# US 2023/0263155 A1 · 5-(1h-indol-3-yl)-oxazole, -oxadiazole and -furan derivatives as enhancers of sperm motility

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2023/0263155 A1
- Document ID: US20230263155A1
- Status: Published application
- Kind: A1
- Application number: 17/922,405
- Filed: 2021-04-30
- Published: 2023-08-24
- Earliest claimed: 2020-04-30
- Assignees: Spermatech AS
- Applicants: Spermatech AS
- Inventors: Ken Roger ROSENDAL; Tuva Holt HERENG; Steffi LUNDVALL; Espen Marcelius GJEMS; Håvard Hildeng HAUGE; Bjørn Steen SKÅLHEGG
- Web page: https://patentgrep.com/patent/US20230263155A1

## CPC

- A01N 1/126: Physiologically active agents, e.g. antioxidants or nutrients
- A61K 31/4245: Oxadiazoles
- A61D 19/02: for artificial insemination
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61D: VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to the use of compounds of formula (I), stereoisomers, and physiologically tolerable salts thereof, to enhance the motility of sperm obtained from a non-human mammal: wherein in formula I: X is —NR′— (in which R′ is H or C1-3 alkyl, e,g, —CH3), —O—, —S— or —CH2—; Y is —S—, —O—, —NR″— (in which R″ is H or C1-3 alkyl, e.g. —CH3), or —CH2—; Z1 and Z2 are independently selected from N and CH; R1 to R3 are independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —OH, —CN, —NO2 and -NR12R13; R4 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, or —OH; R5 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkyl; R6 and R7 are independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —OH, —CN, —NO2 and -NR12R13; R8 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —CN, —NO2 or -NR12R13; R9 is hydrogen or C1-4 alkyl; R10 and R11 are independently selected from hydrogen and C1-3 alkyl; or R10 and R11, together with the intervening —O—and ring atoms, are joined to form a dioxolane ring; and R12 and R13 are independently selected from H and C1-3 alkyl. The compounds find particular use in animal husbandry to increase the rate of fertilization in artificial insemination of livestock, especially pigs. They can also be used to prepare, pre-treat or store semen for use in artificial insemination procedures.

## Claims

### Claim 1

Use of a compound of formula (I), a stereoisomer, or a physiologically tolerable salt thereof, to enhance the motility of sperm obtained from a non-human mammal:
wherein:
X is —NR′— (in which R′ is H or C1-3 alkyl, e.g. —CH3), —O—, —S— or —CH2—;
Y is —S—, —O—, —NR″— (in which R″ is H or C1-3 alkyl, e.g. —CH3), or —CH2—;
Z1 and Z2 are independently selected from N and CH;
R1 to R3 are independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —OH, —CN, —NO2 and -NR12R13;
R4 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, or —OH;
R5 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or C1-6 haloalkyl;
R6 and R7 are independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —OH, —CN, —NO2 and -NR12R13;
R8 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, —CN, —NO2 or -NR12R13;
R9 is hydrogen or C1-4 alkyl;
R10 and R11 are independently selected from hydrogen and C1-3 alkyl;
or R10 and R11, together with the intervening —O— and ring atoms, are joined to form a dioxolane ring; and
R12 and R13 are independently selected from H and C1-3 alkyl.

### Claim 2 (depends on 1)

Use as claimed in claim 1, wherein X is —NR′— (in which R′ is H or —CH3) or —O—, preferably wherein X is —NH— or —O—, e.g. —NH—.

### Claim 3 (depends on 1, 2)

Use as claimed in claim 1 or claim 2, wherein Y is selected from —S—, —O—, —NR″— (in which R″ is H or —CH3), and —CH2—, preferably wherein Y is —S—.

### Claim 4 (depends on 1)

Use as claimed in claim 1, wherein said compound is a compound of formula (II), or a stereoisomer or physiologically tolerable salt thereof:
(wherein Z1, Z2, and R1 to R11 are as defined in claim 1).

### Claim 5

Use as claimed in any one of the preceding claims, wherein both Z1 and Z2 are N, or one of Z1 and Z2 is N and the other of Z1 and Z2 is CH.

### Claim 6 (depends on 1, 2, 3, 4)

Use as claimed in any one of claims 1 to 4, wherein both Z1 and Z2 are N.

### Claim 7 (depends on 1, 2, 3)

Use as claimed in claim 1, wherein said compound is a compound of formula (III), or a stereoisomer or physiologically tolerable salt thereof:
(wherein X, Y and R1 to R11 are as defined in any one of claims 1 to 3).

### Claim 8

Use as claimed in any one of the preceding claims, wherein R1 to R3 are independently selected from hydrogen, halogen (e.g. —F, —Cl or —Br), C1-4 alkyl, and C1-4 haloalkyl (e.g. —CF3).

### Claim 9

Use as claimed in any one of the preceding claims, wherein R4 is hydrogen, halogen (e.g. —F, —Cl or —Br), C1-4 alkyl, or C1-4 haloalkyl (e.g. —CF3).

### Claim 10

Use as claimed in any one of the preceding claims, wherein R5 is hydrogen, halogen (e.g. —Cl or —Br), C1-4 alkyl, or C1-4 haloalkyl (e.g. —CF3).

### Claim 11

Use as claimed in any one of the preceding claims, wherein R6 and R7 are independently selected from hydrogen, halogen (e.g. —F, —Cl or —Br), C1-4 alkyl, and C1-4 haloalkyl (e.g. —CF3).

### Claim 12

Use as claimed in any one of the preceding claims, wherein R8 is hydrogen, halogen (e.g. —F, —Cl or —Br), C1-4 alkyl, or C1-4 haloalkyl (e.g. —CF3).

### Claim 13

Use as claimed in any one of the preceding claims, wherein R9 is hydrogen or —CH3, preferably hydrogen.

### Claim 14

Use as claimed in any one of the preceding claims, wherein R10 and R11 are independently selected from hydrogen and C1-3 alkyl (e.g. —CH3).

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

Use as claimed in any one of claims 1 to 13, wherein R10 and R11, together with the intervening —O— and ring atoms, are joined to form a dioxolane ring.

### Claim 16 (depends on 1, 2, 3, 5, 6, 8, 9, 10, 11, 12, 13)

Use as claimed in claim 1, wherein said said compound is a compound of formula (IV), or a stereoisomer or physiologically tolerable salt thereof:
(wherein Z1, Z2, X, Y and R1 to R9 are as defined in any one of claims 1 to 3, 5, 6 and 8 to 13).

### Claim 17 (depends on 1)

Use as claimed in claim 1, wherein the compound of formula (I) is:
or a stereoisomer, or physiologically tolerable salt thereof.

### Claim 18

Use as claimed in any one of the preceding claims in enhancing progressive sperm motility.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

A composition comprising a compound as defined in any one of claims 1 to 17, in combination with one or more physiologically tolerable carriers, excipients or diluents.

### Claim 20 (depends on 19)

A composition as claimed in claim 19, wherein said carriers, excipients or diluents are selected from sugars, antibiotics, proteins, membrane protecting agents, antioxidants, phospholipids, glycerol, citric acid, solvents (e.g. DMSO or water), and buffers.

### Claim 21 (depends on 19, 20)

Use of a composition as claimed in claim 19 or claim 20 to enhance the motility of sperm obtained from a non-human mammal, for example to enhance the progressive motility of said sperm.

### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20)

A method of treating or preparing sperm for use in an artificial insemination procedure, said method comprising:
(a) providing a sperm sample from a non-human mammalian male subject; and
(b) contacting said sperm sample with a compound as defined in any one of claims 1 to 17 or a composition as defined in claim 19 or claim 20.

### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20)

A method of artificial insemination, said method comprising:
(a) providing a sperm sample from a non-human mammalian male subject;
(b) contacting said sperm sample with a compound as defined in any one of claims 1 to 17 or a composition as defined in claim 19 or claim 20; and
(c) introducing the sperm sample contacted with said compound or composition into the vaginal tract of a non-human mammalian female subject.

### Claim 24 (depends on 23)

A method as claimed in claim 23, wherein the sperm sample is from a ram, bull or boar, preferably from a boar.

### Claim 25

A compound of general formula (I), or a stereoisomer or physiologically tolerable salt thereof, wherein said compound is other than:
.