Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension

• US 6,429,226 B1
• Filed: 05/01/2000
• Issued: 08/06/2002
• Est. Priority Date: 09/06/1988
• Status: Expired due to Fees

• Current Assignee: Pharmacia AB (Pharmacia Corp.)
• Original Assignee: Pharmacia AB (Pharmacia Corp.)
• Inventors: Stjernschantz, Johan Wilhelm, Resul, Bahram
• Primary Examiner(s): Gerstl, Robert
• Application Number:
  US09/562,447
• Time in Patent Office: 827 Days
• Field of Search: 514/530, 514/570, 514/573
• US Class Current: 514/530
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/5578 having a pentalene ring system, e.g. carbacyclin, iloprost
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof

Abstract

The invention relates to ophthalmological compositions for topical treatment of glaucoma or ocular hypertension comprising an effective intraocular pressure reducing amount of a prostaglandin derivative of PGA, PGB, PGD, PGE or PGF, in which the omega chain contains a ring structure, in an ophthalmologically compatible carrier. The invention further relates to the preparation of said compositions and their use for treatment of glaucoma or ocular hypertension.

Claims

1. A therapeutic composition for topical treatment of glaucoma or ocular hypertension in humans containing a prostaglandin PGA, PGB, PGE or PGF in an amount sufficient to reduce intraocular pressure without causing substantial ocular irritation and an ophthalmologically compatible vehicle,

wherein the omega chain of the prostaglandin has the formula C₁₃—

B—

C₁₄—

D—

R₂ wherein

C is a carbon atom (the number according to standard prostaglandin nomenclature being indicated by the subscript);

B is a single bond or double bond;

D is a subchain of 3 carbon atoms, having a hydroxyl group substituent; and

R₂ is 17-phenyl which is urnsubstituted or has at least one substituent selected from the group consisting of

C₁-C₅ alkyl groups,

C₁-C₄ alkoxy groups,

trifluoromethyl groups,

C₁-C₃ aliphatic acylamino groups,

nitro groups, and

a phenyl group.

2. A method of treating glaucoma or ocular hypertension in humans by topical application of a therapeutic composition according to claim 1.

3. The therapeutic composition of claim 1, wherein B is a single bond.

4. The therapeutic composition of claim 1, wherein B is a double bond.

5. The therapeutic composition of claim 1, wherein R₂ is an unsubstituted 17-phenyl group.

6. The therapeutic composition of claim 1, wherein R₂ is a 17-phenyl group having at least one substituent selected from the group consisting of

C₁-C₅ alkyl groups,

C₁-C₄ alkoxy groups,

trifluoromethyl groups,

C₁-C₃ aliphatic acylamino groups, nitro groups, and

a phenyl group.

7. The therapeutic composition of claim 1, wherein the prostaglandin is a PGF prostaglandin.

8. The therapeutic composition of claim 1, wherein said hydroxyl group substituent is on the C₁₅ atom of the D subchain.

9. The therapeutic composition of claim 8, wherein R₂ is an unsubstituted 17-phenyl group.

10. The therapeutic composition of claim 8, wherein the prostaglandin is a PGF prostaglandin, the hydroxyl group substituent on the C₁₅ atom of the D subchain is a 15-(R) hydroxy substituent, and R₂ is an unsubstituted 17-phenyl group.

11. The therapeutic composition of claim 1, wherein said prostaglandin is 17-phenyl-18,19,20-trinor-PGF_2α

-isopropylester.

12. The therapeutic composition of claim 1, wherein said prostaglandin is 15-(R)-17-phenyl-18,19,20-trinor-PGF_2α

-isopropylester.

13. The therapeutic composition of claim 1, wherein said prostaglandin is 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF_2α

-isopropylester.

14. The therapeutic composition of claim 1, wherein said prostaglandin is 15-(R,S)-17-phenyl-18,19,20-trinor-PGF_2α

.

26. The therapeutic composition of claim 1, wherein said prostaglandin is 15-(R)-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF_2α

-isopropyl ester.

27. The therapeutic composition of claim 8, wherein the prostaglandin is a PGF prostaglandin, the hydroxyl group substituent on the C₁₅ atom of the D subchain is a 15-(S) hydroxy substituent, and R₂ is an unsubstituted 17-phenyl group.

28. The therapeutic composition of claim 9, wherein the prostaglandin is a PGF₆₀ prostaglandin and B is a double bond.

15. A therapeutic composition for topical treatment of glaucoma or ocular hypertension in humans containing a prostaglandin PGA, PGB, PGE or PGF in an amount sufficient to reduce intraocular pressure without causing substantial ocular irritation and an ophthalmologically compatible vehicle,

wherein the omega chain of the prostaglandin has the formula C₁₃—

B—

C₁₄—

D—

R₂ wherein

C is a carbon atom (the number according to standard prostaglandin nomenclature being indicated by the subscript);

B is a single bond or double bond;

D is a subchain of 2-5 carbon atoms, with a substituent at C₁₅ selected from the group consisting of hydroxyl and oxo; and

R₂ is a terminal phenyl group which is unsubstituted or has at least one substituent selected from the group consisting of

C₁-C₅ alkyl groups,

C₁-C₄ alkoxy groups,

trifluoromethyl groups,

C₁-C₃ aliphatic acylamino groups,

nitro groups, and

a phenyl group.

16. A method of treating glaucoma or ocular hypertension in humans by topical application of a therapeutic composition according to claim 15.

17. The therapeutic composition of claim 15, wherein B is a single bond.

18. The therapeutic composition of claim 15, wherein B is a double bond.

19. The therapeutic composition of claim 15, wherein D is a subchain of 3 carbon atoms and R₂ is an unsubstituted 17-phenyl group.

20. The therapeutic composition of claim 15 wherein the substituent at C₁₅ is hydroxyl.

21. The therapeutic composition of claim 15 wherein the substituent at C₁₅ is oxo.

22. The therapeutic composition of claim 19 wherein the substituent at C₁₅ is hydroxyl.

23. The therapeutic composition of claim 19 wherein the substituent at C₁₅ is oxo.

24. The therapeutic composition of claim 15, wherein D is a subchain of 3 carbon atoms and R₂ is a phenyl group having at least one substituent selected from the group consisting of

C₁-C₅ alkyl groups,

C₁-C₄ alkoxy groups,

trifluoromethyl groups,

C₁-C₃ aliphatic acylamino groups,

nitro groups, and

a phenyl group.

25. The therapeutic composition of claim 15, wherein the prostaglandin is a PGF prostaglandin.

29. A therapeutic composition for topical treatment of glaucoma or ocular hypertension in humans containing a PGF_2α

prostaglandin in an amount sufficient to reduce intraocular pressure without causing substantial ocular irritation and an ophthalmologically compatible vehicle,

wherein the omega chain of the prostaglandin has the formula C₁₃—

B—

C₁₄—

D—

R₂ wherein

C is a carbon atom (the number according to standard prostaglandin nomenclature being indicated by the subscript);

B is a double bond;

D is a subchain of 3 carbon atoms, having a hydroxyl group substituent on the C₁₅ atom of the D subchain; and

R₂ is an unsubstituted 17-phenyl group.