JPS58148817A - Cardiotonic agent - Google Patents

Abstract

PURPOSE:A cardiotonic agent containing a carbostyril derivative, e.g. 6- N- methyl-N-(4-methoxybenzyl)carbamoyl -3,4-dihydrocarbostyril, and a salt thereof as active constituents with almost no increasing action on the heart rate. CONSTITUTION:A cardiotonic agent containing a carbostyril derivative expressed by formula 1 (R<1> is H, alkyl, alkenyl, alkynyl, etc.; R<2> and R<3> are alkyl or lower phenylalkyl or R<2> and R<3> together with N form a 5- or 6-membered saturated heterocyclic ring which may contain O or N; the carbon-carbon bond between the 3- and 4-positions of the carbostyril skeleton is a single or double bond) and a salt thereof as active constituents. The compound expressed by formulaIis obtained by reacting a carbostyril deriavative expressed by formula 2 with an amine expressed by formula 3 by the amide bond forming reaction. The compound expressed by formula 1 has improved positive inotropic action, increasing action on coronary blood stream and hypotensive action.

Description

[Detailed description of the invention] The present invention relates to Fi, #i core agent.

The strong/D agent of the present invention contains a sulfonaryl derivative represented by the general formula (1) and its - as active ingredients.

2 1 [Onaka 81 is Motoko Mizuki, lower ar+ru group, low number?
L Kenyl group, lower al-nyl group or phenyl lower alk+
Indicates a group. 12 and R3 are in the same phase, and may be a lower atom that may have an atom or an asteroid as a substituent, or a lower atom as a substituent on the phenyl ring. I
j4batt indicates a phenyl lower alkyl group which may contain a 1 to 3 or a lower alkyl group. In addition, R2 and R3 may form a 5-membered or 6-membered O saturated element llI with or without the intermediary of one or more molecules or molecules. . However, lower alkyl, phenyl, lower alkyl, or phenyl may be replaced with ill.筐霉子I [When the base ring is pelagic, lower Ashikanyl, Kōgen Algynyl group, Schiff0alkyl group, Schiff0algyl lower alkyl group, lower alkanoyl group, lower alkanoyl lower Al+L group, lower alkoxyl + radical = LA, lower alkoxyl group, lower alkoxyl group, )0yl group, lower alysyl group
10rsul base nyl group, #Itmendoro as cyano group, besylyyl-on-(Ktja-class al on this phenyl ring) 1-3 groups may be substituted and 4), 11o Geshi Hinako,
Shido 0 + Shi group, lower alkanoyl, 1, 1 car, 8 t
Lower alkyl with yl group tl, Kk on phenyl salt
- As a group, phenol which may have 1 to 3- or lower alkoxyl group 1-3- or lower alkoxyl group iM from salmon is a +lower alkyl+L group, a phenyl group, a lower alkoxyl group, a lower alkoxy group, a halogen adenoid, a nido O group, an amino group, a lower alkanoylamino group, and a lower alkyl+ruthio group. phenyl lower alkyl group, which can be substituted with 1 to 3 groups or Fi lower alkyl group, phenyl lower alkoxy group, phenyl lower alkyl group, lower alkoxy group, 1 to 3 or Fi
Lower Al 10 L1h4 as one group in besiliyl, phenyl, which can be said to have a lower Al 10 + 2 group.
” Phenylsulfonyl h1 which may have 1 to 3 layers
1 to 3 groups selected from the group consisting of Shido O + Shi group, Halokeshi Foshi 1 lower Al + Ru group, lower alkoxy group and lower alkanoylamino group as a wax substituent on Fenyl L.
All on the besilyl lower acyl group, which can have a besilyl group, and the phenylene IL+ mass! Ill as a bald daughter-in-law and 4
#, the group extending m from the cape of class Alco + Shi 1 to 3ii
A phenyl lower alkenylcarbonyl group which may have one to three lower alkoxy groups as a Klk substituent on the phenyl ring is at the 4th position of the 5th position! th may also be present, and the #31kkU bond between the 3rd and 4th positions of the rickshaw styril skeleton represents a single irises bond or a 2111 bond. ] The calfostyril age conductor and its salt represented by the above-mentioned formula (11) have the effect of enhancing the brain convergence of 7th (positive force effect), the effect of increasing the flow rate of 11m, and the effect of pressure reduction, for example. Depressive heart failure, Koji-ben lI#7E, Shinkomat!lLmk
IJ, lli hunch, paroxysmal atrial dysfunction ~ O each calcaneus 1
11 Effective as a cardiotonic agent for Ot7i elephants. In particular, the carbostyril derivative expressed by the above formula (1) and its excellent positive inotropic effect, increased blood pressure and antihypertensive effect, and increased heart rate by 510%. A special feature of a circle is that it has almost no shape.

Above-f, the general formula (1 + each represented by R1, R2, and R3) is shown below.

Examples of the lower number a L + L1 include methyl, ethyl, durohil, isodil, butyl, ttrl -butyl, besityl, and straight or branched alkyl + L1 & can be exemplified.

Examples of low-number alkyl groups include di-nyl, allyl, 2-di-tenyl, 3-phthynyl, l-methylallyl, 2-vesitenyl, 2-dimethyl, and 2 to 6 carbonyl groups. An example of a branched akenyl group is t-.

Examples of alkyl groups include ethynyl, 2-dimethyl, 2-dithenyl, 3-butynyl, l-methylL-2-dimethyl,
Hinyl, 2-hecytinyl, 2-hecytinyl Shima O Tabisun 2
~6 straight or branched altenyl m can be represented by 911.

Examples of phenyl lower alkyl groups include besidyl, 2-phenylethyl, 1-phenylethyl, 3-phenyl-2-O, 4-phenylbutyl, 1.1-dimethyl-2-phenylethyl, 5-phenylethyl, 6 -Phenyl + syl, 2-methyl-3-phenyl + sil, #i2 Hayabusa 1
Examples include phenyl alkyl having a linear or branched alkyl group of 60 to 60.

Examples of the lower alkyl group include Schiff's dimethyl, 4-Schiff'syl butyl, 2-Schiff's ethyl, Schiff's methyl, 2-Schiff's besityl, 5 - to Schiff 0 + silprogol, 2- to Schif 0 + silprogol, 2- to Schif 0 + silp Oe, 2- to Schif 0 butyl ethyl, 3- to Schif 0 butyl ethyl, 1,1-remethyl L-2-cycO hedecylethyl, l-methyl-2-cycO peshylethyl,
2-Schiff 0 octylethyl, 5-Schiff 0 to Shisil Pesthyl, 6- to Cyclo+Sil+44 o'clock station"IAlk3~
The l- or branched alkyl groups of 1 to 6 can be exemplified by using the Schiff0'PL+ group of 8 as a substituent.

Low-grade alkamile noodles include HoL Mil, Acetoshi, and J.
Ohi Saijiri, butyryl, isodutyryl, peshitanoyl,
1zrl-dutylcarbonyl, straight or branched alkanoyl having 1 to 6 strands! t-Th
I can show it.

As for the low-grade Atco + Shika L Bonyl crystals, Meto + Shika L Fujiri, Eto + Shika L Fujiri, Pro mainland Shika 1 Army Niru, Isozu 0 Hon raw Shikaru Niru, Buto + Shikar Ratio 2l, ,,1
zrl-zutojushikaLhonyl, pesinaruo+shikaruhonyl, he+shiruo+shikaLhonylhao017R1-6 lpeng or branched alkoxy↑shi group having a]+dicarbonyl group I can give an example.

As for low-grade A carving + Rusu L prison nil, Me 51 this rate 2'', Tech 5 sis L book 2'', Pu 0 Basisle book 2 ttrl -
J Tashisu L Car Niru, Beshita Shisuru Hon Niru, Hetosu Shisu L
Rate 2 L * t) * Straight chain or branched Al + L with bulk Ml ~ 6
An example is a sulfony L group.

Examples of the KIiTh group on the phenol ring include pheno+dimethyl, 2-phenoloxyethyl, 2-phenoxylOeL, 3 -pheno+sipyl, l-methyL-2-pheno+diethyl, 2-pheno+diptyl, 3
-pheno + diptyl, 4-pheno + diptyl, 1.1-
Dimethyl-2-pheno↑diptyl, 2-pheno+cipesiti L.

3-pheno 1,000 cypesitil, 4-pheno + 1,000 cipecil, (
2 or 3-meth+diphenol methyl, 2-(4
-methox diphenol) ethyl, (2-etho + dipheno + di) methyl, 1-(3-etho + dipheno + di) ethyl, 3-(4-etho + dipheno + di) ethyl, 6 -(4
-isopro-dipheno+sil), 4-(4-dipheno+sil)butyl, 1,1-dimethyl-
2-(3,4-dimeth+dipheno+cy)ethyl, 5-(
3,4-Shedo+dipheno+shi)pesityl・6-(3,
4,5-)limeth+dipheno+sil), 2-methyl-3-(2,5-dipheno+dipheno+sil),
(2-rioopheno+shi)methyl, (3-p〇7pheno+shi)methyl, (4-iodopheno+shi)methyl, 2-
(4-fluoropheno+shi)ethyl, 1-(3-chlorophenono+shi)ethyl, 6-(4-)〇7pheno+shi)he+sil, 5-(3,4-jiriOOpheno+ C) Besityl, 1,1-cymethy L-2~(2,5-sibromophenoxy)furozyl, (3,4,5-)rif00pheno+C)
Methyl, (2- or 3-methylphenoloxy)methyl,
2-(4-methylphenoxy)ethyl, (2-ethylphenoxy)methyl, I-(3-ethylpheno+cy)ethyl, 3-(4-ethylphenoxy)p[]eL, 6-(
4-isodu0gorupheno+shi)he+sil, 4-(4-hedecylpheno+shi)butyL,I,I-dimethyl-2-(
3,4-dimethylpheno+cy)ethyl, 5-(3,4-
diethylphenol, 6-(3,5-dimethylphenol+sil), 2-methyl-3-(2,5-
Dimethylpheno+diphenol, (3,4-methyldiphenol)methyl, 2-(5,4-methylidiphenol+diphenol)ethyl, 2-(5,4-ethylenediphenol)diphenol 2)ethyl, 2-(2,3-methyledidiodipheno+d)ethyl, 2-(3,4-trimethyledidiodipheno+d)ethyl, 1-(3I4-methyledidiodipheno+d)butyl, (3, 4-ethyloxydipheno+di)methyl, (2,3-methyldipheno+di)methyl, 1-(3,4-methyldipheno+diphenof)ethyl, 3-(3,4-methyldipheno+di)ethyl, 5O2dipheno+shi)zuoeL, 6-(3,4-jtireshiruo+shi')technical)to+sil, (3,4,5-)limethylpheno+shi)methyl, (3,4 , 5-trimethoxydipheno+di)methyl, 2-(3,4,5-trimethoxydipheno+di)ethyl as a turtle removal on the phenyl ring, A L of translations 1 to 6 ko + shi group and IX ridge 1-6 (DPL + ru group, which is the yearning that emanated from the cape, 1 to 3 or station'l A number 1 to 4 a L + L, shidio + shi group t
A number of 1 to 6 straight or branched alkyl groups can be substituted for station 3 having a phenol group, which can be 4i, as a substituent.

As an additional group, a cyano group, a beco9yl group (1 to 311 groups may be substituted with lower alkyl groups on this phenyl ring), a cyano group, a beco9yl group, Examples of the lower alkanoyl group or the lower alkanoyl group having one carboxyl group include cyanomethyl, carbasylmethyl, 2-cyanoethyl, 2-carbasyl ethyl, 2- or 3-cyanoyl group, 2- or 3-calhet
1-methyl-2-cyanoethyl, 1-methyl-2-carethyl, 2-13- or 4
-Cyanobutyl, 2-13- or 4-carb7ylbutyl, l,I-dimethyIL-2-cyabutyl, 1.
1-=; Methyl L-2-carbatylbutyl, 2- or 3-cyanoethyl 2- or 3-carbatylbutyl, 4-cyanoethyl, hydroxylhexyl, dimethyl, 2- Shido + diethyl, 2- Shido 0 + Shizu 0jil, 2- Human 00 diptyl, 3- Shido 0+
Sibutyl, 4-sido 0,000 sidyl, 5-sido 0+ diptyl, 5-sido 0+ dibutyl, 6-sido 0+ cyhexyl, attylo-ten-dimethyl, 2-acetyl-o-f Cheryl, 2-rtfLJ+Shibu0 Pill, 3-AtfL-Oshibu-0Jil, 4-Attyl-O-Shin-Dyptyl, 3-At-Til-O+
SchifffL, 5-atfL+shibesityl, 6-acetero+shihe+shiL, 2-1odionylodiethyl, 3-
Tokou 7 Sanrisai + Shizuojiru, 2-Putiriruojushizuojiru, 4-Isolanaririoshi Shiftir, 2-Pesitanoi L
Saishi diethyl, 1zrl-zuthylcal table 2 Luo + Shimechi L, 2-to + Sano Iruo 10 Shiechi L1 Besiri Iruo + Ximena t, 2-159141 Shidiethyl, 3-Pesisoyl Oju Shizu 0jiru, 6-Beshi Soil Ojushi + 5L %4-
Methyl, 2 or 3-Metho + Methyl, 2-(4-method) Methyl
ethyl, 2-ethyl, 1-(3-ethyl)ethyl, 3-
(4-eth + 4-ethyl)propyl, 6-(4
-Isopro reformer Shibeshi Soiruo + Shi) + Sil, Shi - (
4-to+silo-10-butyl, 1,1
-dimethyl-2-(3,4-cymeth+cybecy9iluo+
c) Ethyl, 5-besylyyl, 5-(3
, 4-Sugi Eto + Shibeshirii L Saijushi) Peshitil, 6-(
3゜4.5-Trimethic acid + ci) he + syl, 2-methyl-3-(2,5-dimeth + cibesiliyl io + cy), 2- (3,4-dimethic) + shi) ethyl, 5- (3,4, ratrimetoshishibeshizoi L sai + shi) pu 0, ri 00 methic.

Polymethyl, iodomethyl, fluoromethyl, 2-OOethyl, 2-pomoethyl, 2-or #13-2
00propyl, 2-fluoropropyl.

3-iodobutylene 0 and 1% 1-methyl-2-ethyl, 2-93-or Fi4-butyl, 3-quaO
Butyl, 2-iodobutyl, 4-fluorobutyl, 1.
1-Q methyl-2-riOObutyl, 2- or U3-9
00 Pestil, 4-P0 Mhegyu Sil, 6-ri00 + Sil, 5-P0 Mpeshitil I*Osiaha L Besili Iluo+
cy group (this phenyl ring may be substituted with 1 to 3 silica groups and 1 to 60 straight or branched alkyl groups), halogen diatomic, hydro+cy group, Direct or 11-branched alkanoyl group or carboxy group of 1 to 6 or carboxy group 14
One Ik! ! Choices 1-6 to have as jIjili
An example is 01&- or a-al+R group.

As a substituent on the phenylene L ring, lower alk + LI&, lower a L co + shi group, halogen) k-nido 0 group, amino group, lower alkanoyl amino group and lower alkyl thio crystal to h#
Examples of phenyl 4#-alkyl groups in which the C group has 1 to 3 groups or a low number alkyl group include benzyl, 2-phenylethyl, 3-phenyl:
Propyl, 6-phenylh+cyl, 4-phenylbutyl, diphenylmethyl, 1,2-diphenylethyl, 2-
or 3-meth+sibesi5yl, 2-(4-methocycediL)ethyl, 2-etho+sibesidyl, 1-(3-etho+sipheniL)ethyl, 3-(4-etho+sipheniL)
) Propyl, 6-(4-isopropyl+diphenyl:L), 1,000syl, 4-(4-isopropyl+diphenyl)butyl, l
, l-5 methyl-2-(3,4-dimethylphenyl)ethyl, 5-phenylethyl, 5-(3,4-shed+diphenyl)pesithit, 6-(3,4,5-)rimethocypheni L) he+sil, 2-methy1l-(2,5-dimethythyl)p0 and 1,2-nitrobesidyl, 3-=
Trobesidil, 1-(3-dithophenyl)ethyl, 6
-(4-di-0-phenyl)hetosyl, 2-200 besidyl, 3-pO'E besidil, 3-dobesidil, 2-
(4-fluorophenyl)ethyl, I-(3-ri[]
0FI:L)
1. l-DimethyL-2-(2,5-sibu0mfeniL)
projiri, 2-or #i5-methimethicidyl, 2-(
4-methylphenyl)ethyl, 2-ethylbesidyl, I
-(3-ethylphenyl)ethyl, 3-(4-Xthyl
Fueni L)zu0hill, 6-(4-isozu0jiruFueniL)
)he+sil, 4-(4-hedecylphenyL)butyl, 1
．． 1-dimethy1-2-(3,4-,, ;methyt-pheniL
) ethyl, 5-(3,4-jethylphenyl)pesityl, 6-(3,5-dimethylphenyl)+sil, 2-X
Methyl-3-(2,5-sibu0mfeniL)tsunjiru, 2-aminobenzyl, 3-aninovesi, ;L,I-
(3-aminophenyl)enae, 6-(4-aminophenyl), 112-acetylaminohesyl, 31 lumylaminobenyl, I-(3-aminophenyl), I-(3-aminophenyl) ) ethyl, 6-(4-11-zutiri L? Sannopheni L) 1,000 syl, 2-(5-besitanoylaminophenyl) ethyl, 4-(6-he + Sano t Σnophenyl) butyl, 2- or 3-methylthiobecol, 2
-(4-Methylthiophenyl)ethyl, 2-ethylthiobenzyl, I-(3-enaLfoffenyl)ethyl, 3
-(4-Ethylthiophenyl)dil, 6-(4-isojOdiLthiophenyl)+sil, 4-(4-hexylthiophenyl)buty'', 1,1-dimethyl-2 −(3
,4-dimethylthio(L)ethyl,5-(3+ 4
- :/ethy”thiophenyl)besityl, 6-(3,5
-dimethylthiophenyl)to+sil, 2-methylL-3-
(2,5-dimethylthiophene L) 0 Hill, 3-Methyl L-4-R 00 Besidyl, 2-200-6-Methyl Ir<
Sydyl, 2-meth+cy3-k00 besidyl, phenyl(4-riOOphenyL)methyl, di(4-methylphenyl)methyl, phenylt(3-methothendiphenyl)methyL
, 3,4゜5-Trimethobyu Shibeshijit, 2-(3,4,
5-trimethodiphenyl)ethyl, 3,4.5-i
Remethylvesi! ;(,3,4,5-tricOobesidyl, 3,4-ethylenedio+sibesidil, 2,3-methyledi!;o+dibenzyl, l-('S, 4-methyledio-bovine diphenidiphenyl, 3-( 3,4-Methyrezidio+
Cyphenyl), 6-(3,4-Methylenediyl), 3,4-methylethyl, 2-(3,4-Methylenediyl) , 2-(3,4-1trimethylethyl)ethyl, 2-(2,3-trimethylethyl)ethyl, 2-(3,4-trimethylethyl)ethyl, - Methyrezidione (L) Alternative plate 1 to 6 straight or branched atoms on the phenyl ring such as butyl
+L group, m- or branched Al] + Shi group with 1 to 6 strands,
Ha0geshimako, NidoOyabu, amino group, next IA number 1-60
Straight or branched alkanoyl amiha 1 and number of strands 1 to 6
A phenyl group which may have 1 to 3 strands or 1 to 3 strands of lk& group, or a phenyl group which may have 1 to 3 strands of al + 5 oxy groups, An example is a branched L + alkyl group having 2 ti and 1 to 6 of the following.

As a substituent on the phenyl ring, a lower alkyl group, a lower a
Examples of the besilyyl group which may have 1 to 3 groups selected from co + shi group, he〇 Gesi adenoid / nido 0 group, and cyano group or lower alk + residio + shi group include besylyyl group, and 2 -,! - or 1i4-ri00 besylyl, 2-. 3-4 and 4-fluorobeslyyl, 2-9
3-or 1L4-bensyl, 2-93- or 4-3-dobesyl, 3.5-zig00 besilyl, 2,6-zigOO besylyl, 3.4-zig0lovesyl, 3. 4-difluorobecy9yl, 3.5-
5-diOmbesilyl, 2-, '5- or U4-methylbesilyl, 2-93- or 4-ethylbesilyl, 3-isopropylbesilyyl, 4-he+silbesilyyl, 3,4-dimethylbesilyyl, 2,5-dimethylbesilyyl, 2-13- or 4-meth+cybesilyyl, 2-15-moshike 4-eth+cybesilyyl, 4-isopro4↑cybesilyyl, 4-hedecylcybesilyyl, 3,4- Lumet + Cipeci Soil, 3.4-Shed +
Shibesi Soil, 2,5-dimeth + Shibesi Soil, 2-9
3-Moshi, 〈1〈4-dito-O-besilyL, 2-13-or Fi4-cyanobesilyyl, 2,4-cyanohesisoyl, 3,4-methysyl-cydio+ 3.4-ethylate, 2.3-methylate, 3.4
-t-tetramethyl, 3-tetramethyl, 3-methyl-4-90
0besisoy L, 2-riO[]-]6-methylbesisoyL
, 2-meth+cy3ri00besylyl, 3,4.5-
) Limeth+shibesilyyl, 3,4.5-trimethylbeshisoyl, 3,4.5-1-rif00besisoyL~ on the phenyl ring of 1 to 6 th- or minute &-like Al+L groups, A prime number of 1 to 6 selected from a group consisting of a direct or branched aL] + cy group, a halogen hydroxide, a nido 0 group, and a cyano group, and having fC1 to 311110m6f conversion, or a Fi station prime number 1 to 6. An example is a besilyyl group having a L+residio-dosi group of 4.

Examples of the phenylsul-based nyl group which may have 1 to 5 lower alkyl groups as substituents on the phenyl ring include phenylsulphonyl, toluesis L*nyl, +silesis L*
disulfonyl, trimethylbenzene, disulfonyl, ethylbenzene, disulfonyl, butylbenzene, disulfonyl, butylbenzene, and several 1 to 6 alkyl groups on the phenyl ring of trimethylbenzene. An example is a phenylsulfonyl group having 1 to 5 groups.

As the iIc substituent on the phenyl ring, nine groups selected from a lower alkoxy group and a horse mackerel, which is a bald radish group, are 1-5- or F
Examples of the lower alkyl group which may have a lower al+rezidio+group include besidyl, 2-phenylethyl, 1-phenylethyl, 3-phenyl, 4-phenyl,
-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpesityl, 6-enylhexyl,
2-methyl-3-phenyl, diphenylmethyl, 2,2-5 phenylethyl, 3,3-diphenylpropyl, 1,1-dimethyl-2,2-diphenylethyl,
2-Metho + Shibesidil, 3-Metho + Shibesidil, 4-Metho + Shibesidil, 3-eth + Shibesidil, 2-zu0 Mainland Shibesidil, 3-Isopro Kyoji Shibesidil, Imaichi 1tr
l-buto+cypesidil, 2-(3-meth+cypheniL)
Ethyl, 2-(4-methocypheni)ethyl, 2-(
2-ethyl)ethyl, 2-(3-diphenyl)ethyl.

1-(4-etho+diphenyl)ethyl, 3-(2-meth+diphenyl)purozyl, 2-methyl-3-(4-methofdiphenyl)purozyl, 6-(4-methodiphenyl)ethyl, + diphenyl) to beef sill, 2-ri OL beshi 5L, 3-ri 0 rubeshi L
, 4-pOmpesidil, 2-yoFbesidil, 3-F1
0-besidyl, 2-(3-lylphenyl)ethyl, 2
-(4-diylphenyl)ethyl, 2-(2-butylphenyl)ethyl, 2-(3-3-dophenyl)ethyl
L.

1-(4-90ruphenyl)ethyl, 1-(5-ruphenyl)ethyl, 3-(2-riolphenyl)zuoji, 3-(4-riolfuenyl)pu0ji Le, 3-(3-
Propyl = 1) Propyl, 3-(4-3-Dofenyl)
) Poet, 5-(3-riOL Fe=L) Pestil, 2
．． 3-methylesidio+cybesidil, 3,4-methylesidio-cybesidil, 2,3-methylesidio-cybesidil,
3,4-ethyl, dio+cybesidil, 3-1-trimethylethyresidio-bovine cybesidil, 2-(2,3-methylesidiofdiphenyl)ethyl, 2-(3,4-ethyedio+cybesidil), 1-(5, 4-methyledidiodiphenyl)ethyl, 3-(2,3-methyledidio+diphenyl)propyl, 3-(5,4-methylediphenyl)propyl, I#1-dimethyl-2-(3 , 4-Methyrezidiobovine diphenyl)ethyl, 2-methylL-3-(
3,4-1 Chileshizi Sifueni L)zu0jiru, 2.3
-dimeth + civesidil, 2.4-cymeth + civesidil,
3,4.5-1-rimeth+cypesidil, 2,4-shed+cypesidil, 2-(3,4-shed+cypheniL)ethyl, 2-(3,4°5-trimethycinyl) O
eL, 1.1-cymethyl-2-(3,4,latrimethyl-sifenyl)ethyl, 5-(3,4-cymeth+diphenyl)hecythyl, 2.3-dicol besidyl, 5. Shizu - Jig 01 Beshiji L, 3,4.5- Triku 0 Ru Peshiji L12.4- Jizu 0 Mbesho L, 3.4-Jodo Beshijil, 3,4-Shif L O 0 Beshiji 5 L, 2-Ri 0 Ru 3
-Z0 Mbeshijishi, 2- (2,3-"t90L') to L) ethyl, 2-(3,4,5-tricol phenyl)
Ethyl, 2-(3,4-dibu0mfeniL)ethyl, 2
-(2,4-JodofeniL)1 preL% 1-(3,
4-diqO' phenyl)ethyl, l -(3,4,5
-triz0mphenyl)ethyl, 3-(2,4-S)0
The number of substituents on the phenyl ring of 3-(3,4-")propyl, 5-(3,4-zig0ruphenyl)pesitel as a noodle substituent is 1 to 1. 6 straight chain or branched alpha+shi groups and 9 groups selected from 1 to 5 Ill or ti#!*@1 to
jii'$ having 1 or 21ii phenyl groups which may have 40 straight-chain or branched alk+ and may have 1&
Illustrative examples include straight chain or branched aruyl groups having numbers 1 to 6.

Examples of lower alkoxy groups include meth+cy, etoshishi, and pu0.
Bo+shi, isopropoxy, buto+shi, 1zrl-buto+
shi, peshitiro + shi, he + shiruo + shi when o ietake 1 [1~
60 A straight chain or a straight chain branch can be represented by -'.

As bald poppy glands, fluorine, chlorine, bromine and tklI
! Showing pigs.

Lower alk+Lthio groups include methylthio, ethylthio, propylthio, isopylthio, butylthio, 1t
rl-Butylthio, Beshichi IL-Ff, He + Sil 5 years old, etc. station number 1-60 straight or branched Al + L child's M & -
” can be shown.

Examples of the primary Al+Residio+Si group include methyledidio+C, ethyrezidio+C, trimethysidio+C and #prime number 1 to 4 single or branched Al+Residio+C groups.

Examples of the low acid alkanoylamino group include lumi'amino,
Acetylamino, P0goonylamino, Butyrylamino, Isobutyrylamino, Besitanoylamino, tt
ri-butylka L-bonylamino, he+linoylamino*
Examples include straight or branched alkaline amino acids having a prime number of 1 to 6.

Schiff 0 a LfL & as welfare, shiku o pujiru, shifu 0 butyl, schif 0 peshtil, schiff 0 to + sil, cycloheptyl, schif 0 octyl, etc., between car 1 [3 to 8 shifu 0 al +
An example is L group.

Phenyl Lid may have 1 to 3 groups as m*i, including a droxy group, a halogen atom, a lower alkyl group, a lower alkoxyl group, and a lower alkanoyl group. Examples of the besilyl low-alkyl group include besylyl methyl, 2-besilylethyl, 3-besilyylpyl, 6-besilyylbutyl, 4-besisoylbutyl, (2- or 3-meth+sibesilyyl)methyl, 2-( 4-meth+cybecysyl) ethyl, 2-ethythocybecy9ylmethyl, 1-(3-ethycecybecylyyl)
Ethyl, 3-(4-ethocybenlyyl)propyl, 6
−(4-isopropocypecylyyl) + sil, 4-(
4-he+silo↑sibesilyl)butyl, 1,1-dimethyt-2-(3,4-dimeth+sibesilyyl)ethyl,
5-vesilii L-vesityl, 5-(3,4-shed+sivesilyyl)vesityl, 6-(5,4,5-trimethoxybesilii L)he+sil, 2-methyL-3-(2,5-
(2-dimethyl) methyl, (3-methyl) methyl, (4
-Iodovesylyl)methyl, 2-(4-)L)ethyl, 1-(3-lyOI]vesyl)ethyl, 6-(4-propylene)methyl, 5-(5
,4-! ; ri00besiliiL)peshitiL, 1,1-dimethylL-2-(2,5-dibe Ωmbeshi9il)zu0jiru,
(2-
or 3-methylbesisoyl)methyl, 2-(4-methylbesilyl)ethyl, (2-ethylbesilyyl)methyl, 1-(3-ethylbesidiyl)ethyl, 3-(4
-Ethylbesisoylump0vir, 6-(4-isoprop0dirubesilyyl)to+sil, 4-(4-to+silbesidiyl)butyl, 1.1-:! ;Methyl-2-(3,4,;
Methyl beslyyl) ethyl, 5- (3,4-≦ethyl besilyl) besityl, 6-(3,5-5 methyl besilyl) ethyl, 2-methyl L-3-(2, large methyl phenol, ethyl) , (2-acetyl-3) methyl, (3-$L) methyl, 1-(3-jD dionylated-3) hesyl-L) ethyl,
6-(4-〃-Butyri LP Minobesirii L)+sil,
2-(5-besitanoylatrinobesilyyl)ethyl, 4
-(6-hetoichinoylaminobesilyyl)butyl, (2
-, 3~ or even less do○+shibesilyyl)methyl,
2-(4-ethyl)ethyl, 1-(:l
-edo0+sibesilyyl)ethyl, 6-(4-shido0+
1,000 syl, 5-(3,4-dihydrocybesisoyl)pesityl, 1,1-dimethyl-2-(2
, 5-dihydro-propyl, (3,4,
5-) Rinichido 0 Cow Shibeshirii L) Methyl feeding Feniti
As a turtle substituent on the
3111kl-6c + kiln or branched al + l group, yellow book 11 kl ~ 6 kiln-mata branched a L ] + shi group, Ekidakahan l ~ 6 1 kl or branched a L Select from the three salmon of power, Maru & 1-3 or Warabi 1-4 Al +
Examples include straight or branched alkyl groups having a besisoyl group which may have a residio+sil group.

Fueni L lump top Kk! As a group, lower alkoxy group t-1~
31611! Examples of phenyl lower alkanoyl groups that can be used include L, phenylprohionyl, 2-phenylprohionyl, 2-phenylprohionyl, 4-phenylthyl, 2,2-dimethyl-3-phenyl, Dear Oniru,
5-Phenyl Pesitanoy tfL, (3-etho+dipheniL) acetyl, (2-'jOpojenyl
) acetyl, (3-isoprobo+diphenyl)atfL
, (4-ttrt-dutodediphenyl)acetyl, 3-
(3-methoxydiphenyl)polydionyl, 3-(4-methoxydiphenyl)polydionyl, 3-(2-etho+diphenyl)diyonyl%3-(3-methydiphenyl)
%4-(2-methoxyphenylene-L)-tyryl, 3-methyl-4-(4-meth+cipheni-L)butyryl, 6-(4-metho+cipheni-L) + Sanoi-L, (2,
3-, methoxydiphenyl)acetyl, (2,4-dimeth+diphenyl)acetyl, (3,4,5-)rimethodiphenyl)acetyl, (2,4-′!:Ieth+siphenyL)acetyl, 3 - (3,4-diethoxyphenyl)dionilyl, 3-(3,4,5-)rimeth+diphenyl)dioniyl, 4-(2,3-dimeth4diphenyl)butyryl, 4- (3-Metho+C)Butyryl, 2,2-dimethyl-3-(3,4,
5-trimethane, 6-(3,
4-dimeth + diphenyl)
IjL#Ii of selection plates 1 to 6 as wrinkle crystals on 1ilI
Examples include 2 to 60 straight or L-shaped alkanoyl groups containing a phenyl group that may have 4 or branched 4#, #al]+sil group at 1 to 3.

11! ll11 to do 0shi group or hao 'f
) Lower alkyl groups which may have atoms include straight-chain or branched alkyl groups and O
O-methy, di-methyl, iodomethyl,) di-oro-methyl, 2-ethyl, 2-ethyl, 2- or 3-ethyl, 2-fluoro-methyl, 3-iodo zu0 pill, l-methyL-2-900ethyl, 2-,
3- or 4-zu0muzuchiru, 3-riDOzuchiru, 2
-3-doptyl, 4-dimethyl, 1,1-dimethy3, -2-butyl, 2- or 3-pexyl, 4-pyl, 6- To ri00 + sill, 5
-zuO Mvesina L, Shido 0+ dimethyl, 2- Shidoro 1,000 diethyl, 2- Shidoro + ShizuD Hill, 2- Shidoro + Diptyl, 3- Human 0 + Shizuojil, Shido - Shido 0+ diptyl,
3-Human 0↑diptyl, cypestil, 6-
Gen 111 [1 to 6 (D
An example is @@ or a branched alkyl group.

A bald atom or lower atom as a substituent on the phenyl ring
Examples of the L group for phenyl lower alkenyl group 1 which may have 1-1 groups include silna-tyl, phenyl-3-butenoyl, 4-phenyl-2-butenoyl, 5
-Phenyl-4-besitenoyl, 5-phenyl-5-besitenoyl, 5-phenyl-2-besitenoyl, 6-phenyL-5-+t Noyl, 6-phenyl-4-+t
NeuL, 6-phenyL-5- to bovine t-noyl, 6-phenyl-2-to+t-noyl, 2-methyL-4-phenyl-5
-butenyl, 2-methyl-sicina7yl, 1-methyl-ylyrnyyl, 2-. 3-or OO-Syl, 2-. 3-4L〈is 4 to full fO shishinanayl, 2-. 3- or 4-zu0 mushiinatyl, 2-1
3- or 4-iododyls7-yl, 3,5-dikuo
o Sil Ding T Il, 2.6-! ;ri00shishisutil, 3
, 4-dikuOOsilnatyl, 3,4-difluoroDsilnatyl, 3,5-difluoroDsilnatyl, 3,4.5
-Toriku 0 Rossi Shisu Seven Il, 1-Furufa Fueni L-3
-PtenoyL, 4-(3-90Lofenyl)-2-dutenoyl, 5-(4-P00mphenyl)-4-pesitenoyl, 6-(3,4-dibu00)12L)-5- Noyl, 2-methyl-(2,5-dibutyl)-methyl, 1-methyl-(3-dimethyl, 6-(3,4,5-triphenyl)-3
-to + senoyl, 2-. 3-, or 14-meth+sil: ,, 2,3-or 1i-eth+silyl, 2-93- or 4-methoxyl
il, 2-butojushi, / shije yl, 3- (lz
rg-buto+ci)cil 1t-yl, 髫-peshityluoshisilcinnat-yl, )-to+silo-decilcinnat-yl, 3.5
-dimeth+silcinatyl, 2,6-dimethodocylcinyl, 3,4-dimeth+silcininyl, 3,4-shed+silcininyl, 3,5-sheddecylcinyl, 3,4 .5-) rimeth + silcyityl, 4-etho + cypheni L-3-butenoyl, 4-(3-1trt
-buto+diphenyl)-2-butenoyl, 5-(4-hedecyl-diphenyl)-pesitenoyl, 6-(5
,4-! ;Metho+Sipheni L)-5-to+tnoisi, 2
-Methyl-(2,5-shed+sipheniL)sil'f℃
Ishi, l-methyl-(3-meth+sipheniL)dilus
yl, 6-(3,4,5-)liethodiphenyl)-5
− to
3 to 6 1- or branched alkenyl groups having stationary bulk L
An example of this is Boni Llk.

Examples of lower alkanoyl groups include acetylmethyl, 2-acetylethyl, 2-acetyl [,
3-atfL, 4-acetyl, 3-acetyl, 5-acetyl, 6-acetyl +
ShiL, 2-zu0 pionyl ethyl, 3~this RusanshizuD hit
, 2-Punalylph Oe1.4-Isoptyrylphthyl, 2
-pecitanoylethyl ttrl-butyl carbonyl,
IR volume of methyl-2-acetyl ethyl fat! 1 to 6 linear or branched aL
Illustrative examples include a straight or branched alkyl group having an i1noyl shape.

As the lower alkyl group, meth+silyl-nylmethyl, 2-(meth+silyl-L1-nyl)
Ethyl, ethyl + dicarbonyl methyl, l-(eth + dicarbonyl) ethyl, 3-(meth + dicarbonyl) propyl, probo + carbonyl methyl, 2-(10 dicarbonyl) methyl, 4 -(buto19dicarbonyl)butyl, 1-(buto19dicarbonyl)ela1,1trl-but+cycarfonylmethyl,
3-(tzrl-buto-thousandicarbonyl)propylene, pesityl+silo+cyclomethyl, 2-(he+silo+cyclocarbonyl)ethyl, 5-(methoxycarbonyl)pethyl, 6-(eth+ Stations such as Chicalhonil) + ShiL! Il
Number 1 to 60 direct or branched alkyl + dicarbonyl group to 1
do#! Examples include straight or branched alkyl groups having a bulk of 1 to 6.

The 5-membered or #i6-membered O-compound complex formed by 12 and R3 includes diOlydino, 1-diberidyl, 7ruphorino, l
-diperazinyl, 4-methyl-1-diperazinyl, 4-
Ethyl-1-diverazinyl, 4-methyl-1-diberidyl, 2-methyl-1-pibericyl, 4-proyl-1-
Perazinil, 4-butyL-1-goberazinil, 4-isozuOgolule'(5:,;2L,4-ttr
t-Butyl-1-diperazinyl, 4+5et-butyl-1-diperazinyl, 4-besity-1-diverazinyl, →-hetyl-1-diperazinyl, 4-ber5yl O-lysine, benzyl-l-diperazinyl, 3-benzyl-l-diperazinyl, 4-benzyl-l-diperazinyl,
3-(2-phenylethyl)-1-diberidyl, 4-(
1-Phenylethyl)-1-hyperidiL, 4-(3-phenyldi0dyl)-1-diveracinyl, 4-(4-phenylbutyl)-1-dibericyl, 3-(6-phenyl+sil) )-1-diberidyl and 4-(4-phenylbutyl)-1-dipelaginyl are examples.

11LIFM05.6.7 and ti8th place.

- The compound of the formula (1) is, for example, the first reaction formula - reaction stroke IM length -1 #2 (2) (1
) [In the formula, R1, R2, R3 and carne styryl skeleton 03
The 1st and 4th place OI #Kakaseki combinations are hooked to the record. ] The method shown in the above reaction step-1 is based on the combination of a rickshaw styryl derivative represented by the general formula (27) or an aged conductor that has been converted into a rickshaw styryl derivative represented by the general formula (27) and a rickshaw styryl derivative represented by the general formula (27). J* is carried out by reacting the amyl or its amino acid with a compound that can be activated in a reaction to form a amide bond. Synthetic acid anhydride method, e.g. d carbostyryl hook conductor (2) K Al +
A method in which L is reacted with carbodiic acid to form a mixed anhydride, and amyl (3) is warped on this; A method of reacting a, nidi (3) with a ester of fue-rueste L, N-sido-O decisuccinic acid diester, l-1-do-O+cypessiditriaryl ester, and (3); e 14
4-stop (2) Amil (31 to Ziruk 0 10 Zirka L book 3, Kal army 2 L 5 I 3 Taril etc. method to combine in the presence of viscous fossil; to) Other O force, e.g. Kal A method to make Amil (3) retaliate by changing Table Stitch Lm Guide (2) to acetic anhydride, etc.0 theory water A41 and making Amil (3) react to it, Cal Army Stiri L Cavalry Stop (2) and low class A41. Amil (3) is reacted at 1 V pressure and temperature with the L]-le, and the carbostyril cast conductor (2) is converted into an acid halide. How to make reaction (3) take place can be done depending on the situation. It is also possible to activate Mayu carbostyril conductor (2) with a triphenyl phosphide or diethyl sulfate compound, and then convert it into amyl (J5L!lA).

In the mixed acid anhydride solution shown in k) K above, the mixed acid anhydride Fi used is obtained by the usual Schottessee Baumashi reaction, and is usually reacted with amyl (3) without isolation. In particular, a compound of the general formula (11) is produced.The Schottsey-Baumashi reaction is usually used to produce a compound with the general formula (11). Methylanilisi,
N-methyl heptal 1.4-p azajischiff o (2,2,2
) octacy (DAkjCU) - group and potassium acid, sodium envyate.

Potassium hydrogen leg acid, j! Diacid hydrogen hydroxide sodium 9 peaks 6 to 50
The reaction between the anhydride and the amino acid; b) RJ is carried out at FiIO ~ 50° C. for rJ S min ~ lO hr, preferably J 5 min ~ 5 #&threshold.

In addition, the above 11c mixed acid anhydride is a combination of mixed acid anhydrides and four commonly used acids, specifically yc is methylene chloride, riOO rum, jig 00 etashi wa 0geshi conversion water. 'k114
, beshiseshi, to'niji, +jirushi, etc. O aromatic group stationary water 3, diethyl ether, tetrashi FO fluoride, dimethic acid 10, ethyl group ether, #acid methyl, age enemy ethyl group esthetics LJII4, h The process is carried out in the presence of an excess of 1 kl IM rope such as non-polar polar bath ropes such as , N-dimethyl trifluoride, dimethyl sulfur trifluoride, and hesyl methyl chlorine trifluoride. The above mixture #i7 is used in the original 9th grade as O Cal rate as 00 methyl formate L1 DE methyl formate, 200 ethyl formate, fotm# ethyl, 00-isobutyl acid. Koji is an example of Koji, and Nijima is at least III-III for derivative (2), preferably f-! ~2 times as many graves. In addition, (I) C) the binding is preferably at least 1 to 2 times the value of λ, and preferably about 1 to 2 times the value of λ.

The above-mentioned KiF active ester droplet is, for example, N-11
Example 1C shows the case of using doo + c]
The attack is carried out in an unreasonable manner that does not give any chance to the reaction. #I ropes include specific KFi-loaded methane, ri00 rum, diku 0 rope, etc.
lIh like, beshideshi, torunizi, fjirushi, etc.'s 1&translation Mizutake - 15 ethyl ether, tetrashi FO flazi, dimeth ↑ sietashi hao's ether ship, 1 string methyl, drunken ethyl hao's ester - 1tw, N -5 methyl lumua tride,
Examples include mimethylsuruhongyu υdo, he + limethyllisi aya tria three do tVJv-pu0toshi polarity #1 rope, etc.

The reaction is completed in 5 to 30 hours at 0 to 150°C, preferably FiIO to 100°C. (8) and N-shidoro+shikohaku imidoesthe [drinking sweetfish name d, for the latter, it is desirable to make &I41 at least 1 liter, preferably 1 liter to 2 liters.

When employing the reaction method (3) in which a reaction field is applied to KiF (as described above), the reaction is carried out in the presence of a dehalogenated woody field. . As this crest-shaped 0-geshi converted water hawk copper, JIIIN's carpenter compound can be used, and as the 4M compound, well-known compounds can be widely used. Compounds such as sodium hydroxide, water-forged potassium, woody sodium, woody potassium, ji2il
&, Sodium methylate, Puttrium ethylate, Alclad, etc. can be used. Hammer, Ami: J (
J can be used for sharks as a sea bream water treatment for Hanha O). As a yukata rope, the above shotte sea tS Umashi IX
For example, methanol, ethanol, 'jo bano 1, tanol, 3-meth+9-
1-Butanol, ethyl alcohol 70 solp, methyl chloride 0 solf halo alcohol, jiri 5 shi, at toshi, acetonitrile haze or upper t! #1 You can sit in two or more mixed baths. The imitative combination of (3) with carboxylic acid halide is not particularly limited and is selected within a wide range of 1ikIv5, but it is usual to favor the former and at least a little of the latter.
The reaction is carried out at 11-30 to 180°C, preferably 0 to 150°C, and generally for 5 minutes to 30°C. The reaction is completed in between.

In the above, the carbostyryl # conductor (2) and the halogelling agent are not used for the carbostyryl # conductor (2) and the halo gelling agent.
#By reacting in the presence of rope! Manufactured. As a yukata rope, any one that does not give the shadow 1 is tf
& Can be used, -J can be used for fragrances such as beshiseshi, torunigi, +jiru/shi, etc. Examples include ethers such as 5-year-old sashimi, tetrashidorofurazi, 5-ena-lambda ether, dimethyl ester, dimethyl sulfo+cyto, and the like. As the halogenation agent, 32iI-rich copper halides can be conveniently used, in which the hydroxyl group of the carboxylic group is reduced to a halogen, such as tj thionyl chloride, O + oxybromide, O + oxybromide, Examples include gomokukasushi and gobrokasushi. The power table Styril cavalry conductor (2), the halogenated field, and the 1st case for 0* are especially selected at random, and when the reaction is performed under a no-bath rope, -% mark J is observed. If the reaction is to be carried out in a hot bath, the latter should be added in an amount of at least 0 μl, preferably 2 to 4 μl per 1 min. There is a circle in 1. Isn't that reaction attitude (and reaction time) also especially 1 added, im 'ih"!i
ri temperature ~100℃ moderately good, mountain pass IL < FA 50~8
At 0°C, 30 minutes to 6 hours of hydration is carried out.Matahirimoto Stiri L conductor (2) is activated with a lithium compound such as triphenyl phosphide or diethyl 20 phosphate, and then amici (3 ) is 1m,
It can be performed in a proper bath rope. Here f # as a rope F
You can drink anything that does not affect the i-reaction, but specifically KFi woodcutter methane.

ri 00 holmjig 00 etashichi O ha 0 Geshi ka Hiroka hydrogen order, Beshi Seshi, Torniji, Ushijirushiho O Yoshu & translation water 3
esters, diethyl ether, tetrofluorinated acid, dimethic acid ether-1st methyl acid, ethyl acetate, etc., N,N-dimethylformamide, dimethyl sulfate, triethyl trisilicate In the above reaction, amici (3j itself acts as a basic compound, and by using one amount of this in an amount lower than the amount of coffee, the reaction is good. However, if necessary, other oborobase compounds such as
Triethyl LF misi, trimethylamisi, diridyl, dimethylanilisi%N-methyl℃rumotosu 5, nBN, DBt
Inorganic bases such as KUIMM potassium such as y, n1Bco, thorium sulfate, potassium hydrogen urate, and phthorium hydrogen chlorate can also be used. The reaction FiF+o~
The lithic compound and amici (3
) is usually at least equal to ttt, preferably 1 to 3 times El lid.

7/ , , / Among the cal ratio styryl rust conductors represented by the O-h formula (1) of the present invention, compounds having a basic group can be easily converted to p1 by acting with an acid acceptable in @Juku. It can be an acid addition salt. For example, salt #5 is an acid, ricinic acid, hydrobromic acid, or an inorganic acid.

Mention may be made of organic acids such as oxalic acid, malic acid, fumaric acid, ricinic acid, tartaric acid, citric acid, and benzoic acid.

Target compound 4iEiFi in each step obtained by guessing
However, W4 can be more easily isolated using the separation method of Takitomi. Examples of the separation means include a bathtub extraction method, an abrasive method, a recrystallization method, and a kalamuku 0 madotarahui 1 prebarataipu #kori 0 madotarahui.

Incidentally, the present invention naturally also includes optical isomers.

Compounds of general formula (1) are usually used in the form of common pharmaceutical preparations. Fillers commonly used in manufacturing, increase 1[M, &iin agents, moisturizing agents, disintegrants, surfactants,
It is prepared using a diluent such as a thickening agent or a pot-shaped agent. Various forms of this pharmaceutical preparation can be selected depending on the treatment, and representative examples include 1 pill, powder,
Examples include liquid preparations, stimulant preparations, emulsions, granules, force-controlled L preparations, semi-drugs, and injection M (solutions, suspensions, etc.). When forming into a tablet, a wide variety of carriers known in the art can be used, such as milk-1 sucrose, thorium, grapevine, urea, deshizushi, calcium calcium, and phosphorus. , crystalline cellulose, potable preparations such as KeitlI, water,
Ethanol, 1 liter of grapes
I &, Desipsi Wave, Zera Chishi #I liquid, Karuho + Shimechi L
Binding agents such as t-ruse, t-lac, meyoILtL[]-su, rishiken potassium, borivinyl hydride, Kkendesipsi, strium alph-silate, Kasiteshi powder, Usanbashi powder , sodium hydrogen sulfate, esters of calcium sulfate, esters of fatty acids, lauri L
Sodium sulfate, stearic acid heptanotalihylide, deciduous, lactose, etc., 1aM, sucrose, stearic acid, cocoa butter, water and IA-added oil, etc. TP*m inhibitors, quaternary acyl base, sodium lauryl fR acid Rice stimulants such as glycerin, moisturizers such as Decide, Decide.

Ill agents such as lactose, lactose, becitosuite, colloidal silicic acid, purified talc, stearic acid, boric acid powder,
Cleaning agents such as polyethylene cyclohol can be added. moreover! lIi! Tablets prepared by applying the same formulation to the drug #i, such as cylindrical tablets, gelatin-covered tablets, bath-covered tablets, film-coated tablets or 2]L-packed tablets, and multi-layered tablets. Can be done. When forming a round steel plate, a wide variety of carriers conventionally known in this field can be used, such as glucose.

Excipients such as emulsions, decimals, cocoa powder, hardened oils, talc, etc., binders such as arabicum powder, tragacite powder/gelatin, ethanol, etc.

Examples include mayo 1a agents such as Laminarashi and Kashideshii. When molding into the form of a locust, a wide variety of materials known in the art can be used as the partner, such as polyethylene diglycol, cacao butter, higher alcohols, esters of higher alcohols, Zeratis, semi-synthetic silitrides, etc. can be mentioned. When manufactured in-house as an injection, the liquid and 1IAAil are preferably yli and blood and samurai, and these are formed into the form of T& fine, emulsion and string koji. As a diluent, all those commonly used in this field can be used, such as water, ethyl alcohol, diglycol, isostearyl ethyl ocyanate, and diluent. Isostearyl alcohol thiocytide, polyoxyethyl didecyl alcohol
Examples include jI/J#I Esthetics Lk4.

In this case, an iso-strength bath solution may be prepared (sufficient Jk salts, glucose or glycerin may be included in the tablets, and the tablets may contain the usual stimulatory aids, laxatives, pain relief agents, etc.). A curing agent or the like may be added.

Coloring agents, preservatives, perfumes, flavoring agents, sweeteners, and other pharmaceutical agents may be included in the sample formulation, depending on the gloss.

Thus, medicine I is made of steel! The amount of the O compound of general formula (1) to be contained in the ia (cardiotonic agent) is not particularly limited and is selected from a wide range, but is usually 1 to 7 in gold Mmm-
The amount is preferably 1 to 30% by weight.

19 There are no particular restrictions on the above method of administering inotropic MO, and it is subject to various conditions such as the age of thinking, gender and other conditions, disease, JIO.
It is administered according to the previous method depending on the condition.

For example, tablets, round steel, enemy fields, Ill katado, emulsions, granules, and force! In case of L formulation O, it is administered orally. In addition, in the case of notable NM, KU can be administered intravenously alone or mixed with a 0M solution such as grapes, amino acids, etc., and can be administered alone intramuscularly, subcutaneously, subcutaneously, or intraperitoneally depending on the needs of the patient. . In the case of ischia l1iII, it is administered rectally.

The dosage of Ichito Kiyoshi 1 Lo drug is appropriately selected depending on the usage, patient's age, gender and other conditions, degree of disease, etc., but usually the mFi of the compound of general formula (1), which is the active ingredient, is reduced per day. Approximately 0.0 kg per Ikg. It is preferable to set OI to 10■.

Further, it is preferable that the dosage unit form contains 0.1 to 200% of the active ingredient.

/″ /″ 7/ / 6-Carboshi Sea 3.4-Jishidoroki L Boss Chili 13.
51 is interpreted as dimethyl booklumua Σdo 30sJKjl. Add 2.41 grams of triethyl amici to this. While stirring and cooling with ice water, 2.75 f of isobutyl chloride was added dropwise and the mixture was stirred for 30 minutes. To this was added KN-methyl-N- under stirring at iii temperature.
3.19 f of <4-methoxy)benzylamine are added dropwise and stirred for 5 hours. The reaction solution was concentrated and dried, and extracted with RI00 form and an aqueous solution of IN thorium oxide. ri0
Wash the 0 form layer with water, add ether to the residue and crystallize it.

This was recrystallized from methanol to form colorless needle-like 6-[N
-Methyl-N-(4-meth↑sibesidyl)carb7yl)-3,4-dididrocarbostyril 1.84 ft- is obtained.

Waste door, 144.5-146.5 ℃I*Example
2 The following compound was obtained in the same manner as in Example 1.

06-(N-Methyl-N-(3,4-methylesidio+sibesidiL)carhetyl)-3,4-dihydrocarbostyryl solution, 170-171 °C Colorless lithium crystals o6-CN -Methyl-N-(4-riOlupesidyl)ph”
171.5 ~ 172.5°C colorless prismatic crystals 3,4-;
6-Calhon f sylate 127 ~ and diethanolamic acid 3
9 drops were dissolved in 2d of dimethyl hydroxide and stirred overnight. Water is added to the reaction mixture, extracted with 000 form, and washed sequentially with water and saturated iK brine. After drying with sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was crystallized by adding acetate to give 6-(!; ethanolamizuka L-bonyl).
-3,4-dididrocarbostyryl 48MII is obtained.

Cod door, 131-134℃ Dormitory Example 4 6-(jetanolamizuka L-bonyl)-3,4-dihydrocarbostyryl 2.2fK Thionyl chloride 301 was added, stirred at room temperature for 5 hours, and then concentrated under reduced pressure. Brain, then add Besisese 50 resistance. Repeat the vacuum concentration operation three times to obtain 6-1 [di(2-di-OL-eth-IL)) Amitsukka L-boni-IL-3, Shi-di-sidodrocarbostyril].

East Example 5 Succinimide 3.4-'': r-drocarbostyryl-6-carboxylate + sylate 1. (l and seven-carboxylate 0.3
71 and dimethyl lumatrido 25 (KJI interpretation).

Stir for 3 hours. Water is added to the reaction mixture, extracted with 000 form, and washed sequentially with water and saturated brine. After drying with sodium sulfate, the solvent was distilled off under reduced pressure [2. Add Ashitoshi to the residue to form an island. This yields b-tt-based uncarunyl-3,4-dihydrolyzed styryl.

Collection j1 15011 Wanido, 206-207°C Colorless granular crystals Example 6 Succinimide 3.4-Cydrocarbostyryl-6
-Carbo + sylate 127~ and besidyl jiberajishi 93
#I was dissolved into dimethylene trichloride and stirred overnight. Water was added to the reaction mixture, extracted with fresh O-form, and washed with water and l1ii Japanese food water. value#! Dry the ridge with sodium and remove the yukata under reduced pressure, and add Ananatoshi to the residue to crystallize. Recrystallized from ethanol to obtain 6-(4
-besidyl-1-diveraginyl)-3,4-
Colorless needle crystals obtained at 3°C, 198-200°C in the same manner as in Example 6 using appropriate starting materials to obtain Sunaryl 130~.
*Compounds of Examples 1 and 2 and compounds of Examples 7 to +15 below are obtained.

Example 7 Decomposition: 271-274°C (decomposition) Colorless needle-like crystals Example 8: Decomposition: 240-243°C (decomposition) Pure-colored flakes Example 9 1-1 Mu: 211.5-213°C Colorless needle-like crystals Crystal East -10 Temperature 240-242℃ (decomposition) Colorless granular crystals Example II Solution, 280-283'C (decomposition) Colorless flake-like crystals★Am%12m 284-287 °C (decomposition) Example 13 6-C4-C4-Metho1,000-cybecyle)-1- and feeder, 2
62-264°C (decomposition) Colorless granular crystals Example 14 Misaki To, 300°C or higher colorless needle crystals Example 15 Maroto, 268-27 + 'C (decomposition) Light color granular crystals Example I6 Mayu To, 238-239.5°C [Gold-colored granular crystal] 17 Bostiril L Shoulder door, 294-297°C Meat drop (Color *i E ji Arrow 1←118 L Bostiril Crocodile door, 247-249°C Colorless first 19 o-C4-<3-riOO-besi-soil)-1-goberadini-L-iriri-unyl)-3,4-shishidrocarnestyril cod door, 258.5 ~ 260°C Colorless powdery crystal East Example 20 o-C4-<4-p0mhesilyl)-1-piperazinylcarbonyl)-3,4-dihydrocarbostyryl #1, 265.5-267.5°C Colorless Powdered Crystal I*Example 21 Power L Bostiril L Shoulder 265-267°C (decomposition) Colorless granular crystals Example 22 Bostiril, 287-289°C (decomposed) Light color granular crystals? j23 posturi horse.

Ichinohe, 262-264.5°C Colorless phosphorus foliate wit 24 Riru solution Door, 243.5-244°C Iron-colored granular i True & ←+25 /)-, Cable #Mochichomu 258-259. 5°C (decomposition) Colorless powder book-like crystals 6m 126 -3.4-; Cito0 Carbostyryl A water N"evJ cocoon 199-202°C (minute 1!1) Colorless powdery crystals Example 27 Mo-[4-(to-toluesisulhonyl)]-1-diverazinyl-l-3,4-dishido-0-l-bostyril shoulder, 280-282°C colorless granular powder Example 28 Le cicada Door, 115-116.5℃ Colorless needle-like crystal crystal Example 29 Riru-house, 180-182℃ Colorless powdery crystal cage ft++ 30 Example 31 Chili t・1 woodcutter #1 - colorless flake crystals heated over 100°C Example 32 Fukunmei 1w door, 292-293.5'C (decomposition) heated colored flake crystals Example 33 Salt, 235-238°C (decomposition) Colorless schistose Example 34 6-(4-P-D-LfL-1-hyperazinylcarbonyl)-3,4-dihydrocarbostyryl. L Salt #Salt Cod Door, 249-25 Otori'C (decomposition) Colorless granular crystals!*Example 35 Lupostyril 141 acid to Asahiichi 264-268℃ (decomposition) Colorless granular crystals Refreshing Example 36 L Bostyril, I woodcutter M salt j7. 151-153°C (min. m) Pot-colored powdery crystals Example 37 One house, 254-257°C (decomposition) Colorless powdery crystals East Example 38 Decomposition 269-272°C (decomposed) None 6 Powdered crystal 5*Example 39 m door, 257-259℃ (decomposition)Iron color powder woody island East Example 40nj door, 213.5-214.5°C Selfless granular crystal East Example 41 6-( 4-(4-AttyluaΣnovesidil)-Sea bream 7.2
29-231.5℃ Colorless powder crystal Example 42 Cocoon, 174-176℃ (decomposition) Colorless powder crystal 5*N43 Chiril m Door, 145-146℃ Colorless schistose! *Example 44 Temperature: 239-241°C Colorless powder, crystalline crystallization - +45 1 dihydropower L bostyryl 1 salt #Yellow, 261-264°C Colorless powder, Example 46 -3. ．． 4-,:;j Dorocarbostyril 1 hydrochloric acid preparation 137-139 °C (decomposition) Pale negative color powder Book-like crystals Example 47 Decomposition, 181-183.5 °C Example 48 6-(4 one piece! Niru 1-piverazinyl force rubo two L)
-3,4-jishidrocarbostyril pottery, 198-20
1"C (decomposition) Colorless powdery crystals 9L! Example 49 Dolocarbostyril I jt [M salt net, 160-164°C Colorless needle crystals Example 50 Dishidoro 211L Bostyril crocodile 251-255° C (decomposition) Dark colored powder crystal Example 51 Bostyril dihydrate layer 277-279°C (decomposition) Colorless ridge-shaped crystal Toshibutsu 52 Futo, 170-+72.5 °C Colorless needle-like crystals s*Example 53 M door, 277-279℃ (decomposed) Colorless ridge-like crystal Example 54 Misakimu 173-174℃ Pure color powdery crystal★JIi$155 Sea bream 212-213.5℃ Colorless ridge-like Salmon 1 °C Colorless acicular crystals! *Example 58 Bostili It-1 Woodcutter! 1 layer, 250-252°C Colorless granular crystals East Example 59 6-14-C3-(3-90Ωphenol↑shi)propyl)
-1-piperazinylcarbonyl 1-3.4-cysidocarbostyryl 1 part #jmm mm 254-256.5°
C (decomposition) Colorless acicular crystals I* Example 60 Sea bream door, 256-258"C Colorless powder woody crystals Higashi 1 example 61 Cicada mu 265-266.5°C (decomposition) Waxy colored lisi schistoses 1* Example 62 Colorless needle crystals (decomposed) 9270-272°C (decomposed) Colorless needle crystals Example 63 1111 #Kojimu 164-166°C (decomposed) Colorless needle-like crystals Example 64 Door, 249-25+, 5 °C Colorless powder crystal Higashi Example 65 Chiril 1 woodcutter #11 salt A hydrate - Door, 212-215°C Colorless powder Wiki crystal Higashi Example 66 6- (4-( (4-methofcybesilyyl)methyl]-
凰一jibe 5-dinylcarbonyl j -3,4-5 dorocarbostyril 1 hydrochloride Goto, 266.5-269°C (decomposed) colorless powdery crystals Example 67 Doo, t + t bostyril 1 -Acid acid/% hydrate information 24
2-245°C (decomposition) Colorless Rishi flake crystals Example 68 Dorocarbostyril 1 Asahi sapon salt False aquarium screen door, 14
3.5-146°C (decomposition) Colorless powder crystal I*Example 69 Dorocarbostyril 1 salt rj1 salt m 270-272°C (decomposition) Colorless powder crystal★Example 70 Product, 162- 164°C Colorless powdery crystals'*jHIJ71 Nonstyryl monohydrochloride acid salt, 205-207°C Colorless flaky crystals Example 72 Lupostyryl monochloride salt I hydrate Cod 6241-241. 5°C Colorless needle-like crystals East Example 73 6-(5-besylyylpesityl)-1-carbonyl')-1,4-dihydrocalbostyryl-l to hydrochloric acid 1 Hydrate swp, 239-242°C Colorless powder crystal 1 * applied←i74 Decomposition 230-233°C (decomposition) Oil-colored powder ice crystal '414 Example 75 Hydrate decomposition, 238-240° C Colorless powdery crystal ★Example 76 Shakugi Wamono Wanito, 225-228℃ Colorless powdery crystal Example 77 - Dishidrocarnestyril Shouldato, 224.5-226℃ (decomposition) Colorless crystal Flaky crystal '9e Example 78 Hydrate 204-205°C (decomposed) Colorless ridge-like crystal Example 79 Monohydrate 0-209 Colorless powdery crystal! *Example 80 Misaki To. 239.5 ~ 24'1.5 °C Colorless granular crystals! *Exercise-]81 Solution/. 2 8 1~284℃ Colorless grain crystals*kfAJ82 mm 225~227℃(decomposition) Colorless powdery crystals'*Example 83 L-rate styryl sea bream Door. l 5 6 - 157.5°C colorless lichen flakes Example 84 0 Carbostyryl monocarboxylate % hydrate open door. 239～
241℃ (decomposition) Colorless powdery crystals Example 85 ・1 Hydrochloride decomposition 220-222℃ (decomposition) Colorless powdery crystals East Example 86 Acid kojimu 240-242℃ (decomposition) Colorless edge-shaped crystals Example 87 Colorless granular crystals at 300°C or higher Example 88 Colorless granular crystals at 300°C or higher Example 90 Colorless powdery crystals at 300°C or higher 289°C (decomposition) Refreshing example 91 Acid salt 290-293°C (decomposition) Colorless powder crystal Example 92 Salt layer muco 00°C or higher Colorless powder crystal Example 93 6-(4-isobutyl- 1-diperazinylcarunyl)
Carbostyril 1 citric acid % hydrate Kaido, colorless powdery crystals above 300°C Example 94 6-(4-(3,4-zig00besidyl)-1-piperazinylcarbonyl) Carbostyril 1, acid lumber, dynamic hydrate #1, 300°C or higher, ornate-colored powdery crystals Example 95 Taito, 300°C or higher, scorched nail-shaped island 6-ka 196 5-(4-isobutyl) -1-Jibera Jinilkar FujijL
) Shirikorimoto styryl L hydrochloride A hydrate #p 25+-
254°C (decomposition) Iv color Japanese wood crystal fresh IMvAI97 woodcutter, 2 2 7-2 29°C Colorless powder crystal Example 98 Acid acid/A hydrate m, 181.5 to 184°C Colorless powder crystal Example 99 Acid salt 1 unit, 226-228.5 °C Colorless powder crystal Example 100 Tyryl monosalt % hydrate 236-239 °C (decomposition) Colorless powder crystal implementation Example 101 6-(2-methyl-1-diberidylcarbonyl)-3,
4-Diish FO force Rubostyril cape z, 162-164°C Colorless powder crystal Example 102 Solution? , 260 to 262°C (decomposition) Colorless & crystalline Example 103 tnmu 262 to 264°C (decomposition) Colorless powder <K Crystal Higashi Jm? +104 -I), 205-208°C (min PN) No color 1 fox
i6 Mei-Example 105 7-(4-(2-phenothenodiethyl)-1-dibostyryl 1-asahi acid Nakaito, 177-180°C Colorless lichen flakes Example 106 8-(4-isobutyl) -1-piperazinylcarbonyl)
Power L Bostyril 1 salt gorge loam 251-254°C (decomposition) pot-colored powdery crystal implementation @l07 w woodcutter trout door, 182-184°C colorless powdery crystal Example 108 8-(4-(3- phenyl)-1-diverazinyl chloride carbostyryl 1-carbostyril salt 1117.1
95-+96°C Colorless powder crystal Example 1 l 09-z, 238.5-240'c Colorless powder Example 110 tnp, 238-239° (゛(decomposition) Colorless powder Example 111 m p , 232-234°C (decomposition) Colorless powdery crystal island '4P! Example 112 Ru-nonstyryl hydrochloride M/', 227-229.5°C (decomposition) Colorless powdery crystal Example 113 Acid acid/A hydrate M, 259-262°C Colorless schistose kfi Example +14 1 Hydrochloride Ift/, 300°C or higher Colorless schistose Example 115 Trocarbostyril m, 158-+60 °C Colorless powdery crystals.Examples of "Shun production" and "Rakukon mackerel" experiments using the compounds of the present invention are given below.

Example 1 132 damagnesium stearate 1 BlIv needle
Tablets of the above composition were prepared in one tablet by 200 to 40 minutes.

Rice preparation 9S2 Dorocarbostyril)'j) 12711v
Matanesium stearate 18
200 liters of tablets of the above composition were manufactured by a conventional method (7 tablets).

6-(4-besidyl-1-dipe5dinylka 500
0.31(
Molecule 14000) Sodium chloride 0.9f Polyoleanthinol 0.4f
- Tometa type Sodium sulfate 0.11 methyl parabeci 0. +8 fzuO
Distilled water for injection 0.021 Distilled water for injection 100 - Dissolve the above ingredients, thorium metachloride and thorium chloride in distilled water at 80°C with stirring. The resulting nine-bath solution was cooled to 40°C.

The compound of the present invention, polyethylene cyclohol and Boria ↑ ethyresyl didecinooleate are sequentially dissolved in this, and then distilled water for injection is added to the solution, moxibustion is carried out in the pot, and a suitable filter paper is added. Filter the cocoons using
ib.

formulation? lI4 Chiril lyo sapon salt Acipul 132 ~ Magnesium stearate 18 ~ Milk I
l+ 45 da needle
Tablets of the composition (i) in one tablet were prepared with a concentration of 200% to 200%.

<m increase 1lItkA> For male and female adult dogs with body blood 8~+3#, besitovar and ta L
Anesthetize by intravenously administering the sodium salt of 30 IIv/#. Hebarish sodium to 1o00U/
After intravenous administration, the animals were sacrificed by exsanguination and the hearts were removed into lock solution. Insert a cannula from the right coronary artery toward the tuberosity artery.

Kll the right atrium together with the cannula. Next, the dogs were anesthetized in advance with besitobal and tar sodium salt C30Wf/4 (intravenously administered), and treated with Hebalish treatment (100 (1/9 in 9, intravenously administered)) for adult dogs of both sexes, weighing 18-27. Blood is led from the w4 artery to a cannula inserted into the right coronary artery via the veristaric bossip to perfuse the right atrium.

The perfusion pressure is a constant pressure of 1001 m111#-. The movement of the right atrium determines the contractile force of the atrial muscle under a resting tension of 2f through the force exertion. Coronary blood flow is determined using an electric & i-cover needle. All records shall be recorded on the Issyk writing record needle. The details of this method are reported by Kanhyo et al. [Japan, J., Pkmrwiacol.

25, 433-439 (1975), Newsμm5c
kvrizdbtrq'z Artk, Pkarmac
al., 289.315-325 (1975)').

The test compound was inserted into the right coronary artery, proximal to the tube, and then connected through the tube. 1 in the vein
It can be injected at 0 to 30μI. The positive inotropic effect of the donor compound is expressed as a % change in the developed tension before compound ##J administration, and the change in coronary blood flow is expressed as absolute * (ml/min) from dose 1. The results are summarized below. It is shown in Table 1 and Table 2.

Test compound〉 Compound I & Product name I
0-(1-verazinil)-3,4
-;
4-(4-methoxybesilyl)-1-diverazinyl-J-3,4-5-didrocarbostyryl 8 6-(4-(3-methoxybesilyl)=1-diverazinyl) Rubonyl 1-3,4-dihydrocarbostyryl 9 6-(4-(3,4-dicoopecillyl)+0
6-C4-(4-Zto0vesiliiL)-116-(
4-(4-Methylbesylyyl)-dihydrocarbostyryl +3 6-(4-)0yl-1-diverazinyl)-3,4-dihydrocarbostyryl +4 6-(4-besilyl)-1 -piperazinylcalbenyl)-3,4-! ; cyto0carbostyryl monocarborate +5 6-C4-<4-methylbesidiL)-1-hyperazinylcarbonyl)-3,4-dihydrocarbostyryl+6 6-[4-(4-meth+cybesidiL)-1-hyperazinylcarbonyl) 5L]-1-piperaziniLcarnenyl)-3,4-dididrocarbostyryl 1-destate+7 6-C4-<4-riDOpesidyl)-1-piperaziniIL7]Lbonyl 1-3. -
I-e verazinyl carbonyl: 1l-3,4-dishide 0
Kiribestyryl 1 woodcutter #19 b-C4-<4-nitrobesidyl)-1-dipelazinyl-3,4-didrocarbostyryl 1-carbohydrate 20 b-CN -methyL-N-(4-methythushi2+
6-CN-Methyl-8-(3,4-methyledidiofcybesidyl)carb7yl]-3,4-dide 0 force L
lStyryl 22 6-CN-MethyL-N-(4-rubesidyl)carhetyl J-3,4-dihydrocarbostyryl 23 Amrinosy (anti-rin compound) 24 6-(4-(2- Pheno+siechi L)-1-diverazinylcalhonyl] force L Bostili L・I*ll woodcutter 25 6-(4-(3-phenylp0hiIL)-1=
Verazinylcarbostyril monohydrochloride dihydrocarbostyril 27 Dopta sanshi (comparative compound) 28 6-C
4-<4-opbesidyl)-1-diverazinyl-benzyl]cal thick styryl l salt #wooden 29 6-(4-(3-hesisoylpropyl)-1-
Verazinyl carbonyl) -3,4-dihydrocarbostyryl monohydrochloric acid % hydrate 30 6-(4-(4-dihydrocybesilyyl)methyl-1-diverazinyl carbonyl ]-3,4-dihydrocarbostyryl 14m11!I4・A hydrate 31 6-(4-prodiL-1-diverazinyl)-3,4-dihydrocarbostyryl 32 6-C4-(3-Do-besilyl)methyl-
1-piberazini L carbonyl]-3,4-dihydrocarbostyryl I salt pseudohydrate 33 6-(4-isopesityl-1-goverazini Lj
)-3,4-dihydrocarpostyl[ 34 6- (4-(4-methylthiobesidyl)-1
-piperazinyl carbonyl')-3,4-5 didrorickshaw styryl monocarboxylate 35 6-C4-(3,4,5-trimethoxycypesidil)-1-diverazinylcarbonyl L1- 3,4-Dishido 0 force Bostyril 1 Salt M woodcutter 36 6-(4-(4-Asaninohesidyl)-1-Goverazini LhL BoniIL) -3,4-Dishidoro force Bostyryl 37 6-(4-(4-acetyla trinovesicyl)-
1-goveracinyl-bonyl, -386-(4-isobutyl-1-diperazinyl-carbonyl)carbosteryl
141111 salt -hydrate 39 6-(4-(4-methylbesylylmethyl)-
1- and verazinylcaramyl]-3,4-side o; b
+ L bostyryl 1 hydrochloride 40 6-(4-Schiff0 hedecylmethyl-1-piverazinyl Lbonyl-3,4-, 4-zu0palkoru-1-goberazinyl-l-bonyl) -3,4-di-drocarbostyryl-l-Ki-III-carmine salt 44 6-(4-jl-to-thousyl-1-piperazinyl-l-bonyl) -3,4-dihydrocarbostyryl 1-hydrochloride- 451-methyl-6-(4-benzyl-1-oberazinyl)-3,4-dihydrocarbostyryl 46 6-(4-allyl) -1-doperazinylcarbonyl) -3,4-dihydrocarbostyryl, 1yodocarbostyryl, 1stewstyryl') -3,4-dihydrocarbostyryl hydrochloride 11- 3.4-,! ; Shidrocarbostyril 1 pack # salt 50 6-[4-(2-e de O + siechi) L) -51
6-(1-Pipery5L)-5,4-Dihydrocarbostyryl 52 6-(4-Methyl-1-PiperidiL)-3,4-Dihydrocarbostyryl 53 e+-(
4-Vesil L-1-Perige straining rate 2L)-3,4-
Sj Doro Rimoto Steel T Pseudohydrate 54 e+-(1-pyrrolidylcarbonyl)-3,
-3,4-dihydrocarbostyryl MU11 57 6-14-C2-<3.4-Methyrezidiofstyryl 1-hydrochloric acid woodcutter - Pseudohydrate Tyril l Woodcutter # Woodcutter styryl -3.4-cyhydro carbostyril ag l Table 2 Table 2 <Pharmacological test B> Adult dogs of both sexes weighing 9 to 15 kg were used. Besitoher and tar sodium 3011 for dogs? The animal was anesthetized by a static blunt intracranial injection of /kW, and then 4 ml of hesitobatal sodium was continuously injected in a circular motion to maintain a constant depth of anesthesia. 1k per minute using a respirator
118th IIi? Series, 201/Artificial respiration under conditions at the foot of the phantom intake, - a friend by my side. The left ventricular force was measured using an arch-shaped straigh gauge attached to the outer wall of the left ventricle. A polyethylene tube was inserted into the left femoral artery and systemic blood pressure was measured via a pressure transducer, and all parameters were measured at 1 m! I added 1-1 to my record. The drug is administered through a catheter inserted into the femoral vein. The inotropic effect of the test compound was expressed as % inversion of the tension generated before compound administration. Blood pressure (gg#C) of animals (expressed as absolute silver from before administration of HiFi). Results are shown in Table 3.

No. 311 Pharmacological Test C〉 Blood torrent lactating muscle specimen & miscellaneous l1iII of 8-13kQ & dogs were given intravenous becitobarbital/strium salt at a dose of 30-7/touge. 10001 salt
/After intravenous administration of the phantom dose, the animal was bled to death and 8 eels were born in wedlock. The specimen mainly consists of the mammary muscle and the 8th septum, and a constant pressure of 1100 a #f is applied through the cannula inserted into the 1 d middle artery and the eaves led from the blood donor. Blood donation size F'
The fish, weighing 18-27 mm9, was anesthetized in advance by intravenous administration of Pesitoba L and tar/ythorium 30 Jv/pass, and 1/# of Hebarish sodium wood was administered intravenously. The resting force of the nipple muscle is 1.5f, and the tension generated by the papillary ayu is determined through the force exchange position.

@14 The blood flow in the septal artery is measured using electro-abortion 1. The record of the generated tension and m1 disobedience is Ishiku Kutsukiki-1
Recorded on 1. The details of this method have already been reported by Ichimen and Hashimoto. (All, /, Pkyztρl.

218.1459-1463.1970) The test compound was administered intraarterially in a volume of 10 to 30 μm for 4 seconds.

The reaction force effect of the test compound was expressed as 9I6f against the tension generated by drug administration. The effect on coronary blood flow was expressed as absolute 1i[Of (y/swtm) from dose 1. The results are shown in Table 114.

Table 4 (that's all)

Claims (1)

[Scope of Claims] ■ -h Formula 1, 111 represents a lower alkyl group or a phenyl alkyl group in the lower alkyl crystal, show. R2 and 83 are h- or l1I
It's 4, #111! A lower acyl group which may have 0 + 2 or halo as an R group, or a lower alkyl group which may have 1 as an R group, or a lower alk as a phenyl ring
Represents a phenyl lower alkyl group which is obtained from salmon called poppy roe and may have 1 to 3 9 groups or a lower alkyl group. The circles R2 and R3, together with its Reiko, which they combine, are Iikan Riko or #1iist
5-membered or U6-membered saturated OI with or without adenoids
You may also use the I bulk ring. #i lower acyl group or thiophenyl lower alkyl group may be substituted directly above plan -II. In addition, when the ha vote ring is and beradish, lower alkenyl group, lower alunyl group, Schiff0alyl group, Schiff0
Al+L lower alkyl group, lower alkanoyl group, lower alkanoyl lower alkyl group, lower alkyl group, lower alkyl group, lower alkyl group, lower alkyl group, furoyl group, lower alkanoyl group Rusul book nil group, turtle! 1111 may have a cyano group, a pecylyl group (U lower alkyl on this phenyl ring), or 1 to 3 groups may be substituted LJ
s. A lower alkyl group having one phenyl ring, a lower alkanoyl group, a lower alkanoyl group or a carboxy group, a phenyl ring having one substituent, a lower alkanoyl group, a lower alkanoyl group, a lower alkanoyl group, and a lower alkyl group having one substituent on the phenyl ring. A pheno+sil lower alkyl group derived from a group consisting of 4+L groups and having 1 to 3 fc groups or a lower al+rezidio+sil group, a lower alkyl group as a substituent on a phenyl group Lower A L] + Shi group, H0 Geshi vein,
Nido O! &, A3HA L lower alkanoyl atrino group and lower A L+Lf O group j! 1 phenyl lower alk+Lj&, which can have 1 to 3 groups or lower alk + 5 o + shi groups, to lower alk + shi groups, lower alk + shi groups, as 1lk- groups on 7121m 〇Poppy atom, nido 0 group anti-cyano group to 1! MFi is a besylyyl group which may have 1 to 3 round groups or a lower alkyl group and a cydio+sil group, or a besylyyl group which may have 1 to 3 lower alkyl groups as a 11ik substituent on the phenyl ring.
Nils L book two IL,! , a phenyl ring, which may have from t-1 to 3 groups selected from the group consisting of a doro + si group, a hege, and a lower acycanoyl Σno 1 & as a substituent on the phenyl ring, a phenyl ring A phenyl lower alkenylcarbonyl group having 1 to 3 groups derived from salmon such as bald m-f and lower alkoxy as substituents, or 1 as a substituent on the phenyl ring. The phenyl lower alkamyl group which may have 1 to 311 lower alkyl radicals may have 4 groups of dibela, ; Mae carbostyril skeleton 03 and 4 #
! Bulky bonds represent monosynthetic bonds or 2'IL bonds. ] A cardiotonic agent characterized by containing a force L boss chili 1 conductor and its poles as active ingredients.