# US 5,703,078 A · Antiparasitic marcfortines and paraherquamides

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

- Number: US 5,703,078 A
- Document ID: US5703078A
- Status: Granted
- Kind: A
- Application number: 08/670,306
- Filed: 1996-06-27
- Granted: 1997-12-30
- Earliest claimed: 1996-06-27
- Assignees: Pharmacia & Upjohn Company
- Inventors: Byung H. Lee; Michael F. Clothier
- Web page: https://patentgrep.com/patent/US5703078A

## CPC

- A01N 43/90: having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
- A61P 33/00: Antiparasitic agents
- A61P 33/10: Anthelmintics
- A61P 33/14: Ectoparasiticides, e.g. scabicides
- C07D 491/22: in which the condensed system contains four 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
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention includes various substituted marcfortines of the type exemplfied by the compounds of formula ##STR1## and paraherquamides which are useful as antiparasitic agents.

## Claims

### Claim 1

15-Alkyl-14-hydroxy compounds of formula (III)
where n.sub.1 is 1 thru 3, the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

15-Alkyl-14-hydroxy compounds of formula (III) according to claim 1 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 3 (depends on 1)

15-alkyl-14-hydroxy compound of formula (III) according to claim 1 where n.sub.1 is 1.

### Claim 4

Fluoro compounds of formula (VIII) ##STR8## where n.sub.2 is 0 thru 3 the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 5 (depends on 4)

Fluoro compounds of formula (VIII) according to claim 4 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 6 (depends on 4)

A fluoro compound of formula (VIII) according to claim 4 where n.sub.2 is 0 or 1.

### Claim 7 (depends on 4)

A fluoro compound of formula (VIII) according to claim 4 where n.sub.2 is 1.

### Claim 8

15-Alkyl-16-hydroxy compounds of formula (X) ##STR9## where n.sub.1 is 0 thru 3 the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 9 (depends on 8)

15-Alkyl-16-hydroxy compounds of formula (X) according to claim 8 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 10 (depends on 8)

A 15-alkyl-16-hydroxy compound of formula (X) according to claim 8 where n.sub.1 is 0.

### Claim 11

2-Deoxo-15-alkyl compounds of formula (XXI) ##STR10## where R.sub.14 is --H or C.sub.1 -C.sub.4 alkyl and where R.sub.15 is --H or C.sub.1 -C.sub.4 alkyl the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 12 (depends on 11)

2-Deoxo-15-alkyl compounds of formula (XXI) according to claim 11 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 13 (depends on 11)

A 2-Deoxo-15-alkyl compound of formula (XXI) according to claim 11 which is 14.alpha.-hydroxy-15.alpha.-methyl-2-desoxomarcfortine A.

### Claim 14

A 2-deoxo compound of formula (XXIII) ##STR11## which is 2-desoxomarcfortine A and pharmaceutically acceptable salts thereof.

### Claim 15

14-Hydroxy-2-deoxoparaherquamide B and 14-hydroxy-2-desoxomarcfortine compounds of formula (XXV) ##STR12## where n.sub.3 is 2; where R.sub.14 is --H or C.sub.1 -C.sub.4 alkyl;
where R.sub.15 is --H or C.sub.1 -C.sub.4 alkyl; the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 16 (depends on 15)

A 14-hydroxy-2-deoxoparaherquamide compound of formula (XXV) according to claim 15 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 17 (depends on 15)

A 14-hydroxy-2-deoxoparaherquamide compound of formula (XXV) according to claim 15 which is 2-desoxo-14.alpha.-hydroxy-14.beta.-methylmarcfortine A.

### Claim 18

Compounds selected from the group consisting of:
14.alpha.-hydroxy-15.alpha.-vinyl-17-oxomarcfortine A,
14.alpha.-hydroxy-15.alpha.-hydroxymethyl-17-oxomarcfortine A,
15.alpha.-fluoromethyl-14.alpha.-hydroxy-17-oxomarcfortine A,
14,15-dehydro-15-methylmarcfortine A,
14.alpha.-hydroxy-16,17-dioxo-15.alpha.-methylmarcfortine A,
1.alpha. -hydroxy-16-oxo-15.alpha.-methylparaherquamide B,
16,17-dioxomarcfortine A,
16-oxoparaherquamide B (XVI),
14.alpha.-hydroxy-15.alpha.-methyl-17-oxomarcfortine.

### Claim 19

1,2-Dehydro compound of formula (XXIX) ##STR13## n.sub.3 is 2; where R.sub.14 is --H and C.sub.1 -C.sub.4 alkyl;
where R.sub.15 is --H and C.sub.1 -C.sub.4 alkyl;
where R.sub.16 is --OH, the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 20 (depends on 19)

A 1,2-dehydro compound (XXIX) according to claim 19 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 21 (depends on 19)

A 1,2-dehydro compound (XXIX) according to claim 19 which is:
1,2-dehydromarcfortine A,
1,2-dehydro-14.alpha.-hydroxy-14.beta.-methylmarcfortine A and
1,2-dehydro-14.alpha.-hydroxy-15.alpha.-methylmarcfortine A.

### Claim 22

2-Alkyl-2-desoxo compound (XXXI) ##STR14## where n.sub.3 is 2; where R.sub.14 is --H and C.sub.1 -C.sub.4 alkyl;
where R.sub.15 is --H and C.sub.1 -C.sub.4 alkyl;
where R.sub.16 is --OH;
where R.sub.18 is C.sub.1 -C.sub.4 alkyl, the N-oxides and pharmaceutically acceptable salts thereof.

### Claim 23 (depends on 22)

2-Alkyl-2-desoxo compound (XXXI) according to claim 22 where the pharmaceutically acceptable salts are salts selected from the group consisting of the acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH.sub.3 --(CH.sub.2).sub.n --COOH where n is 0 thru 4, HOOC--(CH.sub.2)n--COOH where n is as defined above.

### Claim 24 (depends on 22)

2-Alkyl-2-desoxo compound (XXXI) according to claim 22 which is 2.beta.-methyl-2-desoxomarcfortine A.