Glycine-substituted thieno[2,3-d]pyrimidines with combined LH and FSH agonistic activity
View Patent ↗The present invention resides in glycine substituted thieno[2,3-d]pyrimidine derivatives according to general formula I, or a pharmaceutically acceptable salt thereof, wherein X is O or H,H A is S, NH, N(R 6 ), O or a bond; R 1 is (1-4C)alkyl, (2-4C)alkenyl, phenyl or (2-5C)heteroaryl, the phenyl or heteroaryl ring optionally being substituted with one or more of the group of substituents: hydroxy, halogen, nitro, trifluoromethyl, cyano, amino or (1-4C)(di)alkylamino and R 2 is H, (1-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl or hydroxy(2-4C)alkyl; R 3 and R 4 can be independently selected from H and hydroxy(1-4C)alkyl; R 5 is H or (1-4C)alkyl; R 6 can be selected from the same groups as described for R 1 . The compounds of the invention have LH as well as FSH receptor activating activity and can be used in fertility regulating therapies.
1. A thieno[2,3-d]pyrimidine compound according to formula I,
or a pharmaceutically acceptable salt thereof,
wherein
X is O or H,H
A is S, NH, N(R 6 ), O or a bond;
R 1 is (1-4C)alkyl, (2-4C)alkenyl, phenyl or (2-5C)heteroaryl, the phenyl or heteroaryl ring optionally being substituted with one or more of the group of substituents: hydroxy, halogen, nitro, trifluoromethyl, cyano, amino or (1-4C)(di)alkylamino;
R 2 is H, (1-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl or hydroxy(2-4C)alkyl;
R 3 and R 4 can be independently selected from H, (1-4C)alkyl and hydroxy(1-4C)alkyl;
R 5 is H or (1-4C)alkyl, and
R 6 can be selected from the same groups as described for R 1 .
2. The compound according to claim 1 , wherein X is H,H.
3. The compound according to claim 1 , wherein R 5 is (1-4C)alkyl.
4. The compound according to claim 1 , wherein R 3 =R 4 .
5. The compound according to claim 1 , wherein R 3 =R 4 =H.
6. The compound according to claim 1 , wherein R 2 is (1-4C)alkyl.
7. A pharmaceutical composition, comprising:
the thieno[2,3-d]pyrimidine compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable auxiliary.
8. A method to treat a fertility disorders in a patients in need of luteinizing hormone and follicle stimulating hormone agonistic treatment, comprising:
administering to the patient an effective amount of the compound or pharmaceutically acceptable salt thereof according to claim 1 .
9. The method of claim 8 , wherein the fertility disorder is selected from the group consisting of hypogonadism and male infertility.
10. The method of claim 8 , wherein the fertility disorder is hypogonadism.
11. The method of claim 10 , wherein the fertility disorder is male infertility.
12. A method for treating infertility in a woman in need of treatment by ovulation induction or by controlled hyperstimulation with a luteinizing hormone and follicle stimulating hormone agonist, the method comprising administering to the woman an effective amount of the compound or pharmaceutically acceptable salt thereof according to claim 1 .