TWI236471B - Substituted piperazine compounds - Google Patents

Abstract

Novel compounds of the general formula: and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.

Description

1236471 Α7 Β7 V. Description of the invention (1) Background of the invention This application was filed longer than US Patent Application No. 60/184182 filed on February 22, 2000, and US Patent filed on February 22, 2000 Application No. 60/184457; U.S. Patent Application No. 60/2063 96 filed on May 23, 2000; U.S. Patent Application No. 60/184306 filed on February 22, 2000; and US Patent Application No. 60/209262, filed on June 5, 2000, has priority, the description of which is incorporated herein by reference. 1. Scope of the invention The present invention relates to a substituted pirho compound, a therapeutic dosage form comprising one or more compounds, and a method of treating mammalian diseases in a therapeutic method, and particularly to a human, the therapeutic method being selected from the group consisting of protection by Protects skeletal muscle from injury, protects against skeletal muscle or systemic diseases (such as intermittent 跛), treats shock symptoms, preserves donated tissues and organs used in transplants, treats cardiovascular disease, including anterior atrium and ventricular arrhythmia , Priezmant's (variant) angina pectoris, stable angina pectoris, angina pectoris caused by exercise, congestive heart disease and myocardial infarction. 2. Technical Description US Patent No. 567,264 (the description of which is incorporated herein by reference) discloses a class of substituted pyridine compounds, including compounds known as ranolazine, ( Soil) · Ν_ (2,6-xylyl) _4_ [2-Light-based 3- (2-methoxyphenoxy) -propyl acetamidine, and its pharmaceutically acceptable salts and Uses in the treatment of cardiovascular diseases, including angina pectoris, myocardial infarction and myocardial infarction. -4- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling out this page} .. 丨 Printed by the Employees ’Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 A7 B7 V. Description of the invention () (Please read the precautions on the back before filling out this page) US Patent No. 5,506,229 (incorporated by this description for reference) Reveals the secret recipe of Xin Xiaoxi in medicine Accepted use of salt and vinegar for the treatment of tissues (including itching of the heart, hypoxia or reperfusion injury to the cardiovascular or skeletal muscle or brain tissue) of physical and chemical attacks, and for transplantation. Especially It is particularly useful for treating angina pectoris, myocardial infarction, and myocardial infarction in a manner that partially inhibits cardiovascular fatty acid oxidation. It has been revealed that oral and parenteral formula (including 爻) Controlled release formulation). Example 7D, particularly in U.S. Patent No. 5,506,229, illustrates the use of capsules containing Reron Lessing microspheres and microcrystalline cellulose coated with a release controlling polymer. Formulated controlled release formula. Although Goronexine is an important discovery for a very useful cardiovascular therapeutic agent, there is still a need for compounds that are partial inhibitors of fatty acid oxidation. Half-life and have at least activity similar to ruilongcaxin. SUMMARY OF THE INVENTION The present invention includes a novel substituted pycnogenol compound, which is a partial fatty acid oxidation inhibitor with good treatment half-life. Printed by the Consumer Cooperative of Intellectual Property Bureau, Ministry of Economic Affairs The invention also includes novel substituted pico compounds' that can be administered to mammals to protect skeletal muscle from injury, protect skeletal muscle-associated muscle or systemic diseases (such as intermittent tadpoles), treat shock symptoms, Preservation of donated tissues and organs used in transplants and treatment of cardiovascular disease, including anterior atrium and ventricular arrhythmia, Priezmant (variant) angina, stable angina and exercise-produced angina, congestive heart disease, and myocardial infarction 0 -5- This paper size applies to China National Standard (CNS) A4 (210 X 29 7 mm) 1236471 A7 V. Description of the invention (

The invention includes a class of substituted pico compounds having the formula: D

X where X is selected from the group consisting of R24 (printed on the back of the note before filling out this page) and printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ 0, where m = 1 or 2 or 3;

Ri, R2, R3, R4 and Ruler 5 are each independently selected from hydrogen, halo, no2, CF3, CN, OR23, sr23, n (r23) 2, s (o) r22, S〇2R22, S02N (R23) 2, NR23C02R22, nr23con (r23) 2, cor23, co2R23, con, (r23) 2, nr23so2r22, ChH alkyl, C2-15 fluorenyl, C2-15 block group, heterocyclic group, aryl group and heteroaryl group Group, in which alkyl and aryl substituents are optionally selected from the group consisting of halo, No. 02, CF3, CN, OR23, SR23, N (R23) 2, S (0) R22, and SO2R22 Substituent group substitution, in which R2 and R3 can be joined -6- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 public love) 1236471 A7 -----______ B7____ V. Description of the invention (4) j together form a fusion ring system with 3 to 4 carbon atoms, and it can be known that the ruler 4 and R5 are joined together to form _CH = CH-CH = CH-; R6, R7 and R8 are each independently selected from hydrogen and A group of alkyl groups;, R9, I. , R ", R12, Rl3, Rl4, Ri5, and Ri6 are each independently selected from the group consisting of hydrogen, C02R23, CON (R23) 2, Ci_4 alkyl, and aryl groups, in which the alkyl group and the aryl substituent group If necessary, it may be substituted with a substituent selected from the group consisting of halo, CF3, CN, OR23, N (R23) 2, C02R23, CON (R23) 2, and aryl, among which H9 and & 1 () can be joined together to form a carbonyl group, or the ruler 11 and ruler 12 can be joined together to form a carbonyl group, or the ruler can be combined with! ^ 4 can be joined together to form a carbonyl group, or Ri5 can be joined together to form a carbonyl group, in which the "with ㈠ or 趴 with Ri5 or trans 9 with Rii or“ "can be joined with! ^ 5 or R9.R1S Form a bridging ring system with 1 to 4 carbon atoms, and R9 and Ri0 or Ri2 or R13 can be combined with ruler or ruler! ^ 6 join together to form a bridge ring system with 1 to 5 carbon atoms, the conditions are that R9, r1q, Rii, Ri2, Ri3, Rl4, Rl5, and Rl6 are not all hydrogen; R22 is selected from C〗 〖_〗 5 alkyl, aryl and heteroaryl groups, in which the fluorenyl and aryl substituents can be selected from the group consisting of self-radical, alkyl, single-pit amino, diamido, and pyridoamine , Arsenamide, heteroaramide, CN, O-Cu pentyl, CF3 and heteroaryl group; R2 3 is selected from fluorene, C! _I5 alkyl, aryl and A group composed of heteroaryl groups, in which the alkyl group and the aryl substituent group can be selected from a female group, ---------------- (please read the note on the back first) Please fill in this page again.) • Line-Printed on the paper by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. The paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 V. Description of the invention (5) Group, monoalkylamino group, dialkylamino group, alkyl group, CN, -0-Ch6 alkyl group, and CF 3; and a group of 2 or 4 is selected from the group consisting of alkyl group and cycloalkyl group. And fused benzene A group formed by a cycloalkyl group, wherein the attachment point is on a cycloalkyl group, wherein the alkyl group, the cycloalkyl group, and the fused phenylcycloalkyl group can be selected from 1 to 3 as required from self-based, CF3, CN, OR20, SR20, S (0) R22, S02R22, SO2N (R20) 2, NR C02R2 2, C i -2 pit group and aryl group. The substituents can be selected from 1 to 3 as required by halo, phenyl, CF3, CN, OR20, and Cu alkyl groups (please read the precautions on the back before filling this page)

Substitute substitution of the group formed by the consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, and Ri 7, R! 8, R! 9, R20, and R2 1 are each independently selected from the group consisting of hydrogen, radical, N02, CF3, CN, OR23, SR23, N (R23) 2, s (〇) R22, SO2R22, S02N (R23) 2, NR23C02R22, NR23CON (R23) 2, COR23, co2r23, CON (R23) 2, NR23S02R22, Ci 15 alkyl group, Chu alkenyl group, Chu alkynyl group, heterocyclic group, aryl group, and heteroaryl group & wherein the alkyl and aryl substituents are optionally selected from self-group, N02, cf3, CN, OR23, SR23, N (R23) 2, s (〇) r22 and -8-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 V. Description of the invention ( ) Substituted by substituents of the group consisting of SO2R22. In yet another specific embodiment, the present invention is a method of administering one or more compositions of the present invention to a mammal to treat a disease selected from the group consisting of protecting skeletal muscle from injury and protecting skeletal muscle from concomitant Muscle or systemic diseases (such as intermittent tadpoles), treatment of shock symptoms, donation of tissues and organs used during transplantation, treatment of cardiovascular diseases, including anterior atrial and ventricular dysplasia, Priezmann's (variant) angina, stability Angina pectoris and exercise-induced angina pectoris, congestive heart disease, and myocardial infarction. Detailed description of the present invention The present invention includes a classification of substituted pico compounds having the formula: (Please read the precautions on the back before filling this page)

Among them, X is selected from the group consisting of: • Line · Ministry of Economic Affairs, Smart House, Consumers, Consumers, Consumers, and Children, -9-This paper size is applicable to China National Standard (CNS) A4 (210 X 297) (Centi) 1236471 A7 B7 V. Description of the invention () where m = l or 2 or 3;

Ri, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, self-base, N02, CF3, CN, OR23, SR23, N (R23) 2, S (0) R22, SO2R22, so2n (r23) 2, NR23C02R22 , Nr23con (r23) 2, C0R23, C02R23, CON (R23) 2, nr23so2r22, Cl_15 alkyl, c2-15 alkenyl, c 2_i5 alkynyl, heterocyclyl, aryl and heteroaryl Group, in which the alkyl and aryl substituents are optionally selected from the group consisting of self-group, no2, CF3, CN, OR23, sr23, N (R23) 2, s (o) r22, and SO2R22 Group substituent substitution, where ~ and can be joined together to form a fused ring system having from 3 to 4 carbon atoms, and R4 and 115 can be joined together to form -CH = CH_CH = CH ·; R6, R7 and Rs are each independently selected from the group consisting of hydrogen and C 5 alkyl;, R10, Rn, R12, R13, r14, Rl5 and R16 are each independently selected from hydrogen, C02R23, CON (R23) 2, Ch A group consisting of a aryl group and an aryl group, in which the alkyl group and the aryl substituent group may be selected from one selected from the group consisting of a southern group, CF3, CN, OR23, n (r23) 2, co2r23, con (r23) 2 and aromatic Group substitution Among them, ~ can be joined with ruler ^ to form a carbonyl group, or ruler can be joined with! ^ 2 to form a carbonyl group, or Rl3 and Rl4 can be joined together to form a carboxyl group, or R15 can be joined together to form a carbonyl group. , Which can be R11 and or ~ and Rii or or, and! ^ 3 is joined together to form a bridge ring system with 1 to 4 carbon atoms, and it can be joined with R10 or Rli and r12 or R13 and 1 ^ 14 or ruler 15 and 1116 to form a group having from 1 to 5 Individual carbon source -10- This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the notes on the back before filling this page) Order --------- Line Economy Village Intellectual Property Bureau Employee Consumption Order System 1236471 A7 B7 8-V. Description of the invention () Child bridge ring system, the conditions are R9, R i Q, R ii, R i 2, ri 3, RW, R15 And R16 are not all hydrogen; R2 2 is selected from the group consisting of C i i5 alkyl, aryl, and heteroaryl, wherein the alkyl and aryl substituents may be selected from the , Mono-fe amine, one-pit amine, fe S amine, aramide, heteroaramide, CN, O-Ci · 6 pit, CF3 and heteroaryl group; R23 is selected from the group consisting of fluorene, alkyl, aryl, and heteroaryl ', in which alkyl and aryl substituents may be selected from one of _, alkyl, monoalkylamino, and dialkylamine, if necessary. Radical Group, CN, -0 · C! _ 6 alkyl and CF3; and R2 4 is selected from the group consisting of fe group, cycloalkyl group and fused phenylcycloalkyl group. Where the attachment point is on a cycloalkyl group, where the alkyl group, cycloalkyl group, and fused phenylcycloalkyl group can be selected from 1 to 3 selected from the group consisting of —yl, CF3, CN, OR20, SR20, S (0 ) R22, S02R22, SO2N (R20) 2, NR2 G CO2R2 2, C i _ 2 fe group and aryl group. Substituent substituents can be substituted, among which aryl substituents can be selected from 1 to 3 as needed. Each is selected from the group consisting of halo, phenyl, CF3, CN, OR2 G, and C 1 _ 6 entertainment * (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

-11-This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 public love)! 236471 A7 B7 V. Description of the invention (Substituent substitution of the group consisting of 9, and R17, R18, R19, r20 and r21 are each independently selected from the group consisting of hydrogen, halo, N02, CF3, CN, OR23, SR23, N (R23) 2, s (o) r22, S02R22, S02N (R23) 2, NR23C02R22, NR23CON (R23) 2, C〇R23, C02R23, CON (R23) 2, NR23S02R22, Cu alkyl, C ^ i5 # group, C2 ^ 5 block group, heterocyclic group, aryl group and heteroaryl group, in which alkane The aryl and aryl substituents may be optionally substituted with one substituent selected from the group consisting of halo, no2, CF3, CN, OR23, sr23, N (R23) 2, S (0) R22, and SO2R22. The invention includes a sub-classification of a substituted pirogen compound of the same type as formula (I), which has the following formula (IA): (Please read the precautions on the back before filling this page) ------- Order- --------line-

^ 19

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, where m = 1, 2;-R1, R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen, commercial base CF3, OR22, and Ci-4 垸Group, and its middle rule 22 is Cl group; 6. -Τ »7 -r, 8 垸 R, R and R are each independently selected from the group consisting of hydrogen and c _ 3 垸 group 12-1236471 V. Description of the invention (R &R; Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, R1 R13, R1 4, R 1 5 and R 1 6 are each independently selected from the group consisting of hydrogen and Ci_4 alkyl and aryl groups, or R9 and Rio May form a carbonyl group together, or R11 and R12 may form a carbonyl group together, or R13 and R may form a carbonyl group together, or feet 15 and feet 16 may form a fluorenyl group, among which ~ 7 knows R and R or R 9 and R 1 5 or R 9 and R 1 1 or R ii and R i 5 or R 9 and R join together to form a bridged ring system, where two R groups may together contain from 1 to 4 carbon atoms, the conditions are r9, R i 0 R n

R

R 1 2

R 12

R 13

R 14 R1 R and R10 are not all hydrogen at the same time;

R 18 R, & 2 () and ruler 21 are each independently selected from the group consisting of hydrogen, CF3, CN, OR22, S (0) R22, S02R22, so (R22) 2, CON (R) 2, and Ci · A group of 4 groups, where r22 is a cii3 ^ group 'or R and R 18 can form together · C C = C Η-C Η = C Η-, or R 1 and R19 can form _〇CH20- . In a more preferred compound of formula IA, each of R1, R2, R3, r4, and r5 is selected from the group consisting of hydrogen, halo, CF3, OR22, and Cl "alkyl, and R22SCi_3 alkyl; R6 Selected from hydrogen and methyl; R, R8, R < (Please read the notes on the back before filling in this page) ------- Order --------- line · ίο R1 R 1 3 , R 1 4, R 1 5 and R 1 6 are each independently selected hydrogen and methyl, or R9 and R1G can form a carbonyl group together, or the ruler and ruler can form a carbonyl group, the conditions are R9, R10, R1 1 , R12, r13, r14, R15, and R16 are not all hydrogen at the same time; Rl7, r18, r19, r20, and R: are each independently selected from the group consisting of hydrogen, halo, CF3, OR22, and Cl3 alkyl; R22 * Cl · 3 alkyl, or ruler and 8 can form -CH —CH_CH = CH-, or R18 and R19 can form _〇ch2〇_ together.

R

R 1 2 -13 This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 A7 _______B7 11 'V. Invention Description () is still better In the compound of formula IA, Ri'RS'RS'Rd'RS, R6, R7 and R8 are each independently selected from the group consisting of methyl and hydrogen; R9'H1Q'H11, R12, R13, Rl4, r15 and R16 is independently selected from the group consisting of hydrogen and methyl, or R9 and Rio can form a carbonyl group together, or Rl3 and R14 can form a carbonyl group together, and the conditions are not all of R9, R1G, Rl, Rl2, R, Rl4, Rl5, and R16. At the same time, it is hydrogen; R18, R19, R20 and R21 are each independently selected from the group consisting of argon, halo, CF3 & 〇r22, where R22 is methyl, or Rl 7 and ruler! 8 can be formed together -CH = CH-CH = CH ·, or can be formed together with-^ CH2〇. In even better compounds of formula IA, Ri and R5 are each methyl; R2, R3, R4, R6, R7 and V are each hydrogen; r9, R10, R11, R12, R13, R14, Ri5 and R16 Each is independently selected from hydrogen and methyl, or R9 and R1G can form a carbonyl group together, or ri3.rM can form a carbonyl group together. The conditions are that R9, Ri0, Rii, Rl2, Rl3, r14, r15, and R16 are not all at the same time. Is hydrogen; Ri7, R18, R19, r20, and r21 are each independently selected from the group consisting of hydrogen, self-radical, methyl, and OR22, where R22 is methyl, or rule 17 and rule 18 can form _ch together = chch = CH-, or R18 and r19 may form -0CH2〇 together. In still more preferred compounds of formula IA, Ri & R5 are each methyl; R2, R3, R4, R6, r7 & R8 are each hydrogen; Is selected from hydrogen, methyl, or may form a carbonyl group together; rh & r12 is selected from hydrogen and methyl, or R13 and R14 are selected from hydrogen and methyl or may form a carbonyl group together; is hydrogen, and the conditions are R9, Ri. , Rh, r12, r13, r14, r15, and R16 are not all hydrogen at the same time; R "is selected from the group consisting of rhenium, gas-based, fluorine-based, or osmium-14.-This paper applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the notes on the back before filling out this page) -I ϋ n tm ϋ ϋ One: mouth, I n · ϋ n — 线 line 0 1236471 A7 B7 V. Description of the invention (12) R18 and R19 are each selected from the group consisting of hydrogen or methoxy, or R18 and R19 can form _〇CH20 ·, or R17 and R18 can form -CH = CH-CH di-CH -, R2. Is hydrogen; and is selected from the group consisting of hydrogen or chloro. A substituted pirogen compound of formula IA is selected from the group consisting of N- (2,6-dimethylphenyl) -2 · {4- [2- Hydroxy-3-(2-methoxyphenoxy) propyl] -3 -oxopyryl} acetamidamine, N- (2,6-dimethylphenyl) -2- {4- [2 -Light-based-3- (2-methoxyphenoxy) propyl] _3,5 · dimethylformyl} acetamidine, 2 -{(5S, 2R) -4- [2 -Cycloyl 3- (2-methoxyphenoxy) propyl] _2,5_ dimethyloxyt t: " 7 Jingji} -N- (2,6-dimethylphenyl) ethyldonylamine, 2_ {2,5-diaz-5--5- [2-hydroxy-3- (2-methoxyphenoxy) propyl] bicyclo [ 4.4.0] dec-2-yl} ^-(2,6-dimethylphenyl) acetamide, Ν- (2,6 · dimethylphenyl) -2- {4 · [2-- -3- (2-methoxyphenoxy) propyl] -3-oxopyryl} ethamidamine, N- (2,6-dimethylphenyl) -2- {4- [2 -Hydroxy-3- (2-methoxyphenoxy) propyl] 3,3-dimethylophenyl} acetamide, 2- {5-[(2 3) -2-hydroxy-3- (2-methoxyphenoxy) propyl] (18,48) -2,5-diazinebicyclo [2.2.1] heptan-2-S} -N- (2,6_dimethylphenyl ) Acetylamine, N- (2,6-dimethylphenyl) -2- {4- [2-Unbased-4- (2-methoxyphenoxy) butyl] pyridyl} ethyl Amidoamine, Ν- (2,6 · dimethylphenyl) -2 · {4- [4- (4-fluorophenoxy) -2-hydroxybutyl] pyridoyl} acetamide,- 15- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page) Printed by the cooperative 1236471 A7 B7_____ 14 V. Description of the invention () 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) · 2-hydroxypropyl] -3 -methylpyridine Phenyl} -N- (2-chlorophenyl) acetamide, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 • hydroxypropyl]- 3-methylpyridyl} -N- (2-chloro-4-methylphenyl) acetamidamine, 2-{(3S) -4-[(2S) _3- (2-fluorophenoxy ) -2 • Hydroxypropyl] -3 -methylpyridyl} -N- [2- (1-methylvinyl) phenyl] acetamidine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl} -N- (2-methylphenyl) acetamidamine, 2 _ {(3S) _4- [ (2S) _3- (2 · Fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl} -N- [6-methyl-2 ((ethylethyl) phenyl] ethylamine , 2-{(3S) -4-[(2S) -3- (2 • fluorophenoxy) _2-hydroxypropyl] -3-methylpyridine. Jingji} -N- (3-methylthiophenyl) acetamide '2-{(3S) -4-[(2S) _3- (2_fluorophenylphenoxy) -2 • hydroxypropyl]- 3-methylpyridyl}-^^-(4-chloro-2-methoxy-5-methylphenyl) acetamide, 2-{(3S) _4-[(2S) -3- ( 2 -Fluorophenoxy) -2- # Lipropyl] -3 -methylaminomethyl} -N- [4- (dimethylamino) phenyl] acetamidamine, 2-{(3S ) -4-[(2S) -3- (2 · Fluorophenoxy) -2-¾propyl] -3 -methylpyridyl} -N- (2,4-dimethoxyphenyl ) Acetylamine, 2-{(3S) -4 _ [(2S) _3_ (2-Fluorophenoxy) -2-¾propyl] · 3 -methyl 17 than ρ Jingyi} _N_ (3,4 · Digas phenyl) ethyl amine, 2-{(3S) -4-[(2S) _3- (2_fluorophenylphenoxy) -2-hydroxypropyl] -3_methylpyridyl} -N -(4-chlorophenyl) ethylamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3 -methylpyridine Well-based} -N- (3-chlorophenyl) amine, -17- ^ Zhang scale applicable to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling in this (Page) ·-丨 Line · Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 A7 B7 16 V. Description of the invention () 2 _ {(3S) -4-[(2S) -3- (2_fluorophenoxy ) -2-hydroxypropyl] -3-methylpyridyl} -N- (3-fluoro-4-methoxyphenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-Gastylophenoxy) -2-¾propyl] _3_methylpyridyl} -N- (3,4,5-trimethoxyphenyl) acetamidine, 2- { (3S) -4-[(2S) -3- (2 · Fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl} _N- (3,4-dimethoxyphenyl ) Ethylamine, 2-{(3S) -4 _ [(2S) -3- (2-Gasylphenoxy) -2- via propyl] _3-methylammonyl} -N- (4- Chloro-2-fluorophenyl) acetamide, and 2-{(3S) -4-[(2S) -3_ (2-fluorophenylphenoxy) -2 • hydroxypropyl] · 3_methylpyridine Phenyl} -N- [2- (hydroxymethyl-6-methylphenyl)] acetamide is more preferred. The present invention includes a sub-classification of a substituted pbihu compound of formula (I), which has the following formula IB:

IB where m = 0, 1 or 2 or 3; R1, R2, R3, R4 and R5 are each independently selected from hydrogen, halo, N02, CF3, CN, OR23, sr23, n (r23) 2, s (o ) r22, -19- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) (Please read the precautions on the back before filling this page) Order --------- Line Economy Printed by the Intellectual Property Cooperative of the Ministry of Intellectual Property, Ϊ236471, Invention Description (S〇2R22, so2N (R23) 2, nr23co2r22, nr23con (r23) 2, c〇R23, co2R23, CON (R23) 2, NR23S02R22, Cl_15 alkane Group consisting of alkyl, C 2 -15 alkenyl, C 2 —i5 alkynyl, heterocyclyl, aryl and heteroaryl, wherein alkyl and aryl substituents may be selected from halo, N02, CF3, CN, OR23, sr23, n (r23) 2, s (o) R22, and SO2R22; R6, R7, and R8 are each independently selected from the group consisting of hydrogen & Cl_15 A group of alkyl groups; R9, R10, R1 1, r12, r13, r14, r15, and r16 are each independently selected from the group consisting of hydrogen, C02R23, CON (R23) 2, Ci-4 alkyl, and aryl Group in which alkyl and aryl substituents may It needs to be substituted with a substituent selected from the group consisting of halogen group, CF3, CN, OR23, N (R23) 2, C02R23, CON (R23) 2 or aryl group, wherein R9 and R1G can form a carbonyl group together , Or R11 and R12 may form a carbonyl group together, or R13 and R14 may form a carbonyl group together, or R15 and R16 may form a carbonyl group together, wherein R11 and R13 or R9 and R15 or R9 and R11 or R11 and R15 or R9 and R13 Join together to form a bridge ring system, where two R groups together contain from 1 to 4 carbon atoms, and among which R9 and R10 or R11 and R12 or R13 and R14 or R15 and R1 6 can be joined together to form a ring system, Wherein two R groups together contain from 1 to 5 carbon atoms; R17, R18, R19, R20 and R21 are each independently selected from the group consisting of hydrogen, halo, no2, CF3, CN, OR23, SR23, N (R23) 2, s (o) r22, so2r22, S02N (R23) 2, NR23C02R22, NR23CON (R23) 2, COR23, CO2R23, CON (R23) 2, NR23SO2R22, base, 20 This paper standard applies to China National Standard (CNS) A4 specifications ( 210 X 297 mm) (Please read the precautions on the back before filling out this page) ------- Order --------- Line _ Staff Consumption of Intellectual Property Bureau of the Ministry of Economic Affairs Printed by Zuosha Co., Ltd. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy. Printed 1236471 A7 ------- B7 18-V. Description of the invention A group composed of heteroaryl groups, in which an alkyl group and an aryl substituent are optionally selected from the group consisting of halo, N02, CF3, CN, OR23, SR23, N (R23) 2, s (〇) R22 and S 〇2R22 is substituted by a substituent, or a ruler and ^^ 8 can be joined together to form _CH = CH-CH = CH-, or R "and R or R or r2〇 and r21 combines to form a saturated ring including from 3 to 6 carbon atoms, wherein 0 to 2 carbon atoms can be substituted with an oxygen atom and the ring can be optionally selected from 1 to 3 selected from hydrogen, dentate, N02 , CF3, CN, OR23, SR23, N (R23) 2, S (0) R22, S02R22, S02N (R23) 2, NR23C02R22, NR23CON (R23) 2, COR23, co2R23, coon (R23) 2, nr23so2r23 , Cl_15 alkyl, c2_15 alkenyl, c 2_i5 alkynyl, heterocyclyl, aryl, and heteroaryl group, wherein the alkyl and aryl substituents can be replaced by 1 as needed Selected from halo, N02, CF3, CN, OR23, SR23, N (R23) 2, S (0) R22 or SC ^ R22; R 2 2 is selected from the group consisting of C i! 5 alkyl, aryl and heteroaryl The group consisting of fluorenyl and aryl substituents can be optionally selected from the group consisting of self-radical, alkyl, monoamine, diamine, amine, arylamine, heteroarylamine, CN, O-Ci-6 alkyl, CF3 or heteroaryl group substituted by a substituent; and R2 3 is selected from the group consisting of fluorene, Ci5 alkyl, aryl and heteroaryl Group, in which the alkyl and aryl substituents may be selected from the group consisting of self-based, fe-based, mono- or di-alkylamine, alkyl, CN, -O-Cm alkyl or CF3, if necessary. Substituent substitution. -21-This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) -------- ^ --------- ^ AW (Please read the precautions on the back first Refill this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 A7 _____B7 19 V. Description of the invention () In the preferred formula IB composition, m = 0, 1 or 2 or 3; , R4 and r5 are each independently selected from the group consisting of hydrogen, halo, CF3, OR22 and Ci_4 alkyl; R6, R7 & R8 are each independently selected from the group consisting of hydrogen and Ci-3 alkyl ; R 9, R 1 〇, R 1 1, R 1 2, R13, R14, R15, and R16 are each independently selected from the group consisting of hydrogen & Ci4 alkyl, or R9 and R1G may form a carbonyl group together, or 1111 and 1112 may form a carbonyl group together, or R13 and R14 may form a carbonyl group together, or R15 and R may form a carbonyl group together, or R11 and R13 or R9 and R15 or R and R11 or R11 and R15 or R9 and R13 may be joined together Together form a ring comprising up to 4 carbon atoms, where r9, R10, Rll, r12, r13, R, R and & not all are chlorine; and R17, R18, R19, R20 and R are each independently selected Free hydrogen, halo, CF3, CN, OR22, S (0) R22, S02R22, SON (R22) 2, CON (R22) 2 & Ci 4 alkyl group 'or R7 and R18 can be formed together_ CH = ch_CH = CH-and phenyl. In other preferred compounds of formula IB, R1, R2, r3, r4, and r5 are each independently selected from the group consisting of hydrogen, halo, CF3, and alkyl, wherein R22 * Ci_3 alkyl; R6, Chi7 And Ki 8 are each independently selected from the group consisting of hydrogen and methyl;, r10, rH, r12, R13, R14, R15 and R16 are each independently selected from the group consisting of hydrogen and Ci2 alkyl, or R9 and R1G may form a carbonyl group together, or "and! ^ 6 may form a alkynyl group together" under the condition that not all of R9, R10, r11, r12, r13, R14, R15, and R16 are hydrogen at the same time; and r11 And RI3 or ruler 9 and ruler 15 or & 9 and ruler 11 or ruler 11 and ruler 15 or ruler 9 and ruler 13 are shaped together-22-This paper size applies to China National Standard (CNS) A4 (210 X 297 (Mm) (Please read the precautions on the back before filling this page) # 衣-线 · 201236471 A7 V. Description of the invention (printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, including a ring with 1 to 4 carbon atoms, And R17, R18, R19, R2 0 and r21 are each independently selected from the group consisting of hydrogen, halo, CF3, CN, OR22, and Ci_4 alkyl, where R22 Ci_3 alkyl; and r! 7 and R18 may together form a substituent selected from the group consisting of -CH = CH_CH = CH- and phenyl. In still other preferred compounds of formula IB, m = 1 or 2; R 1, R, R, R4 and R5 are each independently selected from the group consisting of hydrogen, halo, Cf3, OR2 2 and Cm, wherein r22 is alkyl; r6, R7, R8 , R9, R1., RH, R12, r13, Rl4, Rl5, and Rl6 are each independently selected from hydrogen and methyl; R18, r19, r20, and r21 are each independently selected from hydrogen, fluorenyl, CFs, OR22 & A group of Ci_3 alkyl groups, where R22 is methyl; or ... 7 and together may form _ch = CH-CH = CH-, or Ri% Rl9 may together form _〇CH2〇. In the better In the compound of formula IB, m = 1 or 2; R1, r2, R4, R5, R6, R7 and R8 are each independently selected from methyl and hydrogen; R9, R ::, Rl1, Rl2, Rl3, R14, R15 And R16 are each hydrogen; and R, R18, R ", r2. And r21 are each independently selected from the group consisting of hydrogen, aryl, CF3, or OR22, wherein r22 is methyl; or" "and ... 8 can form -CH = CH-CH = CH- together, or 1118 can be formed with rule 19 Starting from -OCH2O-. In yet other preferred compounds of formula ... m =: 1 or 2; r1 & r5 is methyl; R2, R3, R4, R6, R7, r8, r9 \ R12, R13, R ", Ri5 and r16 are hydrogen; r17, r18, ruler 19, r2. And R21 are each independently selected from the group consisting of hydrogen, 氢 and ⑽22, -23 This paper ruler 2 is applicable to China National Standard (CNS) A4 (210 X 297 public love) (Please read the precautions on the back first (Fill in this page again.) Booklet --------- line »1236471 A7 V. Description of the invention (21) where R22 is methyl; or ^ K can form -CH = CH-CH = CH-, or R18 and R19 may form _0CH2O together. In still other preferred compounds of formula VII, R1 & R5 is fluorenyl;

R R 13

R R 14 R4, R 《

R

K R, R10, R1

R 12 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, R15 and R16 are hydrogen; R17 is selected from the group consisting of hydrogen, chlorine, gas and methoxy; it is selected from hydrogen and methoxy; r19 Selected from hydrogen and methoxy; r2H r21 is selected from hydrogen and chloro; or r17 and R may form -CH = CH-CH = CH- together, or R18 and R19 may form -0CH20- together. The compound of formula IB is selected from the group consisting of N_ (2,6 · dimethylphenyl) -2_ [4_ (2_hydroxy_4_phenylbutyl) pyridinyl] acetamidine, Ν_ (2,6-dimethyl Phenyl) -2- {4- [2-hydroxy_3- (2 · methoxyphenyl) propyl] pyridinyl} acetamidine, 2 [4 · (3-(2 Η -phenylhydrazone) [d] 1,3 · Dioxocene-5 · yl) -2_hydroxypropyl) pyracyl] -N- (2,6-dimethylphenyl) acetamidine, Ν · (2, 6-dimethylphenyl) _2_ {4- [2-hydroxy_3_ (4 · methoxyphenyl) propyl] pyridyl} acetamide, Ν- (2,6 · dimethylphenyl ) _2_ {4_ [2_Hydroxy-3-phenylpropyl] pyridyl} acetamidine, Ν- (2,6-dimethylphenyl) · 2_ {4- [4- (4- -methoxy Phenyl) _2_hydroxybutyl] Outeryl} amine acetate, 2_ {4- [4- (2,6_difluorophenyl) -2-hydroxybutyl] pyridinyl} -N_ (2, 6-Dimethylphenyl) Ethylamine, -24- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 public love) (Please read the precautions on the back before filling this page) 1236471 Λ7 E ; 7 V. Description of the invention (3)

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, 1C where m = 1, 2, or 3; R1, R2, R3, R4, and R5 are each independently selected from the group consisting of argon, halo, N02, CF3, CN, OR20, SR2 〇, N (R20) 2, S (0) R22, so2r22, so2n (r2 °) 2, NR2 ° C02R22, NR2 ° CON (R20) 2, COR2. , Co2R2 (), con (r20) 2, nr2Gso2r22, Cl_15 alkyl, c 2-i5 fluorenyl, C 2 _ i5 alkynyl, heterocyclyl, aryl, and heteroaryl group And aryl substituents may optionally be substituted with one substituent selected from the group consisting of halo, N02, CF3, CN, OR20, SR20, N (R20) 2, S (0) R22, and S02R22; R6, R7 and R8 are each independently selected from the group consisting of hydrogen and ^ _3 alkyl; R9, R1., R11, R1, 2, R13, R14, feet 15 and feet 16 are each independently selected from hydrogen, C02R2G, A group consisting of CON (R20) 2, alkyl group, or aryl group, in which alkyl and aryl substituents can be selected from i by halo, CF3, CN, OR20, N (R20) 2, C02R20, (: 〇 ^^ (1120) 2 or aryl group substituents, where R9 and R1G can form together -26- This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) (Please read the precautions on the back before filling out this page) -------- Order --------- Line ·· Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 A7 ^ ----- B7 _ τ 24 * " " V. Description of the invention () To form a carbonyl group, or R11 and R12 can form a carbonyl group together, or Ri3 and Ri4 can form a carbonyl group together, or R 1 5 and R 1 6 can form a carbonyl group together. The conditions are that R and R13 or R9 and R15 or R9 can be formed. And R11 or R11 and r15 or r9 and r13 are joined together to form a ring including 1 to 3 carbon atoms; and 24 is selected from the group consisting of alkyl, cycloalkyl, and fused phenylcycloalkyl, Wherein, the attachment point is on a cycloalkyl group, and the alkyl group, cycloalkyl group, and fused phenylcycloalkyl group may be selected from 1 to 3 selected from the group consisting of aryl, cf3, CN, OR2, SR20, s ( 〇) R ”, 〇2R22, 〇2N (r20) 2, NR2GC〇2R22, Ci · 2 alkyl and aryl group substituent substitution 'where the optional aryl substituent can be used as needed From 1 to 3 substituted with a substituent selected from the group consisting of phenyl, phenyl, CF3, CN, OR20 and Cl_6 alkyl; R is selected from H, c 1 -15 alkyl, aryl or heteroaryl The group consisting of alkyl groups where the alkyl and aryl substituents are optionally selected from the group consisting of fluorenyl, alkyl, mono · or dialkylamino, alkyl, CN, -0-Cl-6 alkyl, or Cf3 Constitute And R is selected from the group consisting of C 1 _ 1 5 alkynyl, aryl or heteroaryl, wherein alkyl and aryl substituents may be selected from _, Substituents in the group consisting of alkyl, monoalkylamino, dialkylamino, alkylamine, arylamine, heteroarylamine, CN, (6, 6 aryl, CF3, or heteroaryl) To replace. In Equation 1C, it is preferable that m = 1 or 2 and that it is optimal when m = 1. In the preferred composition of Formula 1C, R1, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, halo, CF3, OR22, and alkyl-27- This paper size applies Chinese national standards ( CNS) A4 specification (210 X 297 mm) (Please read the notes on the back before filling this page) -1 ------ Order --------- line 251236471 A7 Intellectual Property Bureau, Ministry of Economic Affairs Printed by Employee Consumer Cooperatives V. Invention Description (group, and its ^ 22 is Cl.3 burn *. In other preferred compositions,

R1, R R, R4 and R5 are each independently selected from hydrogen and cf:

OR 2 0

Or C i · 2 entertainment: group of groups. R 1 and r: are independently selected from hydrogen or methyl, more preferably, R2, R3 & R4 are hydrogen spots ... and R5 is methyl. In other preferred formulas, R6, R7 & R8 are each independently selected from the group consisting of hydrogen and shan-3 alkyl groups, with hydrogenated methyl being preferred, and hydrogen being most preferred. In still other preferred compositions of formula 1C, R9, R10, Rll, R12, R13, R14, f and R16 are each independently selected from the group consisting of hydrogen, CON (Rh, Ci-4 alkyl or aryl The group formed, wherein the alkyl and aryl substituents may each be selected from the group consisting of fluorenyl, CF3, OR2O, N (Rw) 2, GX) N (RM) 2, or aryl, as required. Substituent group substitution, where R9 and RM can form a carbonyl group together, or 1111 and 1 ^ 2 can form a carbonyl group together, or R13 and R14 can form a carbonyl group together, or Rls * Rl6 can form a carbonyl group together. R11 and & 13 or ruler 9 and & 15 or R9 and Rll or R and R or R and ruler 3 are joined together to form a ring. In the alternative and better composition, R9, R1 0, R1 1, R R3, R4, and R5 are each (Please read the note on the back? Matters before filling out this page) 12

R 13

R 14

R15 and R16 are each independently selected from the group consisting of hydrogen and Cl_4 alkyl, or ... form a carbonyl group with R1G, or form a carbonyl group with R11 and R12, or form a carbonyl group with r13a and R14, or R15 · and R16 forms a carbonyl group together, and the ruler forms together with the ruler-CHsCI ^ Ci ^ CH2-. In another specific embodiment, R9, R10, R11, Ri2, Rl4, Rl5, and Rl6 are each independently selected from the group consisting of hydrogen or Ci 2 alkyl, wherein the fluorenyl group is optionally selected from N (R2G) 2 or 1 substituent of aryl group, or r9 & r -28-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) and Du Yao 10 1236471 A7 B7 26- -5. Description of the invention () Can form carboxyl group together. Preferably, R9, R1G, R11, R12, R13, (Please read the note on the back? Matters before filling out this page) R, r15, and R10 are each independently selected from the group consisting of hydrogen or a Cid group, or among them R9 and R1G may form a carbonyl group together. In another specific embodiment, R1 1 and R15 are each selected from the group consisting of hydrogen or methyl, R9, R10, R12, R13, R14, and R16 are each hydrogen, and R9 and r1g may form a carbonyl group together. , Or R16 are each hydrogen. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs in the compound of formula 1C, R24 can be selected from the group consisting of free alkyl, cycloalkyl, and fused phenylcycloalkyl. The attachment point is on the cycloalkyl. Among them, the aryl group, the cycloalkyl group, and the fused phenylcyclofluorenyl group can be selected from 1 to 3 from halo, CF3, CN, OR20, SR20, S (0) R22, S02R22, S02N (R2G) 2, NR2GC02R22, Cu alkyl group and aryl group are substituted by substituents, where aryl substituents may be selected from 1 to 3 as required from the group consisting of # group, phenyl, cf3, CN, OR20 and ci- 6 alkyl groups are substituted with substituents. In a particularly preferred compound of formula I c, R 2 4 is selected from the group consisting of alkyl, cycloalkyl, and fused phenylcycloalkyl, wherein the attachment point is on a cycloalkyl, where alkyl, Cycloalkyl and fused phenylcycloalkyl can be selected from 1 to 2 groups selected from the group consisting of halo, CF3, CN, OR20, SR20, S (0) R22, S02R22, Cb2 alkyl and aryl, as required Group of substituents, wherein the aryl substituent may be optionally selected from 1 to 3 substituents selected from the group consisting of an i group, a phenyl group, a CF3 group, a CN group, an OR2G group, and a Ci-6 alkyl group. To replace. In other preferred compounds of formula 1C, R24 is selected from the group consisting of alkyl, cycloalkyl, and fused phenylcycloalkyl, wherein the attachment point is on a cycloalkyl, wherein alkyl and naphthenic And fused phenylcycloalkyl groups can be selected from 1 to 2 selected from the group consisting of halo, CF3, OR2 G and aryl groups as required. -29- This paper applies Chinese national standard (CNS) A4 Specifications (210 X 297 mm) 1236471 A7 B7 Heart 27 V. Description of the invention () Substituent group substitution, of which aryl substituents can be selected from 1 to 3 as required from halo, phenyl, CF3, CN OR20 and Cb6 alkyl group substituents. In still other preferred compounds of the formula ic, R 2 4 is selected from the group consisting of an alkyl group having from 1 to 6 carbon atoms, a cycloalkyl group having from 4 to carbon atoms, and a fused phenyl group having a phenyl group. The group formed by cycloalkyl group may be substituted by i to 2 substituents selected from the group consisting of halo group, CF3, 〇η, methyl group and aryl group, and the aryl substituent group may be selected as necessary. Substituted from 1 to 2 substituents selected from the group consisting of halo, CF3, OH, Ci-2 alkyl and aryl. In still other preferred compounds of formula Ic, R24 is an alkyl and cycloalkyl group having 1 to 6 carbon atoms or R 2 4 is a fused phenylcycloalkyl group. To two or more substituents selected from the group consisting of halo, CF3, OR2G, Cu alkyl, and aryl, or R24 benzyl, which may be selected from one to two selected from _, CF3, OR2 G, Ci_4 alkyl group and aryl group are substituted by substituents. In the compound of Formula 1C, R20 is selected from the group consisting of η, Cu alkyl, or aryl, and the alkyl and aryl substituents may be optionally selected from the group consisting of fluorenyl, -OMe, and CF3. Substituent group substitution. r20 is more preferably selected from the group consisting of HSCi · 3 alkyl groups, and r20 is most preferably methyl or fluorene. The substituted feeding compound of the formula IC is selected from the group consisting of 2-({2- [4 · (3 · isopropoxy-2 · hydroxypropyl) pyridyl] _ν- (2,6-dimethylbenzene Amino) acetic acid, N- (2,6-dimethylphenyl) -2 · [4- (2-hydroxy-3-indan-2-yloxypropyl) -30-This paper is applicable to China Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling this page)

Order --------- Line J Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 1236471 A7 B7, Description of Invention (28) Pycnogenol] Ethylamine, N- (2,6-dimethylbenzene ) -2- {4- [2-hydroxy-3-(benzyloxy) propyl] pyridoyl} acetamide, 2_ [4- (3-{[4 · (tert-butyl) phenyl ] Methoxy} -2-Propyl) p-PhenylbN · (2,6 · dimethylphenyl) acetamide, N_ (2,6-dimethylphenyl) -2 · ( 4- {3 _ [(2-fluorophenyl) methoxy] · 2_hydroxypropyl} said phenyl) ethyldonylamine, 2-(4- {3-[(2,4-mono-phenylene) methyl Lactyl] -2-¾propyl than π-wellyl (2,6-dimethylphenyl) ethyl amine, Ν- (2,6-dimethylphenyl) · 2_ [4- (2_hydroxy · 3 · {[4_ (trifluoromethyl) phenyl] methoxy} propyl) r [pi] yl] ethynylamine, Ν- (2,6-dimethylphenyl) -2- (4- {2-Hydroxy-3-[(2-methoxyphenyl) fluorenyl] propyl} pyridyl) acetamidamine, 2- (4- {3-[(2,4-dimethoxyl Phenyl) methoxy] _2_hydroxypropyl} pyridyl) -N · (2,6-dimethylphenyl) acetamidamine, Ν · (2,6 · dimethylphenyl) -2 · (4- {2-Hydroxy-3-[(4-methoxyphenyl) methoxy] propylsyl) ethyl amine, N- (2,6- Dimethylphenyl) -2 · (4- {3-[(4-fluorophenyl) methoxy] -2-hydroxypropyl} pyracyl) acetamidamine, Ν · (2,6-bis Methylphenyl) -2- (4- {2 · hydroxy · 3 · [(4 -tolyl) methoxy] propylsyl) ethylamine, N- (2,6-dimethylphenyl ) -2- (4- {2-hydroxy-3-[(4-phenylphenyl) fluorenyloxy] propyl} pyridyl) acetamidamine, 1 ^-(2,6-dimethylbenzene Based) -2- (4- {3-[(4-butylphenyl) methoxy] -2-hydroxy-31-This paper is sized for China National Standard (CNS) A4 (210 X 297 mm) ( (Please read the precautions on the back before filling this page) -------- Order --------- line, printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471 Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the consumer cooperative A7 B7 29 V. Description of the invention () propyl} pyracyl) acetamidamine, N- (2,6-diamidinophenyl) -2- {4 · [2 -hydroxy-3- 3- (2-Methenylmethoxy) propyl] pyridyl} ethenamide, N- (2,6-dimethylphenyl) -2- {4- [3- (cyclohexylmethoxy) _2 -Weipropyl] pyridyl} acetamidine, and N- (2,6-dimethylphenyl) -2- (4- {3-[(4-fluorophenyl) methoxy] _2- Hydroxypropyl}-3,3-di Pyrazolyl call yl} acetyl group consisting of amine best. The following definitions apply to the terms used herein. "Halo" or "halogen", alone or in combination, represents all halogens, that is, chloro (C1), fluoro (F), bromo (Br), and iodo (I). "Hydroxy" represents a -0H group. " "Thiol" or "thiol" represents -SH group. "Alkyl" alone or in combination represents a group derived from an alkane, including from 1 to 20 carbon atoms, with 1 to 15 more (Unless there is a special definition). It is a straight-bonded fluorenyl group, a branched alkyl group, or a sulfanyl group. A linear or branched alkyl group including 1 to 15 carbon atoms is preferred, and 1 8 to 8 are even better, 1 to 6 are better, 1 to 4 are better and 1 to 2 are best, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl And the like. As used herein, the term "lower alkyl" refers to a straight-chain alkyl group as just described. The cycloalkyl system is preferably a monocyclic, bicyclic or tricyclic ring system with 3-8 members per ring, and more preferably 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, Cyclohexyl, auryl and the like. Alkyl may also include linear or branched alkyl groups containing or interrupted by a cycloalkyl moiety. Linear or branched alkyl groups can be attached at any effective point to produce stable compounds. Examples include (but not limited to, this paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm)) (Please read the precautions on the back before filling this page). Order --------- line 1236471 A7 B7 30 Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumers' Cooperatives printed invention description () (Please read the notes on the back before filling out this page) (Isopropyl) Cyclohexylethyl or 2-methylcyclopropylpentyl Substituted alkyl is independently 1 to 3 fluorenyl, hydroxyl, alkoxy, and alkylthio; alkanesulfite, alkylthio, alkoxy, aryloxy, heteroaryloxy, and amine (Optionally mono- or di-substituted with alkyl, aryl, or heteroaryl), fluorenyl, urea (optionally substituted with alkyl, aryl, heteroaryl, or heterocyclic group), sulfamidine (Optionally substituted by N-mono- or N, N-di- with alkyl, aryl or heteroaryl), alkanesulfonylamino, arylsulfonamido, heteroarylsulfonamido, alkylcarbonyl A previously defined straight-chain alkyl, branched alkyl, or cycloalkyl group substituted with an amino group, arylcarbonylamino group, heteroarylcarbonylamino group, or the like substituted with a group or substituent. In combination, "Gui Ji" represents a straight chain, branched or cyclic hydrocarbon including 2-20 carbon atoms, preferably 2 -17, more preferably 2-10, and even 2-8 More preferred are two to four, which have at least one carbon-to-carbon double bond, preferably one to three, more preferably one to two, most preferably one. In cycloalkyl In some cases, the conjugate of more than one carbon-to-carbon double bond will not give ring aromaticity. The carbon-to-carbon double bond can be included in the ring group (except cyclopropyl), or it can be straight or branch Examples of alkenyl groups include vinyl, propionyl, isopropenyl, butenyl, cyclohexenyl, cyclohexenylalkyl, and the like. Substituted alkenyl groups are independently 1 to 3 Self-radical, hydroxyl, alkoxy, sulfanyl, thiosulfanyl, sulfanyl, aryloxy, aryloxy, heteroaryloxy, amine (optionally alkyl, aryl or heteroaryl) Aryl is mono- or di-substituted), fluorenyl, urea (optionally substituted with alkyl, aryl, heteroaryl, or heterocyclyl), sulfamoyl (optionally with alkyl, aryl, or heterocyclic) Aryl via N_mono- or N, N-a- Substituted), amines, amines, aryls, aryls, succinyls, aminos, succinyls, aminos, succinyls, aminos, heteroarylcarbonyls, aminos, etc (CNS) A4 size (210 X 297 mm) 1236471 A7

V. Description of the Invention The previously defined alkenyl, branched alkenyl, or cycloalkenyl group substituted with a (meth), alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, or the like substituent, may be attached to any Effective point to produce stable compounds. "Block group", alone or in combination, represents a linear or branched hydrocarbon comprising 2 to 20 carbon atoms, preferably from 2 to 17 and more preferably from 2 to 10, even more preferably from 2 to 8 2 to 4 are preferred, which include at least one carbon-to-carbon triple bond. Examples of block groups include ethynyl, propynyl, butynyl, and the like. Substituted alkynyl is independently 1 to 3 I group, hydroxyl group, alkoxy group, alkylthio group, alkylsulfinyl group, alkylthio group, fluorenyl group, aryloxy group, heteroaryloxy group, amine group (optionally, alkyl group, aryl group or Heteroaryl is mono- or di-substituted), fluorenyl, urea (optionally substituted with alkyl, aryl, heteroaryl, or heterocyclyl), sulfamoyl (optionally with alkyl, aryl, or Heteroaryl is N-mono- or N, N-di-substituted), alkylsulfonamido, arylsulfonamido, heteroarylsulfonamido, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonyl A previously defined decyl or branched alkynyl: group substituted with an amino or analog group or substituent, which can be attached at any effective point to produce a stable compound. "" Alkenyl ,, representing -11_011, ; = € 11, ,, ruler, ',' group, where the ruler is a lower-carbon alkyl group or a substituted lower-carbon alkyl group, R ,,, R '... may be hydrogen, halogen, a lower-carbon alkyl group, or a substituted lower-carbon group alone Alkyl, fluorenyl, aryl, substituted aryl, heteroaryl, or fluorinated heteroaryl, as defined below. "Alkynyl, represents -RC e CR, where R is lower alkyl or substituted lower alkyl, and R is hydrogen, lower alkyl, substituted lower alkyl, Group, aryl group, substituted aryl group, heteroaryl group, or substituted heteroaryl group 'are as defined below. -34- This paper size applies to the Chinese National Standard (CNS) A4 specification (21 × 297 mm) ) (Please read the notes on the back before filling out this page) Μ ---- tT --------- ^^^ 1 · Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 1236471 Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 heart printed by employee consumer cooperatives 33 5. Description of the invention () group, thiosulfanyl, fluorenyloxy, aryloxy, heteroaryloxy, amine (optionally based on; fe, aryl or heteroaryl The group is mono- or di-substituted), fluorenyl, urea (optionally substituted with a group, a square group, a heteroaryl group or a heterocyclic group), and an amine group (optionally with an alkyl group, an aryl group, or a heteroaryl group) N-mono- or N, N-di-substituted), stilbene amine, sulfonium amine, heteroaryl fluorenylamine, alkylcarbonylamino, alkynylamino, heteroaryl Amine or similar "Substituted aryl" represents an aryl group optionally substituted with one or more functional groups, for example, from a prime, lower alkyl, lower alkoxy, alkylthio , Ethynyl, amine, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocyclic, heteroaryl, substituted heteroaryl, nitro, cyano, thiomethyl, thioamino And the like. "Heterocycle" represents a saturated, unsaturated, or aromatic carbocyclic group having a single ring (e.g., morpholinyl., Pyridyl, or furyl) or a multi-concentrated ring (e.g., pyridyl, quinazole) in its ring Group, quinolinyl, indolinyl, or phenyl [b] hexyl) and having at least one heteroatom, such as Sf, O, or s, which may be unsubstituted as required, or, for example, halogen, low-carbon Alkyl, lower alkoxy, alkylthio, ethyl block, amine, amido, alkyl, aryl, aryl, aryloxy, heterocyclic, heteroaryl, substituted heteroaryl , Nitro, cyano, thiol, thiolamine and the like. "Heteroaryl", alone or in combination, represents a monocyclic aromatic ring structure including 5 or 6 ring atoms or a bicyclic aromatic ring having 8 to 10 atoms, including one or more independently selected from 0, S And N-based heteroatoms (1_4 is better, i_3 is better, or even 1-2 is better), and if necessary, _ to 3_bases, -36- This paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) -------- 1T --------- line (Please read the precautions on the back before filling this page) 1236471 Economy Printed by the Intellectual Property Bureau of the Ministry of Intellectual Property and Consumer Cooperatives A7 34 V. Description of the invention Oxy, amine (optionally mono- or di-substituted with alkyl, aryl or heteroaryl), fluorenyl, urea (optionally substituted with alkyl, aryl, heteroaryl or heterocyclic group) , Amino acid group (optionally substituted with an alkyl group, an aryl group or a heteroaryl group by N · mono · or N, N-di ·), alkanesulfonylamino group, arylenesulfonylamino group, heteroarylsulfonamide Alkyl, alkylcarbonylamino, arylcarbonyl Substituted by amino groups, substituents of aminoamino, heterostilylamino or the like. It is also intended to include oxidized S or N with heteroaryl groups, such as sulfinyl, sulfonyl and tertiary ring nitrogen iN_ oxides. The carbon or nitrogen is at the attachment point of the heteroaryl ring structure of the aromatic ring which can maintain stability. Examples of heteroaryl groups are pyridinyl, sulfonyl, pyrimidinyl, pyranyl, sulfanyl, quinolinyl, isoquinolinyl, pyrimidinyl, pyrrolyl, oxazolyl, thiazolyl, sulfonyl Base, isoxazolyl, oxadiazolyl, isothiazolyl, tetrazolyl, imidazolyl, triazinyl, furyl, phenylsulfanyl, whodoyl, phenylsulfanyl, phenylhydrazone Oxazolyl and the like. "Heterocyclyl", alone or in combination, represents a non-aromatic cycloalkyl group having from 5 to 10 atoms in which from 0 to 3 carbon atoms in the ring are substituted with heteroatoms of 0, S or N, And may optionally be fused with a phenylhydrazone of a 5-6 ring element or a fused heteroatom and / or substituted as required, as in the case of a cycloalkyl group. It is also intended to include a vaporized S or N with a heterocyclic group, For example, the N-oxide of the oxy acid group, the carboxylic acid group and the tertiary ring nitrogen. The attachment point is on the carbon or nitrogen atom. Examples of the heterocyclic group are tetrahydrofuryl, dihydropyridyl, piperidinyl, pyrrolidine Base, pyrenyl, dihydrobenzyl, indolyl, and the like. Substituted 4-ring radicals include substituted nitrogen attached to a valid carbon or nitrogen atom to produce a stable compound. 37 · This paper size applies to China National Standard (CNS) A4 specification (210 X 297 public love) (Please read the precautions on the back before filling this page) -------- Order -------- -Line · 1236471 Printed clothing A7 of the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs __B7_ 35 V. Description of the invention () "Substituted heteroaryl" represents visible Heterocyclic rings that are mono- or poly-substituted with one or more functional groups, for example, from a prime, lower alkyl, lower alkoxy, alkylthio, ethynyl, amine, amido, carboxyl, "Hydroxy, aryl, aryloxy, heterocyclic, substituted heterocyclic, heteroaryl, substituted heteroaryl, nitro, cyano, thiomethyl, thioamino, and the like." `` Alkyl '' represents -R-Ar, where Ar is aryl and R is lower alkyl or substituted lower alkyl. The aryl group may be optionally unsubstituted or substituted with, for example, halogen, low-carbon fe group, alkoxy group, sulfanyl group, ethyl group, amine group, amino group, carboxyl group, hydroxyl group, aryl group, aryloxy group, heterocyclic ring, Substituted heterocyclic ring, heteroaryl group, substituted heteroaryl group, nitro group, cyano group, thiomethyl group, thioamino group and the like.

"Heteroaralkyl" represents -R-HerAr, where HetAr is heteroaryl and R is lower alkyl or substituted lower alkyl. Heteroaralkyl may optionally be unsubstituted or substituted with, for example, hydrogen, lower alkyl, substituted lower alkyl, alkoxy, alkylthio, ethyl, aryl, aryloxy, heterocyclic, Substituted heterocyclic ring, heteroaryl group, substituted heteroaryl group, nitro, cyano, thiomethyl, thiamino and the like. "Cycloalkyl" represents a bivalent or polycyclic system alkyl group including 3 to 15 carbon atoms. `` Substituted cycloalkyl '' means a compound containing one or more compounds having, for example, halogen, lower alkyl, alkoxy, alkylthio, ethynyl, aryl, aryloxy, heterocyclic, substituted Ring, heteroaryl, substituted heteroaryl, cycloalkyl of the substituents of nitro, cyano, thiomethyl, thioamino, and the like.

"Alkylcycloalkyl" stands for -R-cycloalkyl, where cycloalkyl is cycloalkyl and R -38- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the notes on the back before filling this page)

• ϋ n ϋ m ϋ ϋ Yikou, I ala— n 1_1 · ϋ · ϋ ϋ ϋ I 1236471 A7 B7, 36 V. Description of the invention () is a low-carbon alkyl group or a substituted low-breaking alkyl group. The cycloalkyl group may be optionally unsubstituted or substituted with, for example, hydrogen, lower alkyl, lower alkoxy, alkylthio, ethyl, amine, amido, carboxyl, hydroxyl, aryl, aryloxy , Heterocyclic ring, substituted heterocyclic ring, heteroaryl, substituted heteroaryl, ceryl, cyano, thiomethyl, thioamino, and the like. "If necessary," and "optionally" means that the event or environment described herein may or may not occur, and the description includes an illustration of the event or environment and its non-occurrence. For example, "medicine on demand" Excipients, means that the formulations described herein may or may not include pharmaceutical excipients other than those specifically stated to exist, and thus the formulations described include examples of the presence of excipients therein and where no excipient is required. "Treatment π" and "therapeutic effect" represent any disease treatment in mammals (especially humans), and include: (i) prevention of diseases that occur in patients, which can pre-treat the disease, but it has not been diagnosed Some diseases; (ii) Inhibition of disease, that is, to stop its development; or (iii) Elimination of disease, even if the disease recovers. The composition of the present invention is useful for treating mammals in the treatment, which is selected from the group consisting of protecting skeletal muscle caused by trauma Freedom from injury, protection of musculoskeletal and muscular complications such as intermittent dysentery, treatment of shock symptoms, donation of tissues and organs used during transplantation, treatment of cardiovascular disease, including anterior atrium and ventricular arrhythmias, Puri Zemant's (variant) angina pectoris, stable angina pectoris, angina pectoris, cardiac congestive disease, and myocardial infarction. Utilizing a therapeutically effective amount of at least one compound of the present invention -39-This paper is applicable to China National Standard (CNS) A4 Specification (210 X 297 mm) (Please read the precautions on the back before filling out this page) ------- Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1236471

, Invention description (

Equation I

II

(Please read the precautions on the back before filling this page}-衣 protect

VIII • Printed by the Intellectual Property Agency of the Ministry of Economic Affairs and Consumer Cooperatives ν / ι 〇 T? 12 R4 \ Rs Rl6 R15R14 13 νπ

^ 19 Compound VI can be obtained by reacting compound IV with substituted N-protected ρ-βV by warming it in a suitable solvent (e.g., DMF, EtOH). The nitrogen of compound V needs to be protected only for controlling the regiochemistry where compound V is added with compound IV. In some cases, it can be obtained from commercial sources. 41-This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1236471 A7 B7 V. Description of the invention (43

Equation 5 A

CH,

Acetone, k2co3 (please read the precautions on the back before filling this page) --- Order --------- Line-Printed by M OCH from the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, which explains the compounds in Equation 7. 14 special synthetic effects. Epoxide 6 was turned on in a way that boc_ethylenediamine was warmed in rhenium to prepare compound 11. Use of chloroacetamidine in dichloromethane and use of diisopropyl -46- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm 1236471 A7 B7 V. Description of the invention (44

Ethylamine was used as a test to complete the tritiation of compound 11. TFA was used to remove the Boc group and then the ring was closed by warming it in EtOH to produce compound 13. The reaction of compounds 3 and 6 produces compound 14 as described above. Equation 7A ^ oc

HN

► HN

OCH, (Please read the notes on the back before filling this page) 10

2. KtOII, I) IPI: A

OCH, 1-TFA

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Compounds having the general formula i & IB can be prepared using the formulae of Equations 1B-7B. A general synthetic effect of the compounds of the invention is stated in Equation 1 B. Compound IV is prepared by N · fluorination of substituted aniline of general structure 11 and 2- substituted chloroacetamidinyl chloride III. Compound II can be commercially substituted or can be easily prepared by the reduction of the corresponding nitrobenzene derivative (Acid 47 This paper is sized to the Chinese National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 5 Description of the invention (45 / S11CI2 or 4 隹 虱 化 作用 化 '' Refer to a. Wiley-Interscience Advanced Organic Chemistry (1 " 2 years) published by J. March). The general structure of π can be obtained commercially Some examples of substituted anilines include 2,6-dimethylamine 2,3-monomethylaniline, 2-methylaniline, 4-methylaniline, monochloroaniline, 3,4-dichloroaniline, 2, 5_dichlorobenzylamine, 2,4_dichlorobenzylamine 7 2-chloroaniline, 3-chloroaniline, 2,6_difluoroaniline, 2,5_difluoroaniline, '3,4-difluoroaniline , 2-fluoroaniline, 4-fluoroaniline, 3-fluoroaniline, fluoro-6-chloroaniline, 4-fluoro-3-chloroaniline. Soil (Please read the note on the back? Matters before filling out this page}- 1 ------ Order --------- · Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs-48 1236471 A7

V. Invention Description (Equation IB

Λτ R7'r8

Protect (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs vn

Compound VI can be obtained by reacting compound I V with N-protected substituted pyrene V by warming it in a suitable solvent (e.g., DMF, EtOH). The nitrogen of compound V needs to be protected only for controlling the regiochemistry of compound V added to compound iv. In some cases, from commercial sources 49 This paper size applies to the Chinese National Standard (CNS) A4 (210 X 297 mm)

-------- Order --------- line J 1236471 A7 V. Description of the invention (48

R10 1-N (1998), pp. 63, 2564-2573). Compound XI can be prepared by reacting aldehyde IX with methyltriphenylphosphine under Wittig conditions or Horner Emmons conditions. [Advanced Organic Editing by Wiley-Interscience Publishing J. March Editing Chemistry (1992) and S. Pine, G. Shen and H. Hoang (Synthesis) (1991 noon), 1]. The coupling of a halide of general formula X with allylmagnesium bromide can also facilitate the preparation of compound XI. In some cases, compound XI is available from commercial sources. Examples of commercially available compounds corresponding to Formula XI include (here m = 0) 3-fluorostyrene, 4-fluorostyrene, 2-aerostyrene, 3-chlorostyrene, 4-chlorostyrene , 2,6-dichlorostyrene, 3,4-dichlorostyrene, 3,4-dimethoxystyrene. Other examples of commercially available compounds having the general structure XI include (here m = 1) 4-methoxyallylbenzene, 2-hydroxyallylbenzene, 4,5-dimethoxyene Propylbenzene, 2-methylallylbenzene camphor and 丨 _allyl.

Equation 3 B-A η 'yN ~ B〇C with i, Rq.ioMi · ^ Bn " yj—boc XI! Xiii to protect the function (please read the precautions on the back before filling this page) Order ----- ---- · Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs

Bn—-N

XiV

l / H

XV -51 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1236471

V. Description of the invention (53,)

Manga 1 C

Rio? 11 I:

: N v

BOC, CBZ or octyl deprotection >

c Please read the notes on the back before filling out this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

R

CT 1

VIII Compound IV is prepared by converting substituted aniline n and 2-substituted = donkey chloride ββN_ 醯 into hydrazone. Compound 〇 can be prepared from commercial = easily via the corresponding nitrobenzene derivative distant substance < mesogen effect (acid / SnChj 56 This paper size applies Chinese National Standard (CNS) A4 specification (2) 0 X 297- -----

1236471 A7 ------- B7___ τν 54 5. Description of the invention () (Please read the notes on the back before filling out this page) 4 Hydrogenation, refer to A. Wiley-Interscience South published by J. March Advanced Organic Chemistry (1992)) Some examples of commercially available substituted anilines II include 2,6-difluorenylaniline, 2,3-dimethylaniline, 2- Methylaniline, 4-methylaniline, 2,4-dichloroaniline, 3,4-dichloroaniline, 2,5-dichloroaniline, 2,4-dichloroaniline, 2-chloroaniline, 3-chloro Aniline, 2,6-difluoroaniline, 2,5-difluoroaniline, 3,4 _ monopyridamine, 2 _ triamidine, 4-tribenzylamine, 3 · triammine, 2 _ fluoro-6 -Chloroaniline, 4-fluoro-3-chloroaniline. Compound VI can be obtained by reacting Compound IV with N-protected substituted Pyrogen V by warming it in a suitable solvent (e.g., DMF, EtOH). The nitrogen of compound V needs to be protected only when used to control the regiochemistry where compound V is added to compound V. In some cases, compound V is available from commercial sources. Examples of commercially available compounds corresponding to the general structure V include 2-methylpyroxy, 2,5-dimethylpyroxy, 2,6-dimethylpyroxy, and 4-benzyloxycarbonylpyroxy-2 -ketone. The protection of compound VI can be accomplished using standard conditions (for example, for Boc groups, TFA is used, and for CBZ and benzyl groups, hydrogenation is used). Compound I can be prepared by reacting compound VII with epoxide VIII warmly in a suitable solvent (ethanol, DMF). Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs -57- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 V. Description of the invention (57

Equation 4 C

-NH OH f V

Boc—NH OH XIV di bo rant · -NH OR XV R = Me or Et 2. TFA, ring closed R \ ^ ° H—N N-〇H XV i

Bn 1-,-v_p v R14 Specific examples of the preparation of the compounds of the invention are disclosed in equations 5 C and 6 C to further illustrate how to prepare the compounds of the invention. (Please read the precautions on the back before filling this page) ------------- Order --------- Printed by the Consumers' Cooperative of Intellectual Property Bureau of the Ministry of Economy This paper applies Chinese national standards (CNS) A4 specification (210 X 297 mm) 1236471 A7 __B7___ 60 V. Description of the invention () Pharmaceutically acceptable salt, in addition, it may include other medicinal agents, medicines, carriers, adjuvants, diluents, etc. . (Please read the notes on the back before filling out this page.) Of course, the amount of active compound administered depends on the patient to be treated, the weight of the patient, the severity of the infection, the method of administration and the prescriber. However, the effective dose is in the range of 0.1 to 30 g / kg / day, and more preferably 05 to 20 g / kg / day. For an average person of 70 kg, it may be equivalent to 7-2100 grams per day, or more preferably 3 to 1400 grams per day. Because similar mechanisms (partial fatty acid inhibition) can achieve many of the effects of the compounds in this document (muscle or systemic diseases with skeletal muscle complications (such as intermittent 跛), treatment of shock symptoms, preservation of donor tissue used in transplantation, and Organs and treatment of cardiovascular disease, including anterior atrial and ventricular arrhythmias, Priezmann's (variant) angina, stable angina pectoris and exercise-induced angina, congestive heart disease, and myocardial infarction), so the dose for all these uses (And the form of administration) are generally within the same general and better scope. The Ministry of Economic Affairs ’Intellectual Property Bureau's Consumer Cooperatives printed on solid compositions' can use well-known non-toxic solids, including, for example, pharmaceutical grades of mannitol, lactose, starch, stearic acid, sodium saccharin, talc, cellulose, glucose, Sucrose, magnesium carbonate and the like. The active compound as defined above can be formulated as a suppository using, for example, polyalkylene glycol (e.g., polypropylene glycol) as a carrier. The pharmaceutical composition of a liquid composition can be prepared by dissolving and dispersing the active compound as defined above and an optional pharmaceutical adjuvant in an excipient such as water, saline, aqueous dextrose, glycerol, Ethanol and the like form solvents and suspensions. If necessary, the pharmaceutical composition to be administered may also include a small amount of non-toxic auxiliary substances, such as wetting or emulsifying agents, pH buffering agents and the like. -63- This paper is in accordance with China National Standard (CNS) A4 specification (210 X 297 mm) Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, India and India 1236471 A7 -------- —B7 ______ V. Description of the invention (61) For example, steel acetate, pimentol monolaurate, sodium triethanolamine acetate, triethanolamine Oil fe ester and so on. Those skilled in the art know or understand practical methods for preparing these dosage forms, for example, refer to Remington's Pharmaceutical SCiences, 15th Edition, Division 1975, Easton Mack, PA. The pharmaceutical composition or formulation to be administered does not include how to include a therapeutically effective amount of the active compound (class), that is, to effectively reduce the symptoms of the patient to be treated. With regard to oral administration, the formation of a pharmaceutically acceptable non-toxic composition is by incorporating any normally used excipients, such as exemplified pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, Talc, cellulose, glucose, sucrose, magnesium carbonate and the like. These compositions are in the form of solutions, suspensions, tablets, pills, capsules, powders, sustained release formulations and the like. These compositions may include from 10% to 95% of the active ingredient, preferably from 1.70%. Parenteral administration is usually characterized by injection either subcutaneously, intramuscularly, or intravenously. Injectable solutions can be made into well-known forms, or they can be in the form of liquids or suspensions, solid forms suitable for solutions or suspensions in liquids prior to injection. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol or the like. In addition, if necessary, the pharmaceutical composition to be administered may also include a small amount of non-toxic auxiliary substances, such as wetting or emulsifying agents, pH buffering agents and the like, such as sodium acetate, xanthosyl monolaurate, Ethanolamine oleate and the like. A more recently derived method of parenteral administration uses implanted slow-release or sustained-release systems to maintain a fixed dose standard. Reference is made to U.S. Patent No. 3,710,795, which is incorporated herein by reference. In other -64-This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page)

1236471 Α7 Β7 nr 70 t, description of the invention () (Please read the notes on the back before filling this page) Dissolve compound 11 (1.0 g, 3.0 mmol) in 20 ml of DCM and diisopropylethylamine (0.76 g, 4.5 mol). The mixture was cooled to 0 ° C. Chloroacetamidine chloride in 5 ml of DCM was added dropwise to the cold mixture. The reaction mixture was allowed to stir at room temperature for 24 hours. The mixture was diluted with 50 ml of DCM and washed with 50 ml of water and 10% citric acid. The organic layer was dried over MgS04 and filtered. The solvent was evaporated under reduced pressure, and the residue was crystallized from diethyl ether to produce compound 12. Synthesis of 1- [2- # stemyl 3- 3- (2-methoxyphenoxy) propyl] u ratio __2-one (13) Compound 12 (0.5 g, 1.5 mmol) was dissolved in 10 ml Ding 1 ^. The mixture was allowed to stir at room temperature for 2 hours. The tfA was removed under reduced pressure. The residue was dissolved in 20 ml of EtOH and treated with diisopropylethylamine (0 76 g, 4.5 mmol). The mixture was heated under reflux for 24 hours. The solvent was removed under reduced pressure to produce compound 13 using the compound without further purification. Part F Synthesis of N- (2,6-dimethylphenyl) -2- {4- [2-Cyclo-3- (2-methoxyphenoxy) propyl] -3 -oxy Jingji} Ethylamine (14) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, compound 3 (0.7 g, 0.36 mmol) and diisopropylethylamine (0.76 g, 0.36 mmol) ) Was added to a solution of compound 13 (0.1 g, 0.30 mmol) in 10 ml of EtOH. The reaction mixture was heated under reflux for 24 hours. The mixture was concentrated in the air, and the residue was purified using preparative tLC (1 0 · · 1 'DCM · · MeOH) to produce compound 14: mass spectrum (M + 1) = 442 · 34. -73- This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 V. Description of the invention (71 Example 3

(Please read the precautions on the back before filling this page) R-0 Prepare the compounds listed in Table 1 as Compound 1 4 of Example 2 Table 1 R MH + 25 2,6-Dimethylphenyl 430.3 26 2,6-dichlorophenyl 471 27 4-aminocontinylphenyl 481.2 28 3-difluoromethyl-5-methoxyoxyphenyl 500.2 29 5-indanyl 442.2 30 1-fluorenyl 452.3 31 1_ (4 · chlorofluorenyl) 486.3 32 2-N-pyrrolyl-phenyl 467.3 33 phenyl 402.2 34 2-chlorophenyl 436.2 35 2-chloro-4-methylphenyl 450.2 36 2- (1- Methyl ethyl) phenyl 442.3 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -74 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 72 V. Description of the invention () Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 37 2-methylbenzyl 416.2 38 2-isopropyl-6-methylphenyl 458.4 39 3-methylthiophenyl 448.2 40 2_methoxy · 4 · Gasoyl-5-methylphenyl 480.2 41 4-dimethylaminophenyl 445.3 42 2,4-dimethoxyphenyl 462.3 43 3,4-dichlorophenyl 471.1 44 4-chlorophenyl 436.3 45 3-Gaphenyl 436.2 46 3,5-dichloro 471.1 47 4-methoxyphenyl 432.3 48 4-methylbenzyl 416.2 49 3-methylphenyl 416.2 50 4-fluorophenyl 420.2 51 4-chlorophenyl 427.3 52 4-acetamylphenyl 444 53 2 -Methoxyphenyl 432.4 54 4-trifluoromethylphenyl 470.2 55 3.trifluoromethyl-4 chlorophenyl 504.1 56 3,5-dimethoxyphenyl 462.3 57 4-N-? 1 (1 Linkidongyl 487.4 58 3-fluoro-4-methoxyphenyl 450.2 59 3,4,5-trimethoxyphenyl 492.3 -75- (Please read the precautions on the back before filling this page) Loading ------- --Order --------- · This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 1236471 A7 B7 94 V. Description of the invention () Economy Printed by the Ministry of Intellectual Property Bureau Consumer Cooperatives 24B 10C 100% 97% Noodles 7C 68% Circle Noodles 11C 79% Sleep 12C 41% Noodles Let 13C 30% Circle 14C 21% 15C 100% Noodles 16C 97% Noodles 17C 35% Sleep pain 18C 96% _ 19C 97% 雠 20C 100% _ face 21C 87% 22C 45% face 23C 12% round 24C 15% 25C 38% 26C 70% _ 27C 73% Oxidation-97- Suitable for this paper size National Standard (CNS) A4 Specification (210 X 297 mm) ------------ Install --- (Please read the precautions on the back before filling this page) ·% 951236471 A7 V. Invention Explanation (In 100 microliters total volume containing the following reagents: Oxidation of Palmitoyl Carnitine: 110 mg molecular weight KC1, 33 mg of pH 8.2 T buffer solution, 2 mg molecular weight KPi, 2 mg molecular weight MgCl2, 0.1 mg molecular weight EDTA, 0.1 mg / ml fat-free BSA, 0.05 mg molecular weight malic acid, 3 mg molecular weight ADP, 52 μg mitochondrial protein, and 43 μg molecular weight 1-C14 palmitylcarnitine (Sp 60 mci / mole activity; 20 μCi / ml, 5 μl per analysis). The compound of the present invention was added to a DMSO solution at the following concentrations: 100 microgram molecular weight, 30 microgram molecular weight, and 3 microgram molecular weight. In each analysis, DMSO controls were used. After 15 minutes at 30 ° C, the enzyme reaction was centrifuged (at 20,000 g for 1 minute), and 70 microliters of the supernatant was added to an activated reversed phase silicic acid column (about 0.5 ml of silicic acid). The column was eluted with 2 ml of water and 0.5 ml of the eluent was used for scintillation counting to determine the amount of C 14 trapped as C 1 4 bicarbonate ion. Data are expressed as% control activity. ------- • Installation (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs -98- This paper size applies to China National Standard (CNS) A4 (WO X M7 mm) 1236471 A7 B7 99 V. Description of the invention () Release 100 microliters of the supernatant. The samples were then analyzed at 0 and 30 minutes by changing the ratio of the compound to the internal standard by LC / MS (injection of 10 microliters). Analysis and data calculation: By using internal standards and L C / M S of a 0 ds-C 18 column at a flow rate of 0.25 ml / min, samples were analyzed with starting compounds and latent metabolites / etc. After the above analysis, the following relative stability factors were obtained by comparing Rylon Lessing with the compounds of the present invention, as exemplified in Table 4. In the liver S 9 analysis, if the compound is more stable than Rylone Lessin, the stability factor will be greater than 1.0. If the compound is not as stable as Rylon Lessing, the stability factor will be less than 1.0. (Please read the precautions on the back before filling out this page) Printed on clothing table 4 by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Compound #-- ------ ^ Liver S9 stability factor Ruilong Lessing 1.0 5 0.45 7 ------ " one " 1.51 15 1.20 16 0.15 17 0.45 9B 1.18 10B 1.03 7B 1.46 11B 1.33 102 Fine towels family standard (CNS) A4 specification (210 X 297 mm) 1236471 A7 B7 v 100 V. Description of invention () Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 12B 1.38 13B 0.10 10C 7C 0.37 11C __ 12C 1.48 13C 1.20 14C 0.083 15C 16C 17C 1.0 18C 19C 20C 21C 22C 0.61 23C 0.05 24C 0.02 25C 0.01 26C Negotiable 27C · -103- --- (Please read the precautions on the back before filling this page): This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm)

Claims (1)

1236471 Patent Application No. 090104080 g Chinese Patent Application Replacement (August 1993) 08 1. A substituted picolin compound having the following formula I A: Where m = 1 or 2;, R3, R4 and Chi 5 are each independently selected from the group consisting of hydrogen, halo, cf3 &gt; CN ^ 〇r23 &gt; sr23 &gt; N (R23) 2 &gt; so2N (R23) 2 &gt; C0R23, cii 5 alkyl, c; 2-15 alkyl, heterocyclyl and aryl, or R2 and Rs can be joined together to form a fusion ring system with 3 to 4 carbon atoms, or Join and 4 and Rs with their associated phenyl groups to form a substituted fluorene moiety if necessary; R 6, R 7 and R 8 are each independently hydrogen; R9 '' Rh, R12, Ru, Ri4, Ri5 And Ri6 are each unique. • They are selected from the group consisting of hydrogen and C4, or 9 or 111 (), Rh and R12, r13 and Ri4, or R15 and together form a fluorenyl group. ^ And! ^ 5 or R9 and R13 are joined together to form a bridging group with 1 to 2 carbon atoms, and the condition is that when m is equal to 1, then r9, R iq, R ti, R i 2, R i 3 、 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1236471 R14, R15, and R16 are not all hydrogen; 17 feet 18, R19, feet 20, and feet 21 are each independently selected from the group consisting of hydrogen, halogen, R23 c 1 _ 15 force element base, and base; and 2 3 is selected from the group consisting of fluorene and C i -3 alkyl. 2. The compound according to item} in the scope of patent application, wherein Ri,, r ^, R4 &amp; R5 are each independently selected from the group consisting of hydrogen, halo, CF3, CN, OR23, sr23, n (r23) 2, and 〇2N (R23) 2, coR23, Ci_8 fluorenyl, Gy alkenyl, heterocyclyl, aryl, and heteroaryl group, in which the alkyl substituent may be selected from the group consisting of 〇13 Substituent substituents of the group may join h and R3 together to form a fused ring system with 3 to 4 carbon atoms in it, or r4 # r5 and its associated phenyl group may be joined together to form Optionally substituted naphthalene moieties; and ruler 9, R10, Rh, R12, r13, Ri4, uRi "are each independently selected from the group consisting of hydrogen and c4 alkyl, or trans 9 and heart 0, Rh and R12 , R13 and Ri4 or Ri5 can form a carbonyl group together, or can be joined together with ~ and ^ to form a bridging group with i to 2 carbon atoms. 3 The compound according to item 2 of the scope of the patent application, where R !, R2, R R4, and Chi 5 are each independently selected from the group consisting of hydrogen, south base, CF3 'CN, OR23, SR23, n (r23) 2, so2N (R23) 2, coR23, and Ci.6 _, U group, heterocyclic group and heteroaryl group, in which the alkyl substituent can be -2- This paper size applies to China National Standard (CNS) A4 specifications (210X297 public director) 1236471 8 8 8 8 A BCD ~ ------- 6. The scope of patent application is replaced by 〇23 as needed, or R2 and R3 can be joined together to form a yarn loop system with 3 to 4 carbon atoms, or R4 can be used. Joined with R5 and its associated phenyl group to form an optionally substituted fluorene moiety; R 9, R i 0, R i!, R i 2, R 1 3, R t 4, R i 5 and R i 6 is each independently selected from the group consisting of hydrogen and C 2 2 radicals, or trans 9 and 111 (), Ru and R12, r13 and R14, or R15 and Ri6 may form several groups together; and R17, R18, R19, r20, and r21 are each independently selected from the group consisting of hydrogen, halo, OR23, C [_8alkyl, and phenyl. 4. The compound according to item 3 of the scope of the patent application, where r], r 7, r 3, and R 5 are each independently selected from hydrogen, halo, cf3, CN, OR23, SR23, N (R23) 2, S02N (R.23) 2, Co_r23, Ch alkyl, C2_6 Alkenyl and heterocyclic group In which, the alkyl substituent may be substituted with 0-23 as required, or I and I may be joined together to form a fusion system having from 3 to 4 carbon atoms, or R 4 and R 5 may be linked to it. The phenyl groups are joined together to form a substituted naphthalene moiety if necessary; and R9, Rio, Ru, R12, R13, Rl4, ruler and ruler are each independently selected from the group consisting of hydrogen and C2 pit group Group, or &amp; 9 and 111 (), Rh and R12, R13 and R144R15 and R16 can be shaped-this paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) Into carbonyl. 5. The compound according to item 4 of the scope of patent application, wherein ^ 9,, Ri °, R &quot;, R12, Rl3, Ri4, and 1116 are each independently selected from the group consisting of hydrogen and methyl, or Han 9 And 111 () or R13 and R14 may form a carbonyl group together; R17, Ru, R19, r20, and R2l are each independently selected from the group consisting of hydrogen, halo and C i _ 2 radical; and R 2 3 is selected A group of free hydrogen and methyl groups. 6. The compound according to item 3 of the scope of patent application, wherein ^ τ 18, R19, R202 and 21 are hydrogen, and Ri 7 is selected from the group consisting of halo and OR23. 7. The compound according to item 6 of the scope of patent application, in which Bu Jia and Xin, R1 (), Rn, R13, r14, r15 and Ru are. 8. The compound according to item 6 of the scope of patent application, in which carbonyl can be formed with r 1, R 11, R 12, R 13, R 14, Ri 5 and R 1. 9. The compound according to item 6 of the scope of the patent application, wherein R9, R1, Ri2, R15, and R16 are each hydrogen, and Ri3 and R4 can form a carbonyl group. Medium 10. The compound according to any one of the items 2 to 9 in the scope of the patent application, which is Π1 ^ \ 〇 The compound according to the sixth item in the scope of the patent application, wherein 'R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, Halo, cf3, cn, 〇r ”, SR23, N (R23) 2, S02N (R23) 2, C〇R23, Cl_3 alkyl, c2_3 alkenyl, N-morpholinyl, and ττBiloxi A group consisting of 垸 groups to replace the specifications of this paper-1236471 8 8 8 8 AB CD 6. The scope of patent application can be replaced by Ο 可视 as required, or "quoted in conjunction with" A fused ring system with a complete atom, or R 4 and R 5 can be joined with their associated phenyl groups to form a substituted naphthalene moiety as required. 12. According to the first item of the scope of the patent application, Ri, R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen, halo, CF3, OH23, and C9; R9, R10, Ri i, R12, R13, r14, Rl5 And Ri6 are each independently selected from the group consisting of hydrogen and a C _ 4 alkyl group, or feet 9 and Rio, Ru and R12, R13 and R14, or R15 and may Together form a carbonyl group, the condition is that when m = i then R9, R i 〇, R ^ ^, R i 2, Rl3, R14, R15 and R16 are not all hydrogen at the same time, or R 1 1 and R 15 or R 9 is bonded to R 13 to form a bridging group having 1 to 2 carbon atoms; Rh, R18, R19, R20, and R21 are each independently selected from the group consisting of hydrogen, halo, 0R2, C i _4 tiger, and aromatic And R 2 3 is ci _ 2 end group. 13. The compound according to item 12 of the scope of patent application, wherein R 4 and I are each independently selected from the group consisting of hydrogen and methyl. 14. The compound according to item 12 of the scope of the patent application, wherein R9, Rio 'Rh' R13, r14, Ri5 and Ri6 are each independently selected from the group consisting of hydrogen and C! · 2 垸 group, or R9 and RiPtRu and R10 can form a carbonyl group together. The conditions are called Dangyang, ___ _5_ I The paper size is applicable to China National Fresh (CNS) A4 specifications (21Qx 297 public directors)-1236471 Wai Fanli, please refer to AB c D, R When gate, R &quot;, R15, and Ru are not all R, then R9, R1 () 'R 丨 are hydrogen at the same time, or I combines 1 ^ 1 with 1115. or R9.! ^ 3 to form a group with from 1 to 2 children. Bridging group. ', 15. The compound according to item 12 of the scope of the patent application, where ^ 9' 'Rl1, Rl2, Rl3, Rl4, is a group consisting of a free radical and a Ci_2 alkyl group, or ^ and Ru, Ru and r12, Rl3 and Rl4, or r15 and Ru can be carbonyl. Heart ~ Wind 16. According to the compound in the 12th scope of the application for patent, ^ D 9 K 丨 G and /. Must 1 &lt; 1 5 and R 丨 6 together to form a carbonyl group. 17. The compound according to item 12 of the scope of the patent application, and the Chinese /, 18, 17, K i 8, 19, R 2 0 and R 21 are each independently selected from hydrogen, halide, Cl 4 alkyl, and 0. 23, wherein r23 is Ci-2 alkyl. 4 70 土 18. The compound according to item 1 of the scope of patent application, wherein 1; R1 R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen and methyl; R9, Rio, Ru, Ri2, Rl3, Rl4, Ru, and Ri6 are each selected from the group consisting of hydrogen and a C4 · 4 alkyl group, or a rule 9 and 111 (), a countermeasure, and a rule. , Ri3 and Rh or R15 and Rh can form a carbonyl group together, the conditions are that R9, Rio, Ru, R12, r13, Rl4, Rl5 and Rl6 are not all hydrogen at the same time, or Rl1 and Rh or Chinese 9 and 1 ^ 3 joining to form from 1 to 2 carbon atoms-6- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) R1? R18, R19, R2 (^ R21 are each independently selected from the group consisting of hydrogen, dentyl, Ci · 4 alkyl and OR23; and R 2 3 is C 1 _ 2 group. 19. The compound according to the scope of the patent claim VII, wherein each is a methyl group, and R2, R3 and I are hydrogen. 20. The compound according to the scope of the patent claim 18, among them, xin, Rl3 Rl4, Rl5 &amp; Rl6 are argon; and R9 and R1G together form a carbonyl group.-L Compound according to item 18 of the scope of patent application, wherein R, R, R] 1 R12, R15 and R16 are hydrogen; and R13 and Ri4 form together Tan. 22. The compound according to item 18 of the scope of patent application, wherein R9, r㈠, Ru, R12, r13, r14, rm & Ri6 are each independently selected from the group consisting of hydrogen and methyl. 23. According to the application The compound in the scope of the patent No. 18, wherein R9 ', R13, r14, r &quot; and R16 are each hydrogen, and together with the ruler form a bridging group having from 1 to 2 carbon atoms. 24. According to the scope of patent application The compound of item 8 wherein R9, R1 2, R i 3 'R 丨 4, R 丨 5, and R 丨 6 are each hydrogen, and R Η Together with R 1 5 to form a bridging group having 1 to 2 carbon atoms. 25. The compound according to item 18 of the scope of patent application, wherein R 1 and R 2 are each hydrogen, and R 17 and R 18 are each methyl 26. The compound according to item 18 of the scope of the patent application, where ru is _〇CH3 and R18, R19, R20 and R2I are each chlorine. This paper is applicable to GS household fresh (CNS) A4 specifications _χ 297 (Public Director) 1236471 8 8 8 8 A BCD '----------- VI. Patent application scope 27. According to the patent application scope item 18, compounds of Ri7, Ri8, ruler and ruler 21 are each hydrogen, R19 is selected from the group consisting of-OCH3, -F and Ci-4 alkyl. 28. The compound according to item 1 of the scope of patent application, which is selected from the group consisting of N- (2,6-dimethylphenylbenzene 2- {4- [2-hydroxy-3- (2-methoxyphenoxy) ) Propyl] -3 -oxopiryl} acetamidine, N- (2,6-dimethylphenyl) -2- {4- [2 -hydroxy-3-(2-methoxyphenoxy (Propyl) propyl] -3,5-dimethylpyridyl} ethenamide, 2-{(5S, 2R) -4- [2-hydroxy-3- (2-methoxyphenoxy) propyl ] · 2,5-Dimethypyridine N- (2,6-dimethylphenyl) acetamide, 2- {2,5-Diaz-5 — [2-hydroxy-3- ( 2-methoxyphenoxy) propyl] -bicyclo [4,4 · 0] dec-2-yl} to-(2,6-dimethylphenyl) acetamidine, Ν- (2, 6-Dimethylphenyl) -2- {4- [2- # Amino-3- (2-methoxyphenoxy) propyl] -3,3-dimethylform ^ 7-wellyl} ethyl Stuffed amine, 2- {5-[(2S) -2-hydroxy-3- (2-methoxyphenoxy) propyl] (13,48) -2,5-diazinebicyclo [2.2.1 ] Hept-2-yl}-; ^-(2,6-dimethylphenyl) acetamide, N- (2,6-dimethylphenyl) 2- {4- [2-hydroxy-4 -(2-methoxyphenoxy) butyl] pyridyl} ethenamide, N- (2,6-dimethylphenyl) -2- {4- [4- (4-fluorophenylbenzene (Oxy) -2-hydroxybutyl] pyridyl} ethanil 2- (4- {4- [4- (tert-butyl) phenoxy-2-hydroxybutyl} pyracyl) -N- (2,6-difluorenylphenyl) acetamidine, N- (2,6-Dimethylphenyl) -2- {4- [2-hydroxy- 4- (4-phenylphenoxy-8-) This paper size applies to China National Standard (CNS) A4 (210 X 297 Mm) 8 8 8 8 A BCD 1236471 6. Application scope of patents) Butyl] Eujingyl} Ethylamine, N- (2,6-dimethylphenyl) -2- {4- [2 -Hydroxy-4- (4-methoxyphenoxy) butyl] pyridyl} acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy ) -2-hydroxypropyl] -3-methylpyridyl}-N-(2,6-dimethylphenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-Fluorophenoxy) -2-hydroxypropylbutan 3-methylpyridyl}-^^-(2,6-dichlorophenyl) acetamidamine, 2-{(3S) -4- [(2S) -3- (2-Fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-&gt; ^ (4-Aminosulfophenyl) ethanil, 2- {(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl 丨 -N- [5-methoxy-3- (Trifluoromethyl) phenyl] acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropylbutan 3-methylpyridine -N-Indan-5-ylacetamidamine, 2 -{(3S) -4-[(2S) -3- (2-Fluorophenoxy) -2-hydroxypropylbutan 3-methylpyridinib N -fluorenylacetamide, 2-{( 3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylophenyl N- (4-chlorofluorenyl) acetamide, 2 -{(3S) -4-[(2S) -3- (2-fluorophenylphenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(2-pyrrolylphenyl) Acetylamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-phenylethyl Amido, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-^^ (2-chloro Phenyl) acetamide, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3- -9- This paper is applicable to China National Standard (CNS) A4 specification (210X297 mm) 1236471 A8 B8 C8 D8 VI. Application scope of patents Metophenyl}-N-(2 -Chloro-4 -methylphenyl) acetamidine, 2- { (3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-[2-(1 -methyl vinyl ) Phenyl] acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridyl}-N -(2-methylphenyl) acetamide, 2-{(3S)- 4-[(2S) -3- (2-Fluorophenoxy) -2-hydroxypropyl] -3-methylpyridine S} -N- [6 -methyl-2- (methylethyl) phenyl ] Acetylamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(3 -Methylthiophenyl) acetamidamine, 2-{(38) -4-[(2 8) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methanine N- (4-chloro-2 -methoxy-5 -methylphenyl) acetamide, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy ) -2-hydroxypropyl] -3-methylpyridinyl, N- [4- (dimethylamino) phenyl] acetamidamine, 2-{(3S) -4-[(2S)- 3- (2-Fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl} -1 ^-(2,4-dimethoxyphenyl) acetamidine, 2-{( 3S) -4-[(2S) -3- (2-Fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridinib N- (3,4-dichlorophenyl) acetamidine Amine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(4-chlorobenzene Amidyl) acetamide, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridyl, N- (3 -Chlorophenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridinyl}- N- (3,5-dichlorophenyl) ethyl Amine, 2-{(3S) -4-[(2S) _3- (2-fluorophenoxy) -2 -hydroxypropyl] -3- -10-This paper size applies to Chinese National Standard (CNS) A4 Specifications (210X 297 mm) 8 8 8 8 AB c D 1236471 VI. Application scope of patents Metophenyl}-N-(4 -methoxyphenyl) acetamide, 2-{(3S) -4- [(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(4-methylphenyl) acetamidamine, 2-{( 3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl 丨 -N- (3-methylphenyl) acetamidamine , 2-{(3S) -4-[(2S) _3- (2-fluorophenylphenoxy) -2 -hydroxypropyl] -3-methylpyridyl}-N-(4-fluorophenyl) Acetylamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(4- Cyanophenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl (4-Acetylphenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridine }-N-(2-methoxyphenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-] ^-[4- (trifluoro Phenyl) phenyl] acetamidine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl -[4-chloro-3- (trifluoromethyl) phenyl] ethanamine, 2-{(3S) -4-[(2S) -3- (2-fluorophenoxy) -2- Hydroxypropyl] -3-methylophenyl N-(3,5-dimethoxyphenyl) acetamidamine, 2-{(3S) -4-[(2S) -3- (2- -fluoro Phenylphenoxy) -2 -hydroxypropyl] -3 · mepigenyl N-(4 -morpholin-4 -ylphenyl) acetamide, 2-{(3S) -4-[(2S ) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl} -N- (3-fluoro-4-methoxyphenyl) acetamidine, 2 -{(3S) -4-[(2S) -3- (2-Fluorophenoxy) -2 -hydroxypropyl] -3- -11-This paper size applies to China National Standard (CNS) A4 specifications ( 210 X 297 mm) 1236471 Α8 Β8 C8 D8 Application scope of patents methylpyridyl} ^-(3,4,5-trimethoxyphenyl) acetamide, 2'U3S) -4-[(2S) -3- (2-fluorophenoxy) -2-hydroxypropyl] -3-methylpyridyl}-N-(3,4-dimethoxyphenyl) acetamidine, 2 &gt; {( 3S) -4-[(2S) -3- (2-Fluorophenoxy) -2 -hydroxypropyl] -3-methylpyridinib N- (4-chloro-2-fluorophenyl) Acetylamine, and 2_U3S) -4-[(2 S) _3- (2-Fluorophenoxy) -2-hydroxypropyl] -3-methyl p-bihyl}-N-[2-(hydroxymethyl-6 -methylphenyl)] acetamidine A group of amines. .—A substituted pyrido compound having the formula IB: 3 R 9 R IB where 1 or 2 or 3;, feet 2, R3, 114, and 1 ^ 5 are each independently a group consisting of free hydrogen and Cmo alkyl groups; R 6, R7, and R8 are each independently selected from hydrogen And C 1- 1 〇 Tiger-based —____ -12- _________ This paper is suitable for 1¾ medium g g house standard (CNS) μ specifications (·> &lt; 297 public director) T236471 A8 Group; R i 4, R15 and R 丨 6 are respectively R9, Rio, Ri1, R 丨 2, Ri 乂 are rats, Ri7, R18, r19,: a20 and R21 are each independently selected from hydrogen and halo And a group consisting of 0 and 23, and C15, or a saturated ring of R17 and R | s to 6 carbon atoms, in which from 0 to 2 carbon atoms can be substituted with oxygen atoms, or Rl7 and R18 may together form -CH = CH-CH = CH-; and or R &quot; and R19 or R |, R2. Or r2. Combined with r21 to form a group consisting of 5 and 23, selected from the group consisting of Cu alkyl groups. 30. The compound according to item 29 of the scope of patent application, wherein Ri, R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen and alkyl; and R9, R 丨. , Rh, R12, Ri3, Ri4, R 〖5 &amp; R1 "are each independently hydrogen; Rn, R18, R 〖9, R20, and r2i are each independently selected from the group consisting of hydrogen, halo, 03, and Ci-8 The group formed may combine R19 and R2G to form a saturated ring including from 5 to 6 carbon atoms, where 2 carbon atoms may be replaced with oxygen atoms, or Ri7 and R18 may form together -CH = CH-CH = CH-. 31. The compound according to item 30 of the scope of patent application, wherein Ri, 1, R4 and I are each independently selected from the group consisting of hydrogen and 〇1_6 alkyl; Han 6, R7 and Are each independently selected from the group consisting of hydrogen &amp; Cl_3 alkyl; and -13- 1236471 The scope of patent application 17 ^ 18, 19, 20, and 21 are each independently selected from the group consisting of hydrogen, halo, OR23, and C! _6 alkyl groups, or R 19 and R 2 G can be combined to form Includes% of saturation from 5 to 6 carbon atoms, where 0 to 2 carbon atoms may be substituted with oxygen atoms, or R17 and R18 may form together-. 32. The compound according to item 3 of the scope of patent application, wherein L, R 7 and R 8 are each independently selected from the group consisting of hydrogen and methyl. 33. The compound according to item 32 of the scope of patent application, wherein ri, r 2, r 3, chi 4 and R5 are each independently selected from the group consisting of hydrogen and Cl2 alkyl; R6 is hydrogen; trans 7 and R8 Are each independently selected from the group consisting of hydrogen and methyl; and R2 3 is selected from the group consisting of fluorene and methyl. The compound according to item 33 of the patent scope of the application, wherein Rn, R18, R19, R20 and r21 are each independently selected from the group consisting of hydrogen, halo, OR23 and Cij 垸, or R19 can be combined with R2G , Forming a saturated ring including 5 carbon atoms, in which 2 post-atoms can be replaced with oxygen atoms, or R17 and R18 can form together-CH = CH-CH = CH-. 35. The compound according to item 33 of the scope of patent application, wherein R17, R18, R19, &amp; 20 and R21 are each independently selected from the group consisting of hydrogen, halo, OR23 and Cl-4, or R19 and R2Q combine to form -〇-CH2-〇- or -0CH2CH20_, or R17 and R18 can form together-CH = CH-CH = CH-. -14- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1236471 A8 B8 C8 -------- D8 K, scope of patent application '~-36. According to the scope of patent application The compound of item 29, A m = 1 or 2; &quot; ^, R2, R3, RAR5 are each independently selected from the group consisting of hydrogen, dentition and radical;-"Xin, 117 and 118 are independently selected The group consisting of free hydrogen and methyl, · 1117, 18, 1119, 20 and 1121 are each independently selected from the group consisting of fluorene, halo, OR23, and Ci · 3 alkyl, or R "and R18 or r18 and R19 may together form a ring selected from the group consisting of 彳 h = ch_ CbCH-, -〇-CH2-〇, and -〇_Ch2-CH2-〇_; and R 2 3 is C 1 · 2 A. The compound according to item 36 of the patent application, wherein I'R2, I, trans4, and R5 are each independently selected from the group consisting of hydrogen and amidino. 38. According to item 36 of the scope of patent application Compounds of which R, H, and cardiac hydrogen. 39. Compounds according to 36 of the scope of patent application, wherein R 17, R 18, R 19, R 20, and R 21 are each independently selected from hydrogen and halogen. A group consisting of alkyl, alkyl and OR23, and r23 is Ci_2 alkyl. 40. The compound according to item 36 of the scope of patent application, wherein R! 7 and R i 8 or R18 and Ri9 are selected from- ch = CH-CH = CH-and CHr 0-ring of the group. 41. Compound according to item 29 of the patent application scope, where m = 1 or 2; Ri, R2, R3, R4 and r5 are Each independently selected from the group consisting of hydrogen and methyl R7 &amp; R8 is hydrogen; 7Ri8, Rl9, R2O & R2l are each independently selected from the group consisting of hydrogen, haloCu4 alkyl and OR23; and R23 is Ci _2 alkyl. 42. According to item 41 of the scope of the patent application, <Compound, wherein R! And 115 are each a fluorenylmethyl group, and R2, R3 &amp; r4 are hydrogen. 43. The compound according to item 41 of the patent application, wherein R17, R18, R19, R20 and R21 are each selected from the group consisting of chlorine, C1, F, _OH3 and Cm. 44. The compound under the scope of patent application No. 43 in which R18 and R20 are oxygen. 45. The compound according to item 43 of the scope of patent application, wherein u_och. 46. The compound according to item 41 of the scope of application, wherein un and Ru'R19, r2 () and r21 are argon. 47. The compound according to item 4 of the scope of patent application, wherein r 17, r, R2G, and R21 are each hydrogen, and r19 is selected from the group consisting of · 0%,%, and Cu 4 lean group. 48. The substituted pico compound according to item 29 of the application, which is selected from the group consisting of N- (2,6-dimethylphenyl) -2- [4- (2-hydroxyphenylbutyl) Ephyl] ethenylamine, propyl); h pyridyl} ethenylamine, N- (2,6-dimethylphenyl) -2- {4- [2-hydroxy_3- (2 -Methoxybenzene 16- This paper size applies to Chinese National Standard (CNS) A4 specifications (210X 297 mm) 8 8 8 8 A BCD 1236471 Patent application scope 2- [4- (3- (2H-benzo [d ] 1,3-Dioxocene-5_yl) _2_hydroxypropyl) pyridyl] -N-(2,6-dimethylphenyl) acetamidamine, N- (2,6-di Methylphenyl) -2- {4- [2-superyl · 3 -_ (4-methoxyphenyl) propyl] external 1: 17 wells} acetamidine, Ν- (2,6--formyl Phenyl) -2- {4- [2-% yl-3-phenylpropyl] pyridyl} ethenylamine, Ν- (2,6--methylphenyl) -2- {4- [4- (4, methoxyphenyl) · 2-bibutyl] succinyl} acetamidamine, 2- {4- [4- (2,6-difluorophenyl) -2-succinidine Pyridyl} 4- (2,6-dimethylphenyl) ethylamine, N- (2,6-dimethylphenyl) -2- {4- [4- (2-chlorobenzene ) _2-xiangbutyl] pyridoyl} acetamidamine, 2- (4- {4- [4- (tert-butyl ) Phenyl] -2-¾butylbopenhyl—N- (2,6-dimethylphenyl) acetamidamine, N- (2,6-dimethylphenyl) -2- {4 -[4- (2-fluorophenyl) _2-light butyl] pyrimidinyl} acetamide, N- (2,6-dimethylphenyl) -2- (4- {2-hydroxy_4 -[4- (trifluoromethyl) phenyl] butyl} pyridyl) acetamidinium, 2-[4-(3-(2 fluorene-benzo [d] 1,3 -dioxomethylamine) -5 -yl) -2 -hydroxypropyl) pyrimidinyl] -N- (2,6-dimethylphenyl) -2-methylpropanamide, N- (2,6-dimethylbenzene ) -2- [4- (2-hydroxy-3 -phenylpropyl) pyracyl] -2-methylpropionate, N- (2,6-dimethylphenyl) -2- {4 -[2 -Hydroxy-3- (3,4,5-trimethoxyphenyl) propyl] succinyl} -2-methylpropanamine, -17-This paper size applies to Chinese National Standards (CNS) A4 size (210 x 297 mm) 7 3 32 8 8 8 8 AB c D 6. Application scope of patent N- (2,6-dimethylphenyl) -2- [4- (2-hydroxy-5- Phenyl) pyracyl] acetamidine, N- (2,6-dimethylphenyl) -2- {4- [5- (2-fluorophenyl) -2 -hydroxypentyl] p-wellyl} ethylamine and N- (2,6-dimethylphenyl) -2- {4- [5- (2-chlorophenyl) -2-hydroxypentyl ] Leaf dagger farming} group consisting of acetamide. 49. A substituted pico compound having the formula I C: Where m = 1; R1, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen and alkyl; R6, R7 and R8 are each independently hydrogen; R9, Ri0, R1 1, R 12, R 13, R 14, R 15 and R 16 are each independently selected from the group consisting of hydrogen and C i _ 4 alkyl; R 2 4 is selected from C i 0 alkyl, cycloalkyl, and fused Phenylcycloalkyls-18-This paper is sized for China National Standard (CNS) A4 (210X 297mm) The group formed 'wherein the attachment point is on a cycloalkyl group, wherein the alkyl group may be optionally substituted with 1 to 3 substituents selected from the group consisting of a halogen group, CF3, OR20, and Cl_2 alkyl group; R2G It is selected from the group consisting of alkyl groups. SO. The compound according to item 49 of the application, wherein R1, r2, R3, R, and R are each independently selected from the group consisting of hydrogen and Cij alkyl. W. The compound according to item 49 of the scope of patent application, wherein R1, r2, r3, R4 and V are each independently selected from the group consisting of hydrogen & Ci · 5 alkyl; and ruler 2 4 is selected from c 1 -1G alkyl group, cycloalkyl group and fused phenylcycloalkyl group, in which the attachment point is on the cycloalkyl group, where the alkyl group can be selected from 1-2 by aryl groups as required The substituents of the group are selected from the group, wherein the aryl substituents may be selected from 1 to 3 free halo, phenyl, CF3, OR2O, and optionally. The group consisting of the alkyl group is substituted with a substituent. 5 ... According to the 49th compound of the patent scope of the patent, wherein 1, 1, &amp; 2, R4 and R, each independently selected from the group consisting of hydrogen and Ci3 alkyl; R, Ri0, RH 'R &quot; First, P 13 p 14… two ... R, R and trans 16 are each a group consisting of a single planthopper and a C 1,2 alkyl group; and a selection group R second line is selected from the group consisting of Cl.1Q alkyl group, cycloalkyl group and fused phenylcycloalkyl group 2 where the attachment point is on the cycloalkyl group, of which the fluorenyl group is visible * To 2 substituents t * 2 selected from the group consisting of aryl groups. The aryl substituents may be optionally selected from 1 to 3i as a free quotient, phenyl, CF3, OR, C. Composition group-19 This paper is applicable to X297., ^) 1236471 Substituted with a substituent. ) 3. The compound according to item 49 of the scope of patent application, wherein R1, R2, R3, R and R. Each is independently selected from the group consisting of hydrogen and ^ · 3 alkyl. The compound according to item 49 of the scope of the patent application, wherein R R, R and R] are each independently selected from the group consisting of hydrogen and C! _ 2 alkyl groups;.... '..., ..., ^, ..., ^, and ... are each independently selected from the group consisting of hydrogen and C ^ 2 alkyl; and trans-24 are selected from Cl_1G alkyl, cycloalkyl, and fused phenyl naphthenes Group consisting of aryl groups, where the attachment point is on a cycloalkyl group, where the alkyl group can be optionally substituted with from 1 to 2 substituents selected from the group consisting of aryl groups, where aryl substituent groups can be selected as required If necessary, it may be substituted with from 1 to 2 substituents selected from the group consisting of a alkynyl group, a phenyl group, a CF3 group, an OR20 group, and a Ci_4 alkyl group. 55. The compound according to item 49 of the scope of patent application, which is selected from the group consisting of Ci alkyl, cycloalkyl and fused phenylcycloalkyl, wherein the attachment point is on the cycloalkyl, where The alkyl group may be optionally substituted with a substituent selected from the group consisting of an aryl group, wherein the aryl substituent may be optionally selected from 1 to 2 selected from the group consisting of a phenyl group, phenyl group, cp3, OR2 G, (: Substituted by a substituent of the group consisting of -4 alkyl groups. 56. The compound according to item 54 of the patent application scope, wherein r 1, r 2, r 3, R 4 and R 3 are each independently selected from hydrogen Groups and groups consisting of methyl groups. 57. Compounds according to item 54 of the scope of patent application, in which R η is a C 6 alkyl group and a C 3-6 cycloalkyl group. -20- This paper applies to China's national standard Standard (CNS) Α4 size (210 X 297 public love) R3 and R4 are 58. Compounds according to item 54 of the scope of application for patents, in which R 1 is human and Ding 24 is a fused phenylcycloalkyl group. ) 9. The compound according to item 54 of the scope of application for a patent, wherein R σ ^ ^ κ24 疋 winter methyl. 60. The compound according to item 54 of the scope of patent application, wherein R2 and R5 are each hydrogen, and R1 and R5 are each methyl. 61. The compound according to item 49 of the scope of patent application, wherein Ri, R2, R3, R4, and R5 are each independently selected from the group consisting of hydrogen and methyl; R9 &gt; Rl0 ^ R11 ^ R12'R13 &gt; Rl4 ' Rl5 ^ r> 16, KK κ κ ruler and ruler 16 are each hydrogen, and R24 is selected from the group consisting of Ci · 6: ^, alkynyl, and fused phenylcyclopentadiene. 62. The compound according to item 49 of the scope of patent application, which is selected from the group consisting of 2-({2- [4- (3- (isopropoxy-2-¾propyl) pratio)] _ n_ (2 6_ Dimethylphenyl) acetamidamine, N- (2,6-dimethylphenyl) -2- [4- (2-hydroxy-3-indan-2-yloxypropyl: K1: phenyl ] Ethylamine, N- (2,6-dimethylphenyl) -2- {4- [2-hydroxy · 3- (benzyloxy) propyl] pyridyl} ethenylamine, 2-({2- [4- (3-cyclopentyloxy-2-hydroxypropyl) pyridyl] -N- (2,6-dimethylphenyl) acetamidine, 2-({2 -[4- (3-Cyclohexyloxy-2-hydroxypropyl) pyridinyl]-^ (2,6-dimethylphenyl) ethyl amine, -21 This paper is dimensioned to the Chinese National Standard (CNS ) Α4 size (210 X 297 mm) 2- [4- (3-{[4- (tert-butyl) phenyl] methoxyb 2-hydroxypropyl) late, stilyl] -N- (2,6-dimethylphenyl) ethyl Hydrazine, Ν- (2,6-dimethylphenyl) _2- (4- {3-[(2-fluorophenyl) methoxyb 2-propyl} pyridyl) acetamide, 2 · (4- {3-[(2,4-difluorophenyl) methoxy] -2-hydroxypropyl} pyridyl) -N- (2,6-dimethylphenyl) ethyl Amidine, N- (2,6-diamidinophenyl) -2- [4- (2-hydroxy-3-{[4- (trifluoromethyl) phenyl] methoxy} propyl) said Aryl] acetamidine, N- (2,6-dimethylphenyl) -2- (4- {2-hydroxy-3-[(2-methoxyphenyl) methoxy] propyl} Pyridinyl) acetamide, 2_ (4- {3-[(2,4-dimethoxyphenyl) methoxy] -2-1 to propyl} cr than phenyl) -N- (2 , 6-dimethylphenyl) acetamidamine, N- (2,6-dimethylphenyl) -2- (4- {2-hydroxy-3-[(4-methoxyphenyl) methyl Oxy] propyl} pyridyl) acetamidamine, 1 ^ (2,6-dimethylphenyl) -2- (4- {3-[(4-fluorophenyl) methoxy] -2 -Hydroxypropyl} pyridinyl) acetamidamine, N- (2,6-dimethylphenyl) -2- (4- {2-hydroxy-3- 3-[(4-tolyl) methoxy] Propyl} pyridyl) acetamidamine, N-(2,6 -Monomethyl winteryl) -2- (4- (2-¾yl- 3-[(4-phenylphenyl) methoxy] propyl} pyridyl) ethenylamine, N- (2, 6-dimethylphenyl) -2- (4- {3-[(4-butphenyl) methoxy] -2-hydroxypropyl} pyracyl) acetamidamine, N- (2,6 -Dimethylphenyl) -2- {4- [2 -Hydroxy-3- (2-naphthylmethoxy) propyl] tonyl} acetamidine, -22- This paper size applies to Chinese national standards (CNS) A4 specification (210 X 297 mm) '8 8 8 8 AB c D 1236471 Patent scope of application N- (2,6-dimethylphenyl) -2- {4_ [3- (cyclohexyl (Methoxy) _2_hydroxypropyl] pyrolyl} ethylamine, and N- (2,6-dimethylphenyl) _2- (4- {3 _ [(4_fluorophenyl) methoxy The group consisting of kibu 2-propyl bu 3,3-dimethylpyryl} acetamide. 6 for a treatment needs to be selected from the protection of skeletal muscles caused by trauma, such as protecting the bones. Myo-complicated muscle or systemic disease, treatment of shock symptoms, treatment of mammalian pharmaceutical compositions of groups consisting of donated tissues and organs used in transplantation, or treatment of cardiovascular disease, comprising a therapeutically effective amount according to the application Lee scope of the compounds of the first 49 or 29 or Paragraph. 64. The pharmaceutical composition according to item 63 of the scope of patent application, wherein the cardiovascular disease is selected from the group consisting of atrial and ventricular arrhythmia, Priezmann's (variant) angina, stable angina and exercise-induced angina, and heart congestion Or the category of myocardial infarction. 65. The pharmaceutical composition according to item 63 of the scope of patent application, wherein the therapeutically effective range is from about 0.01 to about 100 g / mammalian weight in kilograms. 66. The pharmaceutical composition according to item 63 of the patent application, wherein the mammal is a human. 67. Seeds * Bay I pharmaceutical composition comprising a compound according to item ^ or 29 or 49 of the scope of patent application and one or more pharmaceutical excipients. 68. The pharmaceutical composition of the substance according to item 67 of the application, wherein the pharmaceutical composition has a solution form. -23- 1236471 8 8 8 8 A B c D, scope of patent application 69. The pharmaceutical composition of the substance according to item 67 of the scope of patent application, wherein the medicine composition has a form selected from the category consisting of tablets or capsules. -24 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)