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US 7,544,676 B2Granted
Sulfamoyl benzamides and methods of their use
AssigneeAdolor Corporation
InventorsRoland E. Dolle, Karin Worm
Life of this patent
Estimating the term…
Abstract
Novel sulfamoyl benzamide compounds, pharmaceutical compositions containing the sulfamoyl benzamide compounds, and methods of their pharmaceutical use are disclosed. In certain embodiments, the sulfamoyl benzamide compounds are agonists and/or ligands of cannabinoid receptors and may be useful, inter alia, for treating and/or preventing pain, gastrointestinal disorders, inflammation, auto-immune diseases, ischemic conditions, immune-related disorders, hypertension, neurological disorders, and neurodegenerative diseases, for providing cardioprotection against ischemic and reperfusion effects, for inducing apoptosis in malignant cells, for inhibiting mechanical hyperalgesia associated with nerve injury, and as an appetite stimulant.
Claims74
A compound of formula I:
- wherein:
- R1 is NRyRz;
- each Rx, Ry and Rz is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl;
- or Ry and Rz, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R9)—, —N(R10)—C(═O)—, or —C(═O)—N(R10)—;
- R2 and R3 are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R2 and R3 is other than H;
- or R2 and R3, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R9)—, —N(R10)—C(═O)—, or —C(═O)—N(R10)—;
- R4 is H or alkyl;
- R5 is:
- Z is
- a 1 or 2 heteroatom containing heteroaryl, or a 1 or 2 heteroatom containing heterocycloalkyl, wherein each heteroatom of said heteroaryl or heterocycloalkyl group is independently selected from the group consisting of N, N(R11), O, and S;
- each Ra and Rb is independently H or alkyl;
- Rc is H, alkyl, or aryl;
- Rd and Re are each independently H or alkyl, with the proviso that at least two of Rc, Rd, and Re are other than H;
- or Rd and Re, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring;
- or Rc, Rd, and Re, taken together with the carbon atom to which they are attached, form a bicycloalkyl, tricycloalkyl, heterobicyclic, or heterotricyclic ring;
- R6 and R8 are each independently H or alkyl;
- each R9 is independently H, alkyl, aryl, —C(═O)—R11, —C(═O)—OR11, —[C(R11)(R11)]s—C(═O)—OR11, —SO2R11, or —C(═O)N(R11)R11;
- each R10 is independently H, alkyl, or aryl;
- each R11 is independently H or alkyl;
- r is 0, 1, 2, or 3;
- and
- s is 1, 2, 3, or 4;
- with the provisos that:
- (1) when Rd and Re are each independently H or alkyl, then Rc is H or alkyl;
- (2) when Rc is aryl, then Rd and Re, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring;
- (3) NRyRz is other than an optionally substituted piperazine ring;
- and
- (4) when R4 is H, R5 is sec-butyl, and R6, R8, and one of R2 and R3 is H, then the other of R2 and R3 is other than;
- or a pharmaceutically acceptable salt thereof.
26 more elements
A pharmaceutical composition, comprising:
- a pharmaceutically acceptable carrier;
- and a compound of formula I:
- wherein:
- R1 is NRyRz;
- each Rx, Ry and Rz is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl;
- or and Rz, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R9)—, —N(R10)—C(═O)—, or —C(═O)—N(R10)—;
- R2 and R3 are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R2 and R3 is other than H;
- or R2 and R3, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R9)—, —N(R10)—C(═O)—, or —C(═O)—N(R10)—;
- R4 is H or alkyl;
- R5 is:
- Z is
- a 1 or 2 heteroatom containing heteroaryl, or a 1 or 2 heteroatom containing heterocycloalkyl, wherein each heteroatom of said heteroaryl or heterocycloalkyl group is independently selected from the group consisting of N, O, or S;
- each Ra and Rb is independently H or alkyl;
- Rc is H, alkyl, or aryl;
- Rd and Re are each independently H or alkyl, with the proviso that at least two of Rc, Rd, and Re are other than H;
- or Rd and Re, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring;
- or Rc, Rd, and Re, taken together with the carbon atom to which they are attached, form a bicycloalkyl, tricycloalkyl, heterobicyclic, or heterotricyclic ring;
- R6 and R8 are each independently H or alkyl;
- each R9 is independently H, alkyl, aryl, —C(═O)—R11, —C(═O)—OR11, —[C(R11)(R11)]s—C(═O)—OR11, —SO2R11, or —C(═O)N(R11)R11;
- each R10 is independently H, alkyl, or aryl;
- each R11 is independently H or alkyl;
- r is 0, 1, 2, or 3;
- and
- s is 1, 2, 3, or 4;
- with the provisos that:
- (1) when Rd and Re are each independently H or alkyl, then Rc is H or alkyl;
- and
- (2) when Rc is aryl, then Rd and Re, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring;
- or a pharmaceutically acceptable salt thereof.
26 more elements
Dependencies are inferred from the claim text.