Fluorinated benzenesulfonamides as inhibitors of carbonic anhydrase

Patent metadata

Field	Value
Publication number	US-9725467-B2
Application number	US-201214435649-A
Country	US
Kind code	B2
Filing date	Oct 30, 2012
Priority date	Oct 15, 2012
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

Novel fluorinated benzenesulfonamides compounds of general formula (I)

can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression.

First claim

The invention claimed is:

1. Fluorinated benzenesulfonamides of general formula (I)

where
n is 2 or 3, the fluorine atoms are in any position,
m is 2 or 3, the A groups are identical or different from each other,
n+m must be equal to 5,
A is selected from the group consisting of R 1 , OH, OR 1 , SH, SR 1 , S(O)R 1 , SO 2 R 1 , C(O)R 1 , C(O)OR 1 , OC(O)R 1 , NHR 1 , N(R 1 ) 2 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 , NHC(O)NH 2 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 O(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NR 1 SO 2 R 1 , NHSO 2 NHR 1 , NHSO 2 N(R 1 ) 2 , NR 1 SO 2 NHR 1 , NR 1 SO 2 N(R 1 ) 2 , C(O)NHNOH, C(O)NHNOR 1 , C(O)NHSO 2 R 1 , C(NH)NH 2 , C(NH)NHR 1 , C(NH)N(R 1 ) 2 , NHSO 2 NHR 1 , NHSO 2 N(CH 3 )R 1 , N(CH 3 )SO 2 N(CH 3 )R 1 , Cl, Br, I, CN, NO 2 , N 3 , C(O)H, CHNOH, CH(NOCH 3 ), CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , and C(O)NH 2 ,
R 1 is R 2 , R 3 , R 4 , R 5 , R 6 , R 7 ,
R 2 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 3 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 4 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene,
R 5 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of R 8 , OH, OR 8 , SH, SR 8 , S(O)R 8 , SO 2 R 8 , C(O)R 8 , C(O)OR 8 , OC(O)R 8 , NHR 8 , N(R 8 ) 2 , C(O)NHR 8 , C(O)N(R 8 ) 2 , NHC(O)R 8 , NR 8 C(O)R 8 , NHC(O)OR 8 , NR 8 C(O)OR 8 , NHC(O)NH 2 , NHC(O)NHR 8 , NHC(O)N(R 8 ) 2 , NR 8 C(O)NHR 8 , NR 8 C(O)N(R 8 ) 2 , SO 2 NHR 8 , SO 2 N(R 8 ) 2 , NR 8 SO 2 R 8 , NHSO 2 NHR 8 , NHSO 2 N(R 8 ) 2 , NR 8 SO 2 NHR 8 , NR 8 SO 2 N(R 8 ) 2 , C(O)NHNOH, C(O)NHNOR 8 , C(O)NHSO 2 R 8 , C(NH)NH 2 , C(NH)NHR 8 , C(NH)N(R 8 ) 2 , NHSO 2 NHR 8 , NHSO 2 N(CH 3 )R 8 , N(CH 3 )SO 2 N(CH 3 )R 8 , F, Cl, Br, I, CN, NO 2 , N 3 , C(O)H, CHNOH, CH(NOCH 3 ), CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)OH, and C(O)NH 2 ,
R 8 is R 9 , R 10 , R 11 , R 12 , R 13 , R 14 ,
R 9 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 10 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 11 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene,
R 12 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 13 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 14 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 6 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of R 15 , OH, OR 15 , SH, SR 15 , S(O)R 15 , SO 2 R 15 , C(O)R 15 , C(O)OR 15 , OC(O)R 15 , NHR 15 , N(R 15 ) 2 , C(O)NHR 15 , C(O)N(R 15 ) 2 , NHC(O)R 15 , NR 15 C(O)R 15 , NHC(O)OR 15 , NR 15 C(O)OR 15 , NHC(O)NH 2 , NHC(O)NHR 15 , NHC(O)N(R 15 ) 2 , NR 15 C(O)NHR 15 , NR 15 C(O)N(R 15 ) 2 , SO 2 NHR 15 , SO 2 N(R 15 ) 2 , NR 15 SO 2 R 15 , NHSO 2 NHR 15 , NHSO 2 N(R 15 ) 2 , NR 15 SO 2 NHR 15 , NR 15 SO 2 N(R 15 ) 2 , C(O)NHNOH, C(O)NHNOR 15 , C(O)NHSO 2 R 15 , C(NH)NH 2 , C(NH)NHR 15 , C(NH)N(R 15 ) 2 , NHSO 2 NHR 15 , NHSO 2 N(CH 3 )R 15 , N(CH 3 )SO 2 N(CH 3 )R 15 , F, Cl, Br, I, CN, NO 2 , N 3 , C(O)H, CHNOH, CH(NOCH 3 ), CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)OH, and C(O)NH 2 ,
R 15 is R 16 , R 17 , R 18 , R 19 , R 20 , R 21 ,
R 16 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 17 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 18 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene,
R 19 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 20 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 21 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 7 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from R 22 , OH, OR 22 , SH, SR 22 , S(O)R 22 , SO 2 R 22 , C(O)R 22 , C(O)OR 22 , OC(O)R 22 , NHR 22 , N(R 22 ) 2 , C(O)NHR 22 , C(O)N(R 22 ) 2 , NHC(O)R 22 , NR 22 C(O)R 22 , NHC(O)OR 22 , NR 22 C(O)OR 22 , NHC(O)NH 2 , NHC(O)NHR 22 , NHC(O)N(R 22 ) 2 , NR 22 C(O)NHR 22 , NR 22 C(O)N(R 22 ) 2 , SO 2 NHR 22 , SO 2 N(R 22 ) 2 , NR 22 SO 2 R 22 , NHSO 2 NHR 22 , NHSO 2 N(R 22 ) 2 , NR 22 SO 2 NHR 22 , NR 22 SO 2 N(R 22 ) 2 , C(O)NHNOH, C(O)NHNOR 22 , C(O)NHSO 2 R 22 , C(NH)NH 2 , C(NH)NHR 22 , C(NH)N(R 22 ) 2 , NHSO 2 NHR 22 , NHSO 2 N(CH 3 )R 22 , N(CH 3 )SO 2 N(CH 3 )R 22 , F, Cl, Br, I, CN, NO 2 , N 3 , C(O)H, CHNOH, CH(NOCH 3 ), CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)OH, C(O)NH 2 ,
R 22 is R 23 , R 24 , R 25 , R 26 , R 27 , R 28 ,
R 23 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 24 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane,
R 25 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene,
R 26 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2 , NHCH 3 , N(CH 3 ) 2 , SH, SMe, C(O)NH 2 , C(O)NHOH, CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , C(O)H, C(O)OH, C(O)OC 2 H 5 , OH, OCH 3 , OC 2 H 5 , CH 3 , C 2 H 5 , CH(CH 3 ) 2 , CN, N 3 , NO 2 , F, Cl, Br, and I,
R 27 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of
NH 2

Assignees

• Univ Vilnius

Inventors

• Matulis Daumantas
• Dudutiene Virginija
• Zubriene Asta

Classifications

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07C323/67

  containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton · CPC title

• C07C317/22

  with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton · CPC title

• C07D277/74

  Sulfur atoms substituted by carbon atoms · CPC title