H, brs) 
     Example 38 
     In the same manner as in Example 37, the following compound was obtained. 
     End product: 4-(4-Aminobenzyl)-3,5-dimethyl-1H-pyrazole-1-carboxamidine dihydrochloride 
     Starting compound: 3,5-Dimethyl-4-(4-nitrobenzyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Physico-chemical properties: 
     Melting point: 213° to 217° C. 
     Mass: 243 (M-2HCl)+ 
     
         ______________________________________Elementary analysis (as C.sub.13 H.sub.19 N.sub.5 Cl.sub.2.0.2H.sub.2O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 48.82   6.11      21.90 22.17Measured    48.75   6.12      21.66 22.16______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 2.12 (3H, s), 2.50 (3H, s), 3.54 (2H, brs), 3.81 (2H, s), 7.24-7.30 (4H, m), 9.25 (3H, brs), 10.31 (2H, brs) 
     Example 39 
     A solution of 0.17 g of cyanamide in 0.3 ml of water was added to a solution of 0.46 g of 4-(3-chloropropyl)-3,5-dimethyl-1H-pyrazole hydrochloride in 5 ml of ethanol, and the reaction mixture was stirred for one day at 80° C. the solvent was removed by distillation under reduced pressure, and the resulting residue was recrystallized from isopropanol-diisopropylether to obtain 0.13 g of 4-(3-chloropropyl)-3,5-dimethyl-1H-pyrazole-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 183° to 185° C. 
     Mass: 214, 216 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 1.69-2.11 (2H, m), 2.22 (3H, s), 2.44 (3H, s), 2.48-2.60 (2H, m), 3.50-3.11 (2H, m), 9.27 (4H, brs) 
     Example 40 
     In the same manner as in Example 39, the following compound was obtained. 
     End product: 3,5-Dimethyl-4-(3-methoxypropyl)01H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3,5-Dimethyl-4-(3-methoxypropyl)-1H-pyrazole hydrochloride 
     Physico-chemical properties: 
     Melting point: 155° to 157° C. 
     Mass: 211 (MH-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 1.48-1.78 (2H, m), 2.20 (3H, s), 2.33-2.54 (2H, m), 2.42 (3H, s), 3.24 (3N, s), 3.21-3.35 (2H, m), 9.22 (4H, brs) 
     Example 41 
     A catalytic amount of 10% palladium-carbon was added to a solution of 1.74 g of benzyl 1-amidino-3,6-dimethyl-1H-pyrazole-4-carboxylate hydrochloride in 40 ml of methanol, and stirred for 15 minutes in hydrogen atmosphere of normal pressure at room temperature. The reaction solution was filtered to remove the insoluble solids therefrom, and the solvent was removed by distillation under reduced pressure. The resulting residue as recrystallized from ethanol-ether to obtain 1.11 g of 1-amidino-3,5-dimethyl-1H-pyrazole-4-carboxylic acid hydrochloride. 
     Physico-chemical properties: 
     Melting point: 201° to 203° C. 
     Mass: 182 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.7 H.sub.11 N.sub.4 O.sub.2 Cl.0.1H.sub.2O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 38.14   5.12      25.42 16.08Measured    38.05   5.01      25.70 16.35______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 2.39 (3H, s), 2.72 (3H, s), 9.76 (4H, brs) 
     Example 42 
     0.49 g of chloroamidine hydrochloride were added to a solution of 0.82 g of N-butyl-3,5-dimethyl-1H-pyrazole-4-carboxamide in 30 ml of dioxane, and the reaction mixture was heated at 100° C. for 4 hours. After cooling to room temperature, the product was taken out by filtration. The crude crystals thus obtained were recrystallized from ethanol-diethyl ether to obtain 0.54 g of N-butyl-1-amidino-3,5-dimethyl-2H-pyrazole-4-carboxamide hydrochloride. 
     Physico-chemical properties: 
     Melting point: 182° to 184° C. 
     Mass: 238 (MH-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.20 N.sub.5 OCl.0.1H.sub.2 O):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 47.95   7.39      25.41 12.87Measured    47.93   7.31      25.61 12.98______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 0.91 (3H, t, J=7.3 Hz), 1.30-1.36 (2H, m), 1.45-1.52 (2H, m), 2.31 (3H, s), 2.55 (3H, s), 3.19-3.24 (2H, m), 8.10 (1H, t, J=5.5 Hz), 9.50 (4H, brs) 
     Example 43 
     In the same manner as in Example 42, the following compound was obtained. 
     End product: 3,5-Dimethyl-4-fluoro-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 3,5-Dimethyl-4-fluoro-1H-pyrazole 
     Physico-chemical properties: 
     Melting point: 168° to 169° C. 
     Mass: 157 (MH-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 2.26 (3H, s), 2.47 (3H, d, J=2.4 Hz), 9.42 (4H, brs) 
     Example 44 
     5 ml of pyridine were added to a solution of 0.86 g of 4-amino-3,5-dimethyl-1H-pyrazole-1-carboxamidine dihydrochloride in 20 ml of dimethylformamide with cooling with ice, and successively 0.5 ml of valeryl chloride were dropwise added thereto. The reaction mixture was stirred overnight at 4° C., and 2 ml of methanol were added thereto. The solvent was removed by distillation under reduced pressure, and the resulting residue was diluted with 1N-sodium hydroxide and then extracted with chloroform. The organic layer was dried with anhydrous sodium sulfate, and the solvent was reduced by distillation under reduced pressure. 
     The residue thus obtained was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) and was converted into its hydrochloride, which was then recrystallized from ethanol-diethyl ether to obtain 0.53  g of 3,5-dimethyl-4-pentanamido-1H-pyrazole-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 178° to 180° C. 
     Mass: 238 (MH-HCl)+ 
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.20 N.sub.5 OCl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 48.26   7.36      25.58 12.95Measured    48.00   7.27      25.71 13.21______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 0.91 (3H, t, J=7.3 Hz), 1.29-1.38 (2H, m), 1.54-1.61 (2H, m), 2.11 (3H, s), 2.32 (2H, t, J=7.3 Hz), 2.34 (3H, s), 9.31 (4H, brs), 9.52 (1H, s) 
     Example 45 
     In the same manner as in Example 44, the following compound was obtained. 
     End product: 3,5-Dimethyl-4-ethoxycarbonylamino-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: Ethyl chloroformate 
     Physico-chemical properties: 
     Melting point: 193° to 195° C. 
     Mass: 225 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.16 N.sub.5 O.sub.2 Cl):     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 41.30   6.16      26.76 13.55Measured    41.07   6.06      26.75 13.56______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 1.20-1.26 (3H, m), 2.14 (3H, s), 2.36 (3H, s), 4.08-4.13 (2H, m), 8.96 (1H, brs), 9.34 (4H, brs) 
     
                                           TABLE 3__________________________________________________________________________Formula for Examples 11-45 ##STR31##Example No.  R.sup.1     R.sup.2        R.sup.3             Salt__________________________________________________________________________11     CH.sub.3     CH.sub.3        CH.sub.3 (CH.sub.2).sub.2                            HCl12     CH.sub.3     CH.sub.3        CH.sub.3 (CH.sub.2).sub.3                            HCl13     CH.sub.3     CH.sub.3        (CH.sub.3).sub.2 CHCH.sub.2                            HCl14     CH.sub.3     CH.sub.3        CH.sub.3 (CH.sub.2).sub.5                            HCl15     CH.sub.3     CH.sub.3        φ-CH.sub.2      HCl16     CH.sub.3     CH.sub.3         ##STR32##          HCl17     CH.sub.3     CH.sub.3         ##STR33##          HCl18     CH.sub.3     (CH.sub.2).sub.4       HCl19     CH.sub.3     CH.sub. 3         ##STR34##          HCl20     CH.sub.3     CH.sub.3         ##STR35##          HCl21     CH.sub.3     CH.sub.3         ##STR36##          HCl22     CH.sub.3     CH.sub.3         ##STR37##          HCl23     CH.sub.3     CH.sub.3         ##STR38##          HCl24     CH.sub.3     CH.sub.3         ##STR39##          HCl25     CH.sub.3     CH.sub.3         ##STR40##          HCl26     CH.sub.3     CH.sub.3         ##STR41##          HCl27     CH.sub.3     CH.sub.3         ##STR42##          HCl28     CH.sub.3     CH.sub.3         ##STR43##          HCl29     CH.sub.3     CH.sub.3         ##STR44##          HCl30     CH.sub.3     CH.sub.3         ##STR45##          HCl31     CH.sub.3     CH.sub.3         ##STR46##          HCl32     CH.sub.3     CH.sub.3         ##STR47##          HCl33     CH.sub.3     CH.sub.3         ##STR48##          HCl34     CH.sub.3     CH.sub.3         ##STR49##          HCl35     CH.sub.3     CH.sub.3         ##STR50##          HCl36     CH.sub.3     CH.sub.3        NO.sub.2            HNO.sub.337     CH.sub.3     CH.sub.3        NH.sub.2            HCl38     CH.sub.3     CH.sub. 3         ##STR51##          2HCl39     CH.sub.3     CH.sub.3        Cl(CH.sub.2).sub.3  HCl40     CH.sub.3     CH.sub.3        CH.sub.3 O(CH.sub.2).sub.3                            HCl__________________________________________________________________________ 
    
     Example 46 
     A solution of 1.26 g of pivaloylacetonitrile and 1.37 g of aminoguanidine hydrochloride in 15 ml of methanol and 15 ml of acetic acid was heated under reflux for 5 hours. The solvents were removed by distillation under reduced pressure, and the resulting residue was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) and then recrystallized from ethanol-ether to obtain 0.74 g of 5-amino-3-(1,1-dimethylethyl)-1H-pyrazole-1-carboxamidine hydrochloride having the following physico-chemical properties: 
     Melting point: 197° to 201° C. 
     Mass: 181 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.16 N.sub.5 Cl × 0.1H.sub.2O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 43.78   7.44      31.91 16.15Measured    43.71   7.36      32.08 16.31______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 1.22 (H, s), 5.59 (1H, s), 8.79 (4H, br) 
     In the same manner as in Example 46, compounds of the following Examples 47 to 63 were obtained. 
     Example 47 
     End product: 5-Amino-3-(2-phenylethenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: Cinnamoylacetonitrile 
     Physico-chemical properties: 
     Melting point: 209° to 210° C. 
     Mass: 227 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.12 H.sub.14 N.sub.5 Cl)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 54.65   5.35      26.56 13.44Measured    54.56   5.32      26.50 13.24______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 5.99 (1H, s), 6.87-7.68 (7H, m), 9.01 (4H, br) 
     Example 48 
     End product: 5-Amino-3-(2-thienyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 2-Thienoylacetonitrile 
     Physico-chemical properties: 
     Melting point: 179° to 182° C. 
     Mass: 207 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.10 N.sub.5 OClS × 0.4H.sub.2O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 38.29   4.34      27.91 14.13Measured    38.60   4.12      27.65 14.24______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 5.98 (1H, s), 7.09-7.19 (1H, m), 7.54-7.66 (2H, m), 8.95 (4H, br) 
     Example 49 
     End product: 5-Amino-3-(2-furyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: 2-Furoylacetonitrile 
     Physico-chemical properties: 
     Melting point: 187° to 190° C. 
     Mass: 191 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.10 N.sub.5 OCl)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 42.21   4.43      30.76 15.57Measured    41.81   4.39      30.75 15.38______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 5.92 (1H, s), 6.60-6.65 (1H, m), 6.94-6.98 (1H, m), 7.81 (1H, d, J=1 Hz), 9.21 (4H, br) 
     Example 50 
     End product: 5-Amino-3-(2-methyl-3-furyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (2-Methyl-3-furoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 178° to 181° C. 
     Mass: 205 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.9 H.sub.12 N.sub.5 OCl × 0.1H.sub.2O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 44.40   5.05      28.76 14.56Measured    44.44   5.01      28.51 14.26______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.52 (3H, s), 5.85 (1H, s), 6.75 (1H, d, J=2 Hz), 7.57 (1H, d, J=2 Hz), 9.02 (4H, br) 
     Example 51 
     End product: 5-Amino-3-(4-methylphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Methylbenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 178° to 181° C. 
     Mass: 215 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.14 N.sub.5 Cl × 0.2H.sub.2O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 51.75   5.68      27.43 13.89Measured    51.92   5.67      27.03 13.97______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.35 (3H, s), 6.07 (1H, s), 7.27 (2H, d, J=8 Hz), 7.77 (2H, d, J=8 Hz), 8.88 (4H, br) 
     Example 52 
     End product: 5-Amino-3-(3-trifluoromethylphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (3-Trifluoromethylbenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 209° to 212° C. 
     Mass: 269 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.11 N.sub.5 OClS × 0.4H.sub.2O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 43.22   3.63      22.91 18.64Measured    43.02   3.61      22.98 18.42______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.23 (1H, s), 7.61-7.77 (2H, m), 8.13-8.26 (2H, m), 9.17 (4H, br) 
     Example 53 
     End product: 5-Amino-3-(4-trifluoromethylphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Trifluoromethylbenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 189° to 192° C. 
     Mass: 269 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.11 N.sub.5 F.sub.3 Cl)  C (%) H (%)     N (%)   Cl (%)  F (%)______________________________________Theoretical    43.22   3.63      22.91 11.60   18.64Measured 42.91   3.62      23.01 11.53   18.47______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.18 (2H, s), 6.44 (2H, br), 7.83 (2H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5 Hz), 9.29 (4H, brs) 
     Example 54 
     End product: 5-Amino-3-(4-methoxyphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Methoxybenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 184° to 187° C. 
     Mass: 231 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.14 N.sub.5 OCl)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 49.35   5.27      26.16 13.24Measured    49.16   5.35      25.97 13.23______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 3.80 (3H, s), 6.04 (1H, s), 7.01 (2H, d, J=9 Hz), 7.81 (2H, d, J=9 Hz), 9.02 (4H, br) 
     Example 55 
     End product: 5-Amino-3-(4-trifluoromethoxyphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Trifluoromethoxybenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 182° to 185° C. 
     Mass: 285 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.11 N.sub.5 ClF.sub.3 O ×0.4H.sub.2 O)     C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical 40.17   3.62      21.29 10.78Measured    40.36   3.61      21.00 10.62______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.13 (1H, s), 6.43 (2H, brs), 7.46 (2H, d, J=8 Hz), 8.01 (2H, d, J=8 Hz), 9.27 (4H, br) 
     Example 56 
     End product: 5-Amino-3-(4-fluorophenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Fluorobenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 194° to 198° C. 
     Mass: 219 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.11 N.sub.5 ClF × 0.2H.sub.2  C (%) H (%)     N (%)   Cl (%)  F (%)______________________________________Theoretical    46.32   4.43      27.01 13.67   7.33Measured 46.11   4.31      27.09 13.55   7.25______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.09 (1H, s), 7.20-7.40 (2H, m), 7.85-8.02 (2H, m), 9.05 (4H, br) 
     Example 57 
     End product: 5-Amino-3-(3-chlorophenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (3-Chlorobenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 192° to 194° C. 
     Mass: 235 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.16 (1H, s), 6.42 (2H, br), 7.49-7.52 (2H, m), 7.82-7.84 (1H, m), 7.99 (1H, s), 9.25 (4H, br) 
     Example 58 
     End product: 5-Amino-3-(4-chlorophenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Chlorobenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 192° to 195° C. 
     Mass: 235 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.11 (1H, s), 7.53 (2H, d, J=8.5 Hz), 7.91 (2H, d, J=8.5 Hz), 9.21 (4H, br) 
     Example 59 
     End product: 5-Amino-3-(4-nitrophenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (4-Nitrobenzoyl)acetonitrile 
     Physico-chemical properties: Melting point: 205° to 207° C. 
     Mass: 246 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.11 N.sub.6 O.sub.2 Cl)    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      42.49   3.92      29.73 12.54Measured   42.26   3.81      29.84 12.53______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.22 (1H, s), 8.15 (2H, d, J=8.5 Hz), 8.32 (2H, d, J=8.5 Hz), 9.31 4H, br) 
     Example 60 
     End product: 5-Amino-3-(3,4-dimethoxyphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (3,4-Dimethoxybenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 208° to 210° C. 
     Mass: 261 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.12 H.sub.16 N.sub.5 O.sub.2 Cl)    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      48.41   5.42      23.52 11.91Measured   48.34   5.46      23.45 11.86______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 3.80 (3H, s), 3.83 (3H, s), 6.08 (1H, s), 7.02 (1H, d, J=8 Hz), 7.39 (1H, d, J=8 Hz), 7.48 (1H, s), 9.07 (4H, br) 
     Example 61 
     End product: 5-Amino-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (3,4,5-Trimethoxybenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 199° to 202° C. 
     Mass: 291 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 3.68 (3H, s), 3.83 (6H, s), 6.31 (1H, s), 7.22 (2H, s), 7.98 (4H, br) 
     Example 62 
     End product: 5-Amino-3-(3-methylphenyl)-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: (3-Methylbenzoyl)acetonitrile 
     Physico-chemical properties: 
     Melting point: 192° to 194° C. 
     Mass: 215 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.11 H.sub.14 N.sub.5 Cl × 0.2C.sub.2H.sub.6 O)    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      52.47   6.00      26.37 13.35Measured   51.99   5.95      26.29 13.07______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.37 (3H, s), 6.08 (1H, s), 7.24 (1H, d, J=7.3 Hz), 7.33-7.36 (1H, m), 7.66 (1H, d, J=7.8 Hz) 7.71 (1H, s), 9.18 (4H, br) 
     Example 63 
     End product: 5-Amino-3-propyl-1H-pyrazole-1-carboxamidine hydrochloride 
     Starting compound: Butanoylacetonitrile 
     Physico-chemical properties: 
     Melting point: 166° to 167° C. 
     Mass: 167 (M-HCl) +   
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal) δ: 0.91 (3H, t, J=7.3 Hz), 1.54-1.63 (2H, m), 2.43 (2H, t, J=7.5 Hz), 5.54 (1H, s), 6.15 (2H, brs), 8.98 (4H, brs) 
     Example 64 
     0.1 g of 10% palladium-carbon were added to a solution of 0.6 g of 5-amino-3-(2-phenylethenyl)-1H-pyrazole-1-carboxamidine hydrochloride in 40 ml of methanol and stirred for 30 minutes in hydrogen atmosphere of normal pressure at room temperature. The reaction solution was filtered to remove the insoluble solids therefrom, and the solvent was removed by distillation under reduced pressure. The resulting residue was recrystallized from ethanol-ether to obtain 0.38 g of 5-amino-3-(2-phenylethyl)-1H-pyrazole-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 187° to 189° C. 
     Mass: 229 (M-HCl) +   
     
         ______________________________________Elementary analysis (as C.sub.12 H.sub.16 N.sub.5 Cl × 0.2 H.sub.2O)    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      53.51   6.14      26.00 13.16Measured   53.36   6.07      25.95 13.43______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 2.64-3.04 (4H, m), 5.55 (1H, s), 7.09-7.39 (5H, m), 8.88 (4H, br) 
     Example 65 
     A catalytic amount of 10% palladium-carbon was added to a solution of 0.24 g of 5-amino-3-(4-nitrophenyl)-1H-pyrazole-1-carboxamidine hydrochloride in 40 ml of methanol and stirred for 30 minutes in a hydrogen atmosphere of normal pressure at room temperature. The reaction solution was filtered to remove the insoluble solids therefrom, and 0.5 ml of 4N hydrochloric acid-dioxane were added thereto. The solvents were removed by distillation under reduced pressure, and the resulting residue was recrystallized from ethanol-ether to obtain 0.16 g of 5-amino-3- (4-aminophenyl)-1H-pyrazole-1-carboxamidine dihydrochloride. 
     Physico-chemical properties: 
     Melting point: 219° to 222° C. 
     Mass: 217 (MH-2HCl)+ 
     
         ______________________________________Elementary analysis (as C.sub.10 H.sub.14 N.sub.6 Cl.sub.2 ×0.2H.sub.2 O)    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      41.03   4.96      28.71 24.22Measured   41.10   4.91      28.64 24.42______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 , TMS internal standard): δ: 6.06 (1H, s), 7.22 (2H, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz), 9.14 (4H, br) 
     
                       TABLE 4______________________________________Formula for Examples 46-65 ##STR52##                    (Id)Example No.  R.sup.1        Salt______________________________________46           (CH.sub.3).sub.3 C                       HCl47           φ-CHCH     HCl48         ##STR53##     HCl49         ##STR54##     HCl50         ##STR55##     HCl51         ##STR56##     HCl52         ##STR57##     HCl53         ##STR58##     HCl54         ##STR59##     HCl55         ##STR60##     HCl56         ##STR61##     HCl57         ##STR62##     HCl58         ##STR63##     HCl59         ##STR64##     HCl60         ##STR65##     HCl61         ##STR66##     HCl62         ##STR67##     HCl63           CH.sub.3 CH.sub.2 CH.sub.2                       HCl64           φ-(CH.sub.2).sub.2                       HCl65         ##STR68##     2HCl______________________________________ 
    
     Example 66 
     A solution of 3.06 g of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione in 10 ml of methanol was added little by little to a solution of 1.61 g of aminoguanidine hydrochloride in 5 ml of water, 40 ml of methanol and 1 ml of concentrated hydrochloric acid, and stirred overnight at room temperature. 
     The solvents were removed by distillation under reduced pressure, and the resulting residue was purified by silica gel chromatography(eluent: chloroform/methanol=5/1) and then recrystallized from ethanol-ether to obtain 2.66 g of 3,5-bis(trifluoromethyl)-5-hydroxy-2-pyrazoline-1-carboxamidine hydrochloride. 
     Physico-chemical properties: 
     Melting point: 182° to 187° C. 
     
         ______________________________________Elementary analysis (as C.sub.6 H.sub.7 N.sub.4 OF.sub.6 Cl):  C (%) H (%)     N (%)   F (%)   Cl (%)______________________________________Theoretical    23.97   2.35      18.64 37.92   11.79Measured 23.86   2.35      18.88 38.28   11.99______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 4.03 (2H,s), 8.37 (4H,brs), 10.63 (1H,brs) 
     Example 67 
     In the same manner as in Example 66, the following compound of Example 67 was obtained. 
     End product: 5-Hydroxy-3-methyl-5-trifluoromethyl-2-pyrazoline-1-carboximidamide hydrochloride 
     Starting compound: 1,1,1-Trifluoro-2,4 -pentanedione 
     Physico-chemical properties: 
     Melting point: 190° to 196° C. 
     
         ______________________________________Elementary analysis (as C.sub.6 H.sub.10 N.sub.4 OF.sub.3 Cl.0.5H.sub.2O):   C (%)      H (%)   N (%)______________________________________Theoretical     28.29        4.34    21.92Measured  27.94        3.96    21.77______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 2.07 (3H,s), 3.64 (2H, ABq, J=19.5 Hz, 7.94 (4H,br), 9.99 (1H,s) 
     Example 68 
     In the same manner as in Example 66, the following compound of Example 68 was obtained. 
     End product: 1,3a,4,5,6,6a-Hexahydro-6a-hydroxy-3-methyl-(1H)-cyclopentapyrazole-1-carboximidamide hydrochloride 
     Starting compound: 2-Acetylcyclopentanone 
     Physico-chemical properties: 
     Melting point: 155° to 158° C. 
     
         ______________________________________Elementary analysis (as C.sub.8 H.sub.15 N.sub.4 OCl):    C (%) H (%)     N (%)   Cl (%)______________________________________Theoretical      43.94   6.91      25.62 16.21Measured   43.65   6.96      25.66 16.14______________________________________ 
    
     Nuclear magnetic resonance spectrum (DMSO-d 6 .TMS internal standard): δ: 1.28-1.42 (1H,M), 1.73-1.75 (2H, m), 2.01 (3H,s), 2.03-2.13 (2H, m), 2.22-2.26 (1H, m), 3.36-3.39 (1H,m), 7.40-7.90 (5H, m) 
     
                       TABLE 5______________________________________ ##STR69##Example No.    R.sup.1  R.sup.2   R.sup.3   Salt______________________________________66       CF.sub.3 CF.sub.3  H         HCl67       CH.sub.3 CF.sub.3  H         HCl68       CH.sub.3 CH.sub.2CH.sub.2CH.sub.2                               HCl______________________________________