JPS6150977A - Novel condensed benz(thio)amide, preparation thereof and pharmaceutical containing same as active constituent - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R<1> is expressed by formula II or III(R<5> and R<6> are H, halogen, alkyl, etc.), alkyl, etc.; R<2> is H or alkyl; R<3> is H, halogen, OH, NO2, COOR<7> (R<7> is R<2>), alkyl, etc.; R<4> is COOR<8>, CH2COOR<8> (R<8> is R<2>), 2-tetrazol yl, etc.; A is single bond, methylene, ethylene, etc.; formula IV is formula V, VI, etc.; T is O or S] or a salt thereof. EXAMPLE:8-(p-Pentylbenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. USE:A leukotriene antagonistic agent and phospholipase inhibitor having 5alpha-reductase inhibitory action and aldose reductase inhibitory action. PREPARATION:A compound expressed by formula VII or the corresponding dithioic acid thereof is reacted with a compound expressed by formula VIII to form amide bonds, and the resultant compound is then saponified and esterified if necessary to afford the aimed compound expressed by formula I.

Description

[Detailed description of the invention]

[Industrial Application] The present invention relates to a novel condensed benz(thio)amide. More specifically, the present invention relates to novel condensation/z(thio)amides having an antagonistic effect on leukotrienes, methods for their production, and pharmaceuticals containing them as active ingredients. [Prior art] Prostaglandin (Prostaglanaxn,
Hereinafter abbreviated as vessel. ) Several important discoveries have been made one after another in the last few years in the field of research. Therefore, there have been major changes in the flow of PC research and development in recent years. Newly discovered or newly determined P
Among the G7 ami-IJ-, the PG endoperoxides PGG2 and PGH2) and thromboxa:/A2(
Thrombcy-X&ne A2, hereinafter abbreviated as TXA 2. ), prostacylin
clin, i.e. P(1,I2) and leukotrienes C, D and E (hereinafter referred to as LTC, LT, respectively)
Abbreviated as D and LTE. ) etc. are destroyed. In addition to these compounds, all of the well-known PCs, including various PGs, are biosynthesized in the body as a common parent of arachidonic cough, so the metabolism starts with arachidonic acid. The entire pathway is the Arachidonate cascade.
)It is called. Details of each route. For new explanations and pharmacological properties of each product, see History of Medicine, 114,378 (
1980), 114. 462 (1980), 114, 866 (1980)
,same. 114, 929 (1980), Modern Medicine, 12,909
(1980), same, 12.1029 (1980), same,
12. 1065 (1980) and 12.1105 (198
0) etc. Arachidon is a cascade in which 7-chlorooxygenase acts on arachidonic acid to produce PGG 2, then PGH 2, and then various PGs, such as prostaglandin F (hereinafter referred to as P
It is abbreviated as GF2a. ), Bros Tag 2α U/J/E2 (hereinafter abbreviated as PGE2), PG Engineering 2
, TXA2, etc. and the arachidonic acid chain, ribokinogenase acts on the pathway leading to TXA2, etc.
IPET
It is abbreviated as E. )'tuteichii)'Rokinoniikosatetraenoitsukuansobi (hydroxyyaicos
atetraenoic acid 1 or less) (F,T
It is abbreviated as E. ) or one route leading to leukotrienes. Since the path of 'r>S1 is already well known, we will not discuss it in detail here. For details, see Prostaglandin (197B), edited by Shintori et al. It is known that various compounds are produced. Arachito/branches can be metabolized by a well-known pathway, that is, a pathway that passes through PG endo, -Lipoxygenase, 12-IJz Kingenase or 15-Lipoxygenase acts to produce 5
-) (PETE, 12-[(PETE or 15-[
(PETE is produced. These 1 (PE'rE) are converted into 5-HETE, 12-
Can be converted to HETE or 15-HETE. In addition, among these HPETEs, 5-[(PETE is converted to LTA by dehydration. Furthermore, LTA 4 is essentially converted to leukotriene B4 (hereinafter abbreviated as LTB4) or LTC:4. Then, %LTC4 is converted to LTD4 by γ-glutamyl transeptidase. LTD4 is further converted to LT
It has recently been revealed that it is metabolized to E4 [Mi
ochem, Snake1ophys, Res, Cammu
n+, 91.1266r1979) and Prost
aglandxns, Engineering 9(5), 645 (1980
)reference〕. On the other hand, speaking about SR3, SR6 is 5Lovr
It is an abbreviation of Reactinro5uhstance,
This name was used by fiFeldberg et al. for the substance released when cobra venom lung flow or copra venom was incubated with egg yolk. This substance slowly constricts the isolated guinea pig ileum, and its effect lasts for a long time. It has been reported that (J, Physiol + t9
4.187 (1938)]. By sensitizing the lungs of sensitized guinea pigs with the antigen, Ke'lla et al.
ctingSubstance of Anaptly
5RS-A), and demonstrated for the first time a relationship between 5RS-A and allergic reactions (Quant, J.
, Exp , PhysioL , , 30.121
(1940)]. Also Brocklehurst
When the antigen is applied to surgically removed lung sections of bronchial asthma patients for whom the specific antigen is known, histamine and 5.
R3-A is released and strongly contracts the bronchial muscles, and this contraction is not relieved by antihistamines, so 5RS-A is absorbed during asthma attacks.

[Essential bronchoconstrictor (bro)
[Progr-Aller, gy, 6.539
(1962)]. Subsequently, 5R6-A obtained from human lung tissue was able to contract the bronchial muscle rings of normal humans (Int, Arch. Al16r, gy, Appl-Immunol,...
38.217. (1970)], rat 5R3
-When A is injected intravenously into guinea pigs, an increase in pulmonary airway resistance is observed (see J, C11n. Engineering Best, 53, 1679 (1974)).
Injecting 5H3-A into guinea pigs, rats, and monkeys advances vascular permeability (Advances i
nImmunology, 10.105 (1969)
, J, Allerg'/C'*xn, ImmunoL, .
621.371 (1978), P r OS tag
-1andx*s + 19 (5) + 779 (
There are many reports such as 1980). As mentioned above, SRS uses 5R3-A, calcium ionophore (cal
There are two types of substances, SR3 and SR3, which are released without an immune reaction such as treatment (cium 1onophore), but there are many similarities between the two, and it is thought that there is a strong possibility that they are the same substance. It is being Furthermore, it has become clear that LTC4 and LTD4 are the same substances as SRS or 5RS-A, and therefore the pharmacological properties of these leukotrienes can be considered interchangeably with those of SR3 or 5R3-A. Can be done (Proc, Natl, Acad, 5ci-US
A. 76.4275 (1979), Biochem, Bio
phys-Res. Commun-, 91, 1266 (1979), Pro.
c-Natl-Acad. Sci, IJSA, 77.2014 (1980), Na
ture, 285° 104 (1980)]. Based on the results of many studies such as these, various leukotrienes (LTC4, LTD4, LTE4, and leukotrienes whose structures may be determined in the future) that are biosynthesized from arachidonic acid via LTA are currently considered to be allergic. It is considered to be an important factor involved in the development of tracheal and bronchial or pulmonary diseases, allergic inflammation, and various types of allergic inflammation. Therefore, by suppressing these leukotrienes, mammals including humans, allergic tracheal and bronchial diseases such as asthma, etc.
It is effective in the prevention and/or treatment of various allergic diseases. In addition, arachidonic acid is phospholipase (phosph-
However, if we look closely, we can see two routes: (1) phosphatidylcholine (phosphatidyl-ch);
lorxne) and (2) the pathway in which phospholipase A2 acts on phosphatidyl inonthole (phosph
atxdyl 1nositol) and phospholipase C
acts to produce 1,2-diglyceride (1,2-digl
yceride) is completely produced, and furthermore, digLycerideli-pa
se), then monoglycerai bilipase (mon○-
It is generally thought that the pathway in which glyceride lipase acts and is released [Chemistry and Biology, 21.1
54 (1983)]. The liberated aragidoic acid is further processed by two pathways, namely Tll-cyclooxygenase (cyclooxygenase).
asa) metabolic pathway, prostaglandins (pc)
or (2) lipoxy7 genease (li).
pox-ygenase) 2 pathways, 5R5-A
(Slow Reac”, -ing 5ubstan
ces of Anaphylaxis), Hydroxy/
Physiologically active substances such as diicosatetraene d (I (ETE)) and leukotriene B4 (Leukotriene B4); For example, TXA2 is a substance with strong platelet aggregation and vasodilatory effects;
A? Chemical mediators of asthma (chernxca)
LTB4 is a chemical mediator of inflammation such as gout, and PC
is known to be a chemical mediator that has vasodilatory, proinflammatory, exothermic, and leukodemotactic effects in inflammation [Metabolism 20.317 (1983), The
See Lancet 1122 (1982), Prostaglandin (1978) edited by Makoto Katori et al., Kodansha]. In this way, arachidonic acid is engineered and metabolized into chemical mediators that play physiologically important roles in the body, but it is known that diseases are caused by disruption of the 72-lance of these mediators. There is. In addition, as these SR3 antagonists, the general formula [wherein R-R and R are a hydrogen atom, a hydroxyl group, and a carbon number of 1
-6 alkyl group, C1-6 alkoxy/group, ami7 group, anol group, C2-6 anrulamino group, C2-6 alkenyl...rogen atom or phenyl-
(Characterium represents 1-g) alkokino group, X is carbon number 1-10 optionally substituted with hydroxyl group 90
Represents a carbyl group, and the 8 is a atomic atom? represented or absent, Q is carbon, 422-6 optionally branched alkyne, alkenylene or alkynylene M;
is a carboxy group, 5-tetrazolyl, carbamide-5-
Represents a tetrazolyl group. ] A patent application has been filed for a group of compounds represented by the following (see specification of 1973-127384). [Disclosure of the Invention] The present inventors have synthesized a new group of compounds having the structural feature that the 4-benzene ring represented by the following general formula (11) is substituted with (thio)amide'. As described below, we found that these compounds are very useful as leukotriene (SRS) antagonists, and completed the present invention.In addition, the compounds of the present invention inhibit phospholipase and suppress the release of arachidonic acid from phospholipids. Therefore, it is effective in the prevention and/or treatment of diseases caused by aracutonic acid metabolites, such as TXA2, PC, and leukotrienes, in mammals including humans, especially humans. Examples of target diseases Among these are various allergic diseases and thrombosis caused by the above-mentioned Roy and Triene, such as thrombosis caused by damage to the endothelium and intima of the brain and coronary arteries, and inflammation such as arthritis and rheumatism. Circulation Science 3.484 (1983) and Pharmacy 34,167 (
t983)]. Furthermore, the compounds of the present invention include the aforementioned leuco) IJF.
In addition to its uses as an anti-M agent and a phospholipase inhibitor,
The following 5α-reductase inhibitory effect has also been found. 5α-reductase is present in the endoplasmic reticulum and in the anthelium, and converts Testost A7 ingested into the target Ui castle into an active form of 5σ-
This active form of 5α-dihydrotestosterone causes cell proliferation by binding to intracellular receptors, and when this action progresses, it can lead to benign prostatic hyperplasia, alopecia, and fertility problems. It is said to cause the onset of the disease. The compounds of the present invention naturally have hormone-specific effects,
In addition, it inhibits 5α-reductase, suppresses the increase in 5α-dihydrotestosterone, and suppresses cell proliferation, effectively preventing prostatic hypertrophy, alopecia, and prostatic hyperplasia in mammals, including humans, and humans. and/or treatable. Furthermore, the following aldose reductase inhibitory activity has also been found in the compounds of the present invention. Aldose reductase is an enzyme that reduces chelaldose (glucose, galactose, etc.) to the corresponding polyol (sorbitol, galactitol, etc.) in humans and other animals, and the sorbitol and galactitol produced by the action of this enzyme. may accumulate in the ice crystals, peripheral nerves, kidneys, etc. of diabetic patients (including those with galactosemia), resulting in complications such as retinopathy, diabetic cataracts, neuropathy, and kidney damage. is known (Ja
p. J-OpthalmoL, 2nd, 399 (1
976), Int. Cnngr. Ser Excerpta Med-,
403, 594 (1977) and Metabo
ism, 28, 456 (1979)]. The compounds of the present invention, which inhibit aldose reductase, are effective in preventing and/or treating diabetic complications as described above in mammals including humans and humans. That is, the present invention is directed to the general formula R4 [wherein R represents a straight chain or branched alkyl group having 1 to 20 carbon atoms, an alkenyl group, or an alkynyl group]. (In the formula, R5 and R6 are each independently a hydrogen atom, a halogen atom, or any one, two or three
1 carbon atom represents an oxygen atom, a sulfur atom, or an optionally straight or branched alkyl, alkenyl or alkynyl group having 1 to 20 carbon atoms. ) R represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms. R is a hydrogen atom, a halogen atom, a hydroxide group, a nitro group, the general formula -GOOR (wherein R is a hydrogen atom or a carbon number of 1 to 6
represents a straight-chain or branched-chain alkyl group, ) represents a straight-chain or branched-chain alkyl, alkokino or alkylthio group having 1 to 6 carbon atoms. R4 is a group represented by the general formula -GOOR8 or 1082COOR (wherein R represents a hydrogen atom and a linear or branched alkyl group having 1 to 6 carbon atoms), a 2-tetrazolyl group, or a 2-tetrazolyl group; -Represents a tetrazolylmethyl group. The symbol A is a single bond or a straight + A'' having 1 to 1 carbon atoms: ! or a branched alkyl group or a methylene, ethylene, trimethylene, tetramethylene, hnylene, or fluoro which may be substituted with a branched alkyl group. New condensed benz(thio)amides represented by nylene, phthenylene, phthalenylene, ethynylene group symbol T represents an oxygen atom or a sulfur atom, their non-toxic salts, their production methods and their active ingredients. The compound of the present invention may contain a benzene ring and/or a chromone core, but one of the essential requirements is that it has a (thio)amide in the middle part, and is a chemically completely new group of compounds. The compounds of the present invention can be roughly divided into the following three groups of compounds according to the type of ring represented by the symbol B. That is, the compounds of the present invention can be divided into the following three groups of compounds according to the type of ring represented by the symbol B. In other words, the compounds of the present invention have the same meanings as above in the general formula C. This includes compounds represented by the general formula (In Il, the groups R5 and R61 include, for example, the following groups: O hydrogen atom, halogen atom, 0 carbon atoms, 1 to 20 carbon atoms) Alkyl group, alkenyl having 2 to 20 carbon atoms, alkynyl group, charcoal;
4 Alcoquine having 2 to 19 atoms, alkylthio group, -v alkenyloxy having 3 to 171 prime numbers, alkenylthio, alkynyloxy/, alkynylthio group, O alkyl substituted with a halogen atom having 1 to 19 carbon atoms or a water α group Alkenyl substituted with a halogen atom having 2 to 19 carbon atoms or a hydroxyl group; Halogen atom or water [toad ÷4
9-A alkenyloxy, alkenylthio, alkynyloxy/, alkynylthio group' Flukylaminoalkyl having 2 to 19 carbon atoms, alkenyloxyalkyl, alkyloxyalkenyl group 0 carbon number 4 to 70 carbon alkyl (carbocyclic ), chloroalkyl 7, / chloroalkylthio group o phenyl, phenoxy, phenylthio group 0 carbon 4 ~
An alkyl group having 1 to 19 carbon atoms having 7 carbocycles, benzene rings, or thiophene rings in the middle or at the end 1 to 19 carbon atoms having 4 to 7 carbocycles, benzene rings, or thiophene rings in the middle or at the ends ~18 alcoquine, alkylthio, alkenyloxy, alkenylthio, alkynylokyne, alkynylthio group lophenyltheoalcoquine or phenyloxyalkyloxy (alkyl moiety carbon Zff1-17) group Q carbon number 2
~19 carboxyalkyloxy, alkoxycarbonylalgyloxy 7 groups O alkyl group having 2 to I7 carbon atoms, 7 groups O carbon 1sn 3 to 19 alkenylcarbonyloxy groups O
Alkylcarbonyl group having 2 to 20 carbon atoms Food yield: 1~
19 aminoalkyl, nitroalkyl, aminoalkyl, alkyl 7 minoalkyl, dialkylaminoalgyl crystal O azidoalkyloxy having 1 to 18 carbon atoms, nitroalkyloxy 7, aminoalkyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy group 0 Flukenylluponylamino group having 3 to 19 carbon atoms O Flukylamino group having 1 to 19 carbon atoms Among these, preferable groups as R5 and R6 include the groups shown below. O Hydrogen atom O Halogen atom O Straight chain or branched chain alkyl group having 1 to 20 carbon atoms O Straight chain or branched chain alkoxy group having 1 to 19 carbon atoms O Straight chain or branched chain having 3 to 190 carbon atoms Chain alkenyloxy group O Straight or branched fulkylamino group having 3 to 19 carbon atoms Straight or branched alkylthio group having 1 to 19 carbon atoms O Having 1 to 1 carbon atoms substituted with a halogen atom 18 straight chain or branched alkyl group O straight chain or branched chain alkyl group having 1 to 19 carbon atoms 7
Alkyl group O Ncroalkyl having 4 to 7 carbon atoms which may be substituted with a straight chain or branched alkyl group having 1 to 8 carbon atoms, cyfuroalkyl alkyl (the alkyl moiety has 1 to 8 carbon atoms), Ncroalkyl Dictionary (the alkyl part is carbon 7. 1~a'> = % SO Phenyl, phenyl which may be replaced with r:!L in the 1a chain having 1 to 8 carbon atoms or the alkyl group in the branch 11) Alkyl (alkyl moiety has 1 to 8 carbon atoms), phenylalkyloxy (alkyl moiety has 1 to 8 carbon atoms), 7-enylalkenyloxy (alkenyl straight chain or branched chain alkoxy having 1 to 18 carbon atoms), Alkenyloxy, alkoxy 7 Alkoxy group Q Straight or branched alkoxy group with 1 to 17 carbon atoms substituted with phenoxy or phenylthio group O Straight chain with 1 to 18 carbon atoms substituted with thiophene ring A chain or branched alkoxy azide is a nitro group or an alkyl group having 1 to 6 carbon atoms. A straight chain of 1t21 to 18 carbon atoms or a branched neck alkyl, alkenyl, alkoxy or alkenyloxy group 0 Carbonyl group and amine group, a carbon that is left out! Straight chain with A number of 1 to 18 or Branched chain alkyl, alkenyl, alkoxy or alkenyloxy In the basic invention, the alkyl group having 1 to 20 carbon atoms refers to methyl group, ethyl group, propyl group, butyl group, pennal group, hexyl group, heptyl i, octyl group. , nonyl group, decyl group, kundecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octatenyl group, nonadecyl group, eicosyl group, and isomers thereof, and also those having 1 to 1 carbon atoms The 2o alkenyl and alkynyl groups refer to groups corresponding to the above groups.The alkyl groups having 1 to 6 carbon atoms in the present invention include methyl, ethyl, propyl, butyl, pentyl, hexylg
-b- and its isomers. Examples of the halogen atom in the present invention include chlorine, bromine, iodine, and heptadon atoms. Furthermore, in the present invention, "a carbon atom is replaced by another atom, ring, or group" may be any carbon atom as long as it is chemically and physically permissible. For example, an inmethyl group having a benzene ring in the middle or at the end includes one isopropylphenyl, dimethylphenylmethyl, or 2-722ylpropyl group. However, when replacing, hydrogen atoms can be added or subtracted as appropriate. For example, replacing the 2-position of a pentyl group with a nitrogen atom means an N-propylaminomethyl group. [Method for producing the compound of the present invention (1)] The present invention does not only relate to the compound itself, its non-toxic salt, and its use and usage, but also includes a method for producing the compound. According to the present invention, the compound of the present invention represented by the formula (1) has the general formula % () [wherein all symbols have the same meanings as above]. ] and the general formula [wherein all symbols have the same meanings as above. ] React the compound shown to form an amide bond,
It can be obtained by subjecting it to a saponification reaction or an esterification reaction, if necessary. The reaction of forming an amide bond from an acid and an amine is known, and examples include (A) a method using a mixed acid anhydride, (B) a method using an It halide (a method using qDCiG, etc.). To explain the method specifically, the method using fAl mixed plate anhydride involves, for example, treating an acid represented by the general formula (support) with an inert organic solvent (chloroform, methylene chloride,
In the presence of a tertiary amine (pyridine, triethylamine, picoline, etc.) in diethyl ether, THF, etc.) or in the absence of a solvent, acid-lides (pivaloyl chloride 1, thionyl chloride', tonlu chloride, menlu chloride 1, oxalyl chloride, etc.), - or acid derivatives (
ethyl chlorophyll, inbutyl chlorophyll, etc.) and 0℃
The reaction is carried out at ~40°C, and the resulting mixture has the anhydride and the general formula (
This is carried out by reacting the amine represented by M''rc in an inert organic solvent (same as above) at 0°C to 40°C.
n) in an inert organic solvent (same as above),
Alternatively, the reaction is carried out without a solvent at -20°C to reflux temperature, and the obtained halide is reacted with the amine represented by the general formula (IIL) in the presence or absence of a tertiary aban (same as above). and in an inert organic solvent (same as above).It is carried out by reacting at 0°C to 40°C. Amine gold represented by tertiary amine (
%O′C~40 using DCC (dinochlorohequinolcarbodiimide K) in the presence or absence of (same as above)
It is carried out by reacting at °C. child? The reactions of L et al. (Al, (B) and (Q) are preferably carried out under an inert gas (argon, nitrogen, etc.) atmosphere under anhydrous conditions. [Process for producing the compound of the present invention (2)] The present invention Among the compounds, compounds represented by the general formula [wherein R represents a methyleff group or a single bond, and other symbols have the same meanings as above] are represented by the general formula [wherein, all symbols are as defined above]. 2-tetra/1-nor group can be obtained by reacting the compound represented by ] with an azide. Under anhydrous conditions, in an inert organic solvent (dimethylformamide N-methylpyrrolibin, etc.) in the presence of a weak enemy (dimethylformamide, ammonium chloride, dimethylanimonium chloride, etc.), azide (Ajiihina) IJ um, lithium azide,
This is done by heating using a molten metal (e.g. 100g). [Method for producing the compound of the present invention (3)] Among the compounds of the present invention, the general formula: Represents the same meaning. ] The compound represented by the general formula [wherein all symbols have the same meanings as above]. ] and the general formula % formula % () [In each formula, x 3 and The symbol represents the same meaning as above. ] Compound shown by ? It can be obtained by reacting and, if necessary, subjecting it to an esterification reaction or a saponification reaction. The reaction of ring-closing catechol to form a benzodioxane ring is known, for example, in an inert organic solvent (acet/, methyl ethyl keto/, dioxane, etc.) under anhydrous conditions.
This is done by heating in the presence of a rope binder (potassium carbonate, sodium carbonate, etc.). [Method for producing the compound of the present invention (4)] Among the compounds of the present invention represented by the general formula [11],
Specific compounds can be derived from corresponding compounds of the invention. (ILi) Each nico of C represents the entire substituent R, and the symbol therein represents that it is included in each H and is converted by reaction. The same applies to the next process formula VC. R30 represents alkyl, alkenyl or alkynyl having 1 to 18 carbon atoms. ] Each symbol in the reaction scheme CAI of the previous one represents laziness as shown below, and No. 81 in the pond is 6.
Gomi is the same as in Chapter 11. R, E (-alkyl, alkenyl or alkynyl having 1 to 18 carbon atoms; R-hydrogen atom) or alkyl, alkenyl or alkynyl having 1 to 18 carbon atoms; T - oxygen or sulfur atom - or imide group. Ox - halogen source. O N (-linium, potassium or sodium atom. , each can be obtained by the operations shown in the following reaction scheme. Each symbol in the reaction scheme is as follows: represents the taste, and the other symbols have the same meanings as above. R21 - carbon number 1 ~ Straight chain or branched chain alkyl group of 6. R", R", R53, R56-carbon, c21-6
(') [lI 'jJit fc Id-branched alkyl group. R54-hydrogen atom or straight or branched alkyl group having 1 to 6 carbon atoms. R, Ft −) fluoroacetyl group. y, 10. X20. X30. x4 G,, Rogge/Atom. Furthermore, the intermediate of the 1,4-dithianaphthalene skeleton also has the formula (
In addition to compounds of the general formula NO□ [wherein all symbols have the same meanings as above]. lfj obtained by hydrolyzing the compound shown in ], can be obtained by using the compound shown in phantom. In the method for producing the compound of the present invention, the esterification and saponification reactions are carried out as follows. The reaction (esterification) to convert Yoshiwo to ester is “
These reactions are known, and include, for example, (1) a method using a diazoalkane, (2) a method using an alkyllide (31DMF-dialkyl acetal), and (4) a method of reacting with a corresponding alkanol. Specifically, (1) the method using a diazoalkane is carried out using the corresponding diazoalkane in an inert organic solvent (diethyl ether, diethyl acetate, methylene chloride, acetone, methanol, ethanol, etc.). 2) A method using an alkyl halide is, for example, a base (potassium carbonate, sodium carbonate, sulfur hydrogen carbonate, potassium hydrogen carbonate,
Calcium oxide, etc.) using the corresponding alkylhalaibi. +31 Methods using DMF-dialkyl acetals include, for example, the formation of corresponding DMF-dialkyl acetals in inert organic solvents (benzene, toluene, etc.). It is done using (4) The method of reacting with a corresponding alkanol includes, for example, an acid (hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, hydrogen chloride gas, etc.) or a condensing agent (DC
C, pivaloylnolide, arylsulfonyl halide 1, arylsulfonyl halide, etc.). [ The reaction C saponification to convert Kf is known,
For example, +11 water-miscible organic solvents (THF,
(2) Using an aqueous solution of an alkali (potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium charcoal, sodium carbonate, etc.) in an alkanol (methanol, ethanol, etc.) (dioxane, ethanol, methanol, etc.); It is carried out under anhydrous conditions using an alkali. These reactions are usually carried out at temperatures between -10°C and 100°C. High-speed t”1-body chromatography using silicic magnesium,
It can be purified by four-layer chromatography, column chromatography, washing, recrystallization, or other methods. Purification may be performed for each reaction or after completion of several reactions. [Starting Materials] All starting materials and reagents in the present invention are known per se or can be synthesized by known methods. For example, carboxylic acids represented by the general formula tn+ are
It can be synthesized by the method described in the specifications of No. 8-245531, No. 58-245532, No. 59-1855, etc. Compounds represented by general formula (1) in which R is a hydrogen atom, J-Med, Chem-, 8,446 (1965
)It is described in. Compounds represented by the general formula ('XnF) in which R is a hydrogen atom are J, Am-Chem-3oc, ,
5, 3277 (1953) K. α. Compound represented by general formula (Xv) (d J 0Mea
-Cbern-. 20.371 (1977). Among the compounds represented by the one-immersion formula (XX)J), those where R is a hydrogen atom are J, Or, g, Gillem,
p 42+1925 (1977). [Salts of compounds of the present invention 1] The compounds of the present invention represented by the general formula (11) can form salts at the tetrazolyl or carboxylic acid moieties. Since the solubility of the compound of the invention in water increases, it is useful for i-diλ administration as a pharmaceutical. The compound of the invention can be easily converted into a salt by a known method described below. Preferably, a) is toxic. 9. Non-toxic salts are those that are relatively harmless to animal fibers. Moreover, it refers to a salt consisting of a cation such that, when used in the amount necessary for treatment, the effective pharmacological properties of the compound represented by the general formula fil are not due to side effects caused by the cation. Moreover, it is preferable that the salt is water-soluble. Suitable salts include, for example, alkali metal salts such as sodium or potassium, alkaline earth metal salts such as carnoum or magnesium, ammonium salts and pharmaceutically acceptable (non-toxic) amine salts. Carboxylic acids and such salts? Suitable amines to form are well known and include, for example, amines obtained by theoretically replacing one or more hydrogen atoms of ammonia with other groups. When the group is substituted with one or more hydrogen atoms, it may have one or different carbon atoms, for example, 1 to 1 carbon atoms.
6 alkyl group, and a human akyne alkyl group having 81 to 3 carbon atoms. Suitable non-toxic amine salts include tetramethylammonium salts, methylammonium salts, dimethylamine salts,
Nk O/%? Examples include ethylamine salts, ethylamine salts, ethylamine salts, di(lysine salts, monoethanolamine salts, jetanolamine salts, lysine salts, and arginine salts). The salts of the compounds of the present invention can be prepared by preparing the compounds of the present invention having the formula (1) by a known method, for example, by adding a suitable base such as an alkali gold pA or alkaline earth metal aqueous compound or carbonate in a suitable solvent. The salt can be obtained by reacting with a salt or an organic amine.The salt can be obtained by freeze-drying with a solution, knitting under reduced pressure, or filtering the reaction solution with a light insoluble filter, or if necessary, applying RI. 'A single polymer is formed by removing a portion of the solvent and then releasing the compound. [Pharmacological activity of the compound of the present invention] As described above, the compound of the present invention: 12!7 has leukotriene antagonistic activity, phospholipase inhibitory activity, and 5α-reductase activity. The compound of the present invention has inhibitory activity and aldo-1-threductase inhibitory activity, and for example, in a laboratory experiment, the compound of the present invention exhibited the effects shown in the following table. ) showed antagonistic effects as shown in the following table. Table 1: Compounds represented by the following general formula
Antagonism N=N Table 1]: LTD in the compound represented by the following general formula
4 Antagonism Table I [: Comparison of activity by skeleton f conversion (1) Table ■: Comparison of activity by skeleton conversion (2) Table V: Comparison of activity by conversion of alkylene region As is clear from Table I and the table, the present invention Compound home, 1.4-
Compounds represented by the general formulas (IA') and (IA") having a benzodioxane skeleton have sufficient activity to be used as medicines, regardless of whether R in each formula is no or ν. Furthermore, in Tables ■ and ■, the skeleton is changed from 164-benzodioxane to 4-oxo-4H-1-pyra/, 2.3-
It can be seen that sufficient activity is maintained even when converted to dihi)'o-1,4-diteana7riVn. Based on these facts, compounds that have a useful activity as a pharmaceutical even if the basic skeleton t-L, 4-benzodioxane is replaced with 4-oxo-4H-1-benzopyran, or z3-dihydro-1,4-dithianaphthalene. It is fully predicted that this will be obtained. Moreover, these matters can also be applied to Table VK. The antagonistic effect of the compounds of the present invention on LTD was determined by the following experimental method. rR (2,5 cm) t, ryrr > d at 37 °C, extracted from a male guinea pig weighing 300-400 J
・* was suspended in a Magnus tube venting a mixed gas of oxygen (95 parts) and carbon dioxide (5 parts), and after stabilizing for about 30 minutes, LTD was added at 101/go 0 degrees, and the contraction at this time The compound of the present invention was added at different concentrations, the contraction height was measured, and the IC5o (direct) was calculated from this. By suppressing leukotrienes, it is effective for the prevention and/or treatment of allergic tracheal and bronchial diseases, such as asthma, allergic lung diseases, allergic shock, and various allergic diseases. In addition, by inhibiting phospholipase (phospholipase A2 and/or phospholipase C), diseases caused by arachidonic acid metabolites including the above-mentioned leukotrienes, such as thrombosis, and the endothelium of the brain and coronary arteries, etc. It is effective in the prevention and/or treatment of thrombosis caused by membrane damage and various inflammations such as arthritis and rheumatism.Furthermore, IAi inhibition of 5α-reductase is effective in preventing 1itl glandular hypertrophy, alopecia, and locus C. It is also effective in the prevention or treatment of diabetic complications, such as retinopathy, cataracts, neuropathy, and renal damage, by inhibiting aldose metabolites. General formula In order to use the compound of the present invention represented by [1] or a non-toxic salt thereof for the above-mentioned purposes, each compound is usually administered systemically or locally, orally or parenterally. Dosage depends on age, body weight, symptoms, therapeutic effect, administration method,
Although it varies depending on the processing time etc., it is usually 0.1 m9 to 100 cm per adult, preferably 2 cm at a time.
~20μg orally administered once to several times a day, or 10μg~ per adult, each at a time.
10■, preferably in the range of 0.1η to 1rnIi, 1
It is administered parenterally once to several times a day. Of course, as mentioned above, the dosage varies depending on various conditions, so there are cases where it is sufficient to use a smaller amount than the above-mentioned dosage range, and there are also cases where it is necessary to administer the drug above the range. Solid compositions for oral administration according to the present invention include tablets, tablets, pellets, and the like. In such solid compositions, one or more active substances may be present in at least one inert diluent, such as lactose, mannitol, 7' bijuice, hydroquinepropylcellulose, ta-crystalline cellulose, starch% polyvinylpyrrolidone. , mixed with metasilicified magnesium aluminate. The composition may contain additives other than the inert diluent 41, such as stearin, a lubricant such as magnesium, and a disintegrant such as cellulose gulf(9) cal/lam, in accordance with conventional methods. . Tablets or pills may be coated with a film of a gastric or enteric substance such as white gelatin, gelatin, human quinpropyl cellulose, and hibiloquinopropyl methyl cellulose phthalate, if necessary.
The membrane may rupture in two or more layers. In addition, capsules of absorbable substances such as gelatin are also included. Jilt body compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, 70 tablets, eliquin tablets, etc., commonly used inert diluents, In addition to inert diluents, the compositions may also contain adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, aromatic agents, and preservatives. Other compositions for oral administration include sprays containing one or more active substances and formulated in a manner known per se. Injections for parenteral administration according to the present invention include aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of aqueous solutions and suspensions include e.g. Includes distilled water and saline. Examples of water-insoluble solvents and suspending agents include propylene glycol, #? Examples include lyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and phorin rubate 80. This solid composition may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. These can be sterilized, for example, by filtration through bacteria-retaining filters, by incorporation with disinfectants or by irradiation. It is also possible to prepare a pure solid composition and dissolve it in sterile water or a sterile injectable solvent before use. Other compositions for parenteral administration include one or more active substances and can be prepared in a manner known per se (
External liquids, soft-bodied liniments prescribed by Teyoshi,
Includes suppositories and nosaries. [Nomenclature and Excluded Compounds] In Specification H, including the claims, the compound of the present invention is 1,4-penfudioquinano. It is named based on 4H-1-benzopyran or 1,4-dithianaphthalene as the core. Further, in the present invention including the claims, all isomers caused by steric configurations (asymmetric carbons, double bonds, etc.) that cannot be particularly limited are included. However, in the case of non-invention, chemically or physically present chemically or physically-extensive combinations (for example, having multiple antagonistic carbon-charcoal alloys adjacent to oxygen, nitrogen, or sulfur atoms': f) are excluded. Ru. [Reference Examples and Examples] An example of the production of the compound of the present invention will be described in detail in Reference Examples and Examples, but the invention is of course not limited to these. ``TLCJ'', ``IR
J1'-NMRJ and IMassJ stand for "thin layer chromatography", "infrared absorption spectrum", "nuclear magnetic resonance spectrum", and "mass spectrometry", respectively. The proportions of solvents listed in the chromatographic separation section represent volume ratios, and the solvent in parentheses indicates the developing solvent or elution solvent used. Unless otherwise specified, infrared absorption spectra were measured using the KBr tablet method, and nuclear magnetic resonance spectra were measured in a mixed solution of heavy chloroform and heavy ethanol. Reference Example 1 Synthesis of 32(m-methoxy-p-steroxynonnamoyl)aminopyrocatechol
Oxalyl chloride (4,5) was added to q), stirred for 30 minutes in a chamber 1 under an argon atmosphere, and concentrated under reduced pressure. Dissolve the residue in methylene chloride (LOmt)! This was added to a mixed acid solution of 3-aminopyrocatechol (275) in methylene chloride (10 ml) and pyridine (31 nl) under a water-cooled bottom under an argon atmosphere, and stirred at the same temperature for 1 hour. After roughly stirring at room temperature for 2 hours,
The mixture was poured into IN hydrochloric acid and the vinegar was extracted with ether. The extract was washed with water and saturated brine, dried, and concentrated under reduced pressure. The obtained solid was washed with hexane and dried to obtain the title compound (700) having the following physical properties. TLC2R70,20 (ethyl acetate dihexane-1:2
); NMR (CDC43): δ 10.00 (IH, s
), 7.75 (IH, a), 7-60 (IH, s),
6.30-7.25 (71-1゜m), 6.10 (L
H,s), 4.10(2)(,t), 1.90(3H,
s); Tom ss: m/e 37] (M”), 247.17
7.145.125.117.89゜Reference Example 2 Synthesis of 8-(m-methquin-p--67teloquincinnamoyl)amino-1,4-dioxane-2-carbonitrile N 5-(rn-methquin Anhydrous potassium (770In9) was added to a solution of -p-intylox7cinnamoyl)aminopyrocatechol (690mg; synthesized in Reference Example 1) in a7tone (10d). -2-chloroacrylonide'
J Le (0,30rfLt) and argon atmosphere fi
The mixture was heated under reflux for 3 hours. The reaction layer cooled at room temperature was poured into ice water (50d), extracted with ethyl acetate, and the extract was dried and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (methylene chloride: dithyl acetate - 10:1) to obtain the title compound (5) having the following physical properties.
fi5#:lj) was obtained. TLC: 81' 0.15 (self-rubbing ethyl:hegisan = 1:2); NMR (CDC63): δ 8.25 (I
H, da), 7.70 (I H. d), 7.55 (IH, s), 7.00-7.25 (
2)1. m ), 6.90 (LH, a), 6.85 (
IH, a), 6.70 (IH. ad), 6.45 (l) (, d), 5.20 (I H
, zud), 4.30-4.55 (2H, m), 4.05
(2H0t), 3.93 (31-1°3); Mass: m/e 422 (M), 247,1
77.145,117゜Reference 13 Synthesis of 8-(p-benthrunnamoyl)amino-1,4-benzodioxane-2-acetic acid methyl ester 3-(p--?nternunnamoyl)aminopyro and 4 −
Promo-2-zthenic acid methyl ester (820 m?) aceto:y (10 m) was added to the bath solution with potassium carbonate (509 m?).
m! 7) was added and heated under reflux for 10 minutes. 1 part reaction mixture in water! ): Extracted with ethyl vinegar, and the extract was concentrated under reduced pressure. The residue was subjected to phosphor gel column chromatography (hexane:ethyl acetate-5:l).
Fl conversion-? ', a (34xyq) km*. Reference example 4 8-(p--?intercinnamoyl)amino-1,4-
Synthesis of benzodioxane-2-acetic acid α-amibi 8-(p-bentylnonnamoyl)amino-1,4-benzodioxane-2-acetic acid methyl ester (3411n9; Reference Example 3
Synthesized with. ) in ethanol saturated with ammonia (20 m
1) and left at 100°C for 3 days. The reaction mixture was concentrated and distilled with the resulting ethyl acid (2:1) to obtain the title compound 47I (191 mq). Reference Example 5 Synthesis of 8-Co-<7thylnonnamoyl)amino-1,4-infudioxane-2-acetonitrile 8-(p-
Intyl/nonamoyl)amino-1,4-benzodioxa/-2-acetic acid amide (191■; synthesized in Reference Example 4) dissolved in THF (lQm/) tUtK over ice, trifluoro- and p-acid anhydride (0.1m/) , then pyridine (0,
02rrLt) and stirred for 10 minutes,
I was in the water. The mixed acids were extracted with ethyl acetate, and the extract was dried and concentrated under reduced pressure to obtain the title compound. Example 1 Synthesis of 8-(p-(3Z-hexenyloxy)benzoylcoamino-2-(5-tetrazolyl)-L4-benzodioxane p-(3Z-hexenyloxy)benzoic acid (110η)
After stirring the mixture and oxalyl chloride (1d) at room temperature for 1 hour, excess oxalyl chloride was removed under reduced pressure. After drying the residue with a vacuum pump, methylene chloride (2d)
dissolved in. 8-Amino-2-(5-tetrazolyl)-1,4-benzodioxane hydrochloride (12
8111g) of methylene chloride (2g) and pyridine (0,
The above solution was added dropwise to the mixed solution of 7). After the addition, the reaction solution was stirred at room temperature for 5 hours and diluted with vinegar ether. The diluted solution was poured into IN salt rJ, (1 g), drained, dried, and concentrated under reduced pressure. The residue was recrystallized from benzene to obtain the title compound (112 Mg) having the following physical properties. TLC:R,? ' 0.57 (chloroform: methanol = 3:1) NMR: δ 7.90 (2H, a),
7.88 (IH, m), 7.46 (IH, aa'), 6
．． 96(2[(,a), 6.92(LH,t), 6.
78 (IH, aa), 5-77 (IH, aa), 5.7
0(2H,n), 4.61(2H,m), 4-04(
2H,t,), 2.57(2H,at), 2.12(2
H, m), 1.01 (3H, t); IF (: u 3600-2300.1000%1
61Q, 1540.1505°-1°1460.1250.1175.1090.840.7
7αs. M? 1ss: m/a 421()4'), 203: Shape: White powder. Example 1 (11-1 (118)) Similar operation as in JA 111
- Compounds shown in the following table [■] were synthesized using the inosysioxane salt 3 salt. Example 1 (201)-1 (253) By the same operation as in Example 1, the corresponding carboxylic acid and the corresponding (8-amino-2-(5-tetrazolyl)-4-okino 4H having the δ substituent R) were prepared. The compounds shown in the following Table 01 were synthesized using salts of -1-benzopyran. N=N Example 1 (301) -1 (302) By the same operation as Example 1, p- cinnamic acid and 8
-amino-2-(5-tetrazolyl)-2,3-dihydro-1,4-dithianaphthalene hydrochloride jπ or 5-amino-2-(5-tetrazolyl)-2,3-dihydro90-
1. Teni [■] using 4-dithianaphthalene hydrochloride
Two compounds shown in were synthesized. Example 1 (↓01) By the same operation as in Example 1, p-heptel okingbe/
Zoditeonic acid and 8-amino-2-(5-tetrazolyl)
The following compound was synthesized using -1,4-benzodioxane salt. However, thionylchloride) # was used instead of oxalylchloride. TLC: R70,14 (chloroform:methanol-1
7:3); NMR: δ 7.87 (2H, d), 7.
77 (11 (, m), 6.90 (4H, m), 5.74
(IH, m), 4.58 (2B, m), 3.98 (2H
, t), 1.78 (2H, m), 1.30 (8H, m)
, 0.88 (3H, t); Engineering R Niji 3600-240.0.1600.1495
．． 1450.1255.1170.1090,]005
．． 960.830 on. Mass: rrv'e 453 (M), 420
．． 354.326.235.219.137.121; Shape: Orange powder. Example 2 Synthesis of 8-(3-methoxy-4-tinyloquinone/nnnnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane 8-(3-methoxy-4-tinyloquinone/nnnnamoyl) Sodium azide (4) was added to a solution of anhydrous dimethylformamide (3y) of amino-1,4-pe/zodiot-2-carbonitrile (560 da; synthesized in Reference Example 2).
9M) and viridinicum chloride (8701ff9) were added, and the mixture was stirred at 100° C. for 1.5 hours under an argon atmosphere. IN salt the reaction solution cooled to room temperature! 2, and extracted with acetic acid. The extract was washed with water and saturated brine, dried, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to obtain a compound (3901719) with the following physical properties of 11.
) I got k. TLC: Rf O, 10 (chloroform:methanol-
5:1); NIJR: δ 7.69 (LH, d), 7.
68 (IH, s), 7.05-7.25 (2H, m),
6.80-7-00 (2H, m), 6.74 (LH, m
), 6.65 (IH, d), 5.73 (IH, m), 4
．． 69 (IH, aa), 4.51 (LH, dd),
4.05 (2H, t), 3.92 (3H, s), 1.8
7 (2H, m), 1.30-1.55 (4H, m) 0.
94 (3H, t); IR:L+ 2940, 2850% 1655.16o
o, 1540゜1505.1450.1260^-1''
Mass: IrI/e 465 (M”), 247.17
7.145°] 1112fll-2<4G g4 By the same procedure as in Example 1.2 and Example 2, using the corresponding carboxy7 acid and 3-aminopyrocater;
The compound shown in the following table (CC) was synthesized. Example 2 rlO1) -2 (108) The same procedure as in Reference Examples 1 and 2 and Example 2 was carried out (by using the corresponding carboxylic acid and the corresponding Iit substituent R , R were used to synthesize the compounds shown in the following table (X). ~=N Example 2 (201) -2 (204) Reference Example 1.2
Follow the same procedure as in Example 2. The first compound was synthesized using 3-7 minopyrocatechol with a carbo/yoshi corresponding to j6 and a corresponding IJ1 convex Ri. p TLC: Rf O, 2N chloroform: methanol =
3:1); NMR: δ 8.03 (LH, a), 7.7
0 (IH, a), 7.48 (2H, d), 720 (2H
, a), 6.71(1)I. d), 6.65 (lH, d), 5.57 (IL a
), 4.70-4.40<2H,m), 2.62(2H
, t); Engineering R Niji 3700-3000.1680.1
625.161α1535, 1470.1440 engineering. Mass: o/e201.179.162; Shape:
White powder. (However, it is a single substance.) TLC: R7 (122 (methylene chloride: methanol-5
:L); NMR: δ 8.21 (LH, a), 7.7
4 (IH, d), 7.57 (IH. d), 7.49 (2H, d), 7.20 (2H, a
), 6.62 (IH,,i), 5.74 (IH, da
), 4-89 (LH. aa), 4.54 (IH, dd); T-R:v 3370.3200-2300.1
695.1630.16]0.1520.1430.1
270.1140-1. (m. Mass: m/e 477 (M), 291.2o
1; Shape: White crystal. a Less polar compound: TLC: Rf O, 18 (methylene chloride: methanol-
5:1); NMR (CDCI 3): δ 9.88 (LH, g), 7.81 (LH, a), 7
．． 45 (3H, s), 7.18 (2H, g), 6.69
(LH,s), 6.64 (LH,d), 6.04
(LH,s), 5.60(IH,s), 4.50(L
H, s), 3.84 (3H, 8) 0.88 (3H, t)
; Engineering R Niji 3600-230α] 695.163 generation 1610.1515% 1470.128〇2. )-(ass 2m/q 477(M), 44
6, 291, 201; Shape: White crystal. o More polar compound: TLC: R7' 0.12 (methylene chloride: methanol - 5:1); NMR (CDC13'): δ 9.44 (IH, s), 7.46 (IH, s), 7
．． 25 (IH,s), 7.13 (2H0s), 6.88
(2La), 6.60-6.30 (2H, g), 5.2
0 (LH, s), 4.20-3.60 (2H, s), 3
．． 72 (3H, Sun) 0.83 (3H, t); Engineering R Niji 3600-3000.1695.1630
-161st generation 1520% 1480.1280 cm. tJass:co/e 477(M), 446.2
91.201: Shape: White crystal Example 2 (301) By the same operation as in Example 2, s-< p-, -! 7-thinnnamoyl)amino-1,4-benzodioxane-
The following compound was synthesized using 2-acetonitrile (synthesized in Reference Example 5). TLC: Rf O, 36 (methylene chloride: methanol-
5:1); NMR: δ 7.88 (IH, a), 7.
70 (IH, a), 7.47 (2H, a), 7.20 (
2H, a), 6.84 (LH, t), 6.63 (IH,
aa), 6.57 (LH, a), 3.36 (2H, a)
;IR:L/ 3300.3200-2300.1
660.1605°1530.1460α. Mass: m/e 433 (M”l, 233.201
;Shape 2: Colorful powder. Example 3 Synthesis of 8-(p--?Nchirunnnamoyl)amino-4-oxo-4H-1-/zopyran-2-carboxylic acid ethyl ester Oxalyl chloride (3,4) 1r: was added, and after stirring at room temperature for 30 minutes, excess oxalyl chloride 1 was removed under reduced pressure. The residue was dissolved in methylene chloride (5d) and added with methylene chloride (5 ml) at 0°C under an argon atmosphere.
8-amino-4-oxo-4H-1-pensohyran-2 dissolved in a mixed solvent of and triethylamine (o,6go)
-Carboxylic acid ethyl ester C420m9) f! :Yukkushi added. After the reaction was stirred at room temperature for 1 hour, 0. IN salt ffK was poured into the mixture and extracted with ethyl acetate. The extract was washed successively with water, saturated aqueous sodium bicarbonate solution, and saturated brine, dried, and concentrated under reduced pressure. The residue was purified by gel column chromatography (ethyl acetate:hexane-1
:3) and has the following physical properties: the title compound (
140ffl'/)'i-obtained. TLC: R7' 0.60 (ethyl acetate:hexano-
1:1): NMR (CDC13): δ 8.76 (1
, aa), 8.23 (IH, B), 7.72 (IH, a
a), 7.65 (IH, d), 7.38 (2H, a),
7.27 (IH, t), 7.07 (2H, a), 7.0
0 (IL8), 6.52 (LH, a); IR Niji 327th generation 2930% 173rd generation 1660, 16
3rd generation 1530, 143rd generation 1290.1260.118 to 770α. Mass: m/e 433 (M”), 404.3B&
376.36th generation 31 & 23 pieces 201.131; Shape: White e-end. Synthesis of Oxo-4H-1-benzopyran-2-carboxylic acid (produced in Example 3) to ethanol (
1011t7) K, dissolve sodium bicarbonate (126
Aqueous solution of 1(lIII/)t7] (1, mg) was heated under reflux for 15 minutes. After cooling the reaction solution to room temperature, water (20g) and IN hydrochloric acid (2rIII) were added, and the vinegar was extracted with ether. The extract was washed with water and saturated water, dried,
It was concentrated under reduced pressure. The residue was dissolved in ethyl acetate-hexane (1:
It was washed with the mixed solvent of 1) and dried to obtain the title compound (62m9) having the following physical properties. TLC: Rf O, 25 (ethyl acetate:methanol-5
:1); NMR: δ 8.66 (LH, aa), 7.8
6 (IH, aa), 7.73 (IH, i), 7.53 (
2H, a), 7.43 (LH, t), 7.22 (2B,
a), 7.15 (LH, s), 7.08 (IHI); I
R (KBr) Niji 3400.2930.1635.1
520°143α1360C! rL. Mass: m/e 405 (M), 361.201
．． 181.1691.131.69; Shape: Yellow powder. The compounds shown in the following table (XI) were synthesized using 8-amino-4-okino 4H-1-benzopyra/-2-carboxylic acid ethyl ester having a substituent R3fc corresponding to the carboxylic acid. ooH (]q) Example 4 (101)-4 (104) By the same operation as in Examples 3 and 4, the corresponding carbo/relative and 8-amino-1,4-benzodioxane-2-carbobo ether ester Using this, the compounds shown in the following table [■] were synthesized. Example 5 Synthesis of 8-(3-(p-inchyl7ninyl)p-a-pionyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane 8-(p--'?inchylcinnamoyl )amino-2-(
5-tetrazolyl)-1,4-benzodioxane<21
6m9; synthesized in Practical Example 2 (1)) and Balazicum carbon (50m9; containing 5%) were suspended in a mixed solvent (6d) of methanol-ethanol-ethyl acetate (1:1:1) and placed in a hydrogen atmosphere. The mixture was stirred at room temperature for 90 minutes. After stirring, filter through a seven-light filter, and reduce the filtrate to QmL under reduced pressure.
The residue was purified by silica gel column chromatography (metele chloride/:methanol=19:1) to obtain the title compound 202m9 having the following physical properties. TLC: R70,54 (methylene chloride: methanol-4
: 1); NMR (CDCi3) : δ 7.28 (IH
, g), 7.11 (4H. 2d), 6.76 (2H, m), 6.60 (IH. aa), 5.68 (LH, t), 4.93 (ILaa)
, 3.04 (2H, t), '2.77 (2H, m) 2.
56 (2H, t), 1.58 (2H, m), 1.30 (
4H, m), 0.88 (3H, t'); Engineering R: υ 3
600-2300, 165th generation 1615.153α146
a%1260SIIQo%780 crr*. Mass: m/e 421 (M), 219:
Shape: White crystal. Example 6 Synthesis of 8-(p-(6-human 10ki15quineluoquino)benzoylcoamino-2-(5-tetrazolyl)-1,4-benzodioxane 8-(p-(6-acetyloxyhequineluoquine) Benzoylcyamino-2-(5-tetrazolyl)-1,4-
To a solution of benzodioxa 7 (100 m9; synthesized in Example 1 (g)) in methanol CO (0.5 ml) was added an aqueous solution of IN sulfur hydroxide (0.! M7 t) at room temperature. The reaction mixture was stirred for 10 minutes, concentrated under reduced pressure, acidified with dilute hydrochloric acid, and extracted with ethyl acetate. The extract was dried and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (methylene chloride: methanol = 100:1) to obtain the title compound 45/J (95 ) was obtained. TLC: R70,23 (metele chloride/:methanol=5
21): NMR: 37.89 (2H, a), 7.46 (
IH, aa), 6.95 (2H, d), 6.92 (IH
, t), 6.76 (LH, aa), 4.02 (2H, t
), 3.60 (2H, t); IR:I/ 3400.3200-2300S16
30,1600.152α1500.1440,125
0 cm. Mass: m/e 439 (M), 221.14
9.121; Shape: White amorphous. Example 7 Synthesis of 8-(p-(5-(N,N-dimethylamino)inchyloxy]nnnamoyl]amino-1,4-benzodioxane sodium salt 8-(p-(5-bromoA?7thyloquine) ) nnnamoyl] amino-1,4-benzodioxane (1761i?)
q; Synthesized in Example 1 (113). ) dimethylformamide (1g) solution with 40 tidimethylamine water solution r<f
- (1 ml) was added dropwise, and after stirring at room temperature for 1 hour, the volatile matter was distilled off using a pure nitrogen pump at room temperature and at 90° C. for 3 hours. The residue was dissolved in methanol r1mt), 2N water (sodium matahate aqueous solution (360 μl) was added, concentrated, a small amount of methanol was added, and Hegijyo (4 ml) was added, and the mixture was filtered. The filtrate was kept in the room at 80°C overnight to remove volatiles using a vacuum pump, and the following physical properties were obtained. The title compound '4'1EC179mQ) was obtained. TLC: R/ 0.33 (ethyl acetate: water = 3
:3:1); NMR: δ 7.87 (2H, a), 7.
62 (LH, aa), 6.98 (2H, d), 6.86
(LH, t), 6.71 (IH, aa), 4 swords 6 (2H
, t), 2.85 (2H, t), 2.64 (GH, a
) ;IR:Ll 3430.2930,1655.
1605,1505°1445.1255m. Mass: m/e 452 (M), 233; shape
: White powder Example 8 8-(p-octyloxy/benzoyl)amino-2-(
5-Tetrazolyl)-4-oxo-4H-1-benzobilane-7-calphone 8-(p-octyloxybenzoyl)amino-2-(
5-Tetrazolyl)-4-okine-4H-1--<Nsohyran-7-carboxylic acid methyl ester C332m;
Synthesized in Example 2 (108). ) to methanol (1,
5ffit) and add INN hydrate to this melt.
Aqueous sodium chloride (1.36 fLt) was added, and the mixture was stirred at room temperature for 50 minutes and then at 40°C for 2 hours. Leave to cool, IN
After adding 21i-17, it was extracted with diethyl acetate, and the extracted material was dried and concentrated under reduced pressure. The residue was filtered by silica gel column chromatography (chloroform:methanol-9:1) to obtain the title compound (263+719) having the following physical properties. TLC: Rf 0.15 (chloroform:methanol 4:1); NMR: δ 8.00 (2H, a), 7.
68 (IH, d), 6.98 (2H, d), 6.82 (
LH, d), 6.04 (IH, m), 4.56 (2H,
m), 4.03 (2H, t), 1.82 (2H, m),
1.31 (10H, m), 0.88 (3H, t); Engineering R
:υ 3600-2300.1680.1640.1
1460.125011170.10 to 600.149
80900.840.760c7n. Mass: rn10495 (M), 477.383
%2:13; Shape: /'u brown powder. Example 9 8-(p-=ntylnonnamoyl)amino-2-(5-
Synthesis of sodium salt of tetrazolyl)-6-methyl-1,4-benzodioxane
0m9: Synthesized in Example 2 (103). ) to methanol (
0.5a/), added 5 amounts of IN sodium hydroxide, stirred, and dried under reduced pressure to obtain the title compound (5a/).
LmQ') was obtained. Example 9 (tl By the same operation as Example 7, Example 1.1 [I)-1
(118), 1 (201) -1 (253), 1 (30
1) -(302). 1 (401'), 2.2 (1) - 2 (4E9.2 (10
1), 2 (302), 2 (104) -2 (107),
2 (201) -2 (204), 2 (301), 4.4
rll -4(31,4(101) 74(104)
, 5.6 and 8 are also discussed)
IJium salt was synthesized. Example 10 8-(p-(32-hexenyl-oquine)benzoylcoamino-2-(5-tetrazolyl)-1,4-benzodioxa 70.5.9% Cellulose gluco/Jaku calcium (disintegrant) 200ff+9, stearin ν Magnesium (lubricating agent) 1001719 and microcrystalline cellulose 9.21
were mixed and tableted in a conventional manner to give 100 tablets containing 5 m9 of active ingredient in each tablet. Agent: Patent Attorney (8107) Kiyotaka Sasaki (
3 others)

Claims (1)

[Claims] 1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, R^1 is general formula (i) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (ii) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or (iii) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ A group represented by or (iv) Straight chain or branched chain alkyl, alkenyl or alkynyl having 1 to 20 carbon atoms Represents a group (R^ in the formula
5 and R^6 are each independently a hydrogen atom or a halogen atom, or any one, two or three carbon atoms are an oxygen atom, a sulfur atom, a halogen atom, a nitrogen atom,
A linear or branched chain having 1 to 20 carbon atoms which may be substituted with a benzene ring, a thiophene ring, a carbon ring having 4 to 7 carbon atoms, a carbonyl group, a carbonyloxy group, a hydroxyl group, a carboxy group, an azide group, or a nitro group. represents an alkyl, alkenyl or alkynyl group of the chain. ). R^2 represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms. R^3 is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group,
A group represented by the general formula -COOR^7 (wherein R^7 represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms), a straight chain or branched chain having 1 to 6 carbon atoms; Represents a branched alkyl, alkoxy or alkylthio group. R^4 is the general formula -COOR^8 or -OH_2COO
A group represented by R^8 (wherein R^8 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms), a 2-tetrazolyl group or a 2-tetrazolylmethyl group represents. Symbol A is a single bond, or methylene, ethylene, trimethylene, tetramethylene, vinylene, propenylene, butenylene, butadienylene, or ethynylene, which may be substituted with a straight or branched alkyl group or phenyl group having 1 to 10 carbon atoms. represents a group. The symbol ▲There are mathematical formulas, chemical formulas, tables, etc.▼ means the ring shown by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ represent. The symbol T represents an oxygen atom or a sulfur atom. ] A novel condensed benz(thio)amide, or a non-toxic salt thereof. 2) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I A) [In the formula, all symbols have the same meaning as stated in claim 1. ] The compound according to claim 1, which is represented by: 3) The compound according to claim 1 or 2, wherein the symbol A is a single bond) and the symbol T is an oxygen atom. 4) R^1 is a general formula ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 have the same meaning as described in claim 1. ] The compound according to any one of claims 1 to 3, which is a group represented by the following. 5) Any one of claims 1 to 4, wherein R^5 is a hydrogen atom and R^6 is a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms. Compounds described in Section. 6) 8-(p-pentylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is 1,4-benzodioxane (-tetrazolyl). 7) 8-(p-pentylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is -tetrazolyl)-6-chloro-1,4-benzodioxane. 8) 8-(m-octylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is 1,4-benzodioxane (-tetrazolyl). 9) 8-(o-pentylbenzoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 10) 8-(p-butylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is 1,4-benzodioxane (-tetrazolyl). 11) 8-(p-hexylbenzoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 12) 8-(p-heptylbenzoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 13) 8-(p-octylbenzoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 14) 8-(p-nonylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is 1,4-benzodioxane (-tetrazolyl). 15) 8-(p-decylbenzoyl)amino-2-(5
2. The compound according to claim 1, which is 1,4-benzodioxane (-tetrazolyl). 16) 8-(p-undecylbenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-1,4-benzodioxane. 17) 8-(p-dodecylbenzoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 18) R^5 is a hydrogen atom, and R^6 has 1 to 1 carbon atoms
9. The compound according to any one of claims 1 to 4, which is a straight chain or branched alkoxy group of 9. 19) 8-(p-pentyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 20) 8-(m-pentyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 21) 8-(o-pentyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 22) 8-(p-butyloxybenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 23) 8-(p-nonyloxybenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 24) 8-(p-propyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 25) 8-(p-hexyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 26) 8-(p-heptyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 27) 8-(p-octyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 28) 8-(p-decyloxybenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 29) The compound according to claim 1, which is 8-(p-isopentyloxybenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 30) The compound according to claim 1, which is 8-(p-isohexyloxybenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 31) The compound according to claim 1, which is 8-[p-(1-methylbutyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 32) 8-[N-methyl-N-(p-octynyloxybenzoyl)amino]-2-(5-tetrazolyl)-1
, 4-benzodioxane. 33) 8-(p-octyloxybenzoyl)amino-
The compound according to claim 1, which is 1,4-benzodioxane-2-carboxylic acid or its methyl ester. 34) The compound according to claim 1, which is 8-(p-isoheptyloxybenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 35) The compound according to claim 1, which is 8-(p-isooctyloxybenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 36) 8-[p-(3,7-dimethyloctyloxy)
benzoyl]amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 37) 8-(p-octyloxybenzoyl)amino-
2-(5-tetrazolyl-1,4-benzodioxane-
The compound according to claim 1, which is a 7-carboxylic acid methyl ester. 38) 8-(p-octyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane-7-carboxylic acid. 39) R^5 is a hydrogen atom, and R^6 has 3 to 1 carbon atoms
9. The compound according to any one of claims 1 to 4, which is a linear or branched alkenyloxy group of 9. 40) The compound according to claim 1, which is 8-[p-(2E-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 41) 8-[p-(3-butenyloxy)benzoyl]
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 42) The compound according to claim 1, which is 8-[p-(3Z-hexenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 43) The compound according to claim 1, which is 8-[p-(2Z-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 44) The compound according to claim 1, which is 8-[p-(2E-nonenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 45) Claim 1 which is 8-[N-methyl-N-[p-(2E-octenyloxy)benzoyl]amino]-2-(5-tetrazolyl)-1,4-benzodioxane compound. 46) The compound according to claim 1, which is 8-[p-(2E-hexenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 47) The compound according to claim 1, which is 8-[p-(3E-heptenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 48) Claim 1 which is 8-[p-(2E-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane-2-carboxylic acid or its methyl ester Compounds described. 49) The compound according to claim 1, which is 8-[p-(2E-heptenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 50) The compound according to claim 1, which is 8-[p-(4-pentenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 51) The compound according to claim 1, which is 8-[p-(2E-decenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 52) 8-(p-geranyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 53) 8-[p-(2E,7-octadienyloxy)
benzoyl]amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 54) The compound according to claim 1, which is 8-[p-(2E-pentenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 55) The compound according to claim 1, which is 8-[p-(2E-butenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 56) The compound according to claim 1 which is 8-[p-(3E-octenyloxy)benzoyl]amino-2-(5-tetrazolyl-1,4-benzodioxane. 57) 8-[p The compound according to claim 1, which is -(7-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 58) 8-[p-(2E,4E-octadienyloxy)benzoyl]amino-2-(5-tetrazolyl)-1
, 4-benzodioxane. 59) The compound according to claim 1, which is 8-[p-(2E-octynyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 60) R^5 is a hydrogen atom, and R^6 has 3 to 1 carbon atoms
9. The compound according to any one of claims 1 to 4, which is a straight chain or branched alkynyloxy group of No. 9. 61) The compound according to claim 1, which is 8-[p-(2-octynyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 62) 8-[p-(2-octynyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane-2-carboxylic acid or its methyl ester according to claim 1 Compound. 63) The compound according to claim 1, which is 8-[p-(2-isooctynyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 64) R^5 is a hydrogen atom, and R^6 has 1 to 1 carbon atoms
9. The compound according to any one of claims 1 to 4, which is a straight chain or branched alkylthio group of 9. 65) 8-(p-pentylthiobenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 66) 8-(m-pentylthiobenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 67) 8-(o-pentylthiobenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 68) 8-(p-heptylthiobenzoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 69) Claims 1 to 4, wherein R^5 is a hydrogen atom and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a halogen atom. A compound described in any of the following sections. 70) The compound according to claim 1, which is 8-[p-(6-chlorohexyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 71) The compound according to claim 1, which is 8-[p-(5-chloropentyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 72) The compound according to claim 1, which is 8-[p-(4-chlorobutyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 73) The compound according to claim 1, which is 8-[p-(7-chloroheptyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 74) The compound according to claim 1, which is 8-[p-(8-chlorooctyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 75) The compound according to claim 1, which is 8-[p-(9-chlorononyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 76) The compound according to claim 1, which is 8-[p-(5-bromopentyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 77) R^5 is a hydrogen atom, and R^6 has 2 to 1 carbon atoms
9. The compound according to any one of claims 1 to 4, which is a linear or branched alkyloxyalkyl group of 9. 78) The compound according to claim 1, which is 8-[p-(hexyloxymethyl)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 79) R^5 is a hydrogen atom, and R^6 has 1 to 8 carbon atoms.
4 to 4 carbon atoms, which may be substituted with a straight or branched chain of
7 is a cycloalkyl, cycloalkylalkyl (alkyl moiety has 1 to 8 carbon atoms) or cycloalkylalkyloxy (alkyl moiety has 1 to 8 carbon atoms) group. Compounds described in the above section. 80) 8-(p-cyclohexylmethoxybenzoyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 81) 8-[p-(4-cyclohexylbutoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 82) The compound according to claim 1, which is 8-[p-(2-cyclohexylethoxy)benzoyl]amino-2-(5-tetrazolyl-1,4-benzodioxane). 83) R^5 is hydrogen is an atom, and R^6 has 1 to 8 carbon atoms
Phenyl, phenylalkyl (alkyl moiety has 1 to 8 carbon atoms), phenylalkyloxy (alkyl moiety has 1 to 8 carbon atoms) group, or phenylalkenyl, which may be substituted with a straight or branched chain alkyl group. The compound according to any one of claims 1 to 4, which is an oxy (alkenyl moiety has 1 to 8 carbon atoms) group. 84) 8-[p-(p-butylphenyl)methoxybenzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 85) The compound according to claim 1, which is 8-[p-(5-phenylpentyloxybenzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 86) 8-[p The compound according to claim 1, which is -(3-phenylpropoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 87) 8-[p-(p-propylphenyl)methoxybenzoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 88) 8-[p-(3-phenyl-2-propenyloxybenzoyl]amino-2-(5-tetrazolyl)-1
, 4-benzodioxane. 89) The compound according to claim 1, which is 8-[p-(4-phenylbutoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 90) 8-[p-(o-pentylphenyl)methoxybenzoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 91) 8-[p-(m-butylphenyl)methoxybenzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 92) The compound according to claim 1, which is 8-(p-phenylmethoxybenzoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 93) The compound according to claim 1, which is 8-[p-(2-phenylethoxy)benzoyl]amino-2-(5-tetrazolyl-1,4-benzodioxane. 94) 8-[p- The compound according to claim 1, which is (4-phenylbutyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 95) R^5 is a hydrogen atom, and R^6 is a linear or branched C1-18 alkoxy, alkenyloxy or alkoxyalkoxy group substituted with a carbonyl group, carbonyloxy group or hydroxyl group. A compound according to certain claims 1, 2, 3, or 4. 96) 8-[p-(5-methoxycarbonylpentyloxy)benzoyl]amino-2-(5-tetrazolyl)
Claim 1 which is -1,4-benzodioxane
Compounds described in Section. 97) 8-[p-(6-acetyloxyhexyloxy)benzoyl]amino-2-(5-tetrazolyl)-1
, 4-benzodioxane. 98) 8-[p-(6-hydroxyhexyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 99) The compound according to claim 1, which is 8-[p-(2E-octenoyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 100) 8-(p-octanoylbenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 101) R^5 is a hydrogen atom, and is a linear or branched alkoxy group having 1 to 17 carbon atoms substituted with a phenoxy or phenylthio group. A compound according to item 3 or 4. 102) 8-[p-(3-phenylthiopropoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 103) 8-[p-(3-phenoxypropoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 104) 8-[p-(2-phenylthioethoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 105) The compound according to claim 1, which is 8-[p-(2-phenoxyethoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 106) Claims 1 and 2, wherein R^5 is a hydrogen atom and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a thiophene ring. ,
A compound according to item 3 or 4. 107) 8-[p-[2-(3-thiophenyl)ethoxy]benzoyl]amino-2-(5-tetrazolyl)-
The compound according to claim 1, which is 1,4-benzodioxane. 108) 8-[p-[4-(2-thiophenyl)butoxy]benzoyl]amino-2-(5-tetrazolyl)-
The compound according to claim 1, which is 1,4-benzodioxane. 109) R^5 is a hydrogen atom, R^6 is an azide group,
Claims 1 and 2 are an alkoxy group having 1 to 18 carbon atoms substituted with a nitro group or an amino group (including dialkylamino) which may be substituted with an alkyl group having 1 to 6 carbon atoms. A compound according to item 1, 3 or 4. 110) 8-[p-(5-azidopentyloxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 111) 8-[p-(5-dimethylaminopentyloxy)benzoyl]amino-2-(5-tetrazolyl)-
The compound according to claim 1, which is 1,4-benzodioxane. 112) The compound according to claim 1, which is 8-[p-(4-nitrobutoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 113) The compound according to claim 1, which is 8-[p-(2-azidoethoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 114) The compound according to claim 1, which is 8-[p-(4-azidobutoxy)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 115) Straight-chain or branched alkyl, alkenyl, alkoxy or alkenyloxy having 1 to 18 carbon atoms, in which R^5 is a hydrogen atom and R^6 is replaced with two groups, a carbonyl group and an amino group. A compound according to claim 1, 2, 3 or 4 which is a group. 116) The compound according to claim 1, which is 8-[p-(2-octenoylamino)benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 117) Claims 1 to 4, wherein R^5 and R^6 are each independently a halogen atom, a linear or branched alkyl group having 1 to 10 carbon atoms, an alkoxy group, or an alkenyloxy group. Compounds described in any of the sections. 118) 8-(p-pentyloxy-m-methoxybenzoyl)amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 119) 8-[p-(2E-octenyloxy)-m-
The compound according to claim 1, which is chloro-benzoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 120) R^1 is a general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 are as described in claim 1] express the same meaning. ] The compound according to any one of claims 1 to 3, which is a group represented by the following. 121) 8-(naphthalene-2-carbonyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 122) Claim 1, wherein the symbol A is a vinylene group optionally substituted with a linear or branched alkyl group having 1 to 6 carbon atoms or a phenyl group, and the symbol T is an oxygen atom, or Compound according to item 2. 123) R^1 is a general formula ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 represent the same meaning as in claim 1. ] The compound according to claim 1, 2 or 122, which is a group represented by the following. 124) Claims 1, 2, and 122 in which R^5 is a hydrogen atom and R^6 is a hydrogen atom or a straight or branched alkyl group having 1 to 20 carbon atoms. or a compound according to any of paragraphs 123. 125) 8-(p-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 126) 8-(p-pentylcinnamoyl)amino-1
, 4-benzodioxane-2-carboxylic acid or its methyl ester. 127) 8-(p-heptylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 128) 8-[N-methyl-N-(p-pentylcinnamoyl)amino]-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 129) 5-(p-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-7-chloro-1,4-benzodioxane. 130) 8-(p-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-6-chloro-1,4-benzodioxane. 131) 8-(p-ethylcinnamoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-1,4-benzodioxane. 132) 8-(p-propylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 133) 8-(p-Butylcinnamoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-1,4-benzodioxane. 134) 8-(p-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-6-methyl-1,4-benzodioxane. 135) 8-(o-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 136) 8-(m-octylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 137) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-1,4-benzodioxane-
The compound according to claim 1, which is a 5-carboxylic acid or a methyl ester thereof. 138) 5-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-1,4-benzodioxane-
The compound according to claim 1, which is 8-carboxylic acid or its methyl ester. 139) 8-(p-hequinlucinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 140) 8-(p-nonylcinnamoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-1,4-benzodioxane. 141) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-1,4-benzodioxane-
The compound according to claim 1, which is 6-carboxylic acid or its methyl ester. 142) 5-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-1,4-benzodioxane-
The compound according to claim 1, which is a 7-carboxylic acid or its methyl ester. 143) 8-(p-octylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-1,4-benzodioxane. 144) 8-(p-decylcinnamoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-1,4-benzodioxane. 145) The compound according to claim 1, which is 8-(p-isopropylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 146) 8-(p-isobutylcinnamoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-1,4-benzodioxane. 147) The compound according to claim 1, which is 8-(p-isopentylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 148) The compound according to claim 1, which is 8-(p-pentyl-2-methylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 149) The compound according to claim 1, which is 8-(p-pentyl-3-methylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 150) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)methyl-1,4-benzodioxane. 151) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
19. A compound according to any one of claims 1, 2, 122 or 123 which is a straight or branched chain alkoxy group of 19. 152) The compound according to claim 1, which is 8-(p-pentyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 153) The compound according to claim 1, which is 8-(m-pentyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 154) The compound according to claim 1, which is 8-(o-pentyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 155) The compound according to claim 1, which is 8-(p-propyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 156) The compound according to claim 1, which is 8-(p-butyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 157) The compound according to claim 1, which is 8-(p-octyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 158) The compound according to claim 1, which is 8-(p-hexyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 159) The compound according to claim 1, which is 8-(p-heptyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 160) 8-(p-isopentyloxycinnamoyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 161) 8-(p-isohexyloxycinnamoyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 162) 8-[p-(1-methylbutyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 163) 8-(p-isoheptyloxycinnamoyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 164) 8-(p-isooctyloxycinnamoyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 165) 8-(p-isohexyloxy-2-methylcinnamoyl)amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 166) 8-(p-isohexyloxy-2-phenylcinnamoyl)amino-2-(5-tetrazolyl)-1
, 4-benzodioxane. 167) R^5 is a hydrogen atom, and R^6 has 3 to 3 carbon atoms.
Claim 1, 2, 122 or 12 which is a straight chain or branched alkenyloxy group of 19
A compound according to any one of Item 3. 168) 8-[p-(2E-octenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 169) The compound according to claim 1, which is 8-[p-(2-propenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 170) The compound according to claim 1, which is 8-[p-(3-butenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 171) 8-[p-(3Z-hexenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 172) 8-[p-(2Z-pentenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 173) The compound according to claim 1, which is 8-[p-(2E-nonenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 174) 8-[p-(3E-heptenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 175) 8-[p-(2E-heptenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 176) 8-[p-(2E-hexenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 177) 8-[p-(2E-pentenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 178) The compound according to claim 1, which is 8-[p-(4-pentenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 179) The compound according to claim 1, which is 8-[p-(2E-butenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 180) The compound according to claim 1, which is 8-[p-(2E-decenyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 181) R^5 is a hydrogen atom, and R^6 has 3 to 3 carbon atoms.
Claim 1, 2, 122 or 12 which is a straight chain or branched alkynyloxy group of 19
A compound according to any one of Item 3. 182) The compound according to claim 1, which is 8-[p-(2-octynyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 183) The compound according to claim 1, which is 8-[p-(2-pentynyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 184) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
19. A compound according to any one of claims 1, 2, 122 or 123 which is a straight or branched alkylthio group of 19. 185) The compound according to claim 1, which is 8-(p-pentylthiocinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 186) The compound according to claim 1, which is 8-(m-pentylthiocinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 187) The compound according to claim 1, which is 8-(o-pentylthiocinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 188) Claims 1 and 2, wherein R^5 is a hydrogen atom and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a halogen atom. ,
A compound according to any of paragraphs 122 or 123. 189) 8-[p-(6-chlorohexyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 190) 8-[p-(4-chlorobutyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 191) 8-[p-(5-chloropentyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 192) 8-[p-(7-chloroheptyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 193) R^5 is a hydrogen atom, and R^6 has 2 to 2 carbon atoms.
19. A compound according to any one of claims 1, 2, 122 or 123 which is a straight chain or branched alkyloxyalkyl group of 19. 194) The compound according to claim 1, which is 8-(p-isopentyloxymethylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 195) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
4 carbon atoms optionally substituted with 8 straight or branched chains
-7 cycloalkyl, cycloalkylalkyl (alkyl part has 1 to 8 carbon atoms) or cycloalalkyloxy (alkyl part has 1 to 8 carbon atoms) group A compound according to item 122 or item 123. 196) The compound according to claim 1, which is 8-(p-cyclohexylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 197) The compound according to claim 1, which is 8-(p-cyclohexylmethoxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 198) 8-[p-(4-cyclohexylbutoxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 199) 8-[p-(2-cyclohexylethoxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 200) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
Phenyl, phenylalkyl (alkyl moiety has 1 to 8 carbon atoms), phenylalkyloxy (alkyl moiety has 1 to 8 carbon atoms) group, or phenylalkenyl which may be substituted with 8 linear or branched alkyl group 124. The compound according to claim 1, 2, 122, or 123, which is an oxy (alkenyl moiety has 1 to 8 carbon atoms) group. 201) The compound according to claim 1, which is 8-(p-phenylmethylcinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 202) The compound according to claim 1, which is 8-(p-phenylmethoxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 203) The compound according to claim 1, which is 8-[p-(2-phenylethoxy)/nnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 204) The compound according to claim 1, which is 8-[p-(4-phenylbutoxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 205) 8-[p-(5-phenylpentyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,
The compound according to claim 1, which is 4-benzodioxane. 206) 8-[p-(3-phenylpropoxy)cinnamoyl]amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 207) Straight chain or branched alkoxy having 1 to 18 carbon atoms, where R^5 is a hydrogen atom and R^6 is replaced with a carbonyl group, carbonyloxy group or hydroxyl group,
Claim 1, 2, 122 or 1 which is an alkenyloxy or alkoxyalkoxy group
A compound according to item 23. 208) 8-[p-(6-acetyloxyhexyloxy)cinnamoyl]amino-2-(5-tetrazolyl)
Claim 1 which is -1,4-benzodioxane
Compounds described in Section. 209) Claims 1 and 2, wherein R^5 is a hydrogen atom and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a thiophene ring. ,
A compound according to item 122 or item 123. 210) 8-[p-[2-(2-thiophenyl)ethoxy]cinnamoyl]amino-2-(5-tetrazolyl)
Claim 1 which is -1,4-benzodioxane
Compounds described in Section. 211) Claims 1 and 2, wherein R^5 and R^6 are each independently a halogen atom, a linear or branched alkyl group having 1 to 10 carbon atoms, an alkoxy group, or an alkenyloxy group. 122 or 123. 212) The compound according to claim 1, which is 8-(m,p-dimethoxycinnamoyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 213) 8-(m-methoxy-p-pentyloxycinnamoyl)amino-2-(5-tetrazolyl)-1,4
- The compound according to claim 1, which is benzodioxane. 214) 8-(p-pentyloxy-m-chlorocinnamoyl)amino-2-(5-tetrazolyl)-1,4-
The compound according to claim 1, which is a benzodioxane. 215) R^1 is a general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 are as described in claim 1] express the same meaning. ] Claims 1, 2, or 12 shown in
Compound according to item 2. 216) 8-[3-(5-indanyl)acryloyl]
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 217) The compound according to claim 1, 2, or 122, wherein R^1 is a linear or branched alkyl, alkenyl, or alkynyl group having 1 to 20 carbon atoms. 218) N-(2-hexadecenoyl)amino-2-(
The compound according to claim 1, which is 5-tetrazolyl)-1,4-benzodioxane. 219) Symbol A is a methylene group or an ethylene group,
3. The compound according to claim 1 or 2, wherein the symbol T is an oxygen atom. 220) The compound according to claim 1, which is 8-(p-pentylphenylacetyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 221) The compound according to claim 1, which is 8-[3-(p-pentylphenyl)propionyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 222) The compound according to claim 1 or 2, wherein the symbol A is an ethynylene group or a butadienylene group, and the symbol T is an oxygen atom. 223) 8-(p-hexylphenylpropioloyl)
The compound according to claim 1, which is amino-2-(5-tetrazolyl)-1,4-benzodioxane. 224) The compound according to claim 1, which is 8-[5-(p-propoxyphenyl)penta-2E,4E-dienoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 225) 8-[5-(p-butylphenyl)penta-2
The compound according to claim 1, which is E,4E-dienoyl]amino-2-(5-tetrazolyl)-1,4-benzodioxane. 226) Symbol A is a single bond or vinylene group and symbol T
The compound according to claim 1 or 2, wherein is a sulfur atom. 227) The compound according to claim 1, which is 8-(p-heptyloxybenzothioyl)amino-2-(5-tetrazolyl)-1,4-benzodioxane. 228) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I B) [In the formula, all symbols have the same meanings as stated in claim 1] Claim 1 Compounds described in Section. 229) The compound according to claim 1 or 228, wherein symbol A is a single bond and symbol T is an oxygen atom. 230) R^1 is a general formula ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 represent the same meaning as described in claim 1. ] The compound according to claim 1, 228, or 229, which is a group represented by the following. 231) R^5 is a hydrogen atom, and R^6 is a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms, Claims 1, 228, and 229 or a compound according to paragraph 230. 232) 8-(p-pentylbenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 233) 8-(p-pentylbenzoyl)amino-4-
5. The compound according to claim 4, which is oxo-4H-1-benzopyran-2-carboxylic acid or its methyl ester. 234) 8-(p-hexylbenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 235) 8-(p-heptylbenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 236) 8-(p-octylbenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 237) 8-(p-nonylbenzoyl)amino-2-(
5-Tetrazolyl)-4-oxo-4H-1-benzopyran. 238) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
Claim 1, 228, 229 or 230 which is a straight chain or branched alkoxy group of 19
Compounds described in Section. 239) 8-(p-Butoxybenzoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 240) 8-(p-pentyloxybenzoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1-
The compound according to claim 1, which is benzopyran. 241) 8-(p-hexyloxybenzoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1-
The compound according to claim 1, which is benzopyran. 242) 8-(p-heptyloxybenzoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1-
The compound according to claim 1, which is benzopyran. 243) 8-(p-nonyloxybenzoyl)amino-
The compound according to claim 1, which is 2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 244) 8-(p-octyloxybenzoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1-
The compound according to claim 1, which is benzopyran. 245) Claim 1 which is 8-(p-heptyloxybenzoyl)amino-2-(5-tetrazolyl)-6-fluoro-4-oxo-4H-1-benzopyran
Compounds described in Section. 246) The compound according to claim 1, which is 8-(p-octyloxybenzoyl)amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran. 247) The compound according to claim 1, which is 8-(p-heptyloxybenzoyl)amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran. 248) R^5 is a hydrogen atom, and R^6 has 3 to 3 carbon atoms.
The compound according to claim 1, 228, 229 or 230, which is a straight or branched alkenyloxy group of 19. 249) 8-[p-(2E,7-octadienyloxy)benzoyl]amino-2-(5-tetrazolyl)-4
-Oxo-4H-1-benzopyran. 250) 8-(p-geranyloxy)benzoylamino-2-(5-tetrazolyl)-4-oxo-4H-1-
The compound according to claim 1, which is benzopyran. 251) 8-[p-(2E-nonenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-
The compound according to claim 1, which is 4H-1-benzopyran. 252) The compound according to claim 1, which is 8-[p-(2E-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 253) 8-[p-(7-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-
The compound according to claim 1, which is 4H-1-benzopyran. 254) The compound according to claim 1, which is 8-[p-(2E-heptenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 255) The compound according to claim 1, which is 8-[p-(2E-hexenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 256) 8-[p-(2E,7-octadienyloxy)benzoyl]amino-2-(5-tetrazolyl)-6
-Fluoro-4-oxo-4H-1-benzopyran. 257) 8-[p-(2E-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran according to claim 1 Compound. 258) 8-[p-(7-octenyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-
The compound according to claim 1, which is 4-oxo-4H-1-benzopyran. 259) 8-[p-(2E,7-octadienyloxy)benzoyl]amino-2-(5-tetrazolyl)-6
-Methyl-4-oxo-4H-1-benzopyran. 260) 8-[p-(2E,7-octadienyloxy)benzoyl]amino-2-(5-tetrazolyl)-6
The compound according to claim 1, which is -chloro-4-oxo-4H-1-benzopyran. 261) R^5 is a hydrogen atom, and R^6 has 3 or more carbon atoms.
19. The compound according to claim 1, 228, 229 or 230, which is a straight chain or branched alkynyloxy group of 19. 262) 8-[p-(2-octynyloquine)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-
The compound according to claim 1, which is 4H-1-benzopyran. 263) R^5 is a hydrogen atom, and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a halogen atom, Claims 1 and 228
229 or 230. 264) 8-[p-(4-chlorobutoxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4
The compound according to claim 1, which is H-1-benzopyran. 265) Claim 1 which is 8-[p-(5-chloropentyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran
Compounds described in Section. 266) Claim 1 which is 8-[p-(6-chlorohexyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran
Compounds described in Section. 267) 8-[p-(6-chlorohexyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran according to claim 1 Compound. 268) Claim 1 which is 8-[p-(7-chloroheptyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran
Compounds described in Section. 269) 8-[p-(8-chlorooctyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-e-benzopyran according to claim 1 Compound. 270) 8-[p-(7-chloroheptyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran according to claim 1 Compound. 271) Claim 1 which is 8-[p-(8-chlorooctyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran
Compounds described in Section. 272) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
Phenyl group, phenylalkyl (alkyl part has 1 to 8 carbon atoms) group, phenylalkyloxy (alkyl part has 1 to 8 carbon atoms) group, which may be substituted with a straight chain or branched chain alkyl group of 8 or phenylalkenyloxy (alkenyl moiety has 1 to 8 carbon atoms) group. Claims 1, 228, 229, or 230
Compounds described in Section. 273) The compound according to claim 1, which is 8-[p-(3-phenylpropoxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 274) The compound according to claim 1 which is 8-[p-(3-phenyl-2E-propenyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran . 275) Claim 1 which is 8-[p-(4-phenylbutyloxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran
Compounds described in Section. 276) 8-[p-(4-phenylbutyloxy)benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran according to claim 1 Compound. 277) Claim 1, 228, 229 or 230, wherein R^5 is a hydrogen atom and R^6 is an alkoxy group having 1 to 18 carbon atoms substituted with a thiophene ring. Compounds described in Section. 278) The compound according to claim 1 which is 8-[p-[4-(2-thiophenyl)butyloxy]benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran . 279) Claim 1 which is 8-[p-[4-(2-thiophenyl)butyloxy]benzoyl]amino-2-(5-tetrazolyl)-6-methyl-4-oxo-4H-1-benzopyran Compounds described in Section. 280) Claim 1, wherein the symbol A is a vinylene group optionally substituted with a linear or branched alkyl group having 1 to 6 carbon atoms or a phenyl group, and the symbol T is an oxygen atom, or A compound according to paragraph 228. 281) R^1 is a general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^5 and R^6 represent the same meaning as described in claim 1. ] The compound according to claim 1, 228, or 280, which is a group represented by the following. 282) R^5 is a hydrogen atom, and R^6 is a hydrogen atom or a straight or branched alkyl group having 1 to 20 carbon atoms, Claims 1, 228, and 280 or a compound according to paragraph 281. 283) 8-(p-pentylcinnamoyl)amino-4
The compound according to claim 1, which is -oxo-4H-1-benzopyran-2-carboxylic acid or its methyl ester. 284) 8-(p-pentylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 285) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-6-methyl-4-oxo-4
The compound according to claim 1, which is H-1-benzopyran. 286) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-6-fluoro-4-oxo-
The compound according to claim 1, which is 4H-1-benzopyran. 287) 8-(p-pentylcinnamoyl)amino-6
-Methyl-4-oxo-4H-1-benzopyran-2-
The compound according to claim 1, which is a carboxylic acid or a methyl ester thereof. 288) 8-(p-Butylcinnamoyl)amino-2-
The compound according to claim 1, which is (5-tetrazolyl)-4-oxo-4H-1-benzopyran. 289) 8-(p-hexylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 290) 8-(p-heptylcinnamoyl)amino-2
The compound according to claim 1, which is -(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 291) The compound according to claim 1, which is 8-cinnamoylamino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 292) R^5 is a hydrogen atom, and R^6 has a carbon number of 1 to
Claim 1, 228, 280 or 281 which is a straight chain or branched alkoxy group of 19
Compounds described in Section. 293) 8-(p-hexyloxycinnamoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1
- The compound according to claim 1 of Patent 1, which is benzopyran. 294) 8-(p-heptyloxycinnamoyl)amino-2-(5-tetrazolyl)-4-oxo-4H-1
- The compound according to claim 1, which is benzopyran. 295) 8-(p-isohexyloxycinnamoyl)
Amino-2-(5-tetrazolyl)-4-oxo-4H
The compound according to claim 1, which is -1-benzopyran. 296) R^5 is a hydrogen atom, and R^6 has 3 to 3 carbon atoms.
Compound 297) 8-[p-(2-octynyloxy)cinnamoyl] which is a straight-chain or branched alkynyloxy group in Claim 1, 228, 280 or 281 Amino-4-oxo-4H-1-benzopyran-
The compound according to claim 1, which is a 2-carboxylic acid or a methyl ester thereof. 298) R^5 is a hydrogen atom, and R^6 is a straight or branched alkoxy group having 1 to 18 carbon atoms substituted with a halogen atom, Claims 1 and 228
A compound according to paragraph 280 or paragraph 281. 299) The compound according to claim 1, which is 8-[p-(5-chloropentyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 300) The compound according to claim 1, which is 8-[p-(6-chlorohexyloxy)cinnamoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran. 301) General formula ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ - (IC) [In the formula, all symbols have the same meaning as described in claim 1. ] The compound according to claim 1, which is represented by: 302) 8-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-2,3-dihydro-1,4-
The compound according to claim 1, which is dithianaphthalene. 303) 5-(p-pentylcinnamoyl)amino-2
-(5-tetrazolyl)-2,3-dihydro-1,4-
The compound according to claim 1, which is dithianaphthalene. 304) A non-toxic salt of a compound according to any one of claims 1 to 303. 305) The non-toxic salt according to claim 304, which is a sodium salt. R^1-A-COOH (II) [In the formula, R^1 is the general formula (i) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (ii) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or (iii) ▲There are numerical formulas, chemical formulas, tables, etc.▼ or (iv) a straight chain or branched chain alkyl, alkenyl, or alkynyl group having 1 to 20 carbon atoms. (R^5 and R^6 in the formula are each independently a hydrogen atom or a halogen atom, or any one, two, or three carbon atoms are an oxygen atom, a sulfur atom, a halogen atom, a nitrogen atom, or a benzene atom. ring, thiophene ring, carbon number 4-7
represents a straight or branched alkyl, alkenyl or alkynyl group having 1 to 20 carbon atoms which may be substituted with a carbon ring, a carbonyl group, a carbonyloxy group, a hydroxyl group, a carboxy group, an azide group or a nitro group. Symbol A is a single bond, or methylene, ethylene, trimethylene, tetramethylene, vinylene, propenylene, butenylene, butadienylene, or ethynylene, which may be substituted with a straight or branched alkyl group or phenyl group having 1 to 10 carbon atoms. represents a group. ] Compounds represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (III) [In the formula, R^2 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. . R^3 is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group,
A group represented by the general formula -COOR^7 (wherein R^7 represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms), a straight chain or branched chain having 1 to 6 carbon atoms; Represents a branched alkyl, alkoxy or alkylthio group. R^4 is the general formula -COOR^8 or -CH_2COO
A group represented by R^8 (wherein R^8 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms), a 2-tetrazolyl group or a 2-tetrazolylmethyl group represents. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ represents the ring shown by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ . The symbol T represents an oxygen atom or a sulfur atom. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) [In the formula, all The symbol represents the same meaning as above. ] A method for producing a condensed (thio)benzamide. 307) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (IV) [In the formula, R^2^0 represents a methylene group or a single bond, and other symbols have the same meaning as described in claim 306 represents. ] A general formula characterized by reacting a compound represented by the above with azide ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I a) [In the formula, R^2^0 represents the same meaning as above, and other The symbols have the same meanings as in claim 306. ] A method for producing a condensed (thio)benzamide represented by: 308) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (V) [In the formula, all symbols have the same meaning as described in claim 306. ] Compound and general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VI) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (VII) [In each formula, X^1^0 and X^2^ 0 represents a halogen atom, R^5^0 represents a linear or branched alkyl group having 1 to 6 carbon atoms, and R^2^0 represents a methylene group or a single bond. ] The compound shown is reacted, and if necessary, esterification,
General formulas characterized by being subjected to saponification reactions ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I b) [In the formula, R^5^5 is a hydrogen atom or a straight chain or branched chain having 1 to 6 carbon atoms] It represents an alkyl group in the chain, R^2^0 has the same meaning as above, and other symbols have the same meanings as described in claim 306. ] A method for producing a condensed (thio)benzamide. 309) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, R^1 is general formula (i) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (ii) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ or (iii) ▲ Numerical formula, chemical formula, table, etc. ▼ or (iv) a straight or branched alkyl, alkenyl or alkynyl group having 1 to 20 carbon atoms. (In the formula, R^5 and R^6 are each independently a hydrogen atom or a halogen atom, or any one, two, or three carbon atoms are an oxygen atom, a sulfur atom, a halogen atom, a nitrogen atom, or a benzene atom. ring, thiophene ring, carbon number 4-7
represents a straight or branched alkyl, alkenyl or alkynyl group having 1 to 20 carbon atoms which may be substituted with a carbon ring, a carbonyl group, a carbonyloxy group, a hydroxyl group, a carboxy group, an azide group or a nitro group. )R^2
represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms. R^3 is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group,
A group represented by the general formula -COOR^7 (wherein R^7 represents a hydrogen atom or a straight or branched alkyl group having 1 to 6 carbon atoms), a straight chain or branched chain having 1 to 6 carbon atoms; Represents a branched alkyl, alkoxy or alkylthio group. R^4 is the general formula -COOR^8 or -CH_2COO
A group represented by R^8 (in the formula, R^8 represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms), a 2-tetrazolyl group, or a 2-tetrazolylmethyl group. represent Symbol A is a methylene, ethylene, trimethylene, tetramethylene, vinylene, propenylene, butenylene, butadienylene or ethynylene group which may be substituted with a single bond or a straight or branched alkyl group having 1 to 10 carbon atoms or a phenyl group. represents. The symbol ▲There are mathematical formulas, chemical formulas, tables, etc.▼ means the ring shown by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ represent The symbol T represents an oxygen atom or a sulfur atom. ] A leukotriene (SRS) antagonist containing a novel condensed benz(thio)amide or a non-toxic salt thereof as an active ingredient.