# US 5,348,966 A · Method for treating pyoderma and Sezary's syndrome using FK 506 and related compounds

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- Number: US 5,348,966 A
- Document ID: US5348966A
- Status: Granted
- Kind: A
- Application number: 08/155,533
- Filed: 1993-11-22
- Granted: 1994-09-20
- Earliest claimed: 1990-10-24
- Assignees: Fujisawa Pharmaceutical Co., Ltd.
- Inventors: Thomas E. Starzl; Satoru Todo
- Web page: https://patentgrep.com/patent/US5348966A

## CPC

- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- 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)

## Abstract

Administration of FK506 or related macrolide compounds is effective for the treatment of pyoderma and Sezary's syndrome.

## Claims

### Claim 1

A method for treating pyoderma, comprising administering, to a patient in need thereof, an effective amount of a compound of the formula (I) ##STR3## wherein each vicinal pair of substituents (R.sup.1 and R.sup.2), (R.sup.3 and R.sup.4), (R.sup.5 and R.sup.6) independently
a) represent two vicinal hydrogen atoms, or
b) form a second bond between the vicinal carbon atoms to which they are attached;
in addition to its significance above, R.sup.2 may represent an alkyl group;
R.sup.7 represents H, OH, protected hydroxy or O-alkyl, or in conjunction with R.sup.1 it may represent .dbd.O;
R.sup.8 and R.sup.9 independently represent H or OH;
R.sup.10 represents H, alkyl, alkyl substituted by one or more hydroxyl groups, alkenyl, alkenyl substituted by one or more hydroxyl groups, or alkyl substituted by .dbd.O;
X represents O, (H,OH), (H,H) or --CH.sub.2 O--;
Y represents O, (H,OH), (H,H), N--NR.sup.11 R.sup.12 or N--OR.sup.13 ;
R.sup.11 and R.sup.12 independently represent H, alkyl, aryl or tosyl;
R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.22 and R.sup.23 independently represent H or alkyl;
R.sup.20 and R.sup.21 independently represent O, or they may independently represent (R.sup.20 a,H) and (R.sup.21 a,H) respectively;
R.sup.20 a and R.sup.21 a independently represent OH, O-alkyl or OCH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or R.sup.21 a is protected hydroxy;
in addition, R.sup.20 a and R.sup.21 a may together represent an oxygen atom in an epoxide ring;
n is 1, 2 or 3;
in addition to their significances above, Y, R.sup.10 and R.sup.23, together with the carbon atoms to which they are attached, may represent a 5- or 6- membered N-, S- or O- containing heterocyclic ring, which may be saturated or unsaturated, and which may be substituted by one or more groups selected from alkyl, hydroxy, alkyl substituted by one or more hydroxyl groups, O-alkyl, benzyl and --CH.sub.2 Se(C.sub.6 H.sub.5);
and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein said compound of formula (I) is FK506.

### Claim 3 (depends on 1)

The method of claim 1, wherein said administering is oral administration.

### Claim 4 (depends on 1)

The method of claim 1, wherein said effective amount is 0.05 mg/kg of body weight/day to 1.0 mg/kg of body weight/day.

### Claim 5

A method for treating Sezary's syndrome, comprising administering, to a patient in need thereof, an effective amount of a compound of formula (I) ##STR4## wherein each vicinal pair of substituents (R.sup.1 and R.sup.2), (R.sup.3 and R.sup.4), (R.sup.5 and R.sup.6) independently
a) represent two vicinal hydrogen atoms, or
b) form a second bond between the vicinal carbon atoms to which they are attached;
in addition to its significance above, R.sup.2 may represent an alkyl group;
R.sup.7 represents H, OH, protected hydroxy or O-alkyl, or in conjunction with R.sup.1 it may represent .dbd.O;
R.sup.8 and R.sup.9 independently represent H or OH;
R.sup.10 represents H, alkyl, alkyl substituted by one or more hydroxyl groups, alkenyl, alkenyl substituted by one or more hydroxyl groups, or alkyl substituted by .dbd.O;
X represents O, (H,OH), (H,H) or --CH.sub.2 O--;
Y represents O, (H,OH), (H,H), or N--NR.sup.11 R.sup.12 or N--OR.sup.13 ;
R.sup.11 and R.sup.12 independently represent H, alkyl, aryl or tosyl;
R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.22 and R.sup.23 independently represent H or alkyl;
R.sup.20 and R.sup.21 independently represent O, or they may independently represent (R.sup.20 a,H) and (R.sup.21 a,H) respectively;
R.sup.20 a and R.sup.21 a independently represent OH, O-alkyl or OCH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or R.sup.21 a is protected hydroxy;
in addition, R.sup.20 a and R.sup.21 a may together represent an oxygen atom in an epoxide ring;
n is 1, 2 or 3;
in addition to their significances above, Y, R.sup.10 and R.sup.23, together with the carbon atoms to which they are attached, may represent a 5- or 6- membered N-, S- or O- containing heterocyclic ring, which may be saturated or unsaturated, and which may be substituted by one or more groups selected from alkyl, hydroxy, alkyl substituted by one or more hydroxyl groups, O-alkyl, benzyl and --CH.sub.2 Se(C.sub.6 H.sub.5);
and pharmaceutically acceptable salts thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein said compound of formula (I) is FK506.

### Claim 7 (depends on 5)

The method of claim 5, wherein said administering is oral administration.

### Claim 8 (depends on 5)

The method of claim 5, wherein said effective amount is 0.05 mg/kg of body weight/day to 1.0 mg/kg of body weight/day.

### Claim 9 (depends on 1, 5)

The method of claims 1 or 5, in which said compound has the following formula: ##STR5## wherein R.sup.24 is hydroxy or protected hydroxy,
R.sup.25 is hydrogen, hydroxy or protected hydroxy,
R.sup.26 is methyl, ethyl, propyl or allyl,
n' is an integer of 1 or 2, and
the symbol of a line and dotted line is a single bond or a double bond,
and pharmaceutically acceptable salts thereof.

### Claim 10 (depends on 9)

The method of claim 9, wherein
R.sup.24 is hydroxy or pharmaceutically acceptable protected hydroxy selected from 1-(lower alkylthio)(lower)-alkyloxy, tri(lower)alkylsilyloxy, lower alkyldiphenylsilyloxy, pharmaceutically acceptable organic carboxylic acyloxy, pharmaceutically acceptable organic sulfonic acyloxy, and pharmaceutically acceptable organic carbamic acyloxy, and
R.sup.25 is hydrogen or the same meanings as R.sup.24.

### Claim 11 (depends on 10)

The method of claim 10, wherein
R.sup.24 is hydroxy, C.sub.1 -C.sub.4 -alkanoyloxy which may have carboxy substituents, cyclo(C.sub.5 -C.sub.6)alkyloxy(C.sub.1 -C.sub.4)alkanoyloxy having two (C.sub.1 -C.sub.4)alkyl groups on the cycloalkyl moiety, camphorsulfonyloxy, carboxy(C.sub.1 -C.sub.4)alkylcarbamoyloxy, tri(C.sub.1 -C.sub.4)alkylsilyl(C.sub.1 -C.sub.4)alkoxycarbonyl(C.sub.1 -C.sub.4)alkylcarbamoyloxy, benzoyloxy which may have one or two nitro substituents, benzenesulfonyloxy having halogen substituents, or phenyl(C.sub.1 -C.sub.4)alkanoyloxy having C.sub.1 -C.sub.4 alkoxy and trihalo(C.sub.1 -C.sub.4)alkyl substituents, and
R.sup.25 is hydrogen, hydroxy or C.sub.1 -C.sub.4 alkanoyloxy.

### Claim 12 (depends on 11)

The method of claim 11, wherein n' is an integer of 2.

### Claim 13 (depends on 12)

The method of claim 12, wherein the symbol of a line and dotted line is a single bond.

### Claim 14 (depends on 13)

The method of claim 13, wherein R.sup.24 and R.sup.25 are each hydroxy.

### Claim 15 (depends on 1, 5)

The method of claims 1 or 5, wherein said administering is external administration.