Dimethyl amino ethyl ether psoralens and methods for their production and use

1. A compound of Formula (I):

wherein

R is hydrogen, NO 2 , NH 2 , halo, (C 1 -C 6 )alkoxy, cyano, (C 1 -C 6 )alkyl or triazene;

R 1 is hydrogen;

R 2 is —O—(CH 2 ) 2 N(Me) 2 ;

A-B is CH═CH;

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable vehicle.

3. A microbiocidal composition comprising a compound of claim 1 .

4. A method for preparing a pharmaceutically acceptable salt of a compound of Formula (I) comprising:

(a) contacting a solution of a compound (A)

wherein

R is hydrogen, NO 2 , NH 2 , halo, cyano, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl or triazene;

R 1 is hydrogen;

R 2 is —OH;

A-B is CH═CH;

in an organic solvent with a inorganic base;

(b) adding a solution or slurry of a dimethyl aminoethyl halide salt and refluxing the resultant mixture;

(c) isolating the compound of Formula (I) as a free base;

(d) adding a pharmaceutically acceptable acid to form an acid addition salt of the free base; and

(e) isolating the resultant pharmaceutically acceptable salt of the compound of formula (I).

5. A method for preparing a compound of formula (I) comprising:

a) dissolving a compound of formula (A):

wherein

R is hydrogen, NO 2 , NH 2 , halo, cyano, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl or triazene;

R 1 is hydrogen;

R 2 is —OH;

A-B is CH═CH;

in acetone containing a suspension of K 2 CO 3

b) adding 2-(N,N-dimethylamino)ethyl chloride hydrochloride salt in an organic solvent to the resultant mixture of step (a);

c) stirring the resultant mixture from step (b) at reflux;

(d) removing the organic solvent from the refluxed mixture of step (c) to produce a solid comprising the compound of Formula (I);

(e) contacting the solid with heated water and hot-filtering the resultant contacted heated solid;

(f) extracting the heat-treated solid that has been hot-filtered of step (e) with chloroform;

(g) drying the extracted solid of step (f) to an oil; and

(h) precipitating the compound of Formula (I) from the oil.

6. A method for preparing a pharmaceutically acceptable salt of the compound of formula (I) comprising:

(a) mixing a compound of Formula (A)

wherein

R is hydrogen, NO 2 , NH 2 , halo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl or triazene;

R 1 is hydrogen;

R 2 is —OH;

A-B is CH═CH;

with solid NaOH;

(b) dissolving the resultant mixture of step (a) in an organic solvent;

(c) adding 2-(N,N-dimethylamino) ethyl chloride hydrochloride salt in an organic solvent to the resultant solution of step (b);

(d) stirring the resultant mixture of step (c) at reflux;

(e) filtering the stirred mixture of step(d) while hot;

(f) evaporating the resultant filtrate of step (e) to an oil; and

(g) reconstituting the oil of step (f) with an organic solvent and bubbling the resultant reconstituted oil with HCI gas to form a precipitate of a hydrochloride salt of the compound of claim 1 .

7. A method for treating a proliferative skin disorder in a mammal comprising administering to the mammal an effective amount of a compound of claim 1 and irradiating the mammal with ultraviolet light.

8. The method of claim 7 wherein the compound is administered topically, parenterally or orally.

9. A method for treating a microbial infection in a mammal comprising administering to the mammal an effective amount of a compound of claim 1 and irradiating the mammal with ultraviolet light.

10. The method of claim 9 wherein the compound is administered topically, parenterally or orally.

11. A method for treating a disease of blood or bone marrow in a mammal comprising:

(a) obtaining cells from blood or bone marrow of a mammal;

(b) introducing to the obtained cells in vitro a compound of claim 1 ;

(c) exposing the cells to ultraviolet radiation; and

(d) returning the cells to the blood or bone marrow.

12. A method for treating a disease of blood or bone marrow in a mammal comprising:

(a) administering to a mammal a compound of claim 1 ;

(b) removing cells of blood or bone marrow from the mammal;

(c) irradiating ex-vivo the removed blood or bone marrow cells; and

(d) returning the irradiated cells to the mammal.

13. A method for sterilizing blood or a blood product comprising contacting the blood or blood product with a compound of claim 1 and irradiating the blood or blood product to activate the compound in the blood or product so that microorganisms in the blood or blood product are killed.

14. A method for sterilizing a surgical implant or catheter comprising contacting the surgical implant or catheter with a compound of claim 1 and irradiating the surgical implant or catheter to activate the compound on the surgical implant or catheter so that microorganisms on the surgical implant or catheter are killed.

15. A method for controlling growth of a microorganism on a substrate comprising contacting the substrate with the microbiocidal composition of claim 3 and irradiating the substrate to activate the compound in the composition so that growth of the microorganism on the substrate is controlled.