Kinase inhibitors

A compound according to formula I:

• wherein
• n is 1;
• Ring (1) is of formula
• wherein —X may be absent or denotes substitution with 1-4 substitutents X that are independently chosen from halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted or unsubstituted aryl, nitro, hydroxyl and a substituted or unsubstituted amino group;
• Ring (3) is a 1,3-phenylene, 1,4-phenylene, 1,3-cyclohexylene, or 1,4-cyclohexylene optionally substituted with 1-4 substitutents that are independently selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted or unsubstituted aryl, nitro, hydroxyl, an amino group;
• Ra is hydrogen;
• a linear or branched, optionally substituted C1-C6-alkyl;
• a linear or branched, optionally substituted C1-C6-alkoxy;
• or an optionally substituted aryl;
• represents a group selected from
• R1 is selected from the group consisting of hydrogen;
• a substituted or unsubstituted, saturated, unsaturated or aromatic 3-, 4-, 5-, 6-, 7-or 8-membered ring containing carbon atoms and optionally one or two heteroatoms;
• substituted or unsubstituted C1-C6 alkyl and cyano,
• or a salt, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, tautomer, isomer, and/or stereochemical isomer thereof.

A compound selected from the group consisting of

• N-pyridin-4-yl-4-pyrrolidin-2-yl-benzamide;
• 4-piperidin-2-yl-N-pyridin-4-yl-benzamide;
• 1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid pyridin-4-yl-amide;
• 4-(4,5-dihydro-1H-imidazol-2-yl)-N-pyridin-4-yl-benzamide;
• N-pyridin-4-yl-4-(1,4,5,6-tetrahydro-1H-pyrimidin-2-yl)-benzamide;
• 4-(1-amino-phenyl-methyl)-N-pyridin-4-yl-benzamide;
• 4-[1-amino-(4-fluorophenyl)-methyl]-N-pyridin-4-yl-benzamide;
• 4-[1-amino-(4-methoxyphenyl)-methyl]-N-pyridin-4-yl-benzamide;
• 4-(1-amino-ethyl)-naphthalene-1-carboxylic acid pyridin-4-ylamide;
• 4-aminomethyl-2,5-dimethyl-N-pyridin-4-yl-benzamide;
• 4-(1-amino-ethyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-cyclopentyl-ethyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid-N (1H pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-piperidin-2-yl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-cyclobutyl-ethyl)-N-pyridin-4-yl-benzamide;
• 4-(1-amino-2,2-dimethyl-butyl)-N-pyridin-4-yl-benzamide;
• 1-amino-indan-5-carboxylic acid pyridin-4-yl-amide;
• 4-(1-amino-butyl)-N-pyridin-4-yl-benzamide;
• 4-(1-amino-pentyl)-N-pyridin-4-yl-benzamide;
• 4-(1-amino-2-methyl-propyl)-N-pyridin-4-yl-benzamide;
• 4-(1-amino-2,2-dimethyl-propyl)-N-pyridin-4-yl-benzamide;
• 4-(1-amino-propyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-cyclopropyl-ethyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-cyclobutyl-ethyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-2,2-dimethyl-butyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 1-amino-indan-5-carboxylic acid(1H-pyrrolo[2,3-b]pyridin-4-yl)-amide;
• 5-amino-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (1H-pyrrolo[2,3-b]pyridin-4-yl)-amide;
• 4-(1-amino-butyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• 4-(1-amino-2,2-dimethyl-propyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;
• and
• or salt, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, tautomer, isomer, and/or stereochemical isomer thereof.

A method for the treatment or prevention of a metabolic disease or disorder, or complications and/or symptoms thereof, in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound according to the following formula, or a salt or prodrug thereof:

• wherein
• Ring (1) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, 6-, 7-, or 8-membered ring containing carbon atoms and at least one hydrogen-accepting heteroatom and optionally 1 or 2 further heteroatoms;
• Ra is a hydrogen or a linear or branched, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy or substituted or unsubstituted aryl;
• Ring (3) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, 6-, 7-, or 8-membered ring containing carbon atoms and optionally 1 or 2 further heteroatoms;
• each R1 or R2 may be the same or different and is independently selected from the group consisting of hydrogen, a substituted or unsubstituted, saturated, unsaturated or aromatic 3-, 4-, 5-, 6-, 7-or 8-membered ring containing carbon atoms and optionally one or two heteroatoms, substituted or unsubstituted C1-C6 alkyl or cyano;
• n is 0, 1, or 2;
• and
• Rb and Rc are such that the amino group —NRbRc is essentially in a protonated form at a pH between 5.0-9.0;
• and wherein
• (1) the group Ra, the nitrogen atom to which group Ra is bound, the carbon atom of Ring (1) to which the N—Ra nitrogen atom is bound, and one carbon atom of Ring (1) adjacent to the carbon atom of Ring (1) to which the N—Ra nitrogen atom is bound may form Ring (7) wherein Ring (7) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, or 6-membered ring that contains carbon atoms, the N—Ra nitrogen atom and optionally one further heteroatom chose from oxygen, sulfur, and nitrogen;
• (2) where Ring (3) is a 1,4-phenylene group, one of R1 and R2, the carbon atom to which R1 and R2 are bound and two of the carbon atoms belonging to the 1,4-phenylene group may form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (3) where Ring (3) is a 1,4-phenylene group, one of Rb or Rc, the nitrogen atom to which Rb or Rc are bound, the carbon atom to which R1 or R2 are bound and two of the carbon atoms belonging to the 1,4-phenylene group may form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (4) one of Rb and Rc may, together with the nitrogen atom of the amino group NRbRc, one of R1 and R2 and the carbon atom to which R1 and R2 are bound, form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (5) Rb, Rc and the nitrogen atom to which they are bound may together form a substituted or unsubstituted ring with between 3 and 10 atoms in the ring, including the nitrogen atom to which both Ra and Rb are bound, so that the ring so formed consists of a nitrogen atom, carbon atoms and optionally one further heteroatom chose from oxygen, nitrogen, and sulfur;
• and wherein
• the distance between the at least one hydrogen-accepting heteroatom in Ring (1) and the NRaRb nitrogen atom, as determined using a Scatter Plot, is in the range of 11.0 to 11.8 Angstroms.

A method for inhibition of the activity of at least one kinase, comprising contacting said kinase with a compound according to the following formula, or a salt or prodrug thereof:

• wherein
• Ring (1) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, 6-, 7-, or 8-membered ring containing carbon atoms and at least one hydrogen-accepting heteroatom and optionally 1 or 2 further heteroatoms;
• Ra is a hydrogen or a linear or branched, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy or substituted or unsubstituted aryl;
• Ring (3) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, 6-, 7-, or 8-membered ring containing carbon atoms and optionally 1 or 2 further heteroatoms;
• each R1 or R2 may be the same or different and is independently selected from the group consisting of hydrogen, a substituted or unsubstituted, saturated, unsaturated or aromatic 3-, 4-, 5-, 6-, 7-or 8-membered ring containing carbon atoms and optionally one or two heteroatoms, substituted or unsubstituted C1-C6 alkyl or cyano;
• n is 0, 1, or 2;
• and
• Rb and Rc are such that the amino group —NRbRc is essentially in a protonated form at a pH between 5.0-9.0;
• and wherein
• (1) the group Ra, the nitrogen atom to which group Ra is bound, the carbon atom of Ring (1) to which the N—Ra nitrogen atom is bound, and one carbon atom of Ring (1) adjacent to the carbon atom of Ring (1) to which the N—Ra nitrogen atom is bound may form Ring (7) wherein Ring (7) is a substituted or unsubstituted, saturated, unsaturated or aromatic 4-, 5-, or 6-membered ring that contains carbon atoms, the N—Ra nitrogen atom and optionally one further heteroatom chose from oxygen, sulfur, and nitrogen;
• (2) where Ring (3) is a 1,4-phenylene group, one of R1 and R2, the carbon atom to which R1 and R2 are bound and two of the carbon atoms belonging to the 1,4-phenylene group may form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (3) where Ring (3) is a 1,4-phenylene group, one of Rb or Rc, the nitrogen atom to which Rb or Rc are bound, the carbon atom to which R1 or R2 are bound and two of the carbon atoms belonging to the 1,4-phenylene group may form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (4) one of Rb and Rc may, together with the nitrogen atom of the amino group NRbRc, one of R1 and R2 and the carbon atom to which R1 and R2 are bound, form a substituted or unsubstituted 5-, 6-, 7-, or 8-membered ring that contains carbon atoms, the nitrogen atom of the amino group NRbRc and optionally one further heteroatom chosen from oxygen, sulfur, and nitrogen and that may be saturated or contain one double bond;
• (5) Rb, Rc and the nitrogen atom to which they are bound may together form a substituted or unsubstituted ring with between 3 and 10 atoms in the ring, including the nitrogen atom to which both Ra and Rb are bound, so that the ring so formed consists of a nitrogen atom, carbon atoms and optionally one further heteroatom chose from oxygen, nitrogen, and sulfur;
• and wherein
• the distance between the at least one hydrogen-accepting heteroatom in Ring (1) and the NRaRb nitrogen atom, as determined using a Scatter Plot, is in the range of 11.0 to 11.8 Angstroms.