SULFAMOYL-ARYLAMIDES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

• US 20150274653A1
• Filed: 08/28/2013
• Published: 10/01/2015
• Est. Priority Date: 08/28/2012
• Status: Abandoned Application

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Inventors: Vandyck, Koen, Last, Stefaan Julien, Rombouts, Geert, Verschueren, Wim Gaston, Raboisson, Pierre Jean-Marie Bernard
• Application Number:
  US14/423,981
• Publication Number:
  US 20150274653A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4453 only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/04 : with a four-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2602/08 : the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 : the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 311/14 : Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07C 311/16 : having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
• CPC Class Codes: C07C 311/20 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/37 : having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/51 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07D 205/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 207/14 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 207/273 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
• CPC Class Codes: C07D 207/36 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 211/28 : to which a second hetero atom is attached
• CPC Class Codes: C07D 211/56 : Nitrogen atoms nitro radicals C07D211/38
• CPC Class Codes: C07D 211/76 : attached in position 2 or 6
• CPC Class Codes: C07D 211/96 : Sulfur atom
• CPC Class Codes: C07D 213/42 : having hetero atoms attached to the substituent nitrogen atom nitro radicals C07D213/26
• CPC Class Codes: C07D 213/81 : Amides; Imides
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 223/06 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms halogen atoms C07D223/04
• CPC Class Codes: C07D 233/84 : Sulfur atoms
• CPC Class Codes: C07D 233/90 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 295/13 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/26 : Sulfur atoms
• CPC Class Codes: C07D 305/08 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms
• CPC Class Codes: C07D 307/22 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 307/60 : Two oxygen atoms, e.g. succinic anhydride
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 309/14 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/48 : by oxygen atoms
• CPC Class Codes: C07D 491/107 : with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 493/08 : Bridged systems

Abstract

Inhibitors of HBV replication of Formula (I)

including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein B, R₁, R₂ and R₄ have the meaning as defined herein.

The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HBV inhibitors, in HBV therapy.

Claims

1. A compound of Formula (I)

2. A compound as claimed in claim 1, wherein at least one R₄ is fluoro, and one other R₄ is selected from the group consisting of C₁-C₃alkyl, C₁-C₃alkenyl, CHF₂ and cyclopropyl.

3. A compound as claimed in claim 1 wherein one R₄ is fluoro and one other R₄ is methyl or CHF₂ and wherein the location of said fluoro is in the para position and the location of said methyl or CHF₂ is in the meta position with respect to the

4. A compound as claimed in claim 1, wherein R₂ is a 4-7 membered saturated ring containing carbon and one or more oxygen atoms, said 4-7 membered saturated ring optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C₁-C₄alkyloxy, C₁-C₄alkyloxycarbonyl, C(═

O)—

C₁-C₃alkyl, C₁-C₄alkyl, OH, CN, CFH₂, CF₂H and CF₃.

5. A compound as claimed in claim 1, wherein R₂ is a 4-7 membered saturated ring containing carbon and one or more oxygen atoms, said 4-7 membered saturated ring optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C₁-C₄alkyloxy, C₁-C₄ alkyloxycarbonyl, C(═

O)—

C₁-C₃alkyl, C₁-C₄ alkyl, OH, CN, CFH₂, CF₂H and CF₃ wherein said compound is not

6. A compound as claimed in claim 1, wherein B is phenyl or thiophene, optionally being substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, C₁-C₃alkyl, CN, CFH₂, CF₂H and CF₃.

7. A compound as claimed in claim 1, wherein said compound of Formula (I) is a compound of Formula (Ib)

8. A compound as claimed in claim 1, wherein said compound of Formula (I) is a compound of Formula (Id)

9. A compound as claimed in claim 7, wherein R₃ is hydrogen.

10. A compound for as claimed in claim 1, wherein said compound of Formula (I) is a compound of Formula (Ic)

11. A method of treating an HBV infection in a mammal, comprising the administration of a therapeutically effective amount of at least one compound as claimed in claim 1.

12. A pharmaceutical composition comprising a compound as claimed in claim 1, and a pharmaceutically acceptable carrier.

13. A product comprising a compound of formula (I) as claimed in claim 1, and another HBV inhibitor, as a combined preparation for simultaneous, separate or sequential use in the treatment of HBV infections.

14. A compound as claimed in claim 8, wherein R₃ is hydrogen.