Enhancer of fertilization function of sperm

Patent metadata

Field	Value
Publication number	US-12139459-B2
Application number	US-201915734579-A
Country	US
Kind code	B2
Filing date	Jun 4, 2019
Priority date	Jun 5, 2018
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

An object of the present invention is to provide an agent for enhancing fertilization function of a mammal sperm, which comprises a low molecular compound which can be produced relatively easily and inexpensively as an active ingredient, and a method for enhancing fertilization function of a mammal sperm and a method for preparing a mammal fertilized egg, which use a low molecular compound which can be produced relatively easily and inexpensively. An agent comprising one or more compounds selected from the group consisting of compounds of the following formula (I 0 ), formula (II), and formula (III), and physiologically acceptable salts thereof when R 3 is OH is used as an agent for enhancing fertilization function of a mammal sperm.

First claim

The invention claimed is:

1. A method for increasing fertilization rate of a mammal sperm with a mammal ovum, comprising step (a) of transferring at least one collected mammal sperm into a physiological aqueous solution containing one or more compounds selected from the group consisting of compounds of the following formula (I 0 ), formula (II), and formula (III), and physiologically acceptable salts thereof when R 3 is OH:

[wherein R 1 is a benzoylmethyl group whose benzene ring is unsubstituted or a benzoylmethyl group whose benzene ring is substituted by an alkyl group having 1 to 7 carbon atoms, an alkoxyl group having 1 to 7 carbon atoms, fluorine, and/or chlorine; an unsubstituted or fluorine-substituted linear or branched alkyl group having 4 to 6 carbon atoms; or phenyl group-or cyclopentyl group-substituted methylene or ethylene; wherein the phenyl group is optionally further substituted by one or more phenyl groups, Z 1 , Z 2 , Z 3 and Z 4 are the same or different and each is a hydrogen atom, a halogen atom, a C1 to C6 alkyl group, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, an organic oxy group represented by OR 8 , R 8 is a C1 to C7 alkyl group, a C2 to C6 alkenyl group or a C2 to C6 alkynyl group, Z 5 is a hydrogen atom or a C1 to C6 alkyl group, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms],

[wherein R 6 is hydrogen or a methyl group, X is an alkylene group having 4 to 6 carbon atoms or an ether group having 4 carbon atoms, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms], and

[wherein A is indole or naphthalene, and when A is indole, positions 3 and 5 of the indole are substituted by an acetic acid group and R 7 O, respectively, and when A is naphthalene, positions 1 and 7 of the naphthalene are substituted by an acetic acid group and R 7 O, respectively, R 7 is an alkyl group having 1 to 5 carbon atoms or a benzyl group, wherein the benzene ring of the benzyl group is optionally substituted by one or more alkyl groups having 1 to 3 carbon atoms or alkoxyl groups having 1 to 3 carbon atoms, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms].

2. The method according to claim 1 ,
wherein the compound is a compound of the following formula (I-2):

or a physiologically acceptable salt thereof.

3. A method for preparing a mammal fertilized egg, comprising step (a) of transferring at least one collected mammal sperm into a physiological aqueous solution containing one or more compounds selected from the group consisting of compounds of the following formula (I 0 ), formula (II), and formula (III), and physiologically acceptable salts thereof when R 3 is OH:

[wherein R 1 is a benzoylmethyl group whose benzene ring is unsubstituted or a benzoylmethyl group whose benzene ring is substituted by an alkyl group having 1 to 7 carbon atoms, an alkoxyl group having 1 to 7 carbon atoms, fluorine, and/or chlorine; an unsubstituted or fluorine-substituted linear or branched alkyl group having 4 to 6 carbon atoms; or phenyl group-or cyclopentyl group-substituted methylene or ethylene; wherein the phenyl group is optionally further substituted by one or more phenyl groups, Z 1 , Z 2 , Z 3 and Z 4 are the same or different and each is a hydrogen atom, a halogen atom, a C1 to C6 alkyl group, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, an organic oxy group represented by OR 8 , R 8 is a C1 to C7 alkyl group, a C2 to C6 alkenyl group or a C2 to C6 alkynyl group, Z 5 is a hydrogen atom or a C1 to C6 alkyl group, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms],

[wherein R 6 is hydrogen or a methyl group, X is an alkylene group having 4 to 6 carbon atoms or an ether group having 4 carbon atoms, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms], and

[wherein A is indole or naphthalene, and when A is indole, positions 3 and 5 of the indole are substituted by an acetic acid group and R 7 O, respectively, and when A is naphthalene, positions 1 and 7 of the naphthalene are substituted by an acetic acid group and R 7 O, respectively, R 7 is an alkyl group having 1 to 5 carbon atoms or a benzyl group, wherein the benzene ring of the benzyl group is optionally substituted by one or more alkyl groups having 1 to 3 carbon atoms or alkoxyl groups having 1 to 3 carbon atoms, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms];
and step (b-1) of culturing the mammal sperm of after step (a) in a culture medium containing at least one collected mammal ovum.

4. A method for preparing a mammal fertilized egg, comprising step (b-2) of culturing at least one collected mammal sperm and at least one collected mammal ovum in a culture medium containing one or more compounds selected from the group consisting of compounds of the following formula (I 0 ), formula (II), and formula (III), and physiologically acceptable salts thereof when R 3 is OH:

[wherein R 1 is a benzoylmethyl group whose benzene ring is unsubstituted or a benzoylmethyl group whose benzene ring is substituted by an alkyl group having 1 to 7 carbon atoms, an alkoxyl group having 1 to 7 carbon atoms, fluorine, and/or chlorine; an unsubstituted or fluorine-substituted linear or branched alkyl group having 4 to 6 carbon atoms; or phenyl group-or cyclopentyl group-substituted methylene or ethylene; wherein the phenyl group is optionally further substituted by one or more phenyl groups, Z 1 , Z 2 , Z 3 and Z 4 are the same or different and each is a hydrogen atom, a halogen atom, a C1 to C6 alkyl group, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, an organic oxy group represented by OR 8 , R 8 is a C1 to C7 alkyl group, a C2 to C6 alkenyl group or a C2 to C6 alkynyl group, Z 5 is a hydrogen atom or a C1 to C6 alkyl group, R 3 is any group selected from OH, OR 4 , NHR 4 , and NR 4 R 5 , and R 4 and R 5 are the same or different and each is a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms],

[wherein R 6 is hydrogen or a methyl group, X is an alkylene group having 4 to 6 carbon atoms or an ether group having 4 carbon atoms, R 3

Assignees

• Univ Tohoku
• Kake Educational Inst

Inventors

• Abe Takaaki
• Yaegashi Nobuo
• Tachibana Masahito
• Hayashi Kenichiro

Classifications

• C07D209/20

  substituted additionally by nitrogen atoms, e.g. tryptophane · CPC title

• C07D209/18

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C12N2501/999

  Small molecules not provided for elsewhere · CPC title

• C12N2500/30

  Organic components · CPC title