# US 5,705,528 A · Farnesyl derivatives and pharmaceutical compositions containing them

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

- Number: US 5,705,528 A
- Document ID: US5705528A
- Status: Granted
- Kind: A
- Application number: 08/338,764
- Filed: 1994-11-10
- Granted: 1998-01-06
- Earliest claimed: 1993-11-12
- Assignees: Ramot University Authority for Applied Research and Industrial Development Ltd.
- Inventors: Yoel Kloog
- Web page: https://patentgrep.com/patent/US5705528A

## CPC

- C07D 213/79: Acids; Esters
- A61P 3/06: Antihyperlipidemics
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 229/60: with amino and carboxyl groups bound in meta- or para- positions
- C07C 323/62: having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Novel farnesyl derivatives which are inhibitors of the prenylated protein thyltransferase enzyme, and useful as anti-cancer drugs, have the following formula: ##STR1## wherein R.sup.1 represents farnesyl, geranyl or geranyl-geranyl; Z represents C--R.sup.6 or N; R.sup.2 represents H, CN, the groups COOR.sup.7, SO.sub.3 R.sup.7, CONR.sup.7 R.sup.8 and SO.sub.2 NR.sup.7 R.sup.7, wherein R.sup.7 and R.sup.8 are each independently hydrogen, alkyl, alkenyl, and the groups COOM and SO.sub.3 M, wherein M is a cation; R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently hydrogen, carboxyl, alkyl, alkenyl, aminoalkyl, nitroalkyl, nitro, halo, amino, mono- or di-alkylamino, mercapto, mercaptoalkyl, azido, or thiocyanato; X represents O, S, SO, SO.sub.2, NH or Se; and the quaternary ammonium salts and N-oxides of the compounds of formula I wherein Z is N.

## Claims

### Claim 1

A compound of the formula: ##STR6## wherein R.sup.1 represents farnesyl, geranyl or geranyl-geranyl;
Z represents C--R.sup.6 ;
R.sup.2 represents H, CN, the groups COOR.sup.7, SO.sub.3 R.sup.7, CONR.sup.7 R.sup.8 and SO.sub.2 NR.sup.7 R.sup.8, wherein R.sup.7 and R.sup.8 are each independently hydrogen, alkyl, alkenyl, and the groups COOM and SO.sub.3 M, wherein M is a cation;
R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently hydrogen, carboxyl, alkyl, alkenyl, aminoalkyl, nitro, halo, amino, mono- or di-alkylamino, or mercapto, alkylthio and wherein only one of R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are other than hydrogen, alkyl, or halogen;
X represents O, S, SO, SO.sub.2, or NH; and
when R.sup.1 is geranyl, X is O, R.sup.2 is H and two of R.sup.3, R.sup.4 and R.sup.5 are each H, then the third one is not alkyl, alkylthio or F;
when R.sup.1 is geranyl, X is SO.sub.2 and R.sup.2 and two of R.sup.3, R.sup.4 and R.sup.5 are each H then the third is not alkyl; and
when R.sup.1 is farnesyl and either X is O and R.sup.4 is NH or OH or X is S, SO, SO.sup.2 or NH and R.sup.4 is OH and at least one of R.sup.2, R.sup.3 and R.sup.5 is different from hydrogen, alkyl or halogen.

### Claim 2 (depends on 1)

A compound according to claim 1 having the formula: ##STR7##

### Claim 3 (depends on 1)

A compound according to claim 1 having the formula ##STR8##

### Claim 4 (depends on 2)

A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 2 together with a pharmaceutically acceptable carrier.

### Claim 5 (depends on 3)

A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 3 together with a pharmaceutically acceptable carrier.

### Claim 6

A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of the formula: ##STR9## wherein R.sup.1 represents farnesyl, geranyl or geranyl-geranyl;
R.sup.2 represents H, CN, CO.sub.2 M and SO.sub.3 M, wherein M is a cation, CO.sub.2 R.sup.7, SO.sub.3 R.sup.7, CONR.sup.7 R.sup.8 and SO.sub.2 NR.sup.7 R.sup.8, wherein R.sup.7 and R.sup.8 are independently hydrogen, alkyl, alkenyl; and
R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently hydrogen, alkyl, alkenyl, aminoalkyl, nitro, halo, amino, mono- or di-alkylamino, mercapto, or alkylthio and wherein only one of R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are other than hydrogen, alkyl, or halogen;
X represents O, S, SO, SO.sub.2, or NH; and
when R.sup.1 is farnesyl and either X is O and R.sup.4 is NH.sub.2 or OH or X is S, SO, SO.sub.2 or NH and R.sup.4 is OH and then at least one of R.sup.2, R.sup.3 and R.sup.5 is different from hydrogen alkyl or halogen together with a pharmaceutically acceptable carrier.