Compounds with sulphonamide group and pharmaceutical compositions containing these compounds

• US 7,507,725 B2
• Filed: 05/08/2001
• Issued: 03/24/2009
• Est. Priority Date: 05/31/2000
• Status: Expired due to Fees

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Hillisch, Alexander, Schwarz, Sigfrid, Elger, Walter, Schollkopf, Klaus, Hedden, Annemarie
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/296,973
• Publication Number:
  US 20040014781A1
• Time in Patent Office: 2,877 Days
• Field of Search: 424/1.11, 424/1.65, 424/9.1, 424/9.2, 514/176, 514/182, 552/617, 552/625
• US Class Current: 514/182
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07J 41/0038 with an androstane skeleton, including 18- or 19-substituted derivatives, 18-nor derivatives and also derivatives where position 17-beta is substituted by a carbon atom not directly bonded to a further carbon atom and not being part of an amide group
• CPC Class Codes: C07J 41/0044 with an estrane or gonane skeleton, including 18-substituted derivatives and derivatives where position 17-beta is substituted by a carbon atom not directly bonded to another carbon atom and not being part of an amide group
• CPC Class Codes: C07J 41/005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to compounds which, acting as a prodrug and/or support, enable an active agent to be taken up by the erythrocytes and/or an active agent to bind to the erythrocytes. The uptake of these compounds by and/or the binding thereof to the erythrocytes is made possible by a group of formula —SO2NR1R2, wherein R1 and R2, independently of each other, mean a hydrogen atom, an acyl group, an alkyl group, a cycloalkyl group, an aryl group, a cyano group or a hydroxy group. The inventive prodrugs enable active agents such as endogenic substances, natural substances and synthetic substances with therapeutically useful properties which have a high “first path” effect, to be administered orally effectively or significantly improve the oral activity thereof.

Claims

1. A prodrug of the following formula

Active ingredient - Spacer SO₂NH₂

in which - SO₂NH₂ enhances uptake of said active ingredient with an erythrocyte,

wherein

the spacer is

3. A prodrug according to claim 1, wherein the active ingredient is estradiol.

4. A depot forming pharmaceutical composition comprising a prodrug according to claim 1 and a pharmaceutically acceptable carrier.

5. A prodrug according to claim 1, wherein the active ingredient is estriol.

6. A prodrug according to claim 1, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group, a naphthylene group, pyridine, furan, thiophene, pyrrole, imidazole, pyrazine, pyrimidine or pyridazine ring.

7. A prodrug according to claim 1, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group or a naphthylene group.

8. A prodrug according to claim 1, wherein D is a phenylene group.

18. A prodrug according to claim 1, wherein D is an arylene group, which is not substituted.

2. A method of facilitating the uptake of an active ingredient into a erythrocyte and/or binding an active ingredient to a erythrocyte comprising administering to the erythrocyte a prodrug of the following formula

Active ingredient Spacer - SO₂NH₂

in which - SO₂NH₂ enhances uptake of said active ingredient with an erythrocyte,

wherein

the spacer is

13. A method according to claim 2, wherein the active ingredient is estradiol.

14. A method according to claim 2, wherein the active ingredient is estriol.

15. A method according to claim 2, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group, a naphthylene group, pyridine, furan, thiophene, pyrrole, imidazole, pyrazine, pyrimidine or pyridazine ring.

16. A method according to claim 2, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group or a naphthylene group.

17. A method according to claim 2, wherein D is a phenylene group.

9. A prodrug of the following formula

Active ingredient -Spacer-SO₂NH₂

in which -SO₂NH₂ enhances uptake of said active ingredient with an erythrocyte,

wherein

the active ingredient is estradiol or estriol, and

the spacer is

10. A prodrug according to claim 9, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group, a naphthylene group, pyridine, furan, thiophene, pyrrole, imidazole, pyrazine, pyrimidine or pyridazine ring.

11. A prodrug according to claim 9, wherein D is a phenylene group, a halophenylene group, a hydroxyphenylene group or a naphthylene group.

12. A prodrug according to claim 9, wherein D is a phenylene group.