CB1R receptor blockers with acyclic backbones

A compound selected from compounds:

• (A) of the general formula (II):
• wherein
• each of R1 and R2, independently of the other, is a group selected from —H, halide, —CN, —C1-C5alkyl-OH and —OH;
• each of n and m, independently of the other, is an integer between 0 and 5, designating the number of substituents on the ring;
• one of L, L1 and L2 is a nitrogen atom and the others of L, L1 and L2 are each a carbon atom;
• each of R5, R6 and R7, independently of the other, is selected from —H, —C1-C3alkyl, —C(═O)—OH, —C(═O)—O—R8, —C(═O)—NR′R8, halide, —CN, —OH, and —NR′R″;
• or
• one of R5 and R6 or R6 and R7 together with the atoms to which they bond form a 5-, 6-, 7- or 8-membered carbocyclic ring optionally containing between 1 and 3 heteroatoms selected from N, O and S;
• or
• one of R5, R6 and R7 is absent;
• the 5-, 6-, 7- or 8-membered carbocyclic ring is optionally substituted by at least one functionality selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, —C6-C10aryl, an hydroxyl, an amine, a halide, —ONO2, —NO2, —S—, —S—C1-C5alkyl, —S—C2-C5alkenyl, —S—C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C2-C5alkenyl, —C(═O)—O—C2-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—NR′—C(═O)—C1-C25alkyl, —C(═O)—NR′—C(═O)—C2-C25alkenyl, —C(═O)—NR′—C(═O)—C2-C25alkynyl, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —NH—NH2, —NH—NH—C(═O)—C1-C25alkyl, —NH—NH—C(═O)—C2-C25alkenyl, —NH—NH—C(═O)—C2-C25alkynyl, —NH—NH—C(═O)—C6-C10aryl, —NH—NH—C(═O)—C3-C10heteroaryl, —NH—C1-C25alkyl-C(═O)—OH, —NH—C2-C25alkenyl-C(═O)—OH, —NH—C2-C25alkynyl-C(═O)—OH, —NH—C1-C25alkyl-C(═O)—NR′R″R′″, —NH—C2-C25alkenyl-C(═O)—NR′R″R′″, —NH—C2-C25alkynyl-C(═O)—NR′R″R′″, —NH—C1-C25alkyl-NH2, —NH—C2-C25alkenyl-NH2, —NH—C2-C25alkynyl-NH2, —NH—C1-C25alkyl-NH—C(═O)—C1-C25alkyl, —NH—C2-C25alkenyl-NH—C(═O)—C1-C25alkyl, —NH—C2-C25alkynyl-NH—C(═O)—C1-C25alkyl, —NH—C1-C25alkyl-NH—C(═O)—C6-C10aryl, —NH—C2-C25alkenyl-NH—C(═O)—C6-C10aryl, —NH—C2-C25alkynyl-NH—C(═O)—C6-C10aryl, —NH—C1-C25alkyl-NH—C(═O)—C3-C10heteroaryl, —NH—C2-C25alkenyl-NH—C(═O)—C3-C10heteroaryl, —NH—C2-C25alkynyl-NH—C(═O)—C3-C10heteroaryl, —NH—C1-C25alkylene-C(═O)—NR′R″R′″, —NH—C2-C25alkenylene-C(═O)—NR′R″R′″, —NH—C2-C25alkynylene-C(═O)—NR′R″R′″, —NH—C1-C25alkylene-C(═O)—O—C1-C25alkyl, —NH—C2-C25alkenylene-C(═O)—O—C1-C25alkyl, —NH—C2-C25alkynylene-C(═O)—O—C1-C25alkyl, —NHC(═O)C1-C25alkyl, —NHC(═O)C2-C25alkenyl, —NHC(═O)C2-C25alkynyl, —NHC(═O)C1-C25alkylene-NR′R″R′″, —NHC(═O)C2-C25alkenylene-NR′R″R′″, —NHC(═O)C2-C25alkynylene-NR′R″R′″, —NHC(═O)C1-C25alkylene-OH, —NHC(═O)C2-C25alkenylene-OH, —NHC(═O)C2-C25alkynylene-OH, —NHC(═O)C6-C10aryl, —NHC(═O)C3-C10heteroaryl, —NHC(═O)C1-C25alkylene-C6-C10aryl, —NHC(═O)C2-C25alkenylene-C6-C10aryl, —NHC(═O)C2-C25alkynylene-C6-C10aryl, —NHC(═O)C3-C10heteroaryl, —NHC(═O)C1-C25alkylene-C3-C10heteroaryl, —NHC(═O)C2-C25alkenylene-C3-C10heteroaryl, —NHC(═O)C2-C25alkynylene-C3-C10heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl free radical, —NHC(═O)C(CH3)2—O-aryl-Cl, —NHC(═O)CH2C(CH3)2—O-aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″;
• the 5-, 6-, 7- or 8-membered carbocyclic ring is optionally substituted by at least one functionality selected from structures (A) through (H):
• wherein in each functionality (A) through (H), the wavy line indicates point or bond of connectivity, j is 0 or 1 and Ra is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, —C(═O)—C6-C10aryl and —C(═O)—C3-C10heteroaryl,
• wherein in functionalities (G) and (H) the pendant-NH—Ra group appears between 1 and 11 times at any position along the carbocycle;
• R8 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, —C6-C10aryl and C3-C10heteroaryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —ONO2, —NO2, —S—, —S—C1-C5alkyl, —S—C2-C5alkenyl, —S—C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C2-C5alkenyl, —C(═O)—O—C2-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—NR′—C(═O)—C1-C25alkyl, —C(═O)—NR′—C(═O)—C1-C25alkenyl, —C(═O)—NR′—C(═O)—C1-C25alkynyl, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —NH—NH2, —NH—NH—C(═O)—C1-C25alkyl, —NH—NH—C(═O)—C2-C25alkenyl, —NH—NH—C(═O)—C2-C25alkynyl, —NH—NH—C(═O)—C6-C10aryl, —NH—NH—C(═O)—C3-C10heteroaryl, —NH—C1-C25alkyl-C(═O)—OH, —NH—C2-C25alkenyl-C(═O)—OH, —NH—C2-C25alkynyl-C(═O)—OH, —NH—C1-C25alkyl-C(═O)—NR′R″R′″, —NH—C2-C25alkenyl-C(═O)—NR′R″R′″, —NH—C2-C25alkynyl-C(═O)—NR′R″R′″, —NH—C1-C25alkyl-NH2, —NH—C2-C25alkenyl-NH2, —NH—C2-C25alkynyl-NH2, —NH—C1-C25alkyl-NH—C(═O)—C1-C25alkyl, —NH—C2-C25alkenyl-NH—C(═O)—C1-C25alkyl, —NH—C2-C25alkynyl-NH—C(═O)—C1-C25alkyl, —NH—C1-C25alkyl-NH—C(═O)—C6-C10aryl, —NH—C2-C25alkenyl-NH—C(═O)—C6-C10aryl, —NH—C2-C25alkynyl-NH—C(═O)—C6-C10aryl, —NH—C1-C25alkyl-NH—C(═O)—C3-C10heteroaryl, —NH—C2-C25alkenyl-NH—C(═O)—C3-C10heteroaryl, —NH—C2-C25alkynyl-NH—C(═O)—C3-C10heteroaryl, —NH—C1-C25alkylene-C(═O)—NR′R″R′″, —NH—C2-C25alkenylene-C(═O)—NR′R″R′″, —NH—C2-C25alkynylene-C(═O)—NR′R″R′″, —NH—C1-C25alkylene-C(═O)—O—C1-C25alkyl, —NH—C2-C25alkenylene-C(═O)—O—C1-C25alkyl, —NH—C2-C25alkynylene-C(═O)—O—C1-C25alkyl, —NHC(═O)C1-C25alkyl, —NHC(═O)C2-C25alkenyl, —NHC(═O)C2-C25alkynyl, —NHC(═O)C1-C25alkylene-NR′R″R′″, —NHC(═O)C2-C25alkenylene-NR′R″R′″, —NHC(═O)C2-C25alkynylene-NR′R″R′″, —NHC(═O)C1-C25alkylene-OH, —NHC(═O)C2-C25alkenylene-OH, —NHC(═O)C2-C25alkynylene-OH, —NHC(═O)C6-C10aryl, —NHC(═O)C3-C10heteroaryl, —NHC(═O)C1-C25alkylene-C6-C10aryl, —NHC(═O)C2-C25alkenylene-C6-C10aryl, —NHC(═O)C2-C25alkynylene-C6-C10aryl, —NHC(═O)C3-C10heteroaryl, —NHC(═O)C1-C25alkylene-C3-C10heteroaryl, —NHC(═O)C2-C25alkenylene-C3-C10heteroaryl, —NHC(═O)C2-C25alkynylene-C3-C10heteroaryl, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl free radical, —NHC(═O)C(CH3)2—O-aryl-Cl, —NHC(═O)CH2C(CH3)2—O-aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″;
• R10 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, —C6-C10aryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C1-C5alkenyl, —C(═O)—O—C1-C5alkynyl, —C(═O)—NR′R″R′″, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —S—, —S—C1-C5alkyl, —S—C1-C5alkenyl, —S—C1-C5alkynyl, —ONO2, —NO2, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, —NHC(═O)CH2C(CH3)2—O-aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″;
• each of R′, R″ and R″ is independently selected from H, C1-C5alkyl, C2-C5alkenyl, C2-C5alkynyl, —C(═O)—C2-C25alkyl, —C(═O)—C2-C25alkenyl and C5-C25alkynyl;
• or wherein one of R′, R″ and R″ is absent;
• and wherein
• each bond between N-L, L-L1, L1-L2 and L2-C (designated ---) is a single or double bond;
• (B) of formula (III):
• wherein each of R1, R2, n, m, R6 and R7 is as defined for compound (II);
• and
• wherein --- designates a single or a double bond and wherein, in case it is a double bond, the carbon atom bearing variant R7 does not carry a bond to a hydrogen atom;
• (C) of general formula (IV):
• wherein each of R1, R2, n, m and R8 is as defined for compound (II);
• (D) of the formula (V):
• wherein R8 is as defined for compound (II);
• (E) of the general formula (VI):
• wherein each of R1, R2, n, m, R6 and R7 is as defined for compound (II);
• (F) of general formula (VII):
• wherein each of R1, R2, n, m and R8 is as defined for compound (II);
• (G) of the general formula (VIII):
• wherein each of R1, R2, n and m is as defined for compound (II);
• (H) of the formula (IX):
• wherein R8 is as defined for compound (II);
• (I) of the general formula (XI):
• wherein each of R1, R2, n, m and R8 is as defined for compound (II);
• and
• wherein optionally R8 is not C7-C12alkyl;
• (J) of the general formula (XII):
• wherein each of R1, R2, n and m is as defined for compound (II);
• (K) of the formula (XIII):
• wherein each of R1, R2, n and m is as defined for compound (II);
• and
• wherein k is an integer between 0 to 25;
• (L) of the general formula (XIV):
• wherein R8 is as defined for compound (II);
• (M) of the formula (XVI):
• wherein k is an integer between 0 to 25;
• (N) of the general formula (XVII):
• wherein each of R1, R2, n, m, is as defined for compound (II);
• and wherein R11 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, and —C6-C10aryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C1-C5alkenyl, —C(═O)—O—C1-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —S—, —S—C1-C5alkyl, —S—C1-C5alkenyl, —S—C1-C5alkynyl, —ONO2, —NO2, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, —NHC(═O)CH2C(CH3)2—O-Aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″, and wherein R′, R″, R″ and R10 are as defined for compound (II);
• (O) of the general formula (XVIII):
• wherein R11 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, and —C6-C10aryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C1-C5alkenyl, —C(═O)—O—C1-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —S—, —S—C1-C5alkyl, —S—C1-C5alkenyl, —S—C1-C5alkynyl, —ONO2, —NO2, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, —NHC(═O)CH2C(CH3)2—O-Aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″, and wherein R′, R″, R″ and R10 are as defined for compound (II);
• (P) of the general formula (XIX):
• wherein each of R1, R2, n, m, and R10 is as defined for compound (II);
• (Q) of the general formula (XX):
• wherein R10 is as defined for compound (II);
• (R) of the general formula (XXI):
• wherein each of R1, R2, n, m, is as defined for compound (II);
• and wherein R11 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, and —C6-C10aryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C1-C5alkenyl, —C(═O)—O—C1-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —S—, —S—C1-C5alkyl, —S—C1-C5alkenyl, —S—C1-C5alkynyl, —ONO2, —NO2, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, —NHC(═O)CH2C(CH3)2—O-Aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″, and wherein R′, R″, R″ and R10 are as defined for compound (II);
• (S) of the general formula (XXII):
• wherein each of R1, R2, n, m, is as defined for compound (II);
• (T) of the general formula (XXIII):
• wherein R11 is selected from —H, —C1-C25alkyl, —C2-C25alkenyl, —C2-C25alkynyl, and —C6-C10aryl, each of which being optionally substituted by at least one functionality selected from an hydroxyl, an amine, a halide, —C1-C5alkyl, —C2-C5alkenyl, —C2-C5alkynyl, —C(═O)—, —C(═O)—C1-C25alkyl, —C(═O)—O—C1-C5alkyl, —C(═O)—O—C1-C5alkenyl, —C(═O)—O—C1-C5alkynyl, —C(═O)—NR′R″R′″, —C(═O)—OR10, —O—C1-C5alkyl, —O—C1-C5alkenyl, —O—C1-C5alkynyl, —S—, —S—C1-C5alkyl, —S—C1-C5alkenyl, —S—C1-C5alkynyl, —ONO2, —NO2, 2,2,6,6-tetramethylpiperidin-1-ol-4-yl, —NHC(═O)CH2C(CH3)2—O-Aryl-Cl, idebenonyl-derivative, -pyridine-3-C(═O)—OH and —NR′R″R′″, and wherein R′, R″, R″ and R10 are as defined for compound (II);
• (U) of the general formula (XXV):
• wherein each of R1, R2, n, m, and R10 is as defined for compound (II);
• or
• (V) of the general formula (XXVI):
• wherein R10 is as defined for compound (II).