Hydroxylated tricyclic compounds
View Patent ↗The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water-soluble oligomer.
1. A compound of formula:
or at least one pharmaceutically acceptable salt thereof;
wherein:
n is an integer from 1 to 30;
m is an integer from 1 to 4; and
A is selected from —NHCH 3 and —N(CH 3 ) 2 .
2. The compound of claim 1 , wherein m is 2.
3. The compound of claim 2 , wherein A is —N(CH 3 ) 2 .
4. The compound of claim 3 , of the formula:
or at least one pharmaceutically acceptable salt thereof.
5. The compound of claim 3 , of the formula:
or at least one pharmaceutically acceptable salt thereof.
6. The compound of claim 4 , of the formula:
or at least one pharmaceutically acceptable salt thereof.
7. The compound of claim 4 , of the formula:
or at least one pharmaceutically acceptable salt thereof.
8. The compound of claim 4 , wherein the compound is the (E) isomer.
9. The compound of claim 4 , wherein the compound is the (Z) isomer.
10. The compound of claim 4 , wherein n is an integer from 1 to 10.
11. A compound, or at least one pharmaceutically acceptable salt thereof, selected from:
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 4 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 1 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 2 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 6 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 8 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 4 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 6 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 8 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 4 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 6 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
(R)-5-(3-dimethylamino-propylidene)-10-OmPEG 8 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 4 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 6 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
(S)-5-(3-dimethylamino-propylidene)-10-OmPEG 8 -10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-ene;
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-en-2-OmPEG 4 ;
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-en-2-OmPEG 4 ;
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-en-2-OmPEG 6 ;
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-en-2-OmPEG 6 ;
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-E-en-2-OmPEG 8 ; and
5-(3-Dimethylamino-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohept-Z-en-2-OmPEG 8 .
12. A composition comprising a compound of claim 1 , and optionally, a pharmaceutically acceptable excipient.
13. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.
14. The compound of claim 5 , wherein the compound is the (E) isomer.
15. The compound of claim 5 , wherein the compound is the (Z) isomer.
16. The compound of claim 5 , wherein n is an integer from 1 to 10.
17. A composition comprising a compound of claim 11 , and optionally, a pharmaceutically acceptable excipient.
18. A composition of matter comprising a compound of claim 11 , wherein the compound is present in a dosage form.