# US 5,352,671 A · Heteroatoms-containing tricyclic compounds

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- Number: US 5,352,671 A
- Document ID: US5352671A
- Status: Granted
- Kind: A
- Application number: 07/697,864
- Filed: 1991-05-09
- Granted: 1994-10-04
- Earliest claimed: 1989-11-09
- Assignees: Sandoz Ltd.
- Inventors: Karl Baumann; Gerhart Emmer
- Web page: https://patentgrep.com/patent/US5352671A

## CPC

- C07D 498/18: Bridged systems
- C07H 19/01: sharing oxygen
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

The invention concerns the compounds of formula I ##STR1## wherein the substituents have various significances. They are prepared by several processes including epimerizing replacement, treatment with cyanogen bromide or thiophosgene, treatment with an acid having a non-nucleophilic anion, treatment with dimethylsulfoxide and acetic anhydride, acylation, treatment with an oxalyl derivative and ammonia, methylation, oxidation, deprotection and protection. They possess interesting pharmacological activity as antiinflammatory, immunosuppressant, antiproliferative and chemotherapeutic drug resistance reversing agents.

## Claims

### Claim 1

A compound of formula ##STR10## wherein R.sub.1 is a group (d) of formula ##STR11## R.sub.2 is oxo and there is a single bond n 23,24 position; hydroxy or hydroxy protected by a hydroxy protecting group selected from formyl, tert-butoxycarbonyl, and trialkylsilyl and there is a single or a double bond in 23,24 position; or absent and there is a double bond in 23,24 position; and
R.sub.4 is hydroxy and there is a single bond in 10,11 position;
R.sub.3 is methyl, ethyl, n-propyl, or allyl;
in free form or, where such forms exist, in salt form.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein
R.sub.2 is hydroxy or hydroxy protected by a hydroxy protecting group selected from formyl, tert-butoxycarbonyl, and tert-butyldimethyl-silyl and there is a single bond in 23,24 position; or absent and there is a double bond in 23,24 position;
R.sub.4 is hydroxy and there is a single bond in 10,11 position; and
R.sub.3 is as defined in claim 1;
in free form or, where such forms exist, in salt form.

### Claim 3 (depends on 1)

The compound of claim 1 in which R.sub.4 is OH and position 10,11 is a single bond and R.sub.2, R.sub.3, and position 23,24 are a) OH, allyl, and single bond; or b) absent, Et, and double bond.

### Claim 4 (depends on 1)

A compound according to claim 1 in which
R.sub.2 is hydroxy or hydroxy protected by tert-butyldimethylsilyloxy and there is a single bond in 23,24 position; or absent an there is a double bond in 23,24 position;
R.sub.4 is hydroxy and there is a single bond in 10,11 position; and
R.sub.3 is ethyl or allyl;
in free form or, where such forms exist, in salt form.

### Claim 5 (depends on 1)

The compound according to claim 1 which is 29-des-(4-hydroxy-3-methoxycyclohexyl)-29-(3-formylcyclopentyl) -FR 520.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 in free base form or, where such forms exist, in pharmaceutically acceptable salt form, together with a pharmaceutically acceptable carrier therefor.

### Claim 7 (depends on 1)

A method of treating inflammation or inducing immunosuppression or inhibiting cell proliferation or reversing chemotherapeutic drug resistance, which comprises administering to a patient in need of said treatment a therapeutically effective amount of a compound according to claim 1 in free base form or, where such forms exist, in pharmaceutically acceptable salt form.

### Claim 8

A compound of formula I ##STR12## wherein R.sub.1 is a group (b) ##STR13## wherein R.sub.6 is hydroxy or methoxy; R.sub.2 is oxo and there is a single bond in 23,24 position; hydroxy or hydroxy protected by a hydroxy protecting group selected from formyl, tert-butoxycarbonyl, and trialkylsilyl and there is a single or a double bond 23,24 position; or absent and there is a double bond in 23,24 position;
R.sub.4 is hydroxy and there is a single bond in 10,11 position; and
R.sub.3 is methyl, ethyl, n-propyl, or allyl;
in free form or, where such forms exist, in salt form.

### Claim 9 (depends on 8)

A compound according to claim 8 wherein
R.sub.6 is methoxy;
R.sub.2 is hydroxy or hydroxy protected by a hydroxy protecting group selected from formyl, tert-butoxycarbonyl, and tert-butyldimethyl silyl silyloxy and there is a single bond in 23,24 position; or absent and there is a double bond in 23,24 position;
R.sub.4 is hydroxy and there is a single bond in 10,11 position; and
R.sub.3 is as defined in claim 8,
in free form or, where such forms exist, in salt form.

### Claim 10 (depends on 8)

The compound of claim 8 in which R.sub.4 is OH, R.sub.6 is OMe, and position 10,11 is a single bond and R.sub.2, R.sub.3, and position 23,24 are a) OtBDMS, Et and single bond; b) OtBDMS, allyl, and single bond; c) OH, Et, and single bond; d) absent, Et and double bond; e) OH, allyl, and single bond; or f) absent, allyl, and double bond.

### Claim 11 (depends on 8)

A compound according to claim 8 in which
R.sub.6 is methoxy;
R.sub.2 is hydroxy protected by tert-butyldimethylsilyloxy and there is a single bond in 23,24 position; or absent and there is a double bond in 23,24 position;
R.sub.4 is hydroxy and there is a single bond in 10,11 position; and
R.sub.3 is ethyl or allyl;
in free form or, where such forms exist, in salt form.

### Claim 12 (depends on 8)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 8 in free form or, where such forms exist, in pharmaceutically acceptable salt form, together with a pharmaceutically acceptable carrier or diluent.

### Claim 13 (depends on 8)

A method of treating inflammation or inducing immunosuppression or inhibiting cell proliferation or reversing chemotherapeutic drug resistance, which comprises administering to a patient in need of said treatment a therapeutically effective amount of a compound according to claim 8 in free base form or, where such forms exist, in pharmaceutically acceptable salt form.