JPH08217671A - N-(3-acyloxyacyl)glycin derivative - Google Patents

Abstract

PURPOSE: To obtain the subject derivative useful as a preventing and therapeutic agent for phychosis (e.g. depression), epilepsy, cerebral infarction, hemicrania, relief of pain, etc. CONSTITUTION: This N-type calcium channel inhibitor containing an N-(3- acyloxyacyl)glycine of the formula R<1> CH(OCOR<2> )CH2 CONHCH2 CO2 H (R<1> and R<2> are each same or different 1-19C linear or branched chainlike alkenyl group or 2-19C linear or branched chain alkenyl group) or its salt as an active ingredient.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to novel compounds that act selectively on N-type calcium channels.

[0002]

The brain is a tissue that is particularly vulnerable to damage by ischemia or ischemia-reperfusion. When placed in hypoxia due to transient cerebral ischemia such as stroke, memory, learning, such as hippocampus,
Tissues related to emotions are selectively destroyed, resulting in various after-effects such as dementia. During the process from cerebral ischemia to dementia, neuronal membrane depolarization, influx of calcium into nerve cells by opening voltage-gated calcium channels, neurotransmitters of neurotransmitters including excitatory amino acid glutamate Is involved in the release of a large amount of intracellular calcium from intracellular channels due to the opening of agonist-dependent calcium channels (Yoshiyuki Matsuo et al.
Nucleic Acids and Enzymes, 37, 1382-1393, 199
2 years). N-type calcium channel is a kind of membrane voltage-gated calcium channel that specifically exists in the nervous system, and is involved in the release of various neurotransmitters (Abe Teruo, Brain Medical, Vol. 5, 25-31). Page, 1993
Year). Therefore, inhibiting the function of N-type calcium channel suppresses the release of a large amount of neurotransmitters that occur after cerebral ischemia, thereby preventing the neuronal cell death caused by cerebral ischemia. Can be used as an anti-cerebral infarction agent.

Further, it has been reported that barbiturate having an antiepileptic effect inhibits N-type calcium channel (RA Gross et al., Neurology, 38, 44).
3-450, 1988), the involvement of calcium channels in epilepsy is considered. Therefore,
N-type calcium channel inhibitors can be used as antiepileptic agents.

Furthermore, since N-type calcium channels are distributed in the dorsal part of the spinal cord and are involved in pain transmission, N-type calcium channel inhibitors can also be analgesics (A.
B. Malmberg et al., J. Neurosci., Volume 14, 4882-
4890, 1994). Currently, ω as an irreversible inhibitor as a specific inhibitor of N-type calcium channel
-Conotoxin GVIA, ω-conotoxin MVIIA is known as a reversible inhibitor, and ω-conotoxin MVI
IA has been reported to prevent neuronal cell death in the hippocampal region, which is important as a place of memory fixation, in a transient cerebral ischemia experiment using rats (K. Valentino et al., Proc.
Natl. Acad. Sci., 90, 7894-7897,
1993). These ω-conotoxins have a relatively large molecular weight of about 3,000 and have poor transferability into the brain. Therefore, in addition to these compounds, a low molecular weight N-type calcium channel inhibitor having good migration into the brain is desired.

Furthermore, an imidazole compound (JP-A-5-1)
86432) is also known as an N-type calcium channel inhibitor.

N- [15-methyl-3- (13-
Methyltetradecanoyloxy) hexadecanoyl] glycine is a known compound (R. Kawazoe et al., J. Bac
teriology, 173, 5470 (1991)),
No mention is made of its action.

[0007]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention The inventor has conducted research in search of a more potent and highly selective N-type calcium channel acting substance, has found a new acting substance, and has completed the present invention.

[0008]

[Means for Solving the Problems]

1) The present invention has the general formula ^{R 1 CH (OCOR 2) CH} 2 CONHCH 2 CO 2 H (I) ( wherein, R ¹ and R ² are identical or different, straight-chain having 1 to 19 carbon atoms A branched or branched alkyl group or a linear or branched alkenyl group having 2 to 19 carbon atoms).
-Acyloxyacyl) N-type calcium channel inhibitors containing a glycine derivative or a salt thereof as an active ingredient.

[0009] 2) The present invention has the general formula ^{R 1 CH (OCOR 2) CH} 2 CONHCH 2 CO 2 H (I) ( wherein, R ¹ and R ² are the same or different, from 1 to 19 carbon atoms A straight-chain or branched-chain alkyl group having 2 to 19 carbon atoms or a straight-chain or branched alkenyl group having 2 to 19 carbon atoms.
-Acyloxyacyl) glycine derivative or a salt thereof (provided that R ¹ and R ² both exclude a 12-methyltridecanyl group).

Here, R ¹ and R ² are the same or different and are exemplified as follows.

When R ¹ and R ² are linear or branched alkyl groups having 1 to 19 carbon atoms, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl , 2-methylpropyl, 1,
1-dimethylethyl, pentyl, 3-methylbutyl, hexyl, 4-methylpentyl, heptyl, 5-methylhexyl, octyl, 6-methylheptyl, nonyl, 7-
Methyloctyl, decyl, 8-methylnonyl, undecyl, 9-methyldecyl, dodecyl, 10-methylundecyl, tridecyl, 11-methyldodecyl, tetradecyl, 12-methyltridecyl, pentadecyl, 13-methyltetradecyl, hexadecyl, 14- Examples thereof include methylpentadecyl, heptadecyl, 15-methylhexadecyl, octadecyl, 16-methylheptadecyl, nonadecyl, 17-methyloctadecyl.

Preferably, R ¹ and R ² are linear or branched alkyl groups having 10 to 16 carbon atoms.

Optimally, R ¹ and R ² are straight or branched chain alkyl groups having 13 to 15 carbon atoms.

When R ¹ and R ² are linear or branched alkenyl groups having 2 to 19 carbon atoms, for example vinyl, 2,2-dimethylvinyl, isopropenyl, 4-methyl-3- Penten-1-yl, 5-methyl-4-hexen-1-yl, 6-methyl-5-hepten-1-yl, 6-methyl-3-hepten-1-yl, 7
-Methyl-6-octen-1-yl, 7-methyl-5-
Octen-1-yl, 7-methyl-3-octen-1-
Yl, 9-methyl-8-decen-1-yl, 9-methyl-7-decen-1-yl, 9-methyl-3-decene-1
-Yl, 10-methyl-9-undecen-1yl, 10
-Methyl-8-undecen-1-yl, 10-methyl-
3-undecen-1-yl, 11-methyl-10-dodecen-1-yl, 11-methyl-9-dodecen-1-yl, 11-methyl-3-dodecen-1-yl, 12-methyl-11- Tridecen-1-yl, 12-methyl-1
0-tridecen-1-yl, 12-methyl-3-tridecen-1-yl, 12-methyl-1-tridecen-1-
Yl 13-methyl-12-tetradecen-1-yl, 1
3-methyl-11-tetradecen-1-yl, 13-methyl-3-tetradecen-1-yl, 13-methyl-1
-Tetradecen-1-yl, 14-methyl-13-pentadecen-1-yl, 14-methyl-12-pentadecen-1-yl, 14-methyl-3-pentadecene-1-
Yl, 14-methyl-1-pentadecen-1-yl, 1
5-methyl-14-hexadecen-1-yl, 15-methyl-13-hexadecen-1-yl, 15-methyl-
3-hexadecen-1-yl, 15-methyl-1-hexadecen-1-yl, 8,11,14-heptadecatrien-1-yl, 5,8,11-heptadecatriene-
1-yl, 8,11-heptadecadiene-1-yl, 1
6-methyl-15-heptadecen-1-yl, 16-methyl-14-heptadecen-1-yl, 16-methyl-
3-heptadecen-1-yl, 16-methyl-1-heptadecen-1-yl, 4,7,10,13-nonadecatetraen-1-yl, 17-methyl-16-octadecen-1-yl, 17 -Methyl-15-octadecene-1
-Yl, 17-methyl-3-octadecen-1-yl,
17-methyl-1-octadecen-1-yl and the like can be mentioned.

R ¹ and R ² are preferably linear or branched alkenyl groups having 10 to 16 carbon atoms.

Optimally, R ¹ and R ² are straight or branched chain alkenyl groups having 13 to 15 carbon atoms.

The compound of the present invention having the above general formula (I) can be made into a salt by a conventional method.

As the salt, for example, lithium, sodium,
Alkali metal salts such as potassium; alkaline earth metal salts such as calcium and barium; magnesium salts; aluminum salts; metal salts such as triethylamine, pyridine, picoline, ethanolamine, triethanolamine, dicyclohexylamine, ammonium salts, etc. The basic salts of It is preferably a pharmacologically acceptable salt.

The compound having the general formula (I) has an asymmetric carbon atom. Therefore, in the said general formula (I), it has an isomer based on an asymmetric carbon atom. In the above general formula (I), all equal and non-equivalent mixtures of these isomers are represented by a single formula. Therefore,
In the present invention, these isomers and mixtures of these isomers are all included.

Further, when the compound having the general formula (I) forms a solvate (for example, a hydrate), these are all included.

In the compound represented by the general formula (I), (1) preferably, R ¹ and R ² are the same or different, and a linear or branched alkyl group having 10 to 16 carbon atoms. Or a compound having a linear or branched alkenyl group having 10 to 16 carbon atoms, (2) more preferably R ¹ and R ² are the same or different, and have 13 to 15 carbon atoms. Or a linear or branched alkyl group having 13 or 1 to 13 carbon atoms
It is a compound having a linear or branched alkenyl group having 5 alkenyl groups.

Examples of the compound having the general formula (I) of the present invention include the following compounds. R ¹ CH (OCOR ² ) CH ₂ CONHCH ₂ CO ₂ H (I)

[0023]

[Table 1] ─────────────────────────────────── Example R ¹ R ² compound number ──── ─────────────────────────────── 1-1 Methyl methyl 1-2 Ethyl ethyl 1-3 Propyl propyl 1-4 1 -Methylethyl 1-methylethyl 1-5 butyl butyl 1-6 1-methylpropyl 1-methylpropyl 1-7 2-methylpropyl 2-methylpropyl 1-8 1,1-dimethylethyl 1,1-dimethylethyl 1 -9 Pentyl Pentyl 1-10 3-Methylbutyl 3-Methylbutyl 1-11 Hexyl Hexyl 1-12 4-Methylpentyl 4-Methylpentyl 1-13 Heptyl Heptyl 1-14 5-Methylhexyl 5-Methylhexyl 1-15 Tetradecyl Nonyl 1-16 Octyl Octyl 1-17 6-Methylheptyl 6-Methylheptyl 1-18 Nonyl Nonyl 1-19 7-Methyloctyl 7-Methyloctyl 1-20 Decyldecyl 1-21 8-Methylnonyl 8-methylnonyl 1-22 Undecyl 13-methyl tetradecyl 1-23 9-methyl decyl 9-methyl decyl 1-24 dodecyl dodecyl 1-25 10-methyl undecyl 10-methyl undecyl 1-26 10-methyl undecyl 11-methyl dodecyl 1-27 10- Methyl undecyl 12-methyl tridecyl 1-28 10-methyl undecyl 13-methyl tetradecyl 1-29 10-methyl undecyl 14-methyl pentadecyl 1-30 tridecyl undecyl 1-31 tridecyl 10-methyl undecyl Ru 1-32 tridecyl 11-methyldodecyl 1-33 tridecyl 12-methyltridecyl 1-34 tridecyl 13-methyltetradecyl 1-35 tridecyl 14-methylpentadecyl 1-36 11-methyldodecyl tetradecyl 1-37 11-methyldodecyl 10 -Methylundecyl 1-38 11-methyldodecyl 11-methyldodecyl 1-39 11-methyldodecyl 12-methyltridecyl 1-40 11-methyldodecyl 13-methyltetradecyl 1-41 11-methyldodecyl 14-methylpenta Decyl 1-42 tetradecyl tetradecyl 1-43 tetradecyl 10-methylundecyl 1-44 tetradecyl 11-methyldodecyl 1-45 tetradecyl 12-methyltridecyl 1-46 tetradecyl pe Tadecyl 1-47 12-methyltridecyl tetradecyl 1-48 12-methyltridecyl 10-methylundecyl 1-49 12-methyltridecyl 11-methyldodecyl 1-50 12-methyltridecyl 12-methyltridecyl 1- 51 12-methyltridecyl 13-methyltetradecyl 1-52 12-methyltridecyl 14-methylpentadecyl 1-53 pentadecyl pentadecyl 1-54 13-methyltetradecyl 10-methylundecyl 1-55 13-methyltetradecyl 11-methyldodecyl 1-56 13-methyltetradecyl 12-methyltridecyl 1-57 13-methyltetradecyl 13-methyltetradecyl 1-58 13-methyltetradecyl 14-methylpentadecyl 1-59 hexadecylhexe Sadecyl 1-60 14-methylpentadecyl 11-methyldodecyl 1-61 14-methylpentadecyl 12-methyltridecyl 1-62 14-methylpentadecyl 13-methyltetradecyl 1-63 14-methylpentadecyl 14-methyl Pentadecyl 1-64 Heptadecyl Heptadecyl 1-65 15-Methylhexadecyl 12-Methyltridecyl 1-66 15-Methylhexadecyl 13-Methyltetradecyl 1-67 15-Methylhexadecyl 14-Methylpentadecyl 1-6815 -Methylhexadecyl 16-methylheptadecyl 1-69 15-methylhexadecyl 17-methyloctadecyl 1-70 octadecyl octadecyl 1-71 16-methylheptadecyl 11-methyldodecyl 1-72 16-methyl Ptadecyl 12-methyltridecyl 1-73 16-methylheptadecyl 13-methyltetradecyl 1-74 16-methylheptadecyl 14-methylpentadecyl 1-75 16-methylheptadecyl 17-methyloctadecyl 1-76 nonadecyl nonadecyl 1 -77 17-methyloctadecyl 13-methyltetradecyl 1-78 17-methyloctadecyl 14-methylpentadecyl 1-79 17-methyloctadecyl 15-methylhexadecyl 1-80 17-methyloctadecyl 16-methylheptadecyl 1-81 17-methyl octadecyl 17-methyl octadecyl 1-82 tetradecyl heptadecyl 1-83 tetradecyl 13-methyl tetradecyl ───────────────────────────── ─ ─────

[0024]

[Table 2] ─────────────────────────────────── Example R ¹ R ² compound number ──── ─────────────────────────────── 2-1 Vinyl Vinyl 2-2 2,2-Dimethyl Vinyl 2,2-Dimethyl Vinyl 2-3 isopropenyl isopropenyl 2-4 4-methyl-3-penten-1-yl 4-methyl-3-penten-1-yl 2-5 5-methyl-4-hexen-1-yl 5-methyl -4-Hexen-1-yl 2-6 6-methyl-5-hepten-1-yl 6-methyl-5-hepten-1-yl 2-7 6-methyl-3-hepten-1-yl 6-methyl -3-Hepten-1-yl 2-8 7-methyl-6-octen-1-yl 6-methyl-3-hepten-1-yl 2- 7-Methyl-5-octen-1-yl 7-methyl-3-octen-1-yl 2-10 8-methyl-8-nonen-1-yl 8-methyl-8-nonen-1-yl 2-11 8-Methyl-7-nonen-1-yl 8-methyl-7-nonen-1-yl 2-12 8-methyl-3-nonen-1-yl 8-methyl-3-nonen-1-yl 2-13 9-methyl-8-decen-1-yl 9-methyl-8-decen-1-yl 2-14 9-methyl-7-decen-1-yl 9-methyl-7-decen-1-yl 2-15 9-Methyl-3-decen-1-yl 9-methyl-3-decen-1-yl 2-16 10-methyl-9-undecen-1-yl 10-methyl-9-undecen-1-yl 2-17 10-methyl-8-undecen-1-yl 10-methyl-9- Ndecen-1-yl 2-18 10-methyl-3-undecen-1-yl 10-methyl-3-undecen-1-yl 2-19 11-methyl-10-dodecen-1-yl 11-methyl-10- Dodecen-1-yl 2-20 11-methyl-9-dodecen-1-yl 11-methyl-10-dodecen-1-yl 2-21 11-methyl-3-dodecen-1-yl 11-methyl-3- Dodecen-1-yl 2-22 12-methyl-11-tridecen-1-yl 12-methyl-11-tridecen-1-yl 2-23 12-methyl-10-tridecen-1-yl 12-methyl-10- Tridecen-1-yl 2-24 12-methyl-3-tridecen-1-yl 12-methyl-3-tridecen-1-yl 2-25 12-methyl-1-tridecen-1- Il 12-methyl-1-tridecen-1-yl 2-26 13-methyl-12-tetradecen-1-yl 13-methyl-12-tetradecen-1-yl 2-27 13-methyl-11-tetradecene-1- Il 13-methyl-11-tetradecen-1-yl 2-28 13-methyl-3-tetradecen-1-yl 13-methyl-3-tetradecen-1-yl 2-29 13-methyl-1-tetradecene-1- Il 13-methyl-1-tetradecen-1-yl 2-30 14-methyl-13-pentadecen-1-yl 14-methyl-13-pentadecen-1-yl 2-31 14-methyl-12-pentadecene-1- Il 14-methyl-12-pentadecen-1-yl 2-32 14-methyl-3-pentadecen-1-yl 14-methyl-3- Pentadecen-1-yl 2-33 14-Methyl-1-pentadecen-1-yl 14-methyl-1-pentadecen-1-yl 2-34 15-methyl-14-hexadecen-1-yl 15-methyl-14- Hexadecen-1-yl 2-35 15-methyl-13-hexadecen-1-yl 15-methyl-13-hexadecen-1-yl 2-36 15-methyl-3-hexadecen-1-yl 15-methyl-3- Hexadecen-1-yl 2-37 15-Methyl-1-hexadecen-1-yl 15-Methyl-1-hexadecen-1-yl 2-38 8,11,14-Heptadecatrien-1-yl 8,11, 14-Heptadecatrien-1-yl 2-39 5,8,11-Heptadecatrien-1-yl 8,11,14-Heptadecatriene- -Yl 2-40 8,11-heptadecadien-1-yl 8,11-heptadecadien-1-yl 2-41 16-methyl-15-heptadecen-1-yl 16-methyl-15-heptadecen-1-yl 2- 42 16-methyl-14-heptadecen-1-yl 16-methyl-14-heptadecen-1-yl 2-43 16-methyl-3-heptadecen-1-yl 16-methyl-3-heptadecen-1-yl 2- 44 16-Methyl-1-heptadecen-1-yl 16-methyl-3-heptadecen-1-yl 2-45 4,7,10,13-nonadecatetraene-7,10,13-nonadecatetraene- 1-1-yl 2-46 17-methyl-16-octadecen-1-yl 7-methyl-16-octadecen-1-yl 2-47 17-methyl Le-15-octadecen-1-yl 17-methyl-15-octadecen-1-yl 2-48 17-methyl-3-octadecen-1-yl 17-methyl-3-octadecen-1-yl 2-49 17- Methyl-1-octadecen-1-yl 17-Methyl-1-octadecen-1-yl ─────────────────────────────── ─────

[0025]

[Table 3] ─────────────────────────────────── Example R ¹ R ² compound number ──── ─────────────────────────────── 3-1 8-Methyl-3-nonen-1-yldodecyl 3-2 8 -Methyl-3-nonen-1-yl tridecyl 3-3 8-methyl-3-nonen-1-yl tetradecyl 3-4 8-methyl-3-nonen-1-yl 10-methyl undecyl 3-5 8- Methyl-3-nonen-1-yl 11-methyldodecyl 3-6 8-methyl-3-nonen-1-yl 12-methyltridecyl 3-7 8-methyl-3-nonen-1-yl 13-methyltetra Decyl 3-8 8-methyl-3-nonen-1-yl 14-methylpentadecyl 3-9 8-methyl-3-nonene- -Yl 15-methylhexadecyl 3-10 8-methyl-3-nonen-1-yl 16-methylheptadecyl 3-11 8-methyl-3-nonen-1-yl 17-methyloctadecyl 3-12 9-methyl -3-decen-1-yl dodecyl 3-13 9-methyl-3-decen-1-yl tridecyl 3-14 9-methyl-3-decen-1-yl tridecyl 3-15 9-methyl-3-decene- 1-yl tetradecyl 3-16 9-methyl-3-decen-1-yl 10-methylundecyl 3-17 9-methyl-3-decen-1-yl 11-methyldodecyl 3-18 9-methyl-3- Decen-1-yl 12-methyltridecyl 3-19 9-methyl-3-decen-1-yl 13-methyltetradecyl 3-20 9-methyl-3-decen-1- 14-methylpentadecyl 3-21 9-methyl-3-decen-1-yl 16-methylheptadecyl 3-22 9-methyl-3-decen-1-yl 17-methyloctadecyl 3-23 10-methyl- 3-undecen-1-yl octyl 3-24 10-methyl-3-undecen-1-yl uncecyl 3-25 10-methyl-3-undecen-1-yl dodecyl 3-26 10-methyl-3-undecene-1 -Yl tetradecyl 3-27 10-methyl-3-undecen-1-yl 11-methyldodecyl 3-28 10-methyl-3-undecen-1-yl 12-methyltridecyl 3-29 10-methyl-3-undecene -1-yl 13-methyltetradecyl 3-30 10-methyl-3-undecen-1-yl 14-methylpenta Sil 3-31 10-methyl-3-undecen-1-yl 15-methylhexadecyl 3-32 10-methyl-3-undecen-1-yl 16-methylheptadecyl 3-33 10-methyl-3-undecene- 1-yl 17-methyloctadecyl 3-34 11-methyl-3-dodecen-1-ylhexyl 3-35 11-methyl-3-dodecen-1-yl heptyl 3-36 11-methyl-3-dodecene-1- Iruoctyl 3-37 11-methyl-3-dodecen-1-yl nonyl 3-38 11-methyl-3-dodecen-1-yl 11-methyldodecyl 3-39 11-methyl-3-dodecen-1-yl 12 -Methyltridecyl 3-40 11-methyl-3-dodecen-1-yl 13-methyltetradecyl 3-41 11-methyl-3- Decen-1-yl 14-methylpentadecyl 3-42 11-methyl-3-dodecen-1-yl 15-methylhexadecyl 3-43 11-methyl-3-dodecen-1-yl 16-methylheptadecyl 3- 44 11-Methyl-3-dodecen-1-yl 17-methyloctadecyl 3-45 12-methyl-3-tridecen-1-ylhexyl 3-46 12-methyl-3-tridecen-1-yl heptyl 3-47 12 -Methyl-3-tridecen-1-yl octyl 3-48 12-methyl-3-tridecen-1-yl 10-methylundecyl 3-49 12-methyl-3-tridecen-1-yl 11-methyldodecyl 3- 50 12-Methyl-3-tridecen-1-yl 12-methyltridecyl 3-51 12-methyl-3-tridecene 1-yl 13-methyltetradecyl 3-52 12-methyl-3-tridecen-1-yl 14-methylpentadecyl 3-53 12-methyl-3-tridecen-1-yl 15-methylhexadecyl 3-54 12 -Methyl-3-tridecen-1-yl 16-methylheptadecyl 3-55 12-methyl-3-tridecen-1-yl 17-methyloctadecyl 3-56 13-methyl-3-tetradecen-1-ylhexyl 3- 57 13-methyl-3-tetradecen-1-yl heptyl 3-58 13-methyl-3-tetradecen-1-yl octyl 3-59 13-methyl-3-tetradecen-1-yl 10-methylundecyl 3-60 13-methyl-3-tetradecen-1-yl 11-methyldodecyl 3-61 13-methyl-3-te Tradecen-1-yl 12-methyltridecyl 3-62 13-methyl-3-tetradecen-1-yl 13-methyltetradecyl 3-63 13-methyl-3-tetradecen-1-yl 14-methylpentadecyl 3- 64 13-methyl-3-tetradecen-1-yl 15-methylhexadecyl 3-65 13-methyl-3-tetradecen-1-yl 16-methylheptadecyl 3-66 13-methyl-3-tetradecen-1-yl 17-Methyloctadecyl 3-67 14-Methyl-3-pentadecen-1-ylhexyl 3-68 14-Methyl-3-pentadecen-1-yl heptyl 3-69 14-Methyl-3-pentadecen-1-yldodecyl 3 -70 14-Methyl-3-pentadecen-1-yl tetradecyl 3-71 14-me Lu-3-pentadecen-1-yl 11-methyldodecyl 3-72 14-methyl-3-pentadecen-1-yl 12-methyltridecyl 3-73 14-methyl-3-pentadecen-1-yl 13-methyltetra Decyl 3-74 14-methyl-3-pentadecen-1-yl 14-methylpentadecyl 3-75 14-methyl-3-pentadecen-1-yl 15-methylhexadecyl 3-76 14-methyl-3-pentadecene- 1-yl 16-methylheptadecyl 3-77 14-methyl-3-pentadecen-1-yl 17-methyloctadecyl 3-78 15-methyl-3-hexadecen-1-ylhexyl 3-79 15-methyl-3- Hexadecen-1-yl heptyl 3-80 15-methyl-3-hexadecen-1-yl octyl 3-81 15-methyl-3-hexadecen-1-yl nonyl 3-82 15-methyl-3-hexadecen-1-yl 11-methyldodecyl 3-83 15-methyl-3-hexadecen-1-yl 12-methyl Tridecyl 3-84 15-methyl-3-hexadecen-1-yl 13-methyltetradecyl 3-85 15-methyl-3-hexadecen-1-yl 14-methylpentadecyl 3-86 15-methyl-3-hexadecene -1-yl 15-methylhexadecyl 3-87 15-methyl-3-hexadecen-1-yl 16-methylheptadecyl 3-89 16-methyl-3-heptadecen-1-ylhexyl 3-90 16-methyl- 3-heptadecen-1-yl heptyl 3-91 16-methyl-3-heptadecen-1-yl oct Le 3-92 16-methyl-3-heptadecen-1-yl nonyl 3-93 16-methyl-3-heptadecen-1-yl 11-methyldodecyl 3-94 16-methyl-3-heptadecen-1-yl 12- Methyltridecyl 3-95 16-methyl-3-heptadecen-1-yl 13-methyltetradecyl 3-96 16-methyl-3-heptadecen-1-yl 14-methylpentadecyl 3-97 16-methyl-3- Heptadecen-1-yl 15-methylhexadecyl 3-98 16-methyl-3-heptadecen-1-yl 16-methylheptadecyl 3-99 16-methyl-3-heptadecen-1-yl 17-methyloctadecyl 3-100 17-Methyl-3-octadecen-1-ylhexyl 3-101 17-methyl-3-octa Cen-1-yl heptyl 3-102 17-methyl-3-octadecen-1-yl tetradecyl 3-103 17-methyl-3-octadecen-1-yl 10-methylundecyl 3-104 17-methyl-3-octadecene -1-yl 11-methyldodecyl 3-105 17-methyl-3-octadecen-1-yl 12-methyltridecyl 3-106 17-methyl-3-octadecen-1-yl 13-methyltetradecyl 3-107 17 -Methyl-3-octadecen-1-yl 14-methylpentadecyl 3-108 17-methyl-3-octadecen-1-yl 15-methylhexadecyl 3-109 17-methyl-3-octadecen-1-yl 16- Methylheptadecyl 3-110 17-methyl-3-octadecen-1-yl 1 - methyl octadecyl ──────────────────────────────────.

[0026]

[Table 4] ─────────────────────────────────── Example R ¹ R ² compound number ──── ──────────────────────────────── 4-1 Hexyl 8-methyl-3-nonen-1-yl 4-2 Dodecyl 8-Methyl-3-nonen-1-yl 4-3 tetradecyl 8-methyl-3-nonen-1-yl 4-4 10-methylundecyl 8-methyl-3-nonen-1-yl 4-5 11- Methyldodecyl 8-methyl-3-nonen-1-yl 4-6 12-methyltridecyl 8-methyl-3-nonen-1-yl 4-7 13-methyltetradecyl 8-methyl-3-nonene-1- Il 4-8 14-methylpentadecyl 8-methyl-3-nonen-1-yl 4-9 15-methylhexadecyl 8 -Methyl-3-nonen-1-yl 4-10 16-methylheptadecyl 8-methyl-3-nonen-1-yl 4-11 17-methyloctadecyl 8-methyl-3-nonen-1-yl 4-12 Hexyl 9-methyl-3-decen-1-yl 4-13 dodecyl 9-methyl-3-decen-1-yl 4-14 tetradecyl 9-methyl-3-decen-1-yl 4-15 10-methylundecyl 9-methyl-3-decen-1-yl 4-16 11-methyldodecyl 9-methyl-3-decen-1-yl 4-17 12-methyltridecyl 9-methyl-3-decen-1-yl 4- 18 13-methyltetradecyl 9-methyl-3-decen-1-yl 4-19 14-methylpentadecyl 9-methyl-3-decen-1-yl 4-20 15-methylhexa Sil 9-methyl-3-decen-1-yl 4-21 16-methylheptadecyl 9-methyl-3-decen-1-yl 4-22 17-methyloctadecyl 9-methyl-3-decen-1-yl 4 -23 hexyl 10-methyl-3-undecen-1-yl 4-24 dodecyl 10-methyl-3-undecen-1-yl 4-25 tetradecyl 10-methyl-3-undecen-1-yl 4-26 10-methyl Undecyl 10-methyl-3-undecen-1-yl 4-27 11-methyldodecyl 10-methyl-3-undecen-1-yl 4-28 12-methyltridecyl 10-methyl-3-undecen-1-yl 4-29 13-methyltetradecyl 10-methyl-3-undecen-1-yl 4-30 14-methylpentadecyl 10-methyl -3-Undecen-1-yl 4-31 15-methylhexadecyl 10-methyl-3-undecen-1-yl 4-32 16-methylheptadecyl 10-methyl-3-undecen-1-yl 4-33 17 -Methyloctadecyl 10-methyl-3-undecen-1-yl 4-34 hexyl 11-methyl-3-dodecen-1-yl 4-35 dodecyl 11-methyl-3-dodecen-1-yl 4-36 tetradecyl 11- Methyl-3-dodecen-1-yl 4-37 10-Methylundecyl 11-methyl-3-dodecen-1-yl 4-38 11-Methyldodecyl 11-methyl-3-dodecen-1-yl 4-39 12 -Methyltridecyl 11-methyl-3-dodecen-1-yl 4-40 13-methyltetradecyl 11-methyl-3-dode Sen-1-yl 4-41 14-methylpentadecyl 11-methyl-3-dodecen-1-yl 4-42 15-methylhexadecyl 11-methyl-3-dodecen-1-yl 4-43 16-methylhepta Decyl 11-methyl-3-dodecen-1-yl 4-44 17-methyl octadecyl 11-methyl-3-dodecen-1-yl 4-45 hexyl 12-methyl-3-tridecen-1-yl 4-46 dodecyl 12-methyl-3-tridecen-1-yl 4-47 tetradecyl 12-methyl-3-tridecen-1-yl 4-48 10-methylundecyl 12-methyl-3-tridecen-1-yl 4-49 11- Methyldodecyl 12-methyl-3-tridecen-1-yl 4-50 12-methyltridecyl 12-methyl-3-tridecene- -Yl 4-51 13-methyltetradecyl 12-methyl-3-tridecen-1-yl 4-52 14-methylpentadecyl 12-methyl-3-tridecen-1-yl 4-53 15-methylhexadecyl 12- Methyl-3-tridecen-1-yl 4-54 16-methylheptadecyl 12-methyl-3-tridecen-1-yl 4-55 17-methyloctadecyl 12-methyl-3-tridecen-1-yl 4-56 hexyl 13-Methyl-3-tetradecen-1-yl 4-57 dodecyl 13-methyl-3-tetradecen-1-yl 4-58 tetradecyl 13-methyl-3-tetradecen-1-yl 4-59 10-methylundecyl 13 -Methyl-3-tetradecen-1-yl 4-60 11-methyldodecyl 13-methyl-3- Tradecen-1-yl 4-61 12-methyltridecyl 13-methyl-3-tetradecen-1-yl 4-62 13-methyltetradecyl 13-methyl-3-tetradecen-1-yl 4-63 14-methylpenta Decyl 13-methyl-3-tetradecen-1-yl 4-64 15-methylhexadecyl 13-methyl-3-tetradecen-1-yl 4-65 16-methylheptadecyl 13-methyl-3-tetradecen-1-yl 4-66 17-methyloctadecyl 13-methyl-3-tetradecen-1-yl 4-67 hexyl 14-methyl-3-pentadecen-1-yl 4-68 dodecyl 14-methyl-3-pentadecen-1-yl 4- 69 tetradecyl 14-methyl-3-pentadecen-1-yl 4-70 10-methylun Sil 14-methyl-3-pentadecen-1-yl 4-71 11-methyldodecyl 14-methyl-3-pentadecen-1-yl 4-72 12-methyltridecyl 14-methyl-3-pentadecen-1-yl 4 -73 13-methyltetradecyl 14-methyl-3-pentadecen-1-yl 4-74 14-methylpentadecyl 14-methyl-3-pentadecen-1-yl 4-75 15-methylhexadecyl 14-methyl-3 -Pentadecen-1-yl 4-76 16-methylheptadecyl 14-methyl-3-pentadecen-1-yl 4-77 17-methyloctadecyl 14-methyl-3-pentadecen-1-yl 4-78 hexadecyl 15- Methyl-3-hexadecen-1-yl 4-79 dodecyl 15-methyl-3-hexadec -1-yl 4-80 tetradecyl 15-methyl-3-hexadecen-1-yl 4-81 10-methylundecyl 15-methyl-3-hexadecen-1-yl 4-82 11-methyldodecyl 15-methyl-3 -Hexadecen-1-yl 4-83 12-methyltridecyl 15-methyl-3-hexadecen-1-yl 4-84 13-methyltetradecyl 15-methyl-3-hexadecen-1-yl 4-85 14-methyl Pentadecyl 15-methyl-3-hexadecen-1-yl 4-86 15-methylhexadecyl 15-methyl-3-hexadecen-1-yl 4-87 16-methylheptadecyl 15-methyl-3-hexadecene-1- Ile 4-88 17-methyloctadecyl 15-methyl-3-hexadecen-1-yl 4-89 Hexyl 16-methyl-3-heptadecen-1-yl 4-90 dodecyl 16-methyl-3-heptadecen-1-yl 4-91 tetradecyl 16-methyl-3-heptadecen-1-yl 4-92 10-methylundecyl 16-methyl-3-heptadecen-1-yl 4-93 11-methyldodecyl 16-methyl-3-heptadecen-1-yl 4-94 12-methyltridecyl 16-methyl-3-heptadecen-1-yl 4- 95 13-methyltetradecyl 16-methyl-3-heptadecen-1-yl 4-96 14-methylpentadecyl 16-methyl-3-heptadecen-1-yl 4-97 15-methylhexadecyl 16-methyl-3- Heptadecen-1-yl 4-98 16-methylheptadecyl 16-methyl-3-heptadece N-1-yl 4-99 17-methyloctadecyl 16-methyl-3-heptadecen-1-yl 4-100 hexyl 17-methyl-3-octadecen-1-yl 4-101 dodecyl 17-methyl-3-octadecene- 1-yl 4-102 tetradecyl 17-methyl-3-octadecen-1-yl 4-103 10-methylundecyl 17-methyl-3-octadecen-1-yl 4-104 11-methyldodecyl 17-methyl-3- Octadecen-1-yl 4-105 12-methyltridecyl 17-methyl-3-octadecen-1-yl 4-106 13-methyltetradecyl 17-methyl-3-octadecen-1-yl 4-107 14-methylpenta Decyl 17-methyl-3-octadecen-1-yl 4-108 15-methyl Xadecyl 17-methyl-3-octadecen-1-yl 4-109 16-methylheptadecyl 17-methyl-3-octadecen-1-yl 4-110 17-methyloctadecyl 17-methyl-3-octadecen-1-yl ─────────────────────────────────.

In the above table, exemplary compound numbers 1-20, 1-21, 1-22, 1-23, 1-24 are preferred.
1-25, 1-26, 1-27, 1-28, 1-29,
1-30, 1-31, 1-32, 1-33, 1-34,
1-35, 1-36, 1-37, 1-38, 1-39,
1-40, 1-41, 1-42, 1-43, 1-44,
1-45, 1-46, 1-47, 1-48, 1-49,
1-50, 1-51, 1-52, 1-53, 1-54,
1-55, 1-56, 1-57, 1-58, 1-59,
1-60, 1-61, 1-62, 1-63, 1-64,
1-65, 1-66, 1-67, 1-68, 1-69,
2-10, 2-11, 2-12, 2-13, 2-14,
2-15, 2-16, 2-17, 2-18, 2-19,
2-20, 2-21, 2-22, 2-23, 2-24,
2-25, 2-26, 2-27, 2-28, 2-29,
2-30, 2-31, 2-32, 2-33, 2-34,
2-35, 2-36, 2-37, 2-38, 2-39,
2-40, 3-1, 3-2, 3-3, 3-4, 3
-5, 3-6, 3-7, 3-8, 3-9, 3
-12, 3-13, 3-14, 3-15, 3-16, 3
-17, 3-18, 3-19, 3-20, 3-24, 3
-25, 3-26, 3-27, 3-28, 3-29, 3
-30, 3-31, 3-38, 3-39, 3-40, 3
-41, 3-42, 3-48, 3-49, 3-50, 3
-51, 3-52, 3-53, 3-59, 3-60, 3
-61, 3-62, 3-63, 3-64, 3-69, 3
-70, 3-71, 3-72, 3-73, 3-74, 3
-75, 3-82, 3-83, 3-84, 3-85, 3
-86, 4-2, 4-3, 4-4, 4-5, 4-
6, 4-7, 4-8, 4-9, 4-13, 4-
14, 4-15, 4-16, 4-17, 4-18, 4-
19, 4-20, 4-24, 4-25, 4-26, 4-
27, 4-28, 4-29, 4-30, 4-31, 4-
35, 4-36, 4-37, 4-38, 4-39, 4-
40, 4-41, 4-42, 4-46, 4-47, 4-
48, 4-49, 4-50, 4-51, 4-52, 4-
53, 4-57, 4-58, 4-59, 4-60, 4-
61, 4-62, 4-63, 4-64, 4-68, 4-
69, 4-70, 4-71, 4-72, 4-73, 4-
74, 4-75, 4-79, 4-80, 4-81, 4-
82, 4-83, 4-84, 4-85, 4-86.

More preferably, Exemplified Compound Nos. 1-22, 1-23, 1-24, 1-25, 1-26,
1-27, 1-28, 1-29, 1-30, 1-31,
1-32, 1-33, 1-34, 1-35, 1-36,
1-37, 1-38, 1-39, 1-40, 1-41,
1-42, 1-43, 1-44, 1-45, 1-46,
1-47, 1-48, 1-49, 1-50, 1-51,
1-52, 1-53, 1-54, 1-55, 1-56,
1-57, 1-58, 1-59, 1-60, 1-61,
1-62, 1-63, 2-16, 2-17, 2-18,
2-19, 2-20, 2-21, 2-22, 2-23,
2-24, 2-25, 2-26, 2-27, 2-28,
2-29, 2-30, 2-31, 2-32, 2-33,
3-12, 3-13, 3-14, 3-15, 3-16,
3-17, 3-18, 3-19, 3-20, 3-24,
3-25, 3-26, 3-27, 3-28, 3-29,
3-30, 3-38, 3-39, 3-40, 3-41,
3-48, 3-49, 3-50, 3-51, 3-52,
3-59, 3-60, 3-61, 3-62, 3-63,
3-69, 3-70, 3-71, 3-72, 3-73,
3-74, 4-13, 4-14, 4-15, 4-16,
4-17, 4-18, 4-19, 4-24, 4-25,
4-26, 4-27, 4-28, 4-29, 4-30,
4-35, 4-36, 4-37, 4-38, 4-39,
4-40, 4-41, 4-46, 4-47, 4-48,
4-49, 4-50, 4-51, 4-52, 4-57,
4-58, 4-59, 4-60, 4-61, 4-62,
4-63, 4-68, 4-69, 4-70, 4-71,
4-72, 4-73, 4-74.

Particularly preferably, Exemplified Compound Nos. 1-24, 1-25, 1-26, 1-27, 1-28,
1-29, 1-30, 1-31, 1-32, 1-33,
1-34, 1-35, 1-36, 1-37, 1-38,
1-39, 1-40, 1-41, 1-42, 1-43,
1-44, 1-45, 1-46, 1-47, 1-48,
1-49, 1-50, 1-51, 1-52, 1-53,
1-54, 1-55, 1-56, 1-57, 1-58,
2-19, 2-20, 2-21, 2-22, 2-23,
2-24, 2-25, 2-26, 2-27, 2-28,
2-29, 3-25, 3-26, 3-27, 3-28,
3-29, 3-38, 3-39, 3-40, 3-48,
3-49, 3-50, 3-51, 3-60, 3-61,
3-62, 4-24, 4-25, 4-26, 4-27,
4-28, 4-29, 4-35, 4-36, 4-37,
4-38, 4-39, 4-40, 4-46, 4-47,
4-48, 4-49, 4-50, 4-51, 4-57,
4-58, 4-59, 4-60, 4-61, 4-62.

The N- (3-acyloxyacyl) glycine derivative (I) which is the object compound of the present invention can be produced by chemical synthesis. The manufacturing method will be described in detail below.

[0031]

Embedded image

In the formula, R ¹ and R ² have the same meanings as described above. R ³ represents a group such as benzyl, methoxybenzyl, diphenylmethyl, trityl and t-butyl which can be easily removed by an acidic hydrolysis reaction, hydrogenolysis reaction and the like.

First Step The first step is a step of acylating the hydroxyl group of β-hydroxycarboxylic acid (1a) or its ester (1b) to produce compound (3) or compound (2). Β-hydroxycarboxylic acid (1a) used in the reaction of the first step
And its ester (1b) are commercially available products, and the reformate-ski reaction of aldehyde (Japanese Patent Publication No.
No.), alkylation reaction of acetoacetate dianion (SN Huckin et al., J. Am. Chem. Soc., 96, 108).
2 (1974), Reaction of malonic ester with acid halide (Nakahata et al., Bull. Chem. Soc., 55)
Volume, page 2186 (1982)). In this step, the aforementioned β-hydroxycarboxylic acid (1a) or carboxylic acid ester (1a) is used.
It is a reaction in which the hydroxyl group of b) is acylated with an acylation reactive derivative. Examples of the acylation-reactive derivative include acid halides, acid anhydrides and active esters. In this reaction, amines such as pyridine and triethylamine are usually used. The solvent used is not particularly limited as long as it does not affect the reaction, and for example, ether, ethers such as tetrahydrofuran,
Halogenated hydrocarbons such as methylene chloride and chloroform, aromatic hydrocarbons such as benzene and toluene,
Organic acid esters such as ethyl acetate and amines such as pyridine are preferred. The reaction temperature varies depending on the type of reaction, but is preferably 0 ° C to 100 ° C.

Second Step The second step is a step of producing the compound (3) by removing the ester residue (R ³ ) of the compound (2). When this reaction is carried out under alkaline conditions, R ² C introduced in the first step is introduced.
Since the O group is also removed at the same time, it is carried out under neutral or acidic conditions. Usually, when R ³ is a group such as benzyl or methoxybenzyl, it is preferable to carry out the reaction under neutral conditions. The reaction is preferably a catalytic reduction reaction. In this case, it cannot be applied to a compound having a structure such as a double bond in the molecule which is easily affected by the reduction reaction. In this reaction, palladium / carbon, Raney nickel or the like is used as a catalyst. The solvent used is not particularly limited as long as it does not affect this reaction, and alcohols such as ethanol and isopropanol, organic acid esters such as ethyl acetate, and organic acids such as acetic acid are preferable. This reaction is usually carried out at room temperature under a hydrogen pressure of 1 to 5 atm. R
^{When 3} is a group such as t-butyl, diphenylmethyl, trityl, it is preferably carried out under acidic conditions. As the acid used, formic acid, acetic acid, trifluoroacetic acid, toluenesulfonic acid, organic acids such as benzenesulfonic acid, hydrochloric acid,
Inorganic acids such as hydrobromic acid and sulfuric acid may be mentioned.
The reaction is accomplished by contacting with water in the presence of acid. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and dimethoxyethane, amides such as N, N-dimethylformamide, and dimethylsulfoxide. A mixed solvent of a hydrophilic solvent such as sulfoxides and water is suitable. When R ³ is t-butyl, a solvent such as methylene chloride, a halogenated carbon hydrogen such as chloroform, an organic acid ester such as ethyl acetate, an ether such as an ether can be used. The reaction temperature is 0 ° C to 1
00 ° C is preferred.

Third Step In the third step, the compound (3) and the glycine derivative (4) (H
₂ NCH ₂ CO ₂ R ⁴ ; provided that R ⁴ has the same meaning as R ³ described above. And () are condensed via an succinimide active ester to produce compound (5) (see Japanese Patent Publication No. 30586/1990). In the reaction, compound (3) and succinimide were mixed with dicyclohexylcarbodiimide (DC
Condensate in the presence of C). The resulting active ester is reacted with glycine derivative (4) in the presence of a base to produce compound (5). The condensation reaction of the compound (3) with the glycine derivative (4) by DCC is preferably carried out in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not affect the reaction, for example, organic acid esters such as ethyl acetate, ethers, ethers such as tetrahydrofuran, methylene chloride, halogenated carbons such as chloroform. Are preferred. The reaction temperature is 0 ° C to 1
00 ° C is preferred. The active ester thus obtained is reacted with the glycine derivative in the presence of a base. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and for example, amides such as N, N-dimethylformamide and sulfoxides such as dimethylsulfoxide are suitable. Preferable examples of the base used include hydroxides, carbonates and bicarbonates of alkali metals such as sodium and potassium. Reaction temperature is 0 ° C to 10
0 ° C is preferred.

Fourth Step The fourth step is a step for producing the compound (6). In the reaction, the compound (1a) and the glycine derivative (4) were mixed with diethyl cyanophosphate (Yamada et al., Tetrahedron Letters, 1973).
Vol. 1595; S hioiri et al., Tetrahedron 32, 2.
211 (1976)). As the glycine derivative used, esters such as benzyl, diphenylmethyl, trityl and t-butyl are suitable. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and ethers such as tetrahydrofuran, dioxane and dimethoxyethane are preferable. The reaction temperature is preferably 0 ° C to 100 ° C.

Fifth Step The fifth step is a step for producing the compound (5). The reaction is an acylation reaction in which the hydroxyl group of compound (6) is acylated with carboxylic acid or a reactive derivative of carboxylic acid to obtain compound (5). Examples of the reactive derivative include acid halides, acid anhydrides and active esters. In this reaction, amines such as pyridine and triethylamine are usually used. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and examples thereof include amines such as pyridine, ethers, ethers such as tetrahydrofuran, methylene chloride, halogenated hydrocarbons such as chloroform, benzene, Aromatic hydrocarbons such as toluene and organic acid esters such as ethyl acetate are preferable. The reaction temperature varies depending on the acylating agent used, but is usually preferably 0 ° C to 100 ° C.

Sixth Step The sixth step is a step for producing the compound having the general formula (I). In this step, compound (5) is subjected to an acid hydrolysis step (a) or a hydrogenolysis step (b) to produce an N- (3-acyloxyacyl) glycine derivative (I).

(A) Acid Hydrolysis Step When R ⁴ is a group such as t-butyl, benzyl, methoxybenzyl, diphenylmethyl and trityl, acid hydrolysis reaction is preferable. As the acid used in the reaction, organic acids such as trifluoroacetic acid, sulfonic acids such as benzenesulfosulfonic acid and toluenesulfonic acid, and inorganic acids such as hydrochloric acid and sulfuric acid are suitable. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and dimethoxyethane, N, N-
A mixed solvent of a hydrophilic organic solvent such as amides such as dimethylformamide and sulfoxides such as dimethylsulfoxide and water is preferable. When R ³ is t-butyl, solvents such as methylene chloride, halogenated carbon hydrogens such as chloroform, organic acid esters such as ethyl acetate, ethers such as diethyl ether can be used. The reaction temperature is usually preferably 0 ° C to 100 ° C.

(B) Hydrogenolysis step When R ⁴ is a group such as benzyl, methoxybenzyl and diphenylmethyl, a hydrogenolysis reaction is preferable. The reaction is carried out in the presence of a catalyst. Examples of the catalyst used include palladium / carbon, Raney nickel and the like. The reaction is suitably carried out in the presence of solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and for example, alcohols such as methanol and ethanol, lower organic acids such as acetic acid, organic acid esters such as ethyl acetate and the like are preferable. The reaction temperature is usually 0 ° C
Room temperature is preferred. In addition, a method using sodium / liquid ammonia is also effective.

After completion of the reaction, the target compound thus obtained in each step can be purified, if necessary, by a conventional method such as column chromatography, recrystallization, reprecipitation or the like. For example, a solvent is added to the reaction mixture for extraction, and the solvent is distilled off from the extract. The obtained residue can be purified by subjecting it to column chromatography using silica gel or the like to obtain a pure product of the target compound.

Activity on N-type calcium channels
Assay In general, the inhibitory activity of a compound having the general formula (I) or a salt thereof on N-type calcium channels acts specifically on N-type calcium channels [ ¹²⁵ I].
It can be measured by quantifying the inhibition of binding of ω-conotoxin GVIA (manufactured by Amersham) to the guinea pig brain membrane fraction. In addition, we quantify the inhibition of the amounts of these transmitters released by potassium chloride depolarization from chick cerebral cortex synaptosomes loaded with various radiolabeled neurotransmitters such as norepinephrine, dopamine and glutamate. It can be measured by As long as it is a membrane fraction containing N-type calcium channels or synaptosomes, the animal species or collection site used in the measurement is not limited to these.
The activity of the N-type calcium channel can be measured, for example, by the following method. That is, a neutral buffer containing a protease inhibitor is added to the cerebral cortex of an animal and homogenized. Centrifuge this at 3000-8000 xg. The resulting precipitate is suspended in a neutral buffer containing a protease inhibitor,
Centrifuge. The resulting membrane fraction is suspended in the same buffer. After preincubating the sample and membrane fraction in a buffer containing purified serum protein and calcium chelating agent, [ ¹²⁵
I] ω-conotoxin GVIA (manufactured by Amersham) is added and incubated. [ ¹²⁵ I] ω-conotoxin
The membrane fraction bound to GVIA (manufactured by Amersham) is suction filtered with a glass filter treated to prevent non-specific binding, and the radioactivity is measured with a γ-counter.

Activity on L-type calcium channels
Measurement L-type calcium channel activity can be measured, for example, by the following method. That is, a neutral buffer containing a protease inhibitor was added to skeletal muscle of an animal and homogenized.
Centrifuge at 00 to 3000 xg. The supernatant is filtered and
Centrifuge at ~ 50,000 xg. The obtained precipitate is resuspended in a neutral buffer containing sucrose and a protease inhibitor and overlaid on a discontinuous sucrose density gradient. After centrifugation at 100000 xg,
Separate the bands at each interface. This is diluted with a neutral buffer containing the above protease inhibitor and centrifuged at 100,000 × g. The precipitate is again suspended in a neutral buffer solution containing the above-mentioned protease inhibitor, and this is used as a membrane fraction for activity measurement. sample,
The membrane fraction, [ ³ H] -labeled-L-type calcium channel agonist, is incubated in a neutral buffer containing calcium ions. The membrane fraction bound to the agonist is filtered off,
After solubilization, the radioactivity is measured with a liquid scintillation counter.

Inhibitory activity The inhibitory activity was calculated by the following method.

That is, the inhibitory activity was [ ¹²⁵ I] ω-conotoxin GVIA (manufactured by Amersham) or [ ³ H] PN200-110.
Calculated by the percentage of inhibition of membrane binding of (radioligand), the concentration of the sample required for 50% inhibition was calculated, and this value was calculated.
The IC ₅₀ (μg / ml) value was used.

The rate of inhibition of membrane binding of radioligand is calculated by the following method.

Inhibition rate (%) = [1- (radioactivity of radioligand bound to membrane fraction in the presence of inhibitor / radioactivity of radioligand bound to membrane fraction in the absence of inhibitor)] × 100

[0048]

The compound of the present invention having the general formula (I) or a salt thereof is a novel compound which has not been published in the literature and is selective for N-type calcium channels in animals (eg, humans, dogs, cats, rabbits, etc.). And is useful as a preventive or therapeutic drug for mental illness (eg depression), epilepsy, cerebral infarction, migraine, analgesia and the like.

The compound having the above-mentioned general formula (I) of the present invention or a salt thereof is administered in various forms. Examples of the dosage form include oral administration by tablets, capsules, granules, powders, syrups and the like, or parenteral administration by injections (intravenous, intramuscular, subcutaneous), infusions, suppositories, etc. . These various preparations are commonly used in the pharmaceutical preparation technical field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizing agents, suspending agents, coating agents, and the like, in accordance with the usual methods for the main drug. It can be formulated using known adjuvants. The dosage is symptom, age, weight,
Although it varies depending on the administration method and dosage form, for example, for adults, 10 mg to 2000 mg per day is preferably administered once or in several divided doses depending on the symptoms.

[0050]

EXAMPLES Next, the present invention will be described in more detail with reference to production examples and examples, but the present invention is not limited thereto.

Production Example 1 3-Tetradecanoyloxyto
800 mg of t -butyl tridecanoic acid t-butyl ester 3-hydroxytridecanoate was dissolved in 8 ml of anhydrous pyridine, and 1 g of tetradecanoic acid chloride was added dropwise under ice cooling. After the addition was completed, the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into ice water and extracted with ethyl acetate. 1N hydrochloric acid was added to the ethyl acetate layer,
The extract was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. When ethyl acetate was distilled off from the ethyl acetate layer under reduced pressure, 1.50 g of a colorless oily substance was obtained. This was purified by silica gel chromatography (silica gel 20 g, 20% ethyl acetate-hexane) to obtain 1.29 g of the above compound.

Production Example 2 3-tetradecanoyl oxyto
907.6 mg of 3-tetradecanoyloxytridecanoic acid t-butyl ester obtained in Production Example 1 of lydecanoic acid was dissolved in 3 ml of methylene chloride, 2 ml of trifluoroacetic acid was added, and the mixture was allowed to stand at room temperature for 5 hours. After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure to obtain 805 mg of the above compound.

Production Example 3 (1) N- {3- (15-methyl-4-hexadeceno)
(Iloxy) -14-methylpentadecanoyl} glycy
T-Butyl ester 3- (15-methyl-4-hexadecenoyloxy)-
A solution of 103 mg of 14-methylpentadecanoic acid dissolved in 5 ml of ethyl acetate was ice-cooled. To this solution was added 26.5 mg of N-hydroxysuccinimide, followed by 47.2 mg of dicyclohexylcarbodiimide, and then the reaction mixture was stirred at room temperature overnight. The white precipitate formed from the reaction mixture was filtered off, the filtrate was concentrated, and the resulting residue was dissolved in 5 ml of anhydrous dimethylformamide. Glycine t-butyl ester hydrochloride was added to this solution.
Add 34.9 mg and baking soda 19.5 mg and add 5 at room temperature.
Stir for hours. After completion of the reaction, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. After the completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure to obtain 130 mg of the reaction product, which was subjected to 5% ethyl acetate-chloroform 2 on a roller column chromatography (B size).
After purification using 00 ml, the above compound 94.7 m
g was obtained.

1) Molecular formula: C ₃₉ H ₇₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 73.65; H, 11.57; N, 2.20; Measured value C, 73.78; H, 11.83; N, 2.25; 3) EIMS: (m / z) 636, 566, 565, 345, 344, 326, 251, 91 4) Infrared absorption spectrum: Infrared absorption spectrum measured by ν _max cm ^-1 liquid film method is as shown below. Is. 3309, 3005, 2954, 2926, 2855, 1739, 1656, 1545, 14
67, 1393, 1367, 1160, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is It is as shown below. 0.86 (12H, d, J = 6.6Hz), 1.1-1.2 (4H, m), 1.25 (30
H, m), 1.47 (9H, s), 1.51 (2H, m), 1.6-1.7 (2H, m),
2.03 (2H, m), 2.3-2.4 (4H, m), 2.48 (1H, dd, J = 5.3,
14.7 Hz), 2.52 (1H, dd, J = 6.6, 14.7 Hz), 3.92 (2H,
d, J = 4.9Hz), 5.17 (1H, m), 5.2-5.5 (2H, m), 6.18
(1H, br.s) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 22.7 (4xq), 22.8 (t), 25.3 (t), 27.3 (t), 27.4
(t), 28.0 (d), 28.1 (qx3), 〔29.4 (t), 29.5 (t), 2
9.68 (t), 29.74 (t), 29.9 (t)), 34.1 (t), 34.5 (t),
39.1 (t), 41.5 (t), 42.1 (t), 71.4 (d), 82.3 (s),
127.3 (d), 127.8 (d), 169.0 (s), 169.7 (s), 172.8
(s) However, the carbon number in [] is unknown. The same applies hereinafter.

(2) N- {3- (13-methyl-4-
Tetradecenoyloxy) -14-methylpentadecano
Il} glycine benzyl ester 3- (13-methyl-4-tetradecenoyloxy) -14-methylpentadecanoic acid 109 mg, N-hydroxysuccinimide 28.0 m according to Preparation Example 3 (1).
g, dicyclohexacarbodiimide 50.1 mg, glycine benzyl ester p-toluenesulfonate 7
From 8.2 mg and sodium bicarbonate 19.5 mg, the above compound 10
9.0 mg was obtained.

1) Molecular formula: C ₄₀ H ₆₉ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 74.60; H, 10.80; N, 2.18; Measured value C, 74.52; H, 11.02; N, 2.14; 3) EIMS: (m / z) 643, 536, 416, 324, 251, 211, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. Is. 3346, 2958, 2918, 2850, 1736, 1645, 1532, 1469, 14
04, 1357, 1231,1162, 969, 746, 721, 696 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured by using tetramethylsilane as an internal standard in deuterated chloroform. (400 MHz) is as shown below. 0.86 (6H, d, J = 6.7 Hz), 0.86 (3H, t, J = 7.2 Hz), 1.
0-1.2 (2H, m), 1.25 (1H, br.s), 1.57 (1H, m), 1.5-
1.7 (1H, m), 2.30 (2H, t, J = 7.7Hz), 2.50 (1H, dd, J =
5.3, 14.7 Hz), 2.54 (1H, dd, J = 6.6, 14.7 Hz), 4.07
(1H, d, J = 5.2 Hz), 5.16 (1H, m), 5.19 (2H, s), 6.26
(1H, br.t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance measured using tetramethylsilane as an internal standard in deuterated chloroform. The spectrum (100 MHz) is as shown below. 14.1 (q), 22.7 (2xq, t), 25.0 (t), 25.3 (t), 27.4
(t), 28.0 (d), [29.2, 29.3, 29.5, 29.6, 29.7, 30.0
(t)], 32.0 (t), 34.1 (t), 34.5 (t), 39.1 (t), 41.1 (t),
68.1 (t), 71.1 (d), 128.4 (dx2), 128.6 (d), 128.7 (dx
2), 135.2 (s), 169.8 (s), 169.9 (s), 173.5 (s).

(3) N- (3-tetradecanoyloxy
Cyoctanoyl) glycine benzyl ester According to Production Example 3 (1), 570 mg of 3-tetradecanoyloxyoctanoic acid, N-hydroxysuccinimide
195 mg, dicyclohexylcarbodiimide 349 m
g, glycine benzyl ester p-toluene sulfonate 570 mg, and a reaction product 662.7 mg obtained by the reaction of sodium bicarbonate 142 mg were subjected to lover column chromatography (C size) and chloroform 500 ml.
After distilling off with silica gel chromatography (silica gel 30 g), 50% ethyl acetate-hexane 200 m
The compound 337 was obtained as a colorless oil by purification with l.
mg was obtained.

1) Molecular formula: C ₃₁ H ₅₁ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.92; H, 9.93; N, 2.71; Actual value C, 71.53; H, 9.72; N, 3.09; 3) EIMS: (m / z) 518, 452, 410, 383, 353, 308, 290, 236, 125, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the liquid film method is It is as shown below. 3300, 2950, 2920, 2850, 1732, 1652, 1540, 1456, 13
80, 1358, 1176, 1180, 1032, 730, 690 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 nm) measured using tetramethylsilane as an internal standard in deuterated chloroform. MHz) is as shown below. 0.87 (3H, t, J = 6.7 Hz), 0.88 (3H, t, J = 7.2 Hz), 1.
25 (18H, m), 1.4-1.6 (4H, m), 2.30 (1H, t, J = 7.5 H
z), 2.50 (1H, dd, J = 5.6, 14.8 Hz), 2.54 (1H, dd, J =
6.6, 14.8 Hz), 4.07 (1H, d, J = 5.2 Hz), 5.16 (1H, m),
5.19 (2H, s), 6.26 (1H, br.t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Tetramethylsilane was used as an internal standard in deuterated chloroform. The nuclear magnetic resonance spectrum (100 MHz) measured by using is as shown below. 14.0 (q), 14.1 (q), 22.5 (t), 22.7 (t), 24.9 (t),
25.0 (t), [29.2 (t), 29.3 (t), 29.4 (t), 29.5 (t),
29.7 (t)], 31.5 (t), 31.9 (t), 34.0 (t), 34.5 (t),
41.4 (t), 67.2 (t), 71.1 (d), 128.4 (2xd), 128.6
(d), 128.7 (2xd), 135.1 (s), 169.7 (s), 169.8 (s),
173.5 (s).

Production Example 4 (1) N- (3-hydroxyoctanoyl) glycine
Benzyl ester 3-hydroxyoctanoic acid 1.02 g, glycine benzyl ester p-toluenesulfonate 2.16
g and 2.67 ml of triethylamine were dissolved in 40 ml of tetrahydrofuran. While stirring the reaction mixture under ice cooling, 1.25 g of diethyl cyanophosphate was added dropwise. After completion of the dropping, the reaction mixture was returned to room temperature and further stirred for 3 hours. After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure and the obtained residue was dissolved in ethyl acetate. This was washed successively with water, diluted hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off from the reaction mixture under reduced pressure, and the resulting residue was subjected to silica gel chromatography (silica gel 10 g). 30-60% ethyl acetate-hexane fraction was replaced with 10-20% chloroform-
Recrystallization from hexane gave 1.66 g of the above compound having a melting point of 61 ° C-62 ° C.

1) Molecular formula: C ₂₀ H ₃₁ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 66.43; H, 8.20; N, 4.56; Measured value C, 66.40; H, 8.20; N, 4.63; 3) EIMS: (m / z) 308, 289, 236, 216, 173, 132, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. Is. 3260, 3093, 3036, 2951, 2925, 2868, 1762, 1642, 15
85, 1404, 1355, 1169, 697 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is It is as shown below. 0.89 (3H, t, J = 6.9 Hz), 1.2-1.7 (8H, m), 2.32 (1H,
dd, J = 9.1, 15.0 Hz), 2.44 (1H, dd, J = 2.7, 15.0 Hz),
3.32 (1H, d, 3.7 Hz), 4.00 (1H, m), 4.07 (1H, dd, J
= 5.3, 18.4 Hz), 4.12 (1H, dd, J = 5.6, 18.4 Hz), 5.
19 (2H, s), 6.34 (1H, br.s), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Tetramethylsilane was used as an internal standard in deuterated chloroform. The nuclear magnetic resonance spectrum (100 MHz) measured by using is as shown below. 14.0 (q), 22.6 (t), 25.2 (t), 31.7 (t), 36.9 (t),
41.3 (t), 42.7 (t), 67.3 (t), 68.7 (d), 128.4 (2x
d), 128.6 (d), 128.7 (2xd), 135.1 (s), 170.0 (s), 1
72.7 (s).

(2) N- (3-hydroxyhexadeca
Noyl) glycine benzyl ester According to Production Example 4 (1), 1 g of 3-hydroxyundecanoic acid, 1.7 g of glycine benzyl ester p-toluenesulfonate, triethylamine 2.1 ml, diethyl cyanophosphate 0.97 g, tetrahydrofuran
The extract obtained from 30 ml was crystallized. 10 to 20
Recrystallized from ethyl acetate-hexane to give melting point
1.5 g of the above compound having a temperature of 66 ° C.-67 ° C. was obtained.

1) Molecular formula: C ₂₀ H ₃₁ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 68.77; H, 8.88; N, 4.01; Measured value C, 68.77; H, 8.85; N, 4.02; 3) EIMS: (m / z) 349, 331, 288, 274, 258, 236, 215, 167, 132, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the liquid film method is It is as shown below. 3319, 2955, 2921, 2852, 1748, 1645, 1554, 1210, 11
93, 1084, 722,696 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. Is. 0.88 (3H, t, J = 7.2 Hz), 0.94 (3H, t, J = 7.3 Hz), 1.
2-1.4 (12H, m), 2.16 (1H, br.s), 2.32 (1H, dd, J = 9.
0, 15.1 Hz), 2.44 (1H, dd, J = 2.6, 15.1Hz), 4.00 (1
H, m), 4.07 (1H, dd, J = 5.3, 18.4 Hz), 4.12 (1H, dd,
J = 5.3, 18.4 Hz), 5.19 (2H, s), 6.37 (1H, br.s), 7.
3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as follows. As shown in. 14.1 (q), 18.5 (t), 22.7 (t), 25.3 (t), [29.3 (t),
29.5 (t)], 31.9 (t), 36.9 (t), 41.3 (t), 42.7 (t),
67.4 (t), 68.7 (d), 128.4 (2xd), 128.6 (d), 128.7
(2xd), 135.1 (s), 170.0 (s), 169.9 (s), 172.8 (s).

(3) N- (3-hydroxytetradeca
Noyl) Glycine benzyl ester According to Production Example 4 (1), 2.78 g of 3-hydroxytetradecanoic acid, 3.45 g of glycine benzyl ester p-toluenesulfonate, triethylamine
The extract obtained from 4.3 ml, diethyl cyanophosphate 2.00 g and tetrahydrofuran 50 ml crystallized. This is recrystallized from 10 to 20% ethyl acetate-hexane to give the above compound having a melting point of 73 ° C to 74 ° C.
39 g were obtained.

1) Molecular formula: C ₂₃ H ₃₇ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 70.55; H, 9.53; N, 3.58 Measured value C, 70.40; H, 9.51; N, 3.62 3) EIMS: (m / z) 391, 343, 300, 282, 236, 209, 91 4) Infrared absorption spectrum: Infrared absorption spectrum measured by ν _max cm ^-1 liquid film method is as shown below. 3409, 3316, 2919, 2850, 1748, 1647, 1548, 1468, 12
10, 1199, 733,696 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. Is. 0.88 (3H, t, J = 7.2 Hz), 1.25 (18H, m), 1.4-1.6 (4
H, m), 2.32 (1H, dd, J = 9.0, 15.0 Hz), 2.43 (1H, dd,
J = 2.5, 15.0 Hz), 4.00 (1H, m), 4.08 (1H, dd, J = 5.3,
18.4 Hz), 4.12 (1H, dd, J = 5.5, 18.4 Hz), 5.19 (2H,
s), 6.36 (1H, br.t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) measured in deuterated chloroform using tetramethylsilane as an internal standard The nuclear magnetic resonance spectrum (100 MHz) is shown below. 14.1 (q), 22.7 (t), 25.5 (t), [29.4 (t), 29.5 (t),
29.6 (t)], 31.9 (t), 36.9 (t), 41.3 (t), 42.7 (t),
67.4 (t), 68.8 (d), 128.4 (2xd), 128.6 (d), 128.7
(2xd), 135.1 (s), 170.0 (s), 172.8 (s).

(4) N- (3-hydroxyhexadeca
Noyl) glycine benzyl ester According to Production Example 4 (1), 5.44 g of 3-hydroxyhexadecanoic acid, 6.75 g of glycine benzyl ester p-toluenesulfonate, triethylamine
The extract obtained from 8.2 ml, diethyl cyanophosphate (3.60 g) and tetrahydrofuran (60 ml) was crystallized. This was recrystallized from 10 to 20% ethyl acetate-hexane to obtain 7.04 g of the above compound having a melting point of 80.5 ° C-81.5 ° C.

1) Molecular formula: C ₂₅ H ₄₁ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 71.56; H, 9.85; N, 3.34 Actual value C, 71.35; H, 9.65; N, 3.39 3) EIMS: (m / z) 419, 401, 328, 310, 285, 236, 91 4) Infrared absorption spectrum: The infrared absorption spectrum measured by the ν _max cm ^-1 liquid film method is as shown below. 3406, 3316, 2919, 2850, 1748, 1647, 1548, 1210, 11
97, 732, 696 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. Is. 0.88 (3H, t, J = 7.2 Hz), 1.25 (20H, m), 1.4-1.6 (4
H, m), 2.32 (1H, dd, J = 9.0, 15.1 Hz), 2.43 (1H, dd,
J = 2.5, 15.1 Hz), 4.00 (1H, m), 4.08 (1H, dd, J = 5.2,
18.4 Hz), 4.12 (1H, dd, J = 5.4, 18.4 Hz), 5.19 (2H,
s), 6.34 (1H, br.t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Measured in deuterated chloroform using tetramethylsilane as internal standard The nuclear magnetic resonance spectrum (100 MHz) is shown below. 14.1 (q), 22.7 (t), 25.5 (t), 〔29.4 (t), 29.55
(t), 29.60 (t), 29.7 (t)], 31.9 (t), 36.9 (t), 41.3
(t), 42.7 (t), 67.4 (t), 68.8 (d), 128.4 (2xd), 12
8.6 (d), 128.7 (2xd), 135.1 (s), 170.0 (s), 172.8
(s).

(5) N- (3-hydroxyheptadeca
Noyl) glycine benzyl ester According to Production Example 4 (1), 3.15 g of 3-hydroxyheptadecanoic acid, 4.32 g of glycine benzyl ester p-toluenesulfonate, triethylamine
The extract obtained from 5.1 ml, diethyl cyanophosphate (2.39 g) and tetrahydrofuran (60 ml) was crystallized. This is recrystallized from 10-20% ethyl acetate-hexane to give the above compound having a melting point of 86 ° C-87 ° C.
79 g were obtained.

1) Molecular formula: C ₂₆ H ₄₃ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 72.02; H, 10.00; N, 3.23; Actual value C, 71.86; H, 10.05; N, 3.22; 3) EIMS: (m / z) 433, 415, 342, 324, 299, 251, 236, 91 4) Infrared absorption spectrum: infrared absorption spectrum measured by ν _max cm ^-1 liquid film method is as shown below. Is. 3401, 3320, 2919, 2850, 1
746, 1646, 1549, 1466, 12
11, 1195, 731, 6965) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 0.88 (3H, t, J = 7.2 Hz), 1.26 (22H, m), 1.4-1.6 (4
H, m), 2.32 (1H, dd, J = 9.0, 15.0 Hz), 2.43 (1H, dd,
J = 2.5, 15.0 Hz), 4.00 (1H, m), 4.08 (1H, dd, J = 5.3,
18.3 Hz), 4.12 (1H, dd, J = 5.4, 18.3 Hz), 5.19 (2H,
s), 6.34 (1H, br.t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Measured in deuterated chloroform using tetramethylsilane as internal standard The nuclear magnetic resonance spectrum (100 MHz) is shown below. 14.1 (q), 22.7 (t), 25.5 (t), 〔29.4 (t), 29.54 (t),
29.61 (t), 29.7 (t)], 31.9 (t), 36.9 (t), 41.3
(t), 42.7 (t), 67.4 (t), 68.8 (d), 128.4 (2xd), 12
8.6 (d), 128.7 (2xd), 135.1 (s), 170.0 (s), 172.8
(s).

(6) N- [3 (R) -hydroxytet
[Radecanoyl] glycine benzyl ester According to Production Example 4 (1), 3.66 g of 3 (R) -hydroxymyristic acid, 5.57 g of glycine benzyl ester p-toluenesulfonate, 6.2 ml of triethylamine, 2.93 g of diethyl cyanophosphate, The extract obtained from 30 ml of tetrahydrofuran crystallized. This was recrystallized from 10-20% methylene chloride-hexane to give the above compound having a melting point of 86 ° C-87 ° C.
4.1 g was obtained.

(7) N- (3-hydroxy-15-me
Tylhexadecanoyl) glycine benzyl ester According to Production Example 4 (1), 3-hydroxy-15-methylhexadecanoic acid 1 g, glycine benzyl ester p-
An extract obtained from 1.2 g of toluenesulfonate, 1.46 ml of triethylamine, 0.68 g of diethyl cyanophosphate and 60 ml of tetrahydrofuran was crystallized. This was recrystallized from 10 to 20% ethyl acetate-hexane to obtain 1.3 g of the above compound having a melting point of 77 ° C to 78 ° C.

1) Molecular formula: C ₂₆ H ₄₃ NO ₄ 2) Elemental analysis value: (%) Calculated value C, 72.02; H, 10.00; N, 3.23; Measured value C, 71.92; H, 9.94; N, 3.02; 3) EIMS: (m / z) 433, 415, 368, 342, 324, 299, 298 ,, 236, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the liquid film method is as follows. As shown in. 3323, 2955, 2920, 2851, 1743, 1645, 1554, 1498, 14
68, 1455, 1426, 1398, 1356, 1211, 1134, 1076, 1028,
987, 949, 734, 696 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 0.86 (6H, d, J = 6.6 Hz), 1.15 (2H, m), 1.26 (18H, b
rs), 1.4-1.6 (2H, m), 1.51 (1H, m), 2.33 (1H, dd,
J = 9.2, 15.2 Hz), 2.44 (1H, dd, J = 2.7, 15.2 Hz), 4.0
0 (1H, m), 4.08 (1H, dd, J = 5.4, 18.7 Hz), 4.12 (1H,
dd, J = 5.4, 18.7 Hz), 5.20 (2H, s), 6.36 (1H, br.
t), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured in deuterated chloroform using tetramethylsilane as an internal standard. Is as shown below. 22.7 (2xq), 25.5 (t), 27.4 (t), 27.9 (d), 〔29.55
(t), 29.60 (t), 29.7 (t)], 30.0 (t), 36.9 (t), 39.
1 (t), 41.3 (t), 42.7 (t), 67.3 (t), 68.7 (d), 128.
4 (2xd), 128.6 (d), 128.7 (2xd), 135.1 (s), 170.0
(s), 172.8 (s).

Production Example 5 (1) N- [15-methyl-3- (13-methyl-1)
1-tetradecenoyloxy) hexadecanoyl] green
Synbenzyl ester N- (3-hydroxy-15 obtained according to Preparation Example 4
-Methylhexadecanoyl) glycine benzyl ester 1.00 g was dissolved in 20 ml of methylene chloride, and 13-methyl-11-tetradecenoic acid chloride 6 under ice cooling.
50 mg and pyridine 0.3 ml were added. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure, the obtained residue was dissolved in ethyl acetate, and washed successively with 10% aqueous copper sulfate solution, water and saturated brine. The residue (3.00 g) obtained by evaporating the solvent from the reaction mixture under reduced pressure was purified by subjecting it to silica gel column chromatography (silica gel 100 g, 10% ethyl acetate-hexane) to give the above compound 1.3 as a colorless oil.
0 g was obtained.

1) Molecular formula: C ₄₀ H ₆₇ NO ₅ 2) EIMS: (m / z) 641, 550, 420, 402, 330, 312, 237, 91 3) Infrared absorption spectrum: ν _max cm ^-1 liquid film The infrared absorption spectrum measured by the method is as shown below. 3307, 2954, 2925, 2855, 1736, 1655, 1541, 1465, 14
57, 1380, 1360, 1186, 697 4) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is It is as shown below. 0.88 (3H, t, J = 7.2 Hz), 0.93 (6H, d, J = 6.6 Hz), 1.
2-1.4 (26H, m), 1.6-1.7 (12H, m), 2.01 (2H, q, J = 6.
8 Hz), 2.29 (2H, t, J = 7.4 Hz), 2.52 (2H, t, J = 5.1 H
z), 2.56 (1H, m), 4.07 (2H, d, J = 5.1 Hz), 5.1-5.3
(4H, m), 6.26 (2H, br.t, J = 4.9 Hz), 7.3-7.4 (5H,
m) 5) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) A nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. 14.1 (q), 22.7 (2xq), 25.0 (t), 25.3 (t), 26.4
(d), 27.3 (t) [29.2 (t), 29.3 (t), 29.4 (t), 29.5
(t), 29.7 (t), 30.0 (t)], 31.9 (t), 34.1 (t), 34.5
(t), 41.4 (2xt), 67.2 (t), 71.1 (d), 127.5 (d), 12
8.4 (2xd), 128.6 (d), 128.7 (2xd), 128.7 (d), 130.6
(d), 135.1 (s), 137.5 (d), 169.8 (s), 169.9 (s), 1
73.5 (s).

(2) N- (3-tetradecanoyloxy
Cypentadecanoyl) glycine benzyl ester According to Preparation Example 5 (1), N- (3-hydroxypentadecanoyl) glycine benzyl ester 405.6 m
g and a residue obtained from 496 mg of myristic acid chloride were purified by subjecting to silica gel column chromatography (silica gel 30 g, 20-30% ethyl acetate-hexane) to give the above compound 630 having a melting point of 36 ° C.
mg was obtained.

1) Molecular formula: C ₃₈ H ₆₅ NO ₅ 2) Infrared absorption spectrum: ν _max cm ^-1 Potassium bromide The infrared absorption spectrum measured by the tablet method is as shown below. 3342, 2956, 2919, 2850, 1728, 1702, 1655, 1542, 14
66, 1456, 1246, 1233, 1244, 1211, 757, 705 3) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured by using tetramethylsilane as an internal standard in deuterated chloroform. (400 MHz) is as shown below. 0.88 (6H, t, J = 7.0 Hz), 1.25 (40H, br.s), 1.55-1.7
0 (4H, m), 2.30 (2H, t, J = 7.4 Hz), 2.51 (1H, dd, J =
5.4, 14.7 Hz), 2.54 (1H, dd, J = 6.6, 14.7 Hz), 4.08
(2H, d, J = 5.2 Hz), 5.16 (1H, m), 5.19 (2H, s), 6.29
(1H, br.t, J = 5.2 Hz), 7.3-7.4 (5H, m) 4) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Using tetramethylsilane as an internal standard in deuterated chloroform. The measured nuclear magnetic resonance spectrum (100 MHz) is as shown below. 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.1
(t), 29.4 (t), 29.48 (t), 29.54 (t), 29.7 (t)], 3
2.0 (2xt), 34.1 (t), 34.5 (t), 41.4 (2xt), 67.3
(t), 71.2 (d), 128.4 (2xd), 128.6 (d), 128.7 (2xd),
135.1 (s), 169.8 (s), 170.1 (s), 173.6 (s).

(3) N- (3-stearoyloxyoxy
X- decanoyl) glycine benzyl ester N- (3- hydroxyhexadecanoyl) glycine benzyl ester 205.9 m according to Preparation Example 5 (1).
157 mg of the above compound having a melting point of 54 ° C.-56 ° C. was obtained from g, stearic acid chloride 229.4 mg, and pyridine 0.4 ml.

1) Molecular formula: C ₄₃ H ₇₅ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 75.28; H, 11.02; N, 2.04; Measured value C, 75.23; H, 11.29; N, 1.84; 3) EIMS: (m / z) 685, 402, 401, 310, 267, 237, 91 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. Is. 3340, 2956, 2919, 2851, 1728, 1655, 1543, 1466, 14
44, 1415, 1396, 1355, 1246, 1237, 1212, 757, 721, 7
05 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. 0.88 (6H, t, J = 7.2 Hz), 1.26 (50H, m), 1.55-1.70
(4H, m), 2.30 (2H, t, J = 7.4 Hz), 2.51 (1H, dd, J = 5.
4, 14.8 Hz), 2.54 (1H, dd, J = 6.7, 14.8 Hz), 4.08 (2
H, d, J = 5.2 Hz), 5.16 (1H, m), 5.19 (2H, s), 6.31
(1H, br.t, J = 5.2 Hz), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Using tetramethylsilane as an internal standard in deuterated chloroform. The measured nuclear magnetic resonance spectrum (100 MHz) is as shown below. 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.1
(t), 29.2 (t), 29.4 (t), 29.49 (t), 29.54 (t), 27.7
(t)], 32.0 (2xt), 34.1 (t), 34.5 (t), 41.5 (2xt), 6
7.3 (t), 71.1 (d), 128.4 (2xd), 128.6 (d), 128.7 (2
xd), 135.1 (s), 169.8 (s), 170.0 (s), 173.5 (s).

(4) N- [3- (12-methyl-11
-Tridecenoyloxy) hexadecanoyl] glycine
Benzyl ester N- (3-hydroxyhexadecanoyl) glycine benzyl ester 276 mg, 1 according to Preparation Example 5 (1).
From 242 mg of 2-methyl-11-tridecenoic acid chloride, 284 mg of the above compound was obtained.

1) Molecular formula: C ₃₉ H ₆₅ NO ₅ 2) EIMS: (m / z) 627, 536, 420, 402, 330, 312, 237, 91 3) Infrared absorption spectrum: ν _max cm ^-1 liquid film The infrared absorption spectrum measured by the method is as shown below. 3345, 2925, 2850, 1735, 1685, 1515, 1465, 1385, 13
70, 1355, 1190, 695 4) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 0.88 (3H, t, J = 7.2 Hz), 1.56 (6H, d, J = 6.6 Hz), 1.
2-1.4 (32H, m), 1.40-1.80 (12H, m), 2.30 (2H, t, J =
7.5 Hz), 2.51 (1H, dd, J = 5.4, 14.7 Hz), 2.55 (1H, d
d, J = 6.6, 14.7 Hz), 4.08 (2H, d, J = 5.1 Hz), 5.16 (1
H, m), 5.19 (2H, s), 5.1-5.2 (2H, m), 6.26 (2H, br.
t, J = 5.1 Hz), 7.3-7.4 (5H, m) 5) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance measured using tetramethylsilane as an internal standard in deuterated chloroform. The spectrum (100 MHz) is as shown below. 14.1 (q), 22.7 (t), 25.0 (t), 25.1 (t), 25.3 (t),
29.2 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.7 (t), 3
2.0 (2xt), 32.4 (2xq), 34.1 (t), 34.5 (t), 41.4 (2x
t), 46.1 (t), 67.2 (t), 71.1 (d), 128.4 (2xd), 128.
6 (2xd), 128.7 (2xd + s), 130.6 (d), 135.1 (s), 169.8
(s), 169.9 (s), 173.5 (s).

(5) N- (3-tetradecanoyloxy
Siheptadecanoyl) glycine benzyl ester According to Preparation Example 5 (1), N- (3-hydroxyheptadecanoyl) glycine benzyl ester 300 mg,
From myristin chloride 270mg, melting point 49 ° C
466.9 mg of the above compound having -50 ° C. was obtained.

1) Molecular formula: C ₄₀ H ₆₉ NO ₅ 2) EIMS: (m / z) 643, 451, 416, 415, 324, 281, 251, 211, 91 3) Infrared absorption spectrum: ν _max cm ^-1 The infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. 3342, 2919, 2851, 1754, 1
728, 1655, 1542, 1466, 13
55, 1246, 1212, 1107, 102
7, 757 4) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 0.88 (6H, t, J = 7.2 Hz), 1.25 (44H, br.s), 1.55-1.70
(4H, m), 2.30 (2H, t, J = 7.6 Hz), 2.50 (1H, dd, J = 5.
4, 14.9 Hz), 2.55 (1H, dd, J = 6.7, 14.9 Hz), 4.08 (2
H, d, J = 5.2 Hz), 5.16 (1H, m), 5.19 (2H, s), 6.28
(1H, br.t, J = 5.2 Hz), 7.3-7.4 (5H, m) 5) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Using tetramethylsilane as an internal standard in deuterated chloroform. The measured nuclear magnetic resonance spectrum (100 MHz) is as shown below. 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.
1 (t), 29.2 (t), 29.4 (t), 29.48 (t), 29.54 (t), 2
9.6 (t), 29.7 (t)], 32.0 (2xt), 34.1 (t), 34.5 (t),
41.3 (2xt), 67.3 (t), 71.1 (d), 128.4 (2xd), 128.6
(d), 128.7 (2xd), 135.1 (s), 169.8 (s), 170.0
(s), 173.5 (s) (6) N- (3-palmitoyloxyheptadecanoy
) Glycine benzyl ester N- (3-hydroxyheptadecanoyl) glycine benzyl ester (197 mg), palmitic acid chloride (190 mg) according to Production Example 5 (1), melting point 50 ° C.-5
251 mg of the above compound having a temperature of 5 ° C. was obtained.

1) Molecular formula: C ₄₂ H ₇₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 75.06; H, 10.95; N, 2.08; Measured value C, 74.98; H, 10.96; N, 1.97; 3) EIMS: (m / z) 671, 415, 324, 281, 251, 117, 91 4) Infrared absorption spectrum: infrared absorption spectrum measured by ν _max cm ^-1 liquid film method is as shown below. . 3441, 2919, 2851, 1727, 1655, 1542, 1244, 1212, 75
7, 705 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 0.88 (6H, t, J = 7.1 Hz), 1.25 (48H, br.s), 1.55-1.7
0 (4H, m), 2.30 (2H, t, J = 7.6 Hz), 2.50 (1H, dd, J =
5.3, 14.7 Hz), 2.54 (1H, dd, J = 6.6, 14.7 Hz), 4.07
(2H, d, J = 5.2 Hz), 5.16 (1H, m), 5.19 (2H, s), 6.26
(1H, br.t, J = 5.2 Hz), 7.3-7.4 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Using tetramethylsilane as an internal standard in deuterated chloroform. The measured nuclear magnetic resonance spectrum (100 MHz) is as shown below. 14.1 (2xq), 22.7 (t), 25.0 (t), 25.3 (t), [29.2
(t), 29.4 (t), 29.5 (t), 29.6 (t), 29.7 (t)], 31.9
(2xt), 34.1 (t), 34.5 (t), 41.4 (2xt), 67.2 (t), 7
1.1 (d), 128.4 (2xd), 128.6 (d), 128.7 (2xd), 135.1
(s), 169.8 (s), 169.9 (s), 173.5 (s).

(7) N- [3- (12-methyl-11)
-Tridecenonoyloxy) heptadecanoyl] glycy
Emissions benzyl ester Preparation 5 (1) in accordance with N- (3- hydroxy-hepta decanoyl) glycine benzyl ester 300 mg, 1
From 320 mg of 2-methyl-11-tridecenoic acid chloride, 338.5 mg of the above compound was obtained.

1) Molecular formula: C ₄₀ H ₆₇ NO ₅ 2) EIMS: (m / z) 641, 551, 550, 416, 415, 281, 251, 226, 153, 91 3) Infrared absorption spectrum: ν _max cm ^The infrared absorption spectrum measured by the ^-1 liquid film method is as follows. 3450, 2925, 2850, 1735, 1686, 1515, 1466, 1385, 13
70, 1355, 1190, 695 4) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 0.88 (3H, t, J = 7.2 Hz), 1.56 (6H, s), 1.2-1.4 (34H,
m), 1.4-1.5 (2H, m), 1.5-1.7 (4H, m), 1.7-1.8 (2H,
m), 2.30 (2H, t, J = 7.4 Hz), 2.51 (1H, dd, J = 5.7, 1
4.8 Hz), 2.55 (1H, dd, J = 6.7, 14.8 Hz), 4.08 (2H,
d, J = 5.1 Hz), 5.1-5.3 (2H, m), 5.19 (2H, s), 6.27
(1H, br.t), 7.3-7.5 (5H, m) 5) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance measured using tetramethylsilane as an internal standard in deuterated chloroform. The spectrum (100 MHz) is as shown below. 14.1 (q), 22.7 (t), 25.0 (t), 25.3 (t), [29.2 (t),
29.3 (t), 29.4 (t), 29.5 (t), 29.7 (t)], 32.0 (t),
32.4 (2xq), 34.1 (t), 34.5 (t), 41.35 (t), 41.42
(t), 67.3 (t), 71.1 (d), 128.4 (2xd), 128.6 (d), 12
8.7 (2xd), 135.1 (s), 169.7 (s), 170.1 (s), 173.5
(s).

(8) N- [3- (13-methyl-11
-Tetradecenoyloxy) heptadecanoyl] glycy
Emissions benzyl ester Preparation 5 (1) in accordance with N- (3- hydroxy-hepta decanoyl) glycine benzyl ester 350 mg, 1
3-Methyl-11-tetradecenoic acid chloride 400 mg
Thus, 498.7 mg of the above compound was obtained.

1) Molecular formula: C ₄₁ H ₆₉ NO ₅ 2) EIMS: (m / z) 655, 564, 434, 416, 344, 326, 251, 91 3) Infrared absorption spectrum: ν _max cm ^-1 liquid film The infrared absorption spectrum measured by the method is as shown below. 3445, 2920, 2850, 1735, 1675, 1570, 1463, 1393, 13
55, 1193, 696 4) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. Is. 0.88 (3H, t, J = 7.2 Hz), 0.93 (6H, d, J = 6.6 Hz), 1.2
-1.4 (36H, m), 1.55-1.70 (4H, m), 2.20 (2H, m), 2.3
0 (2H, t, J = 7.4 Hz), 2.51 (1H, dd, J = 5.6, 14.9 Hz),
2.55 (1H, dd, J = 6.7, 14.9 Hz), 2.57 (1H, m), 4.08
(2H, d, J = 5.1 Hz), 5.1-5.3 (2H, m), 5.19 (2H, s),
6.25 (1H, br.t), 7.3-7.5 (5H, m) 5) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (100 MHz) is as shown below. 14.1 (q), 22.7 (t), 23.3 (2xq), 25.0 (t), 26.4
(d), 27.3 (t), [29.2 (t), 29.3 (t), 29.5 (t), 29.7
(t)], 30.0 (t), 32.0 (t), 34.1 (t), 34.5 (t), 41.4
(2xt), 67.2 (t), 71.1 (d), 127.5 (d), 128.4 (2xd),
128.6 (d), 128.7 (2xd), 135.1 (s), 137.5 (d), 169.8
(s), 169.9 (s), 173.5 (s).

(9) N- [3- (14-methyl-11)
-Pentadecenoyloxy) heptadecanoyl] glycy
Emissions benzyl ester Preparation 5 (1) in accordance with N- (3- hydroxy-hepta decanoyl) glycine benzyl ester 217 mg, 1
270 mg of 4-methyl-11-pentadecenoyl chloride
Thus, 203.5 mg of the above compound was obtained.

1) Molecular formula: C ₄₂ H ₇₁ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 75.29; H, 10.68; N, 2.0
9; measured value C, 74.99; H, 10.87; N, 2.01; 3) EIMS: (m / z) 669, 578, 416, 344, 326, 251, 91 4) Infrared absorption spectrum: ν _max cm ^-1 liquid The infrared absorption spectrum measured by the film method is as shown below. 3445, 2900, 2825, 1740, 1675, 1515, 1465, 1380, 13
55, 1190, 950,695 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. Is. 0.88 (3H, t, J = 7.2 Hz), 0.89 (6H, d, J = 6.8 Hz), 1.2
-1.4 (34H, m), 1.55-1.70 (7H, m), 2.00 (2H, m), 2.3
0 (2H, t, J = 7.4 Hz), 2.51 (1H, dd, J = 5.4, 14.7 Hz),
2.55 (1H, dd, J = 6.6, 14.7 Hz), 2.55 (1H, m), 4.07
(2H, d, J = 5.1 Hz), 5.1-5.3 (2H, m), 5.19 (2H, s),
5.38 (2H, m), 6.26 (1H, br.t), 7.3-7.5 (5H, m) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Tetramethylsilane was used as an internal standard in deuterated chloroform. The nuclear magnetic resonance spectrum (100 MHz) measured by using is as shown below. 14.1 (q), 22.4 (2xq), 22.7 (t), 25.0 (t), 25.3
(t), 27.3 (t), 28.7 (d), [29.2 (t), 29.3 (t), 29.5
(t), 29.7 (t)], 32.0 (t), 34.1 (t), 34.5 (t), 36.4
(t), 41.5 (2xt), 67.3 (t), 71.1 (d), 127.5 (d), 12
8.4 (2xd), 128.6 (2xd), 128.7 (2xd), 130.6 (d), 13
5.1 (s), 137.5 (d), 169.8 (s), 169.9 (s), 173.5
(s).

(10) N- [15-methyl-3- (1
3-Methyl-4Z-tetradecenoyloxy) hexade
Canoyl] glycine t-butyl ester According to Production Example 5 (1), N- (3-hydroxy-15)
-Methylhexadecanoyl) glycine t-butyl ester 150 mg and 13-methyl-4Z-tetradecenoic acid chloride 74 mg, the above compound 162.3 mg
was gotten.

1) Molecular formula: C ₃₈ H ₇₁ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.38; H, 11.51; N, 2.25; Actual value C, 72.78; H, 11.83; N, 2.25; 3) EIMS: (m / z) 622, 566, 565, 345, 344, 326, 251, 91 4) Infrared absorption spectrum: Infrared absorption spectrum measured by ν _max cm ^-1 liquid film method is as shown below. Is. 3309, 3005, 2954, 2926, 2855, 1739, 1656, 1545, 14
67, 1393, 1367, 1160, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is It is as shown below. 0.86 (12H, d, J = 6.6Hz), 1.1-1.2 (4H, m), 1.25 (34
H, m), 1.47 (9H, s), 1.51 (2H, m), 1.6-1.7 (2H, m),
2.03 (2H, m), 2.3-2.4 (4H, m), 2.48 (1H, dd, J = 5.
3, 14.7 Hz), 2.52 (1H, dd, J = 6.6, 14.7 Hz), 3.92 (2
H, d, J = 4.9Hz), 5.17 (1H, m), 5.2-5.5 (2H, m), 6.18
(1H, br.s) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 22.7 (4xq), 22.8 (t), 25.3 (t), 27.3 (t), 27.4
(t), 28.0 (d), 28.1 (qx3), [29.4 (t), 29.5 (t), 2
9.68 (t), 29.74 (t), 29.9 (t)], 34.1 (t), 34.5 (t),
39.1 (t), 41.5 (t), 42.1 (t), 71.4 (d), 82.3 (s),
127.3 (d), 127.8 (d), 169.0 (s), 169.7 (s), 172.8
(s).

(11) N- [14-methyl-3- (1
3-Methyl-4Z-tetradecenoyloxy) pentade
Canoyl] glycine t-butyl ester According to Preparation Example 5 (1), N- (3-hydroxy-14)
-Methylpentadecanoyl) glycine t-butyl ester 74.7 mg and 13-methyl-4Z-tetradecenoic acid chloride 60 mg to give the above compound 94.7 mg.
was gotten.

1) EIMS: (m / z) 607, 551, 330, 312, 294, 268, 237, 222, 181, 117 2) Infrared absorption spectrum: infrared absorption measured by ν _max cm ^-1 liquid film method The spectrum is as shown below. 3302, 3005, 2954, 2926, 2855, 1739, 1656, 1546, 14
67, 1368, 1248, 1223, 1160, 1036, 850, 722 3) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured using tetramethylsilane as an internal standard in deuterated chloroform. (400 MHz) is as shown below. 0.86 (12H, d, J = 6.7Hz), 1.1-1.2 (4H, m), 1.21-1.4
(32H, m), 1.47 (9H, s), 1.51 (2H, m), 1.6-1.7 (2H,
m), 2.03 (2H, m), 2.3-2.4 (4H, m), 2.48 (1H, dd, J
= 5.31, 14.6 Hz), 2.52 (1H, dd, J = 6.6, 14.6 Hz), 3.9
1 (2H, d, J = 5.0 Hz), 5.17 (1H, m), 5.2-5.5 (2H, m),
6.17 (1H, br.s) 4) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as follows. As shown in. 22.7 (4xq), 22.8 (t), 25.3 (t), 27.3 (t), 27.4
(t), 28.0 (d), 28.1 (d), [29.4 (t), 29.5 (t), 29.
6 (t), 29.7 (t), 29.9 (t)], 34.1 (t), 34.5 (t), 39.
1 (t), 41.4 (t), 42.1 (t), 71.3 (d), 82.3 (s), 127.
3 (d), 131.6 (d), 169.0 (s), 169.6 (s), 172.8 (s)
.

Example 1 N- [15-methyl-3- (1
3-Methyltetradecanoyloxy) hexadecanoyl]
Glycine (known compound, exemplified compound No. 1-50) N- [15-methyl-prepared according to Production Example 5 (1)
3- (13-Methyltetradecanoyloxy) hexadecanoyl] glycine benzyl ester 140 mg was dissolved in ethanol 20 ml, and 10% Pd-C was added thereto.
70 mg was added and catalytically reduced in a hydrogen atmosphere under normal pressure. After the reaction was completed, Pd-C was filtered off, and the filtrate was concentrated under reduced pressure. The obtained solid was recrystallized from 10 to 20% methylene chloride-hexane to obtain 88 mg of the target compound having a melting point of 92 ° C to 94 ° C.

1) Molecular formula: C ₃₄ H ₆₅ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.91; H, 11.54; N, 2.47; Measured value C, 71.62; H, 11.42; N, 2.26; 3) EIMS: (m / z) 567, 493, 342, 325, 282, 242, 199, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is It is as shown below. 3349, 2955, 2921, 2851, 2606, 1746, 1722, 1623, 15
68, 1468, 1379, 1248, 1200, 928, 654 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured using tetramethylsilane as an internal standard in deuterated chloroform (400 MHz) is as shown below. 0.86 (12H, d, J = 6.7Hz), 1.0-1.2 (4H, m), 1.25 (34
H, m) 1.51 (2H, m), 1.55-1.70 (4H, m), 2.31 (2H, t, J = 7.
5 Hz), 2.52 (1H, dd, J = 5.3, 14.8 Hz), 2.56 (1H, dd,
J = 6.8, 14.8 Hz), 4.07 (2H, d, J = 5.2 Hz), 5.16 (1H,
m), 6.41 (1H, br.t) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform. Is as shown below. 22.7 (4xq), 25.0 (t), 25.3 (t), 27.5 (t), 28.0
(d), [29.2 (t), 29.4 (t), 29.6 (t), 29.7 (t), 29.8
(t), 30.0 (t)], 34.2 (t), 34.6 (t), 39.1 (t), 41.3
(t), 41.4 (t), 71.2 (d), 170.8 (s), 172.7 (s), 173.
4 (s).

Example 2 N- [3- (12-methyltri)
Decanoyloxy) hexadecanoyl] glycine (example
Compound No. 1-32) According to Example 1, N- [3- (12-methyl-11-
Tridecenoyloxy) hexadecanoyl] glycine benzyl ester 220 mg was added to give the solid 10
Recrystallized from ~ 20% methylene chloride-hexane to give the desired compound 17 with melting point 90 ° C-91 ° C.
6.4 mg was obtained.

1) Molecular formula: C ₃₂ H ₆₁ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.20; H, 11.39; N, 2.59; Measured value C, 71.63; H, 11.47; N, 2.53; 3) EIMS: (m / z) 539, 465, 424, 371, 312, 268, 237, 185, 117, 76 4) Infrared absorption spectrum: ν _max cm ^-1 Infrared absorption spectrum measured by potassium bromide tablet method Is as shown below. 3349, 2955, 2922, 2851, 2607, 1746, 1721, 1623, 15
68, 1468, 1378, 1248, 1199, 938, 685 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 nm) measured using tetramethylsilane as an internal standard in deuterated chloroform. MHz) is as shown below. 0.86 (6H, d, J = 6.6Hz), 0.88 (3H, t, J = 6.7Hz), 1.2
5 (36H, m), 1.51 (2H, m), 1.55-1.70 (4H, m), 2.31
(2H, t, J = 7.5 Hz), 2.52 (1H, dd, J = 5.3, 14.7 Hz),
2.56 (1H, dd, J = 6.7, 14.7 Hz), 4.07 (2H, d, J = 4.6 H
z), 5.16 (1H, m), 6.41 (1H, br.t) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclei measured using tetramethylsilane as an internal standard in deuterated chloroform. The magnetic resonance spectrum (100 MHz) is as shown below. 14.1 (q), 22.7 (2xq), 25.0 (t), 25.2 (t), 25.3
(t), 28.0 (d), [29.0 (t), 29.2 (t), 29.4 (t), 29.6
(t), 29.7 (t)], 30.0 (t), 32.0 (2xt), 34.1 (t), 3
4.6 (t), 39.1 (t), 41.3 (t), 41.4 (t), 71.2 (d), 17
0.8 (s), 172.8 (s), 173.9 (s).

Example 3 N- [14-methyl-3- (1
3-Methyltetradecanoyloxy) pentadecanoyl]
Glycine (Exemplified Compound No. 1-39) According to Example 1, N- [14-methyl-3- (13-
Methyl tetradecanoyloxy) pentadecanoyl] glycine benzyl ester 109 mg was recrystallized from 10 mg to 20% methylene chloride-hexane to give the desired compound having a melting point of 89 ° C to 90 ° C.
2.3 mg was obtained.

1) Molecular formula: C ₃₃ H ₆₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.56; H, 11.47; N, 2.53; Measured value C, 71.20; H, 11.73; N, 2.53; 3) EIMS: (m / z) 554, 553, 312, 311, 237, 236, 199, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is It is as shown below. 3350, 2954, 2921, 2851, 2603, 1745, 1721, 1623, 156
8, 1467, 1418, 1382, 1343, 1249, 1202, 1178, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (12H, d, J = 6.7 Hz), 1.2-1.4 (4H, m), 1.25 (3
4H, br.s), 1.51 (2H, m), 1.55-1.70 (2H, m), 2.31 (2
H, t, J = 7.4 Hz), 2.52 (1H, dd, J = 5.7, 14.7 Hz), 2.5
6 (1H, dd, J = 6.7, 14.7 Hz), 4.08 (2H, d, J = 5.3 Hz),
5.16 (1H, m), 6.39 (1H, br.t, J = 5.1 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) measured in deuterated chloroform using tetramethylsilane as internal standard The nuclear magnetic resonance spectrum (100 MHz) is shown below. 22.7 (4xq), 25.0 (t), 25.3 (t), 27.5 (t), 28.0 (dx
2), [29.2 (t), 29.4 (t), 29.5 (t), 29.6 (t), 29.7
(t)], 30.0 (t), 34.2 (t), 34.6 (t), 39.1 (t), 41.4
(t), 41.5 (t), 71.2 (d), 170.7 (s), 172.7 (s), 173.
9 (s).

Example 4 N- [3- (13-methylteto
Radecanoyloxy) heptadecanoyl] glycine (eg
Compound No. 1-83) According to Example 1, N- [3- (13-methyltetradecanoyloxy) heptadecanoyl] glycine benzyl ester 224.1 mg was used to give 10 to 10 g of the obtained solid.
When recrystallized using 20% methylene chloride-hexane,
167 mg of the target compound having a melting point of 93 ° C-94 ° C.
was gotten.

1) Molecular formula: C ₃₄ H ₆₇ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.91; H, 11.54; N, 2.47; Actual value C, 71.62; H, 11.73; N, 2.47; 3) EIMS: (m / z) 568, 567, 398, 385, 326,
325, 251, 250, 117, 764) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. 3349, 2956, 2921, 2851, 2605, 1745, 1721, 1623, 15
68, 1468, 1419,1379, 1342, 1249, 1190, 1177, 939,
722, 657 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 0.86 (6H, d, J = 6.6 Hz), 0.88 (3H, t, J = 7.1 Hz), 1.
1-1.2 (2H, m), 1.25 (50H, br.s), 1.51 (1H, m), 1.55
-1.70 (4H, m), 2.31 (2H, t, J = 7.5 Hz), 2.52 (1H, d
d, J = 5.6, 14.7 Hz), 2.57 (1H, dd, J = 6.7, 14.7 Hz),
4.08 (2H, d, J = 5.1 Hz), 5.16 (1H, m), 6.40 (1H, br.
t, J = 5.1 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 14.1 (q), 22.7 (2xq + t), 25.0 (t), 25.3 (t), 27.5
(t), 28.0 (d), [29.2 (t), 29.4 (t), 29.55 (t), 29.5
9 (t), 29.7 (t)], 30.0 (t), 32.0 (t), 34.1 (t), 34.
6 (t), 39.1 (t), 41.3 (t), 41.4 (t), 71.2 (d), 170.
8 (s), 172.8 (s), 173.9 (s).

Example 5 N- [3- (12-methyltri)
Decanoyloxy) heptadecanoyl] glycine (example
Compound No. 1-44) According to Example 1, N- [3- (12-methyltridecanoyloxy) heptadecanoyl] glycine benzyl ester 262 mg gave 196.3 mg of the target compound having a melting point of 85 ° C-86 ° C. .

1) Molecular formula: C ₄₀ H ₆₇ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.56; H, 11.47; N, 2.53; Actual value C, 71.63; H, 11.47; N, 2.41; 3) EIMS: (m / z) 544, 538, 496, 479, 440, 398, 385, 344, 326, 251,
185, 152, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. 3349, 2955, 2923, 2851, 2607, 1746, 1721, 1623, 15
68, 1468, 1378, 1247, 1198, 1180, 935, 722, 659 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (6H, d, J = 6.6Hz), 0.88 (3H, t, J = 7.1 Hz), 1.1
6 (2H, m), 1.25 (38H, m), 1.51 (1H, m), 1.55-1.70
(4H, m), 2.31 (2H, t, J = 7.1 Hz), 2.52 (1H, dd, J = 5.
5, 14.7 Hz), 2.56 (1H, dd, J = 6.7, 14.7 Hz), 4.07 (2
H, d, J = 5.1 Hz), 5.16 (1H, m), 6.42 (1H, br.t) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Tetramethylsilane in deuterated chloroform as internal standard The nuclear magnetic resonance spectrum (100 MHz) measured by using is as shown below. 14.1 (q), 22.7 (2xq), 25.0 (t), 25.2 (t), 25.3
(t), 27.5 (t), 28.0 (d), [29.1 (t), 29.4 (t), 29.6
(t), 29.7 (t)], 30.0 (t), 32.0 (2xt), 34.1 (t), 34.
6 (t), 39.1 (t), 41.3 (t), 41.4 (t), 71.2 (d), 170.
8 (s), 172.7 (s), 173.9 (s).

Example 6 N-3- (14-methylpenta
Decanoyloxy) Heptadecanoylglycine (illustrated
Compound No. 1-46) According to Example 1, from N-3- (14-methylpentadecanoyloxy) heptadecanoylglycine benzyl ester 204 mg, 149.3 mg having a melting point of 96 ° C-97 ° C was obtained.

1) Molecular formula: C ₃₅ H ₆₉ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 72.24; H, 11.61; N, 2.41; Actual value C, 71.87; H, 11.90; N, 2.39; 3) EIMS: (m / z) 582, 581, 326, 325, 251, 250, 213, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is It is as shown below. 3349, 2955, 2921, 2851, 2611, 1745, 1722, 1623, 15
68, 1468, 1418, 1378, 1343, 1248, 1200, 1178, 721 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (6H, d, J = 6.6 Hz), 0.88 (3H, t, J = 6.8 Hz), 1.
1-1.2 (2H, m), 1.25 (52H, br.s), 1.51 (1H, m), 1.55
-1.70 (4H, m), 2.31 (2H, t, J = 7.6 Hz), 2.52 (1H, d
d, J = 5.3, 14.7 Hz), 2.57 (1H, dd, J = 6.7, 14.7 Hz),
4.08 (2H, d, J = 5.0 Hz), 5.16 (1H, m), 6.40 (1H, br.
t, J = 5.0 Hz). 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as follows. As shown in. 14.1 (q), 22.7 (2xq + t), 25.0 (t), 25.3 (t), 27.5
(t), 28.0 (d), [29.2 (t), 29.4 (t), 29.6 (t), 29.7
(t)], 30.0 (t), 32.0 (t), 34.1 (t), 34.6 (t), 39.1
(t), 41.4 (t), 41.5 (t), 71.2 (d), 170.8 (s), 172.8
(s), 173.9 (s).

Example 7 N-3- (14-methylpenta
Decanoyloxy) hexadecanoylglycine (illustrated
Compound No. 1-34) According to Example 1, 130 mg of the target compound having a melting point of 95 ° C-96 ° C was obtained from 150 mg of N-3- (14-methylpentadecanoyloxy) hexadecanoylglycine benzyl ester.

1) Molecular formula: C ₃₄ H ₆₇ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.91; H, 11.54; N, 2.47; Actual value C, 71.40; H, 11.45; N, 2.42; 3) EIMS: (m / z) 568, 567, 312, 311, 256, 237, 213, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is It is as shown below. 3349, 2956, 2921, 2851, 2611, 1746, 1721, 1623, 15
68, 1468, 1419, 1378, 1344, 1247, 1200, 1178, 722,
657 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. 0.88 (3H, t, J = 7.1Hz), 1.25 (50H, br.s), 1.55-1.70
(4H, m), 2.31 (2H, t, J = 7.4 Hz), 2.52 (1H, dd, J =
5.4, 14.7 Hz), 2.55 (1H, dd, J = 6.8, 14.7 Hz), 4.08
(2H, d, J = 5.1 Hz), 5.16 (1H, m), 6.41 (1H, br.t, J =
5.1 Hz). 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. is there. 14.1 (q), 22.7 (2xq + t), 25.0 (t), 25.3 (t), [29.2
(t), 29.4 (t), 29.6 (t), 29.7 (t)], 30.0 (t), 32.0
(2xt), 34.1 (t), 34.6 (t), 39.1 (t), 41.3 (t), 41.5
(t), 71.2 (d), 170.8 (s), 172.8 (s), 173.9 (s).

Example 8 N- (13-methyl-3-teto
Radecanoyloxy) hexadecanoylglycine (example
Compound No. 1-33) According to Example 1, 90 mg of N- (13-methyl-3-tetradecanoyloxyhexadecanoyl) glycine benzyl ester gave 66.7 mg having a melting point of 89 ° C-90 ° C.

1) Molecular formula: C ₃₃ H ₆₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.56; H, 11.47; N, 2.53; Actual value C, 71.22; H, 11.67; N, 2.56; 3) EIMS: (m / z) 554, 553, 326, 325, 251, 250, 228, 185, 117, 76 4) Infrared absorption spectrum: ν _max cm ^-1 Infrared absorption spectrum measured by potassium bromide tablet method Is as shown below. 3348, 2956, 2921, 2851, 2605, 1746, 1722, 1622, 15
68, 1468, 1419, 1379, 1344, 1249, 1199, 1178, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (12H, d, J = 6.7 Hz), 0.88 (3H, t, J = 6.7 Hz),
1.1-1.2 (2H, m), 1.25 (28H, br.s), 1.51 (1H, m), 1.
55-1.70 (4H, m), 2.31 (2H, t, J = 7.4 Hz), 2.52 (1H,
dd, J = 5.6, 14.7 Hz), 2.56 (1H, dd, J = 6.7, 14.7 Hz),
4.08 (2H, d, J = 5.3 Hz), 5.16 (1H, m), 6.40 (1H, b
rt, J = 5.1 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 14.1 (q), 22.7 (2xq, t), 25.0 (t), 25.3 (t), 27.5
(t), 28.0 (d), [29.2 (t), 29.4 (t), 29.5 (t), 29.6
(t), 29.7 (t)], 30.0 (t), 32.0 (t), 34.2 (t), 34.6
(t), 39.1 (t), 41.38 (t), 41.43 (t), 71.2 (d), 170.7
(s), 172.7 (s), 173.9 (s).

Example 9 N- [3- (14-methylpen
Tadecanoyloxy) tetradecanoyl] glycine (eg
Compound No. 1-22) According to Example 1, N- [3- (14-methylpentadecanoyloxy) tetradecanoyl] glycine benzyl ester 370 mg, melting point 97.5 ° C-98 ° C.
275.2 mg of the target compound having a

1) Molecular formula: C ₃₁ H ₅₉ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 70.80; H, 11.34; N, 2.66; Actual value C, 70.75; H, 11.48; N, 2.66; 3) EIMS: (m / z) 526, 525, 451, 356, 343, 284, 283, 209, 208, 117,
76 4) Infrared absorption spectrum: ν _max cm ^{−1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. 3348, 2956, 2921, 2851, 2608, 1746, 1722, 1622, 15
68, 1468, 1250, 1190, 1177, 938, 722, 657 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured by using tetramethylsilane as an internal standard in deuterated chloroform. (400 MHz) is as shown below. 0.86 (6H, d, J = 6.6 Hz), 0.88 (3H, t, J = 6.8 Hz), 1.
15 (2H, m), 1.26 (38H, br.s), 1.51 (1H, m), 1.55-1.
70 (4H, m), 2.31 (2H, t, J = 7.6 Hz), 2.52 (1H, dd, J
= 5.2, 14.7 Hz), 2.56 (1H, dd, J = 6.7, 14.7 Hz), 4.08
(2H, d, J = 5.1 Hz), 5.16 (1H, m), 6.42 (1H, br.s)
.

6) ¹³ C-nuclear magnetic resonance spectrum: (δ;
ppm) Nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. 14.1 (q), 22.7 (2xq + t), 25.0 (t), 25.3 (t), 27.5
(t), 28.0 (d), [29.2 (t), 29.4 (t), 29.54 (t), 29.5
9 (t), 29.7 (t)], 31.9 (t), 34.1 (t), 34.6 (t), 39.
1 (t), 41.3 (t), 41.5 (t), 71.2 (d), 170.9 (s), 17
2.8 (s), 173.9 (s).

Example 10 N- (3-hexadecanoyl
Oxy) Heptadecanoylglycine (Exemplified compound number
1-46) N- (3-hexadecanoyloxy) heptadecanoylglycine benzyl ester according to Example 1 21
From 3.8 mg, 141 mg of the target compound having a melting point of 95 ° C.-96 ° C. was obtained.

1) Molecular formula: C ₃₅ H ₆₇ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 72.24; H, 11.61; N, 2.41; Actual value C, 71.93; H, 11.80; N, 2.40; 3) EIMS: (m / z) 581, 537, 507, 398, 385, 326, 282, 251, 184, 157,
117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. 3348, 2954, 2921, 2851, 2611, 1728, 1622, 1567, 14
67, 1248, 1197,721 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (400 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 0.88 (6H, t, J = 7.2 Hz), 1.25 (48H, br.s), 1.55-1.7
0 (4H, m), 2.31 (2H, t, J = 7.5 Hz), 2.50 (1H, dd, J =
5.4, 14.8 Hz), 2.54 (1H, dd, J = 6.8, 14.8 Hz), 4.07
(2H, d, J = 5.2 Hz), 5.16 (1H, m), 6.44 (1H, br.t, J =
5.2 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.2
(t), 29.4 (t), 29.6 (t), 29.70 (t), 29.74 (t)], 32.
0 (2xt), 34.1 (t), 34.6 (t), 41.3 (t), 41.5 (t), 7
1.2 (d), 170.8 (s), 172.8 (s), 173.9 (s).

Example 11 N- (3-octadecanoyl
Oxy) Heptadecanoylglycine (Exemplified compound number
1-15) N- (3-octadecanoyloxy) heptadecanoylglycine benzyl ester according to Example 1 21
The target compound having a melting point of 96-97 ° C from 0 mg.
142.6 mg was obtained.

1) Molecular formula: C ₃₃ H ₆₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.56; H, 11.47; N, 2.53; Actual value C, 71.29; H, 11.29; N, 2.67; 3) EIMS: (m / z) 553, 342, 326, 325, 251, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. Is. 3348, 2956, 2921, 2851, 2606, 1745, 1722, 1622, 15
68, 1468, 1419, 1378, 1343, 1250, 940, 661 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum measured by using tetramethylsilane as an internal standard in deuterated chloroform. (400 MHz) is as shown below. 0.88 (6H, t, J = 7.1 Hz), 1.25 (44H, br.s), 1.55-1.7
0 (4H, m), 2.31 (2H, t, J = 7.4 Hz), 2.52 (1H, dd, J =
5.5, 14.7 Hz), 2.57 (1H, dd, J = 6.7, 14.7 Hz), 4.08
(2H, d, J = 5.2 Hz), 5.16 (1H, m), 6.42 (1H, br.t, J =
5.2 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.2
(t), 29.4 (t), 29.6 (t), 29.7 (t)], 32.0 (2xt), 34.
1 (t), 34.6 (t), 41.3 (t), 41.5 (t), 71.2 (d), 170.
8 (s), 172.8 (s), 174.0 (s).

Example 12 N- (3-dodecanoyloxy
Si) Hexadecanoylglycine (Exemplified compound number 1-
30) N- (3-dodecanoyloxy) hexadecanoylglycine benzyl ester 160 mg according to Example 1
From the object compound 11 having a melting point of 93 ° C-94 ° C.
0.5 mg was obtained.

1) Molecular formula: C ₃₁ H ₅₉ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 70.81; H, 11.31; N, 2.66; Measured value C, 70.60; H, 11.44; N, 2.69; 3) EIMS: (m / z) 523, 342, 326, 325, 251,
117, 764) Infrared absorption spectrum: infrared absorption spectrum measured by ν _max cm ^-1 potassium bromide tablet method is as shown below. 3348, 2956, 2922, 2852, 2608, 1745, 1722, 1623, 15
68, 1468, 1419, 1378, 1343, 1249, 1200, 937, 658 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.88 (6H, t, J = 7.0 Hz), 1.26 (40H, m), 1.55-1.70
(4H, m), 2.31 (2H, t, J = 7.5 Hz), 2.52 (1H, dd, J = 5.
5, 14.7 Hz), 2.57 (1H, dd, J = 6.7, 14.7 Hz), 4.07 (2
H, d, J = 5.2 Hz), 5.17 (1H, m), 6.45 (1H, br.t, J = 5.
2 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.2
(t), 29.4 (t), 29.6 (t), 29.69 (t), 29.74 (t)], 32.
0 (2xt), 34.1 (t), 34.6 (t), 41.3 (t), 41.5 (t), 7
1.2 (d), 170.9 (s), 172.8 (s), 174.0 (s).

Example 13 N- (3-decanoyloxy
H) heptadecanoylglycine (exemplary compound number 1-
15) According to Example 1, N- (3-decanoyloxy) heptadecanoylglycine benzyl ester 175 mg, the target compound 120 having a melting point 88 ° C-89 ° C.
5 mg was obtained.

1) Molecular formula: C ₂₉ H ₅₅ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 69.98; H, 11.14; N, 2.81; Actual value C, 69.74; H, 11.14; N, 2.78; 3) EIMS: (m / z) 497, 342, 326, 325, 251, 155, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as follows. As shown. 3345, 2954, 2923, 2852, 2606, 1746, 1722, 1623, 15
69, 1468, 1419, 1378, 1344, 1250, 1201, 941, 657 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.88 (6H, t, J = 7.2 Hz), 1.2-1.4 (36H, m), 1.55-1.7
0 (4H, m), 2.31 (2H, t, J = 7.5 Hz), 2.52 (1H, dd, J =
5.6, 14.7 Hz), 2.57 (1H, dd, J = 6.7, 14.7 Hz), 4.07
(2H, d, J = 5.1 Hz), 5.17 (1H, m), 6.44 (1H, br.t, J =
5.1 Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. . 14.1 (2xq), 22.7 (2xt), 25.0 (t), 25.3 (t), [29.2
(t), 29.3 (t), 29.4 (t), 29.5 (t), 29.55 (t), 29.60
(t), 29.7 (t)], 31.89 (t), 31.93 (t), 34.1 (t), 3
4.6 (t), 41.3 (t), 41.5 (t), 71.2 (d), 170.9 (s), 1
72.8 (s), 173.9 (s).

Example 14 N- [15-methyl-3- (
13-Methyl-4Z-tetradecenoyloxy) hexa
Decanoyl] glycine (Exemplified Compound No. 4-50) N- [15-methyl-3- (13-methyl-4Z-tetradecenoyloxy) hexadecanoyl] glycine t- prepared according to Production Example 5 (10). Butyl ester
1 ml of trifluoroacetic acid was added to a solution of 140 mg dissolved in 5 ml of methylene chloride, and the mixture was stirred at room temperature for 24 hours.
The crystals obtained by evaporating the solvent from the reaction mixture under reduced pressure were recrystallized from 10 to 20% methylene chloride-hexane to give the target compound 57 having a melting point of 84 ° C to 85 ° C.
mg was obtained.

1) Molecular formula: C ₃₄ H ₆₃ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 72.17; H, 11.22; N, 2.48; Measured value C, 71.93; H, 12.11; N, 2.47; 3) EIMS: (m / z) 566, 565, 345, 326, 251, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is as shown below. Is. 3348, 2956, 2922, 2851, 2604, 1747, 1715, 1621, 15
69, 1468, 1418, 1383, 1344, 1249, 1203, 1163, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (12H, d, J = 6.7 Hz), 1.1-1.2 (4H, m), 1.25 (3
4H, br.s), 1.51 (2H, m), 1.6-1.7 (2H, m), 2.03 (2H,
m), 2.3-2.4 (4H, m), 2.52 (1H, dd, J = 5.6, 14.7 H
z), 2.56 (1H, dd, J = 6.7, 14.7 Hz), 4.08 (2H, d, J =
5.2 Hz), 5.17 (1H, m), 5.2-5.5 (2H, m), 6.39 (1H, b
rt, J = 4.9Hz) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) The nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is As shown. 22.7 (4xq), 22.8 (t), 25.3 (t), 27.3 (t), 27.4
(t), 28.0 (d), [29.4 (t), 29.5 (t), 29.6 (t), 29.7
(t), 29.9 (t), 30.0 (t)], 34.1 (t), 34.5 (t), 39.1
(2xt), 41.4 (t), 71.4 (d), 127.2 (d), 131.8 (d), 17
0.7 (s), 172.7 (s), 173.2 (s).

Example 15 N- [14-methyl-3- (
13-Methyl-4Z-tetradecenoyloxy) penta
Decanoyl] Glycine (Exemplified Compound No. 4-49) According to Example 14, N- [14-methyl-3- (13
-Methyl-4Z-tetradecenoyloxy) pentadecanoyl] glycine t-butyl ester 93 mg, to give the target compound having a melting point of 74 ° C-76 ° C 48.3 mg.
was gotten.

1) Molecular formula: C ₃₃ H ₆₁ NO ₅ 2) Elemental analysis value: (%) Calculated value C, 71.82; H, 11.14; N, 2.54; Measured value C, 71.63; H, 11.05; N, 2.57; 3) EIMS: (m / z) 552, 551, 331, 330, 312, 237, 236, 117, 76 4) Infrared absorption spectrum: ν _max cm ^{-1 The} infrared absorption spectrum measured by the potassium bromide tablet method is It is as shown below. 3347, 2955, 2922, 2851, 2604, 1746, 1714, 1621, 15
70, 1467, 1420, 1383, 1343, 1250, 1191, 1163, 722 5) ¹ H-nuclear magnetic resonance spectrum: (δ; ppm) Nuclear magnetic field measured by using tetramethylsilane as an internal standard in deuterated chloroform. The resonance spectrum (400 MHz) is as shown below. 0.86 (12H, d, J = 6.6 Hz), 1.1-1.2 (4H, m), 1.25 (2
6H, br.s), 1.51 (2H, m), 1.6-1.7 (2H, m), 2.03 (2H,
m), 2.3-2.4 (4H, m), 2.52 (1H, dd, J = 5.4, 14.7 H
z), 2.56 (1H, dd, J = 6.6, 14.7 Hz), 4.08 (2H, d, J =
5.1 Hz), 5.17 (1H, m), 5.2-5.5 (2H, m), 6.39 (1H, b
rs) 6) ¹³ C-nuclear magnetic resonance spectrum: (δ; ppm) A nuclear magnetic resonance spectrum (100 MHz) measured by using tetramethylsilane as an internal standard in deuterated chloroform is as shown below. 22.7 (4xq), 22.8 (t), 25.3 (t), 27.3 (t), 27.4
(t), 28.0 (d), [29.4 (t), 29.5 (t), 29.6 (t), 29.7
(t), 29.9 (t)], 30.0 (t), 34.1 (t), 34.5 (t), 39.1
(t), 41.4 (tx2), 71.4 (d), 127.2 (d), 131.8 (d), 17
0.7 (s), 172.7 (s), 173.2 (s).

Test Example 1 N-type calcium channel production
In order to examine the selectivity of the thus obtained inhibitor, the action on N-type calcium channel was measured.

Activity on N-type calcium channels
[ ¹²⁵ I] ω-, a measured N-type calcium channel agonist
Using the inhibitory effect of conotoxin GVIA (manufactured by Amersham Co., Ltd.) on the binding to the guinea pig brain membrane fraction as an index, the effect on the N-type calcium channel of the sample was determined by the method of Abe et al. (Neuroscience Letters, Vol. 71, 203-20).
8 (1986)).

That is, 0.1 mM phenyl-methylsulfonyl fluoride was added to the cerebral cortex derived from a male guinea pig (HARTREY system).
(PMSF) in 20 mM sodium bicarbonate buffer (pH
7.2), homogenize in ice-cold, then at 4000 × g 4
Centrifuge for 15 minutes at ℃. The precipitate was suspended in a 20 mM Tris-HCl buffer solution (pH 7.2) containing 0.1 mM PMSF, and similarly centrifuged and washed. The obtained membrane fraction was suspended in the same buffer. 0.1% B of sample and membrane fraction (2 μg protein / tube)
After pre-incubation in 20 mM Tris-HCl buffer (pH 7.2) containing SA and 1 mM EDTA at 4 ° C for 10 minutes, add 20 pM [ ¹²⁵ I] ω-conotoxin GVIA (Amersham Co.) at 4 ° C. Incubated for 1 hour. The reaction volume was 200 μl. This is 0.3
% Polyethylenimine (manufactured by Sigma) treated with a GF / C glass filter (manufactured by Whatman) for rapid suction filtration and membrane-bound [ ¹²⁵ I] ω-conotoxin GVIA (manufactured by Amersham) )
Radioactivity was measured with a γ-counter.

Activity on L-type calcium channels
Measuring a L- type calcium channel agonist ^[3 H] PN200-
The action of 110 on the L-type calcium channel of the sample was measured using the binding of 110 to the rabbit skeletal muscle cell membrane (T-tube membrane) preparation as an index. The preparation of T-tube membrane preparation was performed by Glossmann et al. (Methods in Enzymology, Vol. 109, 513-55).
0 (1985)).

That is, about 300 g of skeletal muscle of the back and legs of a male rabbit (Japanese-white) contained 0.1 μM PMSF.
Ice-cold 20 mM sodium hydrogen carbonate buffer was added, homogenized with Polytron, and centrifuged at 1500 xg at 4 ° C for 15 minutes. Filter the supernatant through gauze and incubate at 48000 xg at 4 ° C.
Centrifuge for 5 minutes. The obtained precipitate is 0.25 M sucrose, 0.1
Resuspend in 50 mM Tris-HCl buffer (pH 7.4) containing μM PMSF, add 30%, 20% (W / W) sucrose and 0.1 μM.
Overlaid on a discontinuous sucrose density gradient consisting of 50 mM Tris-HCl buffer (pH 7.4) containing M PMSF. 100000 x g
After centrifugation at 4 ° C for 17 hours, the white band at each interface was collected. Add this to 50 mM Tris-HCl containing 0.1 μM PMSF.
Dilute with buffer solution (pH 7.4), 100,000 × g, 30 ° C at 4 ° C
Centrifuge for minutes. Precipitate 0.25 M sucrose, 0.1 μM PMSF
It was resuspended in 50 mM Tris-HCl buffer (pH 7.4) containing Sample, membrane fraction (2 μg protein / tube), 5 nM [ ³ H] PN200-110 containing 2 mM calcium chloride 50 m
Incubation was performed in M Tris-HCl buffer (pH 7.4) at 4 ° C for 1 hour. The reaction volume was 200 μl. [
^The membrane fraction bound to ³ H] PN200-110 was subjected to rapid suction filtration using a GF / C glass filter (manufactured by Whatman Co., Ltd.).
After adding 300 μl of% Triton X-100 and allowing it to stand overnight, the radioactivity was measured with a liquid scintillation counter.

All of the inhibitory activity samples were used after being dissolved in ethanol. The final ethanol concentration in the reaction system was 0.5% or less.

Among the compounds of the present invention, compounds having excellent inhibitory activity are shown below.

[0131]

[Table 5] N-type and L-type calcium channel inhibitory activity of each compound ───────────────────────────────── ─── Example N-type L-type number Calcium channel Calcium channel Inhibitory activity Inhibitory activity (IC ₅₀ : μM) ───────────────────────── ─────────── Example 1 5.1> 100 Example 14 4.0> 100 Example 15 2.5> 100 Example 3 4.0> 100 Example 5 4.7> 100 ─────────────────────────────────── The compounds of the present invention are selective for N-type calcium channels. It worked.

Formulation Example 1 Oral Capsule Formulation Compound of Example 14 40 mg Lactose 160 mg Corn Starch 148.8 mg Magnesium Stearate 1.2 mg ──────────────── ─────────────── 350 mg The powders of the above formulation were mixed, passed through a 30 mesh sieve, and 350 mg of this powder was put into a gelatin capsule.
It was used as a capsule.

[0133]

INDUSTRIAL APPLICABILITY The compound having the general formula (I) or a salt thereof of the present invention is a preventive or therapeutic drug for mental illness (eg depression), epilepsy, cerebral infarction, migraine, analgesia, Parkinson's syndrome and the like. Is useful as

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C07C 235/12 9547-4H C07C 235/12 235/28 9547-4H 235/28 (72) Inventor Toda Ichiro Oda 1-258, Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Keiichi Matsuda 1-2-2 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd.

Claims (11)

[Claims] 1. The formula R ¹ CH (OCOR ² ) CH ₂ CONHCH ₂ CO ₂ H (I) (wherein R ¹ and R ² are the same or different and are straight-chain or having 1 to 19 carbon atoms) N- (3 having a branched alkyl group or a linear or branched alkenyl group having 2 to 19 carbon atoms).
-Acyloxyacyl) N-type calcium channel inhibitors containing a glycine derivative or a salt thereof as an active ingredient. 2. A linear or branched alkyl group having 10 to 16 carbon atoms or a straight chain having 10 to 16 carbon atoms, wherein R ¹ and R ² are the same or different. An N-type calcium channel inhibitor comprising an N- (3-acyloxyacyl) glycine derivative, which is a chain or branched alkenyl group, or a salt thereof as an active ingredient. 3. The method according to claim 1 or 2, wherein R ¹ and R ² are the same or different and have 13 to 15 carbon atoms.
N- (3-acyloxyacyl) glycine derivative which is a straight-chain or branched-chain alkyl group having 13 or a straight-chain or branched alkenyl group having 13 to 15 carbon atoms, or a salt thereof An N-type calcium channel inhibitor containing as an active ingredient. 4. The therapeutic agent according to claim 1, 2, or 3, wherein the N-type calcium channel inhibitor is a therapeutic agent for cerebral infarction disease. 5. The therapeutic agent according to claim 1, 2, or 3, wherein the N-type calcium channel inhibitor is a therapeutic agent for migraine disease. 6. The therapeutic agent for epileptic diseases according to claim 1, 2 or 3, wherein the N-type calcium channel inhibitor is a therapeutic agent. 7. The therapeutic agent according to claim 1, 2, or 3, wherein the N-type calcium channel inhibitor is a therapeutic agent for psychotic diseases. 8. The therapeutic agent according to claim 1, 2, or 3, wherein the N-type calcium channel inhibitor is a therapeutic agent for analgesic diseases. 9. A compound represented by the formula R ¹ CH (OCOR ² ) CH ₂ CONHCH ₂ CO ₂ H (I) (wherein R ¹ and R ² are the same or different and are straight-chain or having 1 to 19 carbon atoms) N- (3 having a branched alkyl group or a linear or branched alkenyl group having 2 to 19 carbon atoms).
-Acyloxyacyl) glycine derivative or a salt thereof. However, R ¹ and R ² both exclude a 12-methyltridecanyl group. 10. A linear or branched alkyl group having 10 to 16 carbon atoms or a straight chain having 10 to 16 carbon atoms, wherein R ¹ and R ² are the same or different. A N- (3-acyloxyacyl) glycine derivative which is a chain or branched alkenyl group or a salt thereof. 11. The method according to claim 6 or 7, wherein R ¹
And R ² are the same or different and have 13 to 1 carbon atoms
N- (3-acyloxyacyl), which is a linear or branched alkyl group having 5 or a linear or branched alkenyl group having 13 to 15 carbon atoms
Glycine derivative or a salt thereof.