Trisubstituted-N-[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl] benzamides which inhibit P2X3 and P2X2/3 containing receptors

A compound of formula (I)

• 9
• or a pharmaceutically acceptable salt thereof, wherein
• A1 and A2 are each independently selected from the group consisting of alkoxycarbonyl, alkylcarbonyloxy, carboxy, hydroxy, hydroxyalkyl, (NRA RB)carbonyl, —NRCS(O)2RD, —S(O)2OH and tetrazolyl;
• or
• A1 and A2 together with the carbon atoms to which they are attached form a five membered heterocycle containing a sulfur atom wherein the five membered heterocycle is optionally substituted with 1 or 2 substituents selected from the group consisting of mercapto and oxo;
• A3 is selected from the group consisting of alkoxycarbonyl, alkylcarbonyloxy, carboxy, hydroxy, hydroxyalkyl, (NRA RB)carbonyl, NRCS(O)2RD, —S(O)2OH and tetrazolyl;
• A4, A5, A6 and A7 are each independently selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkenyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkynyl, aryl, carboxy, cyano, haloalkoxy, haloalkyl, halogen, heterocycle, hydroxy, hydroxyalkyl, nitro, —NRERF and (NRERF)carbonyl;
• A8, A9, A10 and A11 are each independently selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkenyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkynyl, aryl, carboxy, haloalkoxy, haloalkyl, halogen, heterocycle, hydroxy, hydroxyalkyl, —NRERFand (NRERF)carbonyl and oxo;
• RA and RB are each independently selected from the group consisting of hydrogen, alkyl and cyano;
• RC is selected from the group consisting of hydrogen and alkyl;
• RD is selected from the group consisting of alkoxy, alkyl, aryl, arylalkoxy, arylalkyl, haloalkoxy and haloalkyl;
• RE and RF are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl and formyl;
• L1 is selected from the group consisting of alkenylene, alkylene, alkynylene, —(CH2)mO(CH2)n—, —(CH2)mS(CH2)n—, and —(CH2)pC(O)(CH2)q— wherein each group is drawn with the left end attached to N and the right end attached to R1;
• m is an integer 0-10;
• n is an integer 0-10;
• R1 is selected from the group consisting of aryl, cycloalkenyl, cycloalkyl and heterocycle;
• L2 is absent or selected from the group consisting of a covalent bond, alkenylene, alkylene, alkynylene, —(CH2)pO(CH2)q—, —(CH2)pS(CH2)q—, —(CH2)pC(O)(CH2)q—, —(CH2)pC(OH)(CH2)q— and —(CH2)pCH═NO(CH2)q— wherein each group is drawn with the left end attached to R1 and the right end attached to R2;
• p is an integer 0-10;
• q is an integer 0-10;
• and
• R2 is absent or selected from the group consisting of aryl, cycloalkenyl, cycloalkyl and heterocycle.